Characteristics of cytokines in the sciatic nerve stumps and DRGs after rat sciatic nerve crush injury.
Cytokines are essential cellular modulators of various physiological and pathological activities, including peripheral nerve repair and regeneration. However, the molecular changes of these cellular mediators after peripheral nerve injury are still unclear. This study aimed to identify cytokines critical for the regenerative process of injured peripheral nerves. The sequencing data of the injured nerve stumps and the dorsal root ganglia (DRGs) of Sprague-Dawley (SD) rats subjected to sciatic nerve (SN) crush injury were analyzed to determine the expression patterns of genes coding for cytokines. PCR was used to validate the accuracy of the sequencing data. A total of 46, 52, and 54 upstream cytokines were differentially expressed in the SNs at 1 day, 4 days, and 7 days after nerve injury. A total of 25, 28, and 34 upstream cytokines were differentially expressed in the DRGs at these time points. The expression patterns of some essential upstream cytokines are displayed in a heatmap and were validated by PCR. Bioinformatic analysis of these differentially expressed upstream cytokines after nerve injury demonstrated that inflammatory and immune responses were significantly involved. In summary, these findings provide an overview of the dynamic changes in cytokines in the SNs and DRGs at different time points after nerve crush injury in rats, elucidate the biological processes of differentially expressed cytokines, especially the important roles in inflammatory and immune responses after peripheral nerve injury, and thus might contribute to the identification of potential treatments for peripheral nerve repair and regeneration.


Effects of stress on catecholamines and tyrosine hydroxylase activity of individual hypothalamic nuclei.
The effects of acute stress on norepinephrine (NE) and dopamine (DA) concentrations and of repeated stress on tyrosine hydroxylase (TH) activity were measured in individual hypothalamic nuclei and other rat brain regions. A microdissection technique and radioisotopic enzymatic assays enables these studies to be performed. NE and DA concentrations were reduced and TH activity increased selectively in the arcuate nucleus. These results suggest that the arcuate nucleus may be selectively involved in the stress response and support the hypothesis that catecholamines in the medial basal hypothalamus mediate certain of the neuroendocrine changes observed in stress.


Time on my side? Life course trajectories of poverty and health.
This study examines the relationship between poverty and health in time. Following the argument that time is significant for shaping the experience of being poor or not poor and growing evidence of heterogeneity in long-term patterns of poverty, we investigate whether different kinds of poverty have distinct consequences for long-term health. Using data from the 1968-1996 annual waves of the United States Panel Study of Income Dynamics Data, we estimate a general growth mixture model to assess the relationship between the longitudinal courses of poverty and health. The model allows us to first estimate latent poverty classes in the data and then determine their effects on latent self-rated health. Four types of long-term poverty patterns characterized as stable nonpoor, exiting poverty, entering poverty and stable poor were evident in the data. These different kinds of poverty affected self-rated health trajectories in distinct ways, but worked in concert with age, education and race to create gaps in initial health status that were constant over time.


Infections and antimicrobial resistance in an adult intensive care unit in a Brazilian hospital and the influence of drug resistance on the thirty-day mortality among patients with bloodstream infections.
The present study aimed to determine the incidence of health care-associated infections (HCAIs) and identify the main resistant microorganisms in intensive care unit (ICU) patients in a Brazilian university hospital. A retrospective cohort study was conducted in a Brazilian teaching hospital between 2012 and 2014. Overall, 81.2% of the infections were acquired in the ICU. The most common resistant pathogenic phenotypes in all-site and bloodstream infections were oxacillin-resistant coagulase-negative staphylococci and carbapenem-resistant Acinetobacter spp. (89.9% and 87.4%; 80.6% and 70.0%), respectively. There is an urgent need to focus on HCAIs in ICUs in Brazil.


Barriers to employment among unemployed drug users: age predicts severity.
Drug users in treatment or exiting treatment face many barriers to employment when entering the job market, such as low levels of education and technical skills, and low levels of interpersonal skills. As a result of these and other barriers, employment rates in these groups are generally low. This article examines the existence and possible predictors of specific barriers to employment related to interpersonal and technical skills in a sample of participants enrolled in a therapeutic workplace intervention for substance abuse. In Study I (N = 77), we characterized and examined predictors of participant scores on a staff-rated scale of interpersonal skills (Work Behavior Inventory). In Study II (N = 29), we examined whether participants had lower levels of computer knowledge than job seekers in the general population, and investigated possible predictors of computer knowledge in the sample. In general, participants in Study I displayed low levels of interpersonal skills, and participants in Study II scored lower on the computer knowledge test than job seekers in the general population. Older participants tended to have lower levels of interpersonal skills and lower levels of computer knowledge. These results suggest that providers of workforce development services for drug users in treatment or exiting treatment should attend to these specific barriers to employment, which may also be more pronounced among older clients.


Lots of Lovely Numbers, but Why Does Everyone Make It So Difficult?
Based on keynote at the 4th International Conference on Administrative Data, Cardiff, UK, December 10, 2019.


Neuronal progenitors of the dentate gyrus express the SARS-CoV-2 cell receptor during migration in the developing human hippocampus.
The COVID-19 pandemic spread around the world is due to the enormous capacity of the SARS-CoV-2 coronavirus to be transmitted between humans, causing a threat to global public health. It has been shown that the entry of this virus into cells is highly facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) in the cell membrane. Currently, we have no precise knowledge of how this receptor expresses in the brain of human fetus and, as a consequence, we do not know how susceptible the neural cells in the developing brain are to being infected through the vertical transmission of this virus, from mother to fetus. In this work, we describe the expression of ACE2 in the human brain at 20 weeks of gestation. This stage corresponds to the period of neuronal generation, migration, and differentiation in the cerebral cortex. We describe the specific expression of ACE2 in neuronal precursors and migratory neuroblasts of the dentate gyrus in the hippocampus. This finding implies that SARS-CoV-2 infection during the fetal period may affect neuronal progenitor cells and alter the normal development of the brain region where memory engrams are generated. Thus, although vertical transmission of SARS-CoV-2 infection was reported in few cases, the massive infection rate of young people in terms of the new variants leads to the possibility of increasing the ratio of congenital infections and originating cognitive alterations, as well as neuronal circuit anomalies that may represent vulnerability to mental problems throughout life.


The female reproductive system of the kissing bug, Rhodnius prolixus: arrangements of muscles, distribution and myoactivity of two endogenous FMRFamide-like peptides.
Phalloidin staining F-actin was used to image muscle fiber arrangements present in the reproductive system of the adult female Rhodnius prolixus. A mesh of muscle fibers encircles the ovaries whereas a criss-cross pattern of finer muscle fibers covers each ovariole. Two layers of muscle fibers (arranged longitudinally and circularly) form the lateral oviducts. The circular layer of muscle fibers extends throughout the common oviduct and spermathecae. A chevron pattern of thicker muscle fibers makes up the bursa. All of these structures show spontaneous contractions that are stimulated in a dose-dependent manner by the endogenous peptides, GNDNFMRFamide and AKDNFIRFamide which belong to the family of the FMRFamide-like peptides (FLP). Immunohistochemistry shows that these peptides could be supplied via nerves to the oviducts, spermathecae and bursa. Although no FMRF-like immunoreactivity was observed on the ovarioles/ovary they still exhibited a stimulatory response to the peptides indicating that they may be under the influence of FLPs as neurohormones. This work implicates FLPs in the control of ovulation, egg movement and oviposition in this insect.


Management of oral leukoplakia with an 808-nm high-power diode laser: a single-center experience.
High-power diode laser emerges as a promising approach to the treatment of oral leukoplakia (OL); however, its short- and long-term effects have been barely explored. This study evaluated the postoperative endpoints and the recurrence rate of high-power diode laser treatment in a well-defined series of patients with OL. A prospective analysis was performed on 22 individuals comprising 31 OL. The lesions were irradiated using the following protocol: Indium-Gallium-Arsenide diode laser, 808 nm, continuous-wave mode, 1.5-2.0 W, 780.0 ± 225.1 J, and 477.1 ± 131.8 s. Postoperative pain was assessed with a visual analog scale at three endpoints. Clinical follow-up was performed on all patients and the Kaplan-Meier test was used to analyze the probability of recurrence. The series consisted mostly of women (72.7%) with a mean age of 62.8 years. A single laser session was performed in 77.4% of cases. The median score on the scale that assessed pain on the 1st, 14th and 42nd postoperative day was 4, 1, and 0, respectively. The mean follow-up period per lesion was 28.6 months (range: 2-53 months). A complete response was observed in 93.5% of OL cases, while 6.5% had recurrence. The probability of recurrence at 39 months was 6.7%. No patient experienced malignant transformation. High-power diode laser for the treatment of OL is safe and effective during the trans- and postoperative period. These findings represent an alternative approach to the management of OL, mainly because a low recurrence rate was observed.


Association between medicare annual wellness visits and prevention of falls and fractures in older adults in Texas, USA.
Fall-related injuries contribute to increased frailty, disability, and premature death in older adults (≥65 years). The US Centers for Medicare and Medicaid Services began reimbursing annual wellness visits (AWVs) in 2011. In the present study, we assessed the effect of AWV receipt in 2017 on fall and fracture prevention through December 31, 2018. Using Texas Medicare data for 2014-2018, we identified cohorts of Medicare beneficiaries ≥68 years, matched for the presence/absence of an AWV in 2017 by propensity score, and observed two outcomes: fracture as a primary diagnosis, and fall occurrences. Rates of each outcome were estimated using the Kaplan-Meier method. Of the 2017 beneficiaries, 32.2% received an AWV. For the 742,494 beneficiaries in the matched cohort, conditional Cox proportional hazards models revealed that receiving an AWV in 2017 was associated with reduced risks for future falls (3.9%) and fractures (4%). The effect of the AWV was stronger on fall reduction in rural residents (HR: 0.799; 95% CI: 0.679 to 0.941) and on fracture reduction in beneficiaries with ≥4 morbidities (HR: 0.918; 95% CI: 0.867 to 0.972). Receipt of an AWV in three consecutive years (2015-2017) further lowered the risk of future falls. We conclude that the risks for future falls/fractures are lower in older adults receiving AWVs. Our study underscores the need for expanded public education programs that raise awareness about AWVs and the potential for AWV data to inform fall prevention interventions and other health promotion practices.


An efficient protocol for the synthesis of quinoxaline derivatives at room temperature using recyclable alumina-supported heteropolyoxometalates.
We report a suitable quinoxaline synthesis using molybdophosphovanadates supported on commercial alumina cylinders as catalysts. These catalysts were prepared by incipient wetness impregnation. The catalytic test was performed under different reaction conditions in order to know the performance of the synthesized catalysts. The method shows high yields of quinoxaline derivatives under heterogeneous conditions. Quinoxaline formation was obtained using benzyl, o-phenylenediamine, and toluene as reaction solvent at room temperature. The CuH(2)PMo(11)VO(40) supported on alumina showed higher activity in the tested reaction. Finally, various quinoxalines were prepared under mild conditions and with excellent yields.


Availability and affordability of cardiovascular medicines in a major city of Afghanistan in 2020.
Affordable access to quality medicines is a critical target of global efforts to achieve universal health coverage. The aim of this study is to measure the affordability and accessibility of cardiovascular medicines in the city of Herat, Afghanistan. The price, affordability, and availability data for 18 most sold generic (MSG) and lowest priced generic (LPG) products were collected from public and private pharmacies located in Herat city in Afghanistan in 2020, which in each area, six pharmacies were randomly selected from a combination of public and private ones based on the standardized methodology developed by WHO/HAI. According to this methodology on Medicine Prices, Accessibility, and Affordability, the minimum daily wage of an unskilled governmental worker, and the price of each type of cardiovascular medicines for one-month use were calculated separately. If the cost of the treatment was more than the minimum daily wage, the medicine was considered unaffordable. The mean availability score for lowest price generic (LPG) in public and private pharmacies and based on the countries of origin including Iran, Pakistan, and India was 60%, 46%, and 31%, respectively. Of the 18 medicines surveyed, just Atenolol (Iranian brand) was found in all 30 pharmacies on the day of data collection. All Indian- brand medicines were less than fifty percent available in any of the surveyed public and private pharmacies. Among the medicines exported to Afghanistan, the population of Herat used more medicines made by Pakistan compared to India and Iran (MSG). Indian medicines were the most expensive ones and the Iranian medicines were the cheapest. A wage of less than one day was enough to afford one-month supply of generic medicines at the lowest price. Access of patients to cardiovascular medicines in Afghanistan was 46% in this study which is regarded as low access. Most of available cardiovascular medicines in the market of this country were made in Iran, Pakistan and India. Although the Iranian ones were the cheapest, but people used more Pakistani medicines. LPG products were affordable to the studied population.


Mutations of the beta2-microglobulin gene result in a lack of HLA class I molecules on melanoma cells of two patients immunized with MAGE peptides.
Mutations have been identified in the beta2-microglobulin gene of tumor cells of two metastatic melanoma patients who received immunizations with MAGE peptides. One mutation abolishes the start codon whereas the other introduces a premature stop codon. The second beta2-microglobulin allele of both tumors appears to be lost on the basis of sequence data and loss of microsatellite heterozygosity. The lack of beta2-microglobulin gene product results in the absence of HLA class I antigens on the surface of the tumor cells. This may explain why the tumors of both patients progressed despite the immunization treatment and shows the necessity of analyzing in depth the antigen presentation capability of the tumor cells for the interpretation of clinical trials involving anti-tumor vaccination.


Binocular vision in glaucoma.
To describe the possible impairment of binocular vision in primary open angle glaucoma (POAG) patients. A cross-sectional study was conducted on 58 glaucoma patients, 76 ocular hypertensives and 82 normal subjects. They were examined with a battery of binocular tests consisting of the measurement of phoria angles, amplitudes of fusion (AF), near point of convergence (NPC) assessment, an evaluation of suppression (Worth test), stereoacuity according to Titmus, and TNO tests. The patients with glaucoma showed significantly increased phoria angles, especially in near vision, compared with the ocular hypertensives and controls (P=.000). AF were reduced mainly in near distances compared to hypertensives and controls (P=.000). The NPC of glaucoma was higher than the other two groups (P=.000). No differences were found in the near-distance suppression test between the three groups (P=.682), but there were differences in the distance vision of patients with glaucoma compared to hypertensives (OR=3.867, 95% CI; 1.260-11.862; P=.008) and controls (OR= 5.831, 95% CI; 2.229-15.252; P=.000). The stereoacuity of patients with glaucoma was reduced in both tests (P=.001). POAG is mostly associated with, an increased exophoria in near vision, a decreased AF in near vision, a far-distance NPC, central suppression in far-vision, and a loss of stereoacuity. These changes do not seem to appear early as they were not observed in hypertensive patients versus controls.


Cardiac injury is associated with inflammation in geriatric COVID-19 patients.
Geriatric patients with coronavirus disease (COVID-19) are at high risk of developing cardiac injury. Identifying the factors that affect high-sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population. One hundred and eighty inpatients who were admitted for COVID-19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients. Age (p < 0.001) significantly correlated with cardiac injury, whereas sex (p = 0.372) and coexisting diseases did not. Rising procalcitonin (p = 0.001), interleukin-2 receptor (p < 0.001), interleukin 6 (p = 0.001), interleukin 10 (p < 0.001), tumor necrosis factor α (p = 0.001), high-sensitivity C-reactive protein (p = 0.001), D-dimer (p < 0.001), white blood cells (p < 0.001), neutrophils (p = 0.001), declining lymphocytes (p < 0.001), and natural killer cells (p = 0.005) were associated with cardiac injury and showed predictive ability in the multivariate logistic regression. Our results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.


Glucose metabolism in glucose-intolerant older people during chromium supplementation.
The effects of chromic chloride (CrCl3) administered orally for 12 weeks to five elderly subjects with glucose intolerance were assessed. Pretreatment and posttreatment, the hyperglycemic clamp technique was employed to determine glucose utilization, beta-cell sensitivity to glucose, and tissue sensitivity to insulin. In addition, erythrocyte insulin binding was studied. Urinary chromium excretion increased approximately 5 fold indicating good compliance with supplementation. The oral glucose tolerance curves following supplementation were lowered from 60 to 120 minutes but only the 60-minute values were significantly lowered. In agreement with this was significantly increased glucose utilization during the hyperglycemic clamp studies. Tissue sensitivity to insulin, receptor affinity, and total insulin binding were unchanged by supplementation while beta-cell sensitivity to glucose increased following supplementation (P less than 0.04), and explained the increased glucose utilization. HDL and LDL and total cholesterol levels were slightly lower after chromium supplementation, but no change reached statistical significance. The LDL/HDL cholesterol ratio was unchanged. This study shows small but statistically significant effects of CrCl3 on carbohydrate metabolism. The clinical relevance of these effects, that is, their prophylactic or therapeutic significance, remains to be determined.


Glutathione S-transferase GSTM 1, null genotype may be associated with susceptibility to age-related cataract.
Age-related cataract (ARC) is the leading cause of visual disability and reversible blindness all over the world. The different expressions of GST isozymes among animals may explain the variations in the cataract formation caused by oxidative stress. In this study, we evaluated the distribution of GST gene polymorphisms in ARC patients and the possible associations between the presence of ARC and GST gene polymorphisms. The epidemiological data was collected by a standard questionnaire and blood samples were obtained from 130 ARC patients and 159 healthy controls. Data about smoking habits of the groups was recorded. Real-time polymerase chain reaction-based methods were used to detect genetic polymorphisms. The GSTM 1 null genotype was found to carry an increased risk for developing ARC (OR: 1.84, 95% CI: 1.13-2.99). The frequency of the GSTT 1 null genotype was not significantly different among the ARC patients and the controls (OR: 1.0, 95% CI: 0.64-1.6). The GSTP 1 Val/Val genotype was also not significantly different among the ARC patients and control groups (OR: 1.06, 95% CI: 0.50-2.23). GSTM 1 null genotype was highly frequent in non-smokers (OR: 3.25, 95% CI: 1.66-6.35) and moderately frequent in smokers (OR: 2.50, 95% CI: 1.28-4.86). Also, carrying the combined genotypes of GSTM 1 null, GSTT 1 and GSTP 1 105-Val allele was seen to have an increased risk of developing ARC (OR: 2.91, 95% CI: 1.31-6.44). This data may provide evidence that GSTM 1 gene polymorphisms may be associated with genetic susceptibility to develop ARC. Larger studies are warranted to verify these findings.


Computer-based detection and analysis of heart sound and murmur.
To develop a digital algorithm that detects first and second heart sounds, defines the systole and diastole, and characterises the systolic murmur. Heart sounds were recorded in 300 children with a cardiac murmur, using an electronic stethoscope. A Digital algorithm was developed for detection of first and second heart sounds. R-waves and T-waves in the electrocardiography were used as references for detection. The sound signal analysis was carried out using the short-time Fourier transform. The first heart sound detection rate, with reference to the R-wave, was 100% within 0.05-0.2R-R interval. The second heart sound detection rate between the end of the T-wave and the 0.6R-R interval was 97%. The systolic and diastolic phases of the cardiac cycle could be identified. Because of the overlap between heart sounds and murmur a systolic segment between the first and second heart sounds (20-70%) was selected for murmur analysis. The maximum intensity of the systolic murmur, its average frequency, and the mean spectral power were quantified. The frequency at the point with the highest sound intensity in the spectrum and its time from the first heart sound, the highest frequency, and frequency range were also determined. This method will serve as the foundation for computer-based detection of heart sounds and the characterisation of cardiac murmurs.


Near-infrared optical responses in feline brain and skeletal muscle tissues during respiratory acid-base imbalance.
The effects of hyper- and hypocapnia on oxidative metabolism were evaluated by near-infrared (NIR) multiwavelength spectroscopy in intact brain and skeletal muscle tissues of the anesthetized cat. A 3-wavelength NIR algorithm was used to monitor cytochrome a,a3 oxidation state, regional blood volume, and tissue oxyhemoglobin and O2 stores simultaneously in brain and muscle in ventilated animals. Incremental hypercapnia was produced in 10 cats by raising arterial pCO2 from 27.0 +/- 1.3 to 95.1 +/- 1.9 mmHg with inspired CO2. Hypercapnia produced progressive increases in cerebral HbO2, blood volume, and cytochrome a,a3 oxidation state (P less than 0.01). In contrast, CO2 simultaneously decreased all 3 NIR parameters in intact hindlimb muscles (P less than 0.01). Blood volume changes during hypercapnia correlated with changes in blood flow measured qualitatively by intravascular injections of indocyanine green dye. Hypocapnia produced by hyperventilation in 8 cats lowered paCO2 from 28.5 +/- 0.4 to 13.5 +/- 0.5 mmHg. Hypocapnia decreased cerebral HbO2, blood volume, and cytochrome a,a3 redox level (P less than 0.05), but NIR changes were not seen in skeletal muscle. These experiments demonstrate preferential distribution of oxygen to brain during hypercapnia and the ability of NIR spectroscopy to assess regional oxygenation in multiple tissues non-invasively.


Mapping and functional characterization of murine kidney injury molecule-1 proteolytic cleavage site.
Kidney injury molecule-1 (KIM-1), also known as T cell immunoglobulin and mucin domain 1 (TIM-1), is a transmembrane glycoprotein expressed on proximal tubule epithelia during acute kidney injury (AKI). Extracellular domain of KIM-1 undergoes spontaneous and activated ectodomain shedding into urine and blood via metalloproteases. Soluble KIM-1 (blood and urinary) is a reliable clinical biomarker of proximal tubular injury, but the biological significance of shedding remains unknown. The aim of this study was to identify the specific shedding enzyme and the proteolytic cleavage site of murine KIM-1, followed by the characterization of its functional relevance. In this regard, isoleucine (I) I202 was identified as the potential cleavage site. Mutation of isoleucine I202 to glutamine (I202Q) or alanine (I202A) significantly reduced both constitutive and induced KIM-1 shedding and ultimately efferocytosis. It was also uncovered that ADAM10 is the major sheddase that mediates the proteolytic cleavage of murine KIM-1. In addition, ADAM10-induced KIM-1 shedding was required for efficient phagocytic clearance of apoptotic cells. Importantly, the findings that the addition of exogenous shed KIM-1 rescued the phagocytic impairment suggest that shed KIM-1 is capable of modulating efferocytosis of apoptotic bodies and could represent a potential functional role of the soluble ectodomain KIM-1 during AKI.


Biodistribution of Vanadium Dioxide Particles in Mice by Consecutive Gavage Administration: Effects of Particle Size, Dosage, and Health Condition of Mice.
The newly developed vanadium dioxide (VO2), a material with excellent reversible and multi-stimuli responsible phase transition property, has been widely used in high-performance and energy-saving smart devices. The rapid growth of the VO2-based emerging technologies and the complex biological effect of vanadium to organisms urge a better understanding of the behavior of VO2 in vivo for safety purpose. Herein, we study the absorption, distribution, and excretion of two commercial VO2 (nanoscale SVO2 and bulk MVO2) in mice after consecutive gavage administration for up to 28 days. The absorption of both types of VO2 is as low as less than 1.5% of the injected dose within 28 days, while MVO2 is several times more difficult to be absorbed than SVO2. Almost all unabsorbed VO2 is excreted through feces. For the absorbed vanadium, bone is the organ with the largest accumulation, followed by liver, kidney, and spleen. The vanadium content in organs shows a size-, dosage-, and animal health condition-dependent manner, and increases gradually to a saturation value along with the consecutive administration. Generally, smaller particle size and higher dosage lead to higher vanadium contents in organs, and more vanadium accumulates in bone and liver in diabetic mice than in normal mice. After the treatment is stopped, the accumulated vanadium in organs decreases a lot within 14 days, even reaches to the background level in some organs, but the content of vanadium in the bone remains high after 14 days post-exposure. These findings provide basic information for the safety assessment and safe applications of VO2-based materials.


Teaching the older patient in the home assessment and adaptation.
The proportion of older patients in the home care and hospice nurses' caseload is increasing. This article focuses on specific assessment and OASIS items to consider when implementing teaching interventions for older patients. Teaching strategies and adaptations are suggested for each assessment area.


New understanding of primary health care nurse practitioner role optimisation: the dynamic relationship between the context and work meaning.
Optimising health professionals' contribution is an essential step in effective and efficient health human resources utilisation. However, despite the considerable efforts made to implement advanced practice nursing roles, including those in primary care settings (PHCNP), the optimisation of these roles remains variable. In this investigation, we report on the subjective work experience of a group of PHCNPs in the province of Quebec (Canada). We used Giddens' structuration theory to guide our study given its' facilitation of the understanding of the dynamic between structural constraints and actors' actions. Using a qualitative descriptive study design, and specifically both individual and focus group interviews, we conducted our investigation within three health care regions in Quebec during 2016-2017. Forty-one PHCNPs participated. Their descriptions of their experience fell into two general categories. The first of these, their perception of others' inadequate understanding and valuing of their role, included the influence of certain work conditions, perceived restrictions on professional autonomy and the feeling of being caught between two professional paradigms. The second category, the PHCNPs' sense of engagement in their work, included perspectives associated with the specific conditions in which their work is situated, for example, the fragility of the role depending on the particular clinic/s in which they work or on the individuals with whom they work. This fragility was also linked with certain health care reforms that had been implemented in Quebec (e.g., legislation requiring greater physician productivity). Several new insights emerged, for example, the sense of role fragility being experienced by PHCNPs. The findings suggest an overarching link between the work context, the meaning attributed by PHCNPs to their work and their engagement. The optimisation of their role at the patient care level appears to be influenced by elements at the organisational and health system context levels. It appears that role optimisation must include the establishment of work environments and congruent health context structures that favour the implementation and deployment of new professional roles, work engagement, effective collaboration in interprofessional teams, and opportunities to exercise agency. Further research is necessary to evaluate initiatives that endeavour to achieve these objectives.


Biochemical Composition of Pulp and Seed of Wild Jack (Artocarpus hirsutus Lam.) Fruit.
Wild jack (Artocarpus hirsutus Lam.) is an endemic perennial tree of Western Ghats of India. Wild jack, a timber purpose tree, is distributed in several Kaan community forests. Although local people consume unripe as well as fully ripe fruits and roasted seeds, wild jack is unrecognized as a fruit tree. It remains almost undocumented with respect to nutritional value in terms of biochemical composition. We carried out biochemical profiling of ripe fruits and seeds of wild jack. Every 100 g fruit pulp was composed of 12 g total soluble sugars, 16.7 g total starch, 441 μg total carotenoids (beta carotene equivalent) and 8.1 mg ascorbic acid, 0.4 mg GAE total phenol and showed total cupric reducing antioxidant activity of 1.9 mg gallic acid equivalents (GAE). Every 100 g whole seed flour was composed of 6 g total soluble sugars, 6.6 g starch, 9.9 g total proteins, 3 mg GAE total phenol and 3.1 mg GAE total antioxidant capacity. Biochemical profiles of wild jackfruit and seeds were comparable with those of other Artocarpus fruits like jackfruit and bread fruit. Our findings suggest that wild jack deserves to be promoted as a minor fruit species of high nutritional importance and must be considered as a potential fruit crop species for further research.


Hydrogen peroxide induced impairment of post-ischemic ventricular function is prevented by the sodium-hydrogen exchange inhibitor HOE 642 (cariporide).
Sodium-hydrogen exchange (NHE) activation is a major mechanism of cardiac injury produced by ischemia and reperfusion. In addition, NHE may mediate the direct effects of hydrogen peroxide (H2O2) in normally perfused hearts. The present study was done to determine whether H2O2 at low concentrations producing mild myocardial depression affects post-ischemic recovery of function and to determine the ability of the NHE inhibitor HOE 642 to modulate this effect. Isolated Langendorff-perfused rat hearts with a left ventricular balloon inflated to an initial end-diastolic pressure of 5 mmHg were subjected to 90 min of global zero-flow ischemia followed by 60 min reperfusion. In Study 1, hearts were randomized for perfusion with or without H2O2 (20 microM) for 15 min before ischemia and throughout reperfusion. In Study 2, identical experiments were done except that the hearts were pretreated with the NHE inhibitor HOE 642 (5 microM). Function was assessed by determining intraventricular pressures. Recovery of developed pressure in Study 1 after 10 min reperfusion was 60.3 +/- 8% of pre-ischemic values in control hearts whereas this was reduced to 29.9 +/- 10% in hearts treated with H2O2 (P < 0.05). After 60 min of reperfusion recovery of developed pressure was 80.3 +/- 5.2% and 60.7 +/- 7% in control and H2O2-treated hearts, respectively (P < 0.05). Recovery of rates of pressure development (+dP/dt) and relaxation (-dP/dt) paralleled the effects seen with developed pressure. Moreover, these effects were associated with significantly elevated end-diastolic pressure during the last 20 min of reperfusion. In Study 2, HOE 642 completely prevented the deleterious effect of H2O2, both with respect to ventricular recovery and to the elevation in end-diastolic pressure during reperfusion. Our results show that very low concentrations of H2O2 significantly impair recovery of function in this rat model of myocardial ischemia-reperfusion. Moreover, our results suggest that this effect is likely dependent on NHE activity and can be prevented by treatment with the NHE inhibitor HOE 642.


Mechanical-ventilatory cardiac support.
A large body of experimental data indicates that blood flows during CPR because of elevations of intrathoracic pressure and the uneven peripheral transmission of this pressure. Data from humans are less extensive, but also strongly support the mechanism of intrathoracic pressure. It should be remembered that the intrathoracic pressure and direct cardiac compression hypotheses are not mutually exclusive, and that effective CPR is above all dependent on vigorous chest compression. Maintenance of sternal displacement for 40% to 50% of each compression-release cycle, intense alpha-adrenergic stimulation, and avoidance of vasodilators are also essential to the maximization of cerebral and myocardial perfusion. Whether movement of blood by manipulation of intrathoracic pressure can be applied successfully to other disease states is unknown. What is established is that vigorous chest compression, adequate ventilation, and generous use of epinephrine, along with prompt defibrillation, form the basis of an effective strategy for life support. Provision of chest compression and mouth-to-mouth ventilation by bystanders prior to delivery of definitive care has been shown to increase survival rates from 8% to 36% in Columbus, Ohio, and from 21% to 43% in Seattle. Bystander-initiated CPR also reduced the frequency of neurologic impairment at the time of hospital discharge from 55% to 4% in the Seattle experience. For patients receiving the full program of chest compression, ventilation, drug therapy, and defibrillation, resuscitation rates in excess of 50% have been reported in both in-hospital and out-of-hospital arrests. Of those who survive to hospital discharge, 6-month survival rates of 80% have been reported from these patients cohorts, with return-to-work rates of 70%. These data demonstrate that CPR is an effective means of supporting the circulation during cardiac arrest. The majority of survivors return to a meaningful existence, and the technique has not burdened society with a large load of neurologically impaired patients. Thus, CPR is very much worthy of the full attention and support of the medical community.


Effects of culture media conditions on production of eggs fertilized in vitro of embryos derived from ovary of high grade Hanwoo.
This study was investigated the effects of culture media conditions on production of eggs fertilized in vitro of embryos from ovaries of high grade Korean native cow, Hanwoo. The IVMD 101 and IVF 100 were used for in vitro maturation of selected Hanwoo oocytes and In vitro embryo culture after in vitro fertilization, respectively. The IVMD 101 and IVD 101 were used for in vitro culture and completely free of serum. The cleavage rates of 2-cell embryos in reference to Hanwoo oocytes were 86.7, 92.9 , and 90.1 % in the control group, IVDM101 medium and IVD101 medium, respectively which indicates that the IVDM101 medium and IVD101 medium may result favorable outcomes. The in vitro development rates of blastocysts were 12.4, 38.4 and 32.4 % in the control group, serum free IVMD101 medium and IVD101 medium, respectively. For hatched blastocysts, it was 5.3, 33.9, and 28.6 % in the control group, serum free IVMD101 medium and IVD101 medium, respectively. Hence, more favorable results were expected for the hatched blastocysts in which the IVMD101 medium and IVD101 medium were used than the control group. Average cell numbers of blastocysts were 128.3, 165.7, and 163.6 in the groups of TCM-199 + 10 % FBS medium, IVMD 101 medium, and IVD 101 medium, respectively which clearly show that the IVMD 101 and IVD 101 medium consequence significantly higher cell numbers compared to the control group (i.e., TCM-199 + 10 % FBS medium). Pregnancy rate after embryo transfer was 39.6 % when the serum free medium was used which is higher than that of the medium supplemented with serum (32.8 %). In addition, stillbirth rates were 4.9 % in the group of serum free medium whereas it was 13.6 % in the serum supplemented medium (13.6 %). Taken altogether, serum free media, the IVMD 101 and IVD 101 represented more favorable results in the embryo development rate of embryos, cell numbers of blastocyst, and pregnancy rate. Of note, the IVMD 101 medium showed better outcomes hence, it might be a better option for future applications for in vitro culture of bovine embryos.


Alterations of renal tissue structure during a 30-day gavage study with nitrilotriacetate.
Nitrilotriacetate (NTA), as the monohydrated trisodium salt, was administered by gavage to male Sprague-Dawley rats at levels of 0, 0.73 or 7.3 mmol/kg body weight/day for periods of up to 30 days. Two animals from each of the groups were killed 24 hr after dosing on day 9, 13, 16, 20, 23, 27 or 30. Cytoplasmic vacuolation and hyperplasia of the proximal convoluted tubules were the most prominent alterations observed by light microscopic examination of kidney tissue from both groups of NTA-treated rats. The number and severity of the lesions was greater in the high-dose group and in this group, erosion and hyperplasia of the pelvic transitional epithelium were also noted. The results of this study suggest that NTA-associated urinary tract lesions develop in a sequential pattern and that the rate and extent of these lesions is dose dependent.


Transmural sigmoid colon endometrioma in a young reproductive age woman.
Endometriosis is a common disease affecting women of reproductive age. Endometrial tissue can implant to various tissues including gastrointestinal tissues and cause significant GI symptoms. Rarely, these implants cause constricting lesions that require surgical intervention. We report a case of a 27-year-old woman with extensive endometriosis and new onset gastrointestinal symptoms. A near-complete constricting endometrioma involving the sigmoid colon was identified and required surgical resection with side-to-side anastomosis. When endometrial tissue implants to gastrointestinal tissues it can cause GI symptoms including rectal bleeding and dyschezia. If left untreated, progressive endometriosis may result in partial or complete bowel obstruction requiring surgical resection. Obstruction of the GI tract by endometrial implantation can be prevented with early identification and treatment (medical and surgical).


Preoperative rectal cancer staging with phased-array MR.
We retrospectively reviewed magnetic resonance (MR) images of 96 patients with diagnosis of rectal cancer to evaluate tumour stage (T stage), involvement of mesorectal fascia (MRF), and nodal metastasis (N stage).Our gold standard was histopathology. All studies were performed with 1.5-T MR system (Symphony; Siemens Medical System, Erlangen, Germany) by using a phased-array coil. Our population was subdivided into two groups: the first one, formed by patients at T1-T2-T3, N0, M0 stage, whose underwent MR before surgery; the second group included patients at Tx N1 M0 and T3-T4 Nx M0 stage, whose underwent preoperative MR before neoadjuvant chemoradiation therapy and again 4-6 wks after the end of the treatment for the re-staging of disease.Our gold standard was histopathology. MR showed 81% overall agreement with histological findings for T and N stage prediction; for T stage, this rate increased up to 95% for pts of group I (48/96), while for group II (48/96) it decreased to 75%.Preoperative MR prediction of histologically involved MRF resulted very accurate (sensitivity 100%; specificity 100%) also after chemoradiation (sensitivity 100%; specificity 67%). Phased-array MRI was able to clearly estimate the entire mesorectal fat and surrounding pelvic structures resulting the ideal technique for local preoperative rectal cancer staging.


Case of Subcutaneous Leiomyosarcoma of the Scrotum Presenting as a Sebaceous Cyst in a 71-Year-old Man: A Case Report and Review of the Literature.
Leiomyosarcoma of the scrotum is a rare genital malignancy with approximately 35 reported cases in literature. We present a case of leiomyosarcoma of the scrotum in a 71-year-old man appearing as a sebaceous cyst that later developed ulcerations. However, because the irregular mass developed ulcerations, this should trigger one to consider that lesion is potentially malignant. The pathology report demonstrated malignant spindle cell neoplasm consistent with leiomyosarcoma, which tested positive for desmin and actin stains. On literature review, a study reported a 5-year survival rate of 50%-80%. The clinical features, diagnosis, histopathologic images, and treatment are reviewed.


The overlooked role of the ocean in mercury cycling in the Arctic.
The rapid and high bioaccumulation of mercury in marine mammals and its spatial and temporal variations have been a major puzzle in the Arctic. While extensive efforts have been focussed on the monitoring and chemistry of atmospheric mercury depletion events, a recent mass budget estimate of mercury in the Arctic suggests that we have overlooked the role of the ocean itself. Only through focussed studies on Hg dynamics in the Arctic Ocean under a changing climate are we going to understand what the risk of mercury is to those marine ecosystems and the people who rely on them.


Prenatal exposure to environmental air pollution and psychosocial stress jointly contribute to the epigenetic regulation of the serotonin transporter gene in newborns.
Antenatal exposures to maternal stress and to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) have been independently associated with developmental outcomes in early infancy and beyond. Knowledge about their joint impact, biological mechanisms of their effects and timing-effects, is still limited. Both PM2.5 and maternal stress exposure during pregnancy might result in altered patterns of DNA methylation in specific stress-related genes, such as the serotonin transporter gene (SLC6A4 DNAm), that might, in turn, influence infant development across several domains, including bio-behavioral, cognitive and socio-emotional domains. Here, we investigated the independent and interactive influence of variations in antenatal exposures to maternal pandemic-related stress (PRS) and PM2.5 on SLC6A4 DNAm levels in newborns. Mother-infant dyads (N = 307) were enrolled at delivery during the COVID-19 pandemic. Infants' methylation status was assessed in 13 CpG sites within the SLC6A4 gene's region (chr17:28562750-28562958) in buccal cells at birth and women retrospectively report on PRS. PM2.5 exposure throughout the entire gestation and at each gestational trimester was estimated using a spatiotemporal model based on residential address. Among several potentially confounding socio-demographic and health-related factors, infant's sex was significantly associated with infants' SLC6A4 DNAm levels, thus hierarchical regression models were adjusted for infant's sex. Higher levels of SLC6A4 DNAm at 6 CpG sites were found in newborns born to mothers reporting higher levels of antenatal PRS and greater PM2.5 exposure across gestation, while adjusting for infant's sex. These effects were especially evident when exposure to elevated PM2.5 occurred during the second trimester of pregnancy. Several important brain processes (e.g., synaptogenesis and myelination) occur during mid-pregnancy, potentially making the second trimester a sensitive time window for the effects of stress-related exposures. Understanding the interplay between environmental and individual-level stressors has important implications for the improvement of mother-infant health during and after the pandemic.


[The effect of MAB225 on radiosensitivity of salivary gland adenoid cystic carcinoma].
To observe the effect of epidermal growth factor receptor's monoclonal antibody(MAB225) on radiosensitivity of salivary gland adenoid cystic carcinoma cell. Bi-fluorescence stain ,MTT test and fluorescence flow cytometry(FCM) were used to observe the apoptosis rate and radiosensitizing effect for MAB225 on ACC-2 cell.SPSS11.0 software package was used for data analysis. Through bi-fluorescence stain, MTT test and fluorescence flow cytometry(FCM),it was found that MAB225 combined with radiation treatment produced a 3-fold induction of apoptosis rate, whereas exposure to radiation alone induced apoptosis only 1 fold, compared to the control group. MAB225 enhanced radiosensitivity and decreased survival rates of ACC-2 cell in vitro after radiation.


Myeloperoxidase, asymmetric dimethyl-arginine and the renin-angiotensin-aldosterone-system in cardiovascular risk patients: Cross-sectional findings from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.
The leukocyte-derived myeloperoxidase (MPO), the nitric oxidase synthase (NOS) inhibitor asymmetrical dimethyl-arginine (ADMA) and the renin-angiotensin-aldosterone-system (RAAS) are associated with cardiovascular diseases (CVD). This study aimed to investigate potential interactions between the RAAS, ADMA and MPO in cardiovascular risk patients. All in all, 1446 patients, who were referred to coronary angiography, were included in this prospective study. MPO, ADMA and circulating serum markers of the RAAS system were measured. Additionally, all-cause and CVD mortality, cardiovascular risk factors, inflammatory and endothelial markers, and medication use were investigated. MPO concentrations were significantly associated with ADMA (P=0.002), renin (P=0.001) and angiotensin II levels (P=0.015), whereas ADMA was in tendency associated with renin (P=0.059) and significantly with angiotensin II (P=0.001). Both, ADMA and MPO were inversely correlated with angiotensinogen, angiotensin I and the angiotensin I/angiotensin II ratio. ADMA and angiotensin II were found stronger independent risk factors for all-cause and CVD mortality compared to MPO. MPO concentrations were significantly associated with higher ADMA levels and an up-regulated circulating RAAS in patients with CVD. Moreover, serum levels of ADMA and angiotensin II were shown to be more predictive for all-cause and CVD mortality compared to MPO.


Spontaneous Intracranial Hypotension Manifesting Orthostatic Headache Worsen by Playing the Trombone.
We present the case of a 13-year-old Japanese girl with no previous medical history who presented with a gradually worsening series of orthostatic headaches. We diagnosed spontaneous intracranial hypotension, which worsened by playing the trombone and its Valsalva maneuver effect. She was admitted to our hospital and treated with rest and hydration, and discharged on day 14 without any headaches during the admission. However, her headache recurred when she played trombone, so she stopped it. She now plays percussions, and no headaches recurred for a year. Our case's headache may have been further exacerbated by cerebrospinal fluid (CSF) leakage due to CSF pressure increase by the Valsalva maneuver while playing the trombone.


Effectiveness of fosfomycin-based antimicrobial prophylaxis for transrectal ultrasound-guided prostate biopsy: A Korean multicenter study.
Recent studies have highlighted increasing infectious complications due to fluoroquinolone (FQ)-resistant organisms in men undergoing transrectal ultrasound-guided prostate biopsy (TRUSPB). This study investigated whether fosfomycin (FM)-based antibiotic prophylaxis reduces infections after TRUSPB and identified risk factors for infective complications. A multicenter study was conducted in the Republic of Korea from January 2018 to December 2021. Patients undergoing prostate biopsy with FQ or FM-based prophylaxis were included. The primary outcome was the post-biopsy infectious complication rate after FQ (group 1) or FM-based antibiotic prophylaxis with FM alone (group 2) or FQ and FM (group 3). Risk factors for infectious complications after TRUSPB were secondary outcomes. Patients (n=2,595) undergoing prostate biopsy were divided into three groups according to the type of prophylactic antibiotics. Group 1 (n=417) received FQ before TRUSPB. Group 2 (n=795) received FM only and group 3 (n=1,383) received FM and FQ before TRUSPB. The overall post-biopsy infectious complication rate was 1.27%. The infectious complication rates were 2.4%, 1.9%, and 0.5% in groups 1, 2, and 3, respectively (p=0.002). In multivariable analysis, predictors of post-biopsy infectious complications included an association with health care utilization (adjusted odds ratio [OR], 4.66; 95% confidence interval [CI], 1.74-12.4; p=0.002) and combination antibiotic prophylaxis (FQ and FM) (adjusted OR, 0.26; 95% CI, 0.09-0.69; p=0.007). In comparison with monotherapy with FM or FQ, combination antibiotic prophylaxis (FQ and FM) showed a lower rate of infectious complications after TRUSPB. Utilization of health care was an independent risk factor for infectious complications after TRUSPB.


Association of physical activity and air pollution exposure with the risk of type 2 diabetes: a large population-based prospective cohort study.
The interplay between physical activity (PA) and air pollution in relation to type 2 diabetes (T2D) remains largely unknown. Based on a large population-based cohort study, this study aimed to examine whether the benefits of PA with respect to the risk of T2D are moderated by exposure to air pollution. UK Biobank participants (n = 359,153) without diabetes at baseline were included. Information on PA was obtained using the International Physical Activity Questionnaire short form. Exposure to air pollution, including PM2.5, PMcoarse (PM2.5-10), PM10, and NO2, was estimated from land use regression models. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs). During a median of 8.9 years of follow-up, 13,706 T2D events were recorded. Compared with a low PA level, the HRs for the risk of T2D among individuals with moderate and high PA were 0.82 (95% CI, 0.79-0.86) and 0.73 (95% CI, 0.70-0.77), respectively. Compared with low levels of air pollution, the HRs for risk of T2D for high levels of air pollution (PM2.5, PMcoarse, PM10, and NO2) were 1.19 (1.14-1.24), 1.06 (1.02-1.11), 1.13 (1.08-1.18), and 1.19 (1.14-1.24), respectively. There was no effect modification of the associations between PA and T2D by air pollution (all P-interactions > 0.05). The inverse associations between PA and T2D in each air pollution stratum were generally consistent (all P for trend < 0.05). A higher PA and lower air pollution level were independently associated with a lower risk of T2D. The beneficial effects of PA on T2D generally remained stable among participants exposed to different levels of air pollution. Further studies are needed to replicate our findings in moderately and severely polluted areas.


Assessment of the role of "enkephalinase" in cholecystokinin inactivation.
Cholecystokinin octapeptide and the C-terminal tetrapeptide are hydrolysed by a highly purified preparation of "enkephalinase" (EC 18.104.22.168). In both cases the Asp-PheNH2 bond is hydrolysed and the Gly4-Trp5 bond of the octapeptide is also cleaved, though more slowly. Evaluated from the appearance of Phe-NH2, the Km for the hydrolysis of the octapeptide by the purified peptidase is 57 microM and that for the tetrapeptide 65 microM. The apparent affinities of these peptides for the enzyme in striatal membranes are similar. The importance of this hydrolysis in the inactivation of endogenous cholecystokinin was assessed by studying the fate of cholecystokinin immunoreactivity released from slices of rat cerebral cortex and striatum by depolarization with potassium. In the absence of any peptidase inhibitor only 16% of the peptide released from the tissue was recovered in immunoreactive form in the medium, indicating that endogenous cholecystokinin octapeptide is, like other neuropeptides, rapidly and extensively hydrolysed following release. Selective inhibition of "enkephalinase" by Thiorphan (DL-3-mercapto-2-benzylpropanoyl glycine) did not significantly alter the recovery from slices of cerebral cortex and had only a very slight effect in the case of striatal slices. This suggests that, while cholecystokinin octapeptide is a substrate for "enkephalinase", this enzyme plays a less important (if any) role in the inactivation of endogenous cholecystokinin than for the opioid peptides.


3D-printed custom-designed prostheses for partial hand amputation: Mechanical challenges still exist.
This is a technical report involving evaluation of two 3D-printed custom-designed prosthetic prototypes for an adult male with partial amputation of his dominant hand. Prosthetic solutions for partial hand amputations have progressed modestly in comparison with advances in full hands for transradial and higher amputations. 3D-printing technology allows Bespoke prosthetic design and rapid prototyping, but evidence regarding functional performance and consumer ratings of devices is lacking. The purpose of this study was to compare grip strength, dexterity, and consumer perceptions for two novel 3D-printed devices with a myoelectric prosthesis. This study involves a 2-year iterative design process with an input from the participant, engineers, a prosthetist, and a hand therapist. The evaluation involved standardized tests of grip/pinch strength and dexterity and participant ratings of key criteria. Both 3D-printed devices had very poor grip and pinch strength but comparable dexterity with the myoelectric prosthesis. The participant was more satisfied with the weight and thermal attributes of the 3D-printed devices. Aspects of both 3D-printed designs showed the potential for future refinements; however, the mechanical solutions to minimize force required at the wrist to activate grip are still required. Future design efforts should be client-centered and involve professionals with specialist prosthetic and engineering knowledge.


An unusual presentation of thoracic cord compression by a dorsal arachnoid cyst in a 14-month-old boy. A discussion of the case and review of the literature.
Spinal arachnoid cysts are a rare cause of spinal cord compression in children and presenting symptoms may be subtle. We present a neurologically intact 14-month-old boy who presented with pain and postural irritability from a thoracic arachnoid cyst.


Rapid Identification of Methicillin-Resistant Staphylococcus aureus (MRSA) by the Vitek MS Saramis system.
A rapid, sensitive, and accurate Vitek MS assay was developed to distinguish clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) from clinical isolates of methicillin-sensitive Staphylococcus aureus (MSSA) by developing an in-house knowledgebase of SuperSpectra. Three unique peaks, including peaks at 2305.6 and 3007.3 Da specific to MRSA, and 6816.7 Da specific to MSSA, were selected for differentiating MRSA and MSSA. This assay accurately identified 84 and 91% of clinical MRSA and MSSA strains out of the total 142 clinically acquired S. aureus strains that were tested. This method will greatly improve the efficiency of single clinical sample identification of MRSA, thereby facilitating a reduction in the transmission of MRSA in clinical settings.


Expanded polyglutamine stretches form an 'aggresome'.
To understand the pathogenetic mechanisms underlying polyglutamine (polyQ) diseases, we investigated the mechanisms of the formation of aggregate bodies containing expanded polyQ stretches, focusing on dentatorubral-pallidoluysian atrophy (DRPLA). We demonstrated that the expression of a truncated DRPLA protein containing expanded polyQ stretches in COS-7 cells resulted in the formation of perinuclear aggregate bodies that are co-localized with gamma-tubulin, a protein marker for the microtubules-organizing center (MTOC). A collapsed vimentin network surrounded these aggregate bodies. Furthermore, disruption of the microtubules (MTs) with nocodazole resulted in the formation of small aggregate bodies that were scattered throughout the cytoplasm. These findings suggest that the truncated DRPLA proteins containing expanded polyQ stretches unfold and form small aggregate bodies in the cell periphery. These aggregates move on MTs to the MTOC, where they remain as distinct 'aggresomes''.


Hard-Soft Thermoset Alloy with Enhanced Toughness, Impact-Resistance, and Electric Conductivity via Interpenetrated Dynamic Crosslinked Interface.
Polymer alloys (PAs) are mixtures of two or more types of polymers to enhance the properties of polymeric materials. However, thermosets with crosslinked structures are immiscible and cannot be prepared PAs. Herein, two immiscible covalent adaptable networks containing phenoxy carbamate bonds are explored as the typical polymeric materials to prepare the hard-soft thermoset alloy (HSTA) by the interpenetrated dynamic crosslinked interface (IDCI) to enhance the toughness. Specifically, two types of polyurethane covalent adaptable networks with either high stiffness (thermoset) or extensibility (elastomer) are prepared, respectively. The granules of thermoset and elastomer are mixed and hot-pressed to prepare the HSTA. The HSTA shows improved mechanical properties with a toughness of 22.8 MJ m-3 which is 14 times higher than that of hard thermoset. In addition, the HSTA shows excellent impact-resistance property after 1000 punctures. Moreover, the obtained HSTA via addition of carbon nanotubes can significantly decrease the electric resistance over six orders of magnitudes as compared to the blending method, which is due to the distribution of the carbon nanotubes at the interfaces of the two networks.


Timing of operation for poor-grade aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial.
Subarachnoid hemorrhage is a common and dangerous disease with an unfavorable prognosis. Patients with poor-grade subarachnoid hemorrhage (Hunt & Hess Grades 4-5) are unconscious on admission. Because of the high mortality and disability rate associated with poor-grade subarachnoid hemorrhage, it is often treated conservatively. Timing of surgery for poor-grade aneurysmal subarachnoid hemorrhage is still controversial, therefore this study aims to identify the optimal time to operate on patients admitted in poor clinical condition. Ninety-nine patients meeting the inclusion criteria were randomly assigned into three treatment groups. The early surgery group received operation within 3 days after onset of subarachnoid hemorrhage (day of SAH = day 1); the intermediate surgery group received operation from days 4 to 7, and surgery was performed on the late surgery group after day 7. Follow-up was performed 1, 3, and 6 months after aneurysm clipping. Primary indicators of outcome included the Extended Glasgow Outcome Scale and the Modified Rankin Scale, while secondary indicators of outcome were assessed using the Barthel Index and mortality. This is the first prospective, single-center, observer-blinded, randomized controlled trial to elucidate optimal timing for surgery in poor-grade subarachnoid hemorrhage patients. The results of this study will be used to direct decisions of surgical intervention in poor-grade subarachnoid hemorrhage, thus improving clinical outcomes for patients. Chinese Clinical Trial Registry: ChiCTR-TRC-12002917.


Unspecific DNA binding of the DNA binding domain of the glucocorticoid receptor studied with flow linear dichroism.
The unspecific interaction between the DNA-binding domain of the human glucocorticoid receptor and DNA was studied using linear dichroism (LD) and circular dichroism (CD) spectroscopy. The amplitude of the LD signal was found to increase upon addition of protein at ionic strengths less than 60 nM Na+, indicating an increased persistence length of the complex compared to uncomplexed DNA. Analysis of the LD spectrum suggests that the binding does not involve intercalation of tyrosine residues. Evidence of saturation is found at a binding stoichiometry of approximately 5 DNA base pairs per protein monomer.


The German version of the Critical-Care Pain Observation Tool for critically ill adults : A prospective validation study.
The implementation of the Critical-Care Pain Observation tool (CPOT) in intensive care units (ICU) has been associated with more frequent pain assessments, a reduced number of complications, and improved administration of analgesics and sedatives. So far no German translation exists. Translating this tool into foreign languages requires further validation testing. The aim of this prospective observational validation study was to translate the original version of the CPOT according to scientific principles for translation and to establish the validity and reliability of the German translation of CPOT for critically ill adult patients. A total of 292 cardiac surgery patients from 2 ICUs of 2 German university teaching hospitals were included (114 patients at center 1 and 178 patients at center 2). Of the included patients 22.6% were female and 76.4% were male with a mean age of 68.5 years ±9.3 SD. Pain was evaluated with the CPOT, the Bhavioral Pain Scale (BPS) and with the Numeric Rating scale (NRS) at three time points (1. intubated + sedated, 2. intubated + awake, 3. extubated + awake) at rest and during nociceptive stimulus (positioning). Assessments were made separately by trained physicians and nursing staff. Good results for interrater reliability and internal consistency could be demonstrated (weighted Cohen's kappa of 0.73, Cronbach's coefficient alpha of 0.8). Spearman correlation between CPOT and NRS was moderate but significant. The receiver operating characteristic (ROC) analysis to obtain optimal thresholds of CPOT to detect pain revealed different results during rest and stimulus and in intubated and extubated patients. The validated German CPOT translation is a reliable tool for pain assessment in cardiac ICU patients in the absence of patients' ability for self-reporting. The use of this German version of CPOT now allows a better international comparability of corresponding data in future studies.


Improved accuracy and fewer outliers with a novel CT-free robotic THA system in matched-pair analysis with manual THA.
Accurate component orientation and restoration of hip biomechanics remains a continuing challenge in total hip arthroplasty (THA). The goal of this study was to analyze the accuracy/reproducibility of a novel CT-free and pin-less robotic-assisted THA (RA-THA) platform compared to manual THA (mTHA). This matched-pair cadaveric study compared this RA-THA system to mTHA (n = 33/arm), both using the assistance of fluoroscopic imaging, in a group of 14 high-volume arthroplasty surgeons. In both groups, surgeons were asked to aim for 40°/15° for cup inclination/version, and 0 mm of leg length discrepancy (LLD). A validated and accurate method using radio-opaque markers measured cup inclination/version and LLD. The accuracy and reproducibility (fewer outliers) of cup inclination was significantly improved in the robotic group (1.8° ± 1.3° vs 6.4° ± 4.9°, respectively, robotic vs manual; p < 0.001), with no significant difference between groups for version. The reproducibility of LLD was significantly improved in the robotic group (p = 0.003). For all parameters studied, the robotic group had an improved accuracy and lower variance (fewer outliers). The percentage of cases within the more restrictive Callanan safe zone was 100% for RA-THA vs 73% for mTHA (p = 0.002). The CT-free RA-THA platform, using only fluoroscopic imaging, demonstrated more accurate acetabular cup positioning, when compared to the mTHA procedures performed by high-volume hip surgeons (naive to this RA-THA platform), with respect to cup inclination and placement within the Lewinnek/Callanan safe zones. Future study must incorporate economic factors, lower volume surgeons, clinical and patient-centric outcomes, and other radiographic parameters in controlled studies in large sample sizes.


Advances in Studies of Chiglitazar Sodium, a Novel PPAR Pan-Agonist, for the Treatment of Type 2 Diabetes Mellitus.
Chiglitazar sodium is a new peroxisome proliferator-activated receptor (PPAR) pan-agonist with independent intellectual property rights in China. It can treat type 2 diabetes mellitus and regulate metabolism by modestly activating PPARα, PPARγ, and PPARδ to improve insulin sensitivity, regulate blood glucose, and promote fatty acid oxidation and utilization. Chiglitazar sodium has a significant insulin-sensitizing effect and is advantageous in reducing fasting and postprandial blood glucose levels, particularly at the 48 mg dose in patients with concomitant high triglycerides in terms of blood glucose and triglyceride level control.


Adapting a US dietary analysis software and nutrient database for use in Brazil.
In many countries, assessing food and nutrient intake for research and surveillance purposes is difficult due to the lack of comprehensive, country-specific food and nutrient databases and/or a dietary analysis software program. In this case study, we describe the approach used to adapt a United States (US) dietary analysis software and nutrient database (Nutrition Data System for Research [NDSR]) for use in analyzing 24-hour dietary recalls collected for the Brazil Kids Nutrition and Health Study (KNHS). A team of experts that included individuals knowledgeable about Brazil and US eating traditions was assembled to devise solutions for between-country differences in eating habits, food supply, food nomenclature, and language. Solutions devised relied on several key resources, including the Brazilian Food Composition Table (TBCA) and a list of 200 foods commonly consumed in Brazil. These solutions included creating data entry rules that specified how each reported food should be entered into NDSR, creation of User Recipes for foods lacking a close nutritionally matching food in the NDSR database, and adjustment for food fortification differences as part of the analysis of study data. This case study illustrates that NDSR can be adapted for use outside of the United States through a structured process.


Mild Cognitive Impairment and Dementia Prevalence: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).
We examined prevalence of mild cognitive impairment (MCI) and dementia in the Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study. Beginning in June, 2011, we invited all surviving ARIC participants to undergo cognitive, neurological and brain imaging assessments to diagnose MCI or dementia and assign an etiology for the cognitive disorder. Of 10713 surviving ARIC participants (age range 69-88 yrs), we ascertained cognitive diagnoses in 6471 in-person, 1966 by telephone interviews (participant or informant) and the remainder by medical record review. The prevalence of dementia was 9.0% and MCI 21%. Alzheimer's disease was the primary or secondary etiology in 76% of dementia and 75% of MCI participants. Cerebrovascular disease was the primary or secondary etiology in 46% of dementia and 32% of MCI participants. MCI and dementia were common among survivors from the original ARIC cohort. Nearly 30% of the ARIC cohort received diagnoses of either dementia or MCI, and for the majority of these individuals (about 75%) the etiologic basis was attributed to Alzheimer's disease.


Grb2 regulates the proliferation of hematopoietic stem and progenitors cells.
Although Hematopoietic Stem and Progenitor Cell (HSPC) proliferation, survival and expansion have been shown to be supported by the cooperative action of different cytokines, little is known about the intracellular signaling pathways that are activated by cytokines upon binding to their receptors. Our study showed that Growth factor receptor-bound protein 2 (Grb2) mRNAs are preferentially expressed in HSC compared to progenitors and differentiated cells of the myeloid and erythroid lineages. Conditional deletion of Grb2 induced a rapid decline of erythroid and myeloid progenitors and a progressive decline of HSC numbers in steady state conditions. We showed that when transplanted, Grb2 deleted bone marrow cells could not reconstitute irradiated recipients. Strinkingly, Grb2 deletion did not modify HSPC quiescence, but impaired LT-HSC and progenitors ability to respond a proliferative signal induced by 5FU in vivo and by various cytokines in vitro. We showed finally that Grb2 links IL3 signaling to the ERK/MAPK proliferative pathway and that both SH2 and SH3 domains of Grb2 are crucial for IL3 signaling in progenitor cells. Our findings position Grb2 as a key adaptor that integrates various cytokines response in cycling HSPC.


Kidney Cysts in Hypophosphatemic Rickets With Hypercalciuria: A Case Series.
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare monogenic disorder caused by SLC34A3 pathogenic variants. HHRH is characterized by kidney phosphate wasting, hypophosphatemia, hypercalciuria, an elevated 1,25-dihydroxyvitamin D level, nephrocalcinosis, and urinary stone disease. Previously, we reported a 100% prevalence of kidney cysts in the related CYP24A1 deficiency. Thus, in the current study, we characterized cysts' presence in HHRH, another monogenic cause of hypercalciuria, nephrocalcinosis, and urinary stone disease. Case series. Medical records from the Mayo Clinic and the Rare Kidney Stone Consortium monogenic stone disease database were queried for patients with a genetically confirmed HHRH diagnosis. The number, sizes, and locations of kidney cysts in each patient were recorded. Twelve patients with SLC34A3 pathogenic variants were identified (7 monoallelic, 5 biallelic). Of these, 5 (42%) were males, and the median (Q1, Q3) ages were 16 years (13, 35 years) at clinical presentation and 42 years (20, 57 years) at genetic confirmation. Kidney cysts were present in 9 of 12 (75%) patients, and the median (Q1, Q3) age at first cyst detection was 41 years (13, 50 years). The median number of cysts per patient was 2.0 (0.5, 3.5). Fifty percent of adult patients had a cyst number that exceeded the 97.5th percentile of an age- and sex-matched control population. All children had at least 2 or more total cysts. None had a family history of cystic kidney disease. Retrospective study, possible selection bias, single-center experience. A strong association between HHRH and kidney cysts was observed. Similarities in the biochemical profiles of HHRH and CYP24A1 deficiency suggest elevated active vitamin D and hypercalciuria may be potential cystogenic factors. Further studies are needed to understand how genetic changes in SLC34A3 favor cyst formation.


Characterization of diphtheria toxin's catalytic domain interaction with lipid membranes.
In response to a low environmental pH and with the help of the B fragment (DTB) the catalytic domain of diphtheria toxin (DTA) crosses the endosomal membrane to inhibit protein synthesis. In this study, we investigated the interaction of DTA with lipid membranes by biochemical and biophysical approaches. Data obtained from proteinase K and trypsin digestion experiments of membrane-inserted DTA suggested that residues 134-157 may adopt a transmembrane orientation and residues 77-100 could be membrane-associated, adopting either a surface or a transmembrane orientation. Fourier transform infrared spectroscopy analysis (FTIR) was used to characterize the secondary and tertiary structure of DTA along its pathway, from the native secreted form at pH 7.2 to the refolded structure at neutral pH after interaction with and desorption from a lipid membrane. We found that the association of DTA with lipid membranes at low pH was characterized by an increase of beta-sheet structures and that the refolded structure at neutral pH after interaction with the membrane was identical to the native structure at the same pH. We also investigated the desorption of DTA from the membrane at neutral pH as a function of temperature. Although a complete desorption was observed at 37 degrees C, no desorption took place at 4 degrees C. A model of translocation involving the possibility that DTA might insert one or several transient transmembrane domains during translocation is discussed.


Sexual (dys)function after radiotherapy for prostate cancer: a review.
Prostate cancer has become the most common nonskin malignant neoplasm in older men in Western countries. As treatment efficacy has improved, issues related to posttherapy quality of life and sexual functioning have become more important. We discuss the various methods used to evaluate erectile and sexual dysfunction and the definition of potency. The etiologies of erectile dysfunction after external beam radiotherapy and brachytherapy for prostate cancer are also reviewed. The literature is summarized, and comparative studies of radiation and surgery are surveyed briefly. Rates of erectile dysfunction vary from 6 to 84% after external beam radiotherapy and from 0 to 51% after brachytherapy. In most of the studies, the analysis is retrospective, the definition of erectile dysfunction is not clear, only one question about sexual functioning is asked, and nonvalidated instruments are used. The etiology of erectile dysfunction after radiation for prostate cancer is not completely understood. Because erectile function is only one component of sexual function, it is necessary to assess sexual desire, satisfaction, frequency of intercourse, and other such factors when evaluating the effects of therapy. Patients should be offered sexual counseling and informed about the availability of effective treatments for erectile dysfunction, such as sildenafil, intracavernosal injection, and vacuum devices.


Overhauling the ecotoxicological impact of synthetic pesticides using plants' natural products: a focus on Zanthoxylum metabolites.
The reduction in agricultural production due to the negative impact of insects and weeds, as well as the health and economic burden associated with vector-borne diseases, has promoted the wide use of chemicals that control these "enemies." However, the use of these synthetic chemicals has been recognized to elicit negative impacts on the environment as well as the health and wellbeing of man. In this study, we presented an overview of recent updates on the environmental and health impacts of synthetic pesticides against agro-pest and disease vectors while exhaustive reviewing the potentials of natural plant products from Zanthoxylum species (Rutaceae) as sustainable alternatives. This study is expected to spur further research on exploiting these plants and their chemicals as safe and effective pesticide entities to minimize the impact of their chemical and synthetic counterparts on health and the environment.


The content of recurrent dreams in young adolescents.
Studies on children's recurrent dreams have been largely anecdotal and based on adults' recollections of dreams experienced during childhood. We collected 102 reports of recurrent dreams from a sample of young adolescents aged between 11 and 15years and scored the narratives using a range of content measures, including in relation to the threat simulation theory (TST) of dreaming. The most frequently reported themes involved confrontations with monsters or animals, followed by physical aggressions, falling and being chased. Recurrent dreams were more likely to include negative content elements than positive elements. Only half of the recurrent dreams contained threatening elements and their analysis provided mixed support for the TST. Differences between the content of recurrent dreams reported by young adolescent versus adults are discussed as are possible sex effects and key issues that remain to be addressed by future research.


Analysis of sodium 2-mercaptoethane sulfonate in rat plasma using high performance liquid chromatography tandem-mass spectrometry.
Sodium 2-mercaptoethane sulfonate (MESNA) is a thiol-containing compound that has proven to be effective in inactivating acrolein, the toxic metabolite of some anti-cancer drugs (e.g., cyclophosphamide and ifosphamide). Also, it scavenges free radicals which cause numerous disorders by attacking biological molecules. Current methods available to analyze MESNA in biological matrices include colorimetry and high-performance liquid chromatography (HPLC) with ultraviolet, fluorescence, or electrochemical detection. These methods have several limitations including low sensitivity, poor selectivity, a high degree of difficulty, and long analysis times. Hence, a rapid, simple, and sensitive HPLC tandem mass spectrometry (MS/MS) method was developed and validated to quantify MESNA in rat plasma following IP administration. The analysis of MESNA was accomplished via plasma protein precipitation, centrifugation, supernatant evaporation, reconstitution, and HPLC-MS/MS analysis. The method showcases an outstanding limit of detection (20 nM), excellent linearity (R2 = 0.999, and percent residual accuracy >90%) and a wide linear range (0.05-200 μM). The method also produced good accuracy and precision (100 ± 10% and <10% relative standard deviation, respectively). The validated method was successfully used to analyze MESNA from treated animals and will allow easier development of MESNA for therapeutic purposes.


Immunization with alum-collagen II complex suppresses the development of collagen-induced arthritis in rats by deviating the immune response.
Collagen-induced arthritis (CIA) is an experimental rat model sharing a number of features with human rheumatoid arthritis (RA). The model is associated with a proinflammatory (TH1) type of immune response and treatments with cytokines associated with TH2 immune responses are beneficial. Since agents with TH1-inducing properties, such as Freund's incomplete adjuvant (FIA), are necessary for disease induction, it is of interest to investigate whether an adjuvant with TH2-inducing properties affects CIA in a different way than does FIA. The authors studied arthritis development in DA rats after immunization with the TH2 stimulatory adjuvant alum adsorbed to rat collagen type II (CII) or collagen II fragments. Such treatments suppressed disease development both prophylactically and therapeutically. This beneficial effect of alum-CII immunization was associated with an increase in the IgG1 anti-CII antibody response as compared to untreated rats or rats pretreated with alum alone. Treatment with alum without the addition of collagen did not have any clinical effect. In addition, alum-CII treated rats had a significantly higher expression of IL-4 mRNA than untreated rats in the lymph nodes, 7 days after CIA induction. The authors suggest that alum-CII induces a TH2 immune response against rat CII which counteracts the development of CIA.


The nonreplicating smallpox candidate vaccines defective vaccinia Lister (dVV-L) and modified vaccinia Ankara (MVA) elicit robust long-term protection.
Current smallpox vaccines are live vaccinia viruses that replicate in the vaccinee inducing immunity against the deadly disease smallpox. Replication resulting in virus spread within the host, however, is the major cause of severe postvaccinal adverse events. Therefore, attenuated strains such as modified vaccinia Ankara (MVA) or LC16m8 are candidates as next generation vaccines. These strains are usually grown in primary cells in which mass production is difficult and have an unknown protective potential in humans. Proven vaccine strains of defined origin and modern production techniques are therefore desirable. In this study, defective vaccinia virus (dVV) lacking a gene essential for replication (derived from the Lister vaccine in a complementing cell line) was compared with the Wyeth smallpox vaccine strain and with MVA in mouse animal models using cowpox and ectromelia virus challenge. Similar to MVA, prime-boost immunizations with defective vaccinia induced robust long-term immunity, suggesting it as a promising next generation smallpox vaccine.


I ride for MS: The impact of bike MS participation on motivation for physical activity in individuals with multiple sclerosis.
Multiple Sclerosis (MS) is a chronic neurodegenerative disease that results in deficits in physical and cognitive functioning. Research supports the use of physical activity (PA) to aid in MS symptom management and slow disease progression, however individuals diagnosed with MS are generally physically inactive. Social support has been shown to increase PA behavior in group exercise settings. Events such as Bike MS, a charity bicycle ride where individuals raise money for MS, could increase motivation for participation and therefore may be an ideal setting to introduce PA to individuals diagnosed with MS. /Hypothesis: The objective of the current research was to explore motives for participation in a Bike MS event in individuals diagnosed with MS and their family members, and examine if their Bike MS participation has translated to long-term PA behavior change and positive quality of life outcomes. A descriptive qualitative approach using semi-structured focus group, individual, and phone interviews, combined with observational field notes, was used to explore the experiences of seven individuals diagnosed with MS and four family members from two regional self-help groups who all actively participated in a Bike MS event. Participants reported important social bonds, raising awareness for the cause, fundraising, long-term physical benefits, and overall increased quality of life as motives for participation. All participants reported long-term PA participation as a result of Bike MS participation. Results support using Bike MS to increase long-term PA participation in individuals with MS, resulting in positive quality of life outcomes.


Cu2+ is required for pyrrolidine dithiocarbamate to inhibit histone acetylation and induce human leukemia cell apoptosis.
Pyrrolidine dithiocarbamate (PDTC) has been considered as a potential anticancer drug due to its powerful apoptogenic effect towards cancer cells, where Cu(2+) plays a distinct yet undefined role. Here we report that Cu(2+) is critically needed for PDTC to inhibit histone acetylation in both human leukemia HL-60 cells and human hepatoma Hep3B cells. The inhibition of histone acetylation mainly resulted from the increase of intracellular Cu(2+), but was not due to the inhibition of NF-kappaB activity by PDTC-Cu(2+) since the combinations of Cu(2+) with SN50, MG132 (two known NF-kappaB inhibitors), or bathocuproine disulfonate (BCS, a specific Cu(2+) chelator that does not cross the plasma membrane), did not lead to obvious inhibition of histone acetylation. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are the enzymes controlling the state of histone acetylation in vivo. Cells exposed to PDTC-Cu(2+) showed a comparable decrease in histone acetylation levels in HL-60 cells in the absence or presence of the HDAC inhibitors, trichostatin A (TSA) or sodium butyrate (NaBu); the inhibition rates were about 45, 44 and 43%, respectively. PDTC-Cu(2+) had no effect on the activity of HDAC in vitro, but significantly inhibited the HAT activity both in HL-60 cells and in a cell-free in vitro system. PDTC-Cu(2+) also induced HL-60 cell apoptosis, and treating cells with TSA, NaBu or BCS significantly attenuated the apoptosis induced by PDTC-Cu(2+). Collectively, these results showed that inhibition of histone acetylation represents a distinct mechanism for the cytotoxicity of PDTC in the presence of Cu(2+), where HAT is its possible molecular target.


A multispectral optical illumination system with precise spatiotemporal control for the manipulation of optogenetic reagents.
Optogenetics is an excellent tool for noninvasive activation and silencing of neurons and muscles. Although they have been widely adopted, illumination techniques for optogenetic tools remain limited and relatively nonstandardized. We present a protocol for constructing an illumination system capable of dynamic multispectral optical targeting of micrometer-sized structures in both stationary and moving objects. The initial steps of the protocol describe how to modify an off-the-shelf video projector by insertion of optical filters and modification of projector optics. Subsequent steps involve altering the microscope's epifluorescence optical train as well as alignment and characterization of the system. When fully assembled, the illumination system is capable of dynamically projecting multispectral patterns with a resolution better than 10 μm at medium magnifications. Compared with other custom-assembled systems and commercially available products, this protocol allows a researcher to assemble the illumination system for a fraction of the cost and can be completed within a few days.


Fatal Yellow Oleander Poisoning Masquerading as Benign Candlenut Ingestion Taken for Weight Loss.
Candlenuts (Aleurites moluccana) and yellow oleander seeds (Thevetia peruviana) bear a physical resemblance to one another. Candlenuts are benign and marketed as weight loss supplements. Yellow oleander seeds, however, contain toxic cardioactive steroids; as few as 2 seeds may cause fatal poisoning. Because of their physical similarities, the potential for a lethal substitution exists. A 63-year-old woman presented to the emergency department with vomiting after ingesting 5 of what she believed to be candlenuts that were ordered online under the colloquial name "Nuez de la India" for the purpose of weight loss. She was bradycardic (nadir pulse of 30 beats/min) and hyperkalemic (serum potassium 7.3 mEq/L). Within hours of presentation she suffered a ventricular fibrillation arrest, followed by a terminal asystolic arrest. Postmortem analyses of liver tissue and the seeds were consistent with fatal T. peruviana poisoning. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: T. peruviana seeds contain toxic cardioactive steroids; their physical resemblance to candlenuts poses a risk of potentially fatal substitution. Therapy with high-dose digoxin specific immune fragments (20-30 vials) may be helpful.


Cultivation of Mycolicibacterium spp. Mutants in Miniaturized and High-Throughput Format to Characterize Their Growth, Phytosterol Conversion Ability, and Resistance to the Steroid Products.
This chapter describes methods for cultivation and characterization of the growth of Mycolicibacterium spp. mutants in a microbioreactor system in the presence of steroids and/or phytosterols followed by high-throughput mass spectrometry analysis to describe their ability to convert phytosterols into the target steroid androstenedione (AD). We focus on Mycolicibacterium neoaurum NRRL B-3805 ΔkstD which can convert phytosterol into androstenedione (AD) as one of its major steroid products, and mutants thereof with increased tolerance towards this end-product. By using BioLector 48-well plates with optodes at the bottom of each well, bacterial growth can be monitored online despite the turbidity of the growth medium resulting from non-dissolved phytosterol and steroid particles. To cope with the large number of samples that accumulate during growth experiments in microbioreactors and similar formats (e.g., microtiter plates), protocols for extraction and subsequent RapidFire-MS analysis are presented. This reduces the analysis time per sample to 10 s from 10 min required for regular LC-MS analysis.


Risk factors in a community experience with carotid endarterectomy.
Experience with 1035 carotid endarterectomies in a single community over a 2-year period was analyzed. Twenty-two surgeons working in six hospitals were involved. All surgeons had full-time or part-time appointments at the University of Rochester, 18 had special interest in vascular surgery, and eight had obtained a certificate of qualification in vascular surgery. Mortality rate was 1.4% (14 deaths), with additional permanent, nonfatal, neurologic morbidity of 3.4%. Mortality and morbidity were independent of surgeon, caseload, or hospital. Age and prior history of myocardial infarction influenced the incidence of postoperative myocardial infarction but not the incidence of death or neurologic morbidity. Factors that increased the risk of postoperative death or neurologic complication included hypertension; contralateral carotid disease as manifested by stroke, endarterectomy, or occlusion; whether the patient was a woman; and symptoms of crescendo ischemia. Lack of preoperative neurologic symptoms was correlated with decreased risk of myocardial infarction and neurologic complications. Overall mortality and neurologic morbidity associated with operation for "asymptomatic stenosis" was 3.1% (seven of 222 cases). However, the incidence of contralateral carotid disease was high in the patients in the asymptomatic group (60%), and all complications in this group occurred in patients with prior contralateral carotid endarterectomy or occlusion (p less than 0.05).


A ratiometric nanosensor based on conjugated polyelectrolyte-stabilized AgNPs for ultrasensitive fluorescent and colorimetric sensing of melamine.
A new ratiometric nanosensor is developed for selective and ultrasensitive detection of melamine based on conjugated polyelectrolyte (CPE)-stabilized silver nanoparticles (P1-AgNPs) by perfectly combining the advantages of CPE and AgNPs. P1 featuring a π-delocalized backbone bearing pyridinyl groups can act as an excellent dual-emission fluorescent probe as well as a polymer localizer for AgNPs. In the presence of melamine, the fluorescence intensity at 386nm increases owing to the turn-on of the fluorescence of P1, whereas FL intensity at 488nm decreases due to the melamine-induced aggregation and subsequent aggregation-enhanced emission quenching of P1-AgNPs, therefore leading to the ratiometric fluorescent sensing of analyte. Moreover, analyte-induced aggregation of P1-AgNPs also allows the ratiometric colorimetric measurement of melamine. Under the optimum conditions, this facile ratiometric nanosensor favors the fluorescent and colorimetric determination of melamine in liquid milk products with the detection limit as low as 0.1 and 0.45nM, respectively.


Advances in NMR structures of integral membrane proteins.
Integral membrane proteins (IMPs) play a central role in cell communication with the environment. Their structures are essential for our understanding of the molecular mechanisms of signaling and for drug design, yet they remain badly underrepresented in the protein structure databank. Solution NMR is, aside from X-ray crystallography, the major tool in structural biology. Here we review recently reported solution NMR structures of polytopic IMPs and discuss the new approaches, which were developed in the course of these studies to overcome barriers in the field. Advances in cell-free protein expression, combinatorial isotope labeling, resonance assignment, and collection of structural data greatly accelerated IMP structure determination by solution NMR. In addition, novel membrane-mimicking media made possible determination of solution NMR structures of IMPs in a native-like lipid environment.


Mining Tacitus: secrets of empire, nature and art in the reason of state.
A new political practice, the 'reason of state', informed the ends and practices of natural study in the late sixteenth century. Informed by the study of the Roman historian Tacitus, political writers gathered 'secrets of empire' from both history and travel. Following the economic reorientation of 'reason of state' by Giovanni Botero (1544-1617), such secrets came to include bodies of useful particulars concerning nature and art collected by an expanding personnel of intelligencers. A comparison between various writers describing wide-scale collections, such as Botero, Francis Bacon (1561-1626), Jakob Bornitz (1560-1625) and Matthias Bernegger (1582-1640), reveals that seventeenth-century natural intelligencers across Europe not only were analogous to political intelligencers, but also were sometimes one and the same. Those seeking political prudence cast themselves as miners, prying precious particulars from the recesses of history, experience and disparate disciplines, including mathematics, alchemy and natural philosophy. The seventeenth-century practice of combining searches for secrets of empire, nature and art contests a frequent historiographical divide between empirical science and Tacitism or reason of state. It also points to the ways political cunning shaped the management of information for both politics and the study of nature and art.


Cross-Cultural Adaptation and Validation of the Dagbani Readiness for Hospital Discharge Scale-New Mother.
The Readiness for Hospital Discharge Scale-New Mother (RHDS-NM), originally developed for use in English-speaking populations, is an instrument designed to measure women's perceptions of readiness for hospital discharge after birth. We translated and cross-culturally adapted the RHDS-NM into Dagbani and conducted reliability and validity assessments of the new Dagbani RHDS-NM in the Tamale Metropolitan Area, Ghana. The average scale-level content validity index was excellent at 1.00. The Dagbani RHDS-NM had a Cronbach's α reliability coefficient of .94. Exploratory factor analysis indicated four factors with Cronbach's α reliability coefficients of .958, .915, .899, and .667 that represented the Personal Status, Knowledge, Expected Support, and Coping Ability subscales, respectively. Our findings provide initial evidence to support the reliability and validity of the Dagbani RHDS-NM.


Identification of mitochondria-rich cells in unstained vital preparations of epithelia by autofluorescence.
To recognize mitochondria-rich cells in unstained vital preparations of heterogeneously composed epithelia we report here the use of an autofluorescence technique. Upon illumination with wavelengths of 400-440 or 450-490 nm mitochondria-rich cells emit fluorescence light of wave-lengths of greater than 470 or greater than 520 nm respectively, which probably arises from flavoproteins. Illumination does not seem to impair cell function and the fluorescence does not show any sign of fading over observation times of 20 min or greater. The method allows us to identify parietal cells from chief cells in gastric glands and obviously also intercalated cells from principal cells in renal collecting ducts. It might also be useful in other epithelia.


Characterization of a metallo-proteinase from Bothrops asper (terciopelo) snake venom.
Metalloproteinase from the venom of Bothrops asper (proteinase G) is a glycoprotein with 1% neutral hexose and 3.5 moles of sialic acid per mole of protein. It hydrolyses a number of protein substrates such as casein, hemoglobin, gelatin and fibrinogen, whose alpha chain is degraded preferentially. The pH optimum of hydrolysis of casein is approximately 9.5. The protease is devoid of hemorraghic, esterolytic and amidolytic activities. The proteolytic activity of the enzyme increases by about 20% in the presence of 0.2 mM Ca2+ and Mg2+. Among the other ions tested, only Cd2+ and Fe2+ markedly decreased its activity. EDTA and cysteine are also strong inhibitors. In the presence of Ca2+ and EDTA, Zn2+ ions restored 50% of the activity. The amino acid composition shows fewer acidic residues than in related proteinases from other snake venoms.