[IR search through Internet].
In our laboratories, we have almost had the complete Sadtler IR database, about 133,000 spectra. Based on Sadtler IR Search Master software, off-line spectrum search through internet has been set up in this work. Customers e-mail their unknown spectra as attached files to firstname.lastname@example.com or firstname.lastname@example.com. After we download the unknown spectra and search them, we will send the search reports in Microsoft Word format back to the customers within 72 hours. Please visit our web site www.microchem.org.cn to know the policy about our IR search program.


Bone-titanium oxide interface in humans revealed by transmission electron microscopy and electron tomography.
Osseointegration, the direct contact between an implant surface and bone tissue, plays a critical role in interfacial stability and implant success. Analysis of interfacial zones at the micro- and nano-levels is essential to determine the extent of osseointegration. In this paper, a series of state-of-the-art microscopy techniques are used on laser-modified implants retrieved from humans. Partially laser-modified implants were retrieved after two and a half months' healing and processed for light and electron microscopy. Light microscopy showed osseointegration, with bone tissue growing both towards and away from the implant surface. Transmission electron microscopy revealed an intimate contact between mineralized bone and the laser-modified surface, including bone growth into the nano-structured oxide. This novel observation was verified by three-dimensional Z-contrast electron tomography, enabling visualization of an apatite layer, with different crystal direction compared with the apatite in the bone tissue, encompassing the nano-structured oxide. In conclusion, the present study demonstrates the nano-scale osseointegration and bonding between apatite and surface-textured titanium oxide. These observations provide novel data in human specimens on the ultrastructure of the titanium-bone interface.


Bisphosphonates: expanded roles in the treatment of patients with cancer.
Bisphosphonates are important inhibitors of osteoclastic bone resorption seen in patients with bone metastases associated with malignancy. Bisphosphonates are used in the treatment of patients with bone metastases and have been shown to reduce skeletal-related events and symptoms, contributing to improved patient outcomes and quality of life. These agents first were approved in the treatment of patients with osteoporosis and have been used for the past two decades in this role. Because bisphosphonates inhibit osteoclast-mediated bone resorption, the bone remodeling cycle slows down and an increase in bone mineral density occurs. These agents are useful in treatment for both hypercalcemia and pain, although they have not definitively shown improvement in survival time. Considerable interest exists in the use of bisphosphonates for prevention of bone metastases and their potential antitumor activity. These drugs are well tolerated and have minimal side effects, but they are not inexpensive. This article discusses the role of bisphosphonates in patients with cancer and future directions for further research.


Interleukin 1 expression is inducible by nerve growth factor in PC12 pheochromocytoma cells.
Expression of the cytokine interleukin 1 alpha (IL-1 alpha) was demonstrated in the rat PC12 pheochromocytoma cell line by (i) immunohistochemistry using rabbit polyclonal antisera raised against the recombinant murine IL-1 alpha, (ii) an ELISA, and (iii) a specific cell conversion bioassay based on the use of LBRM33-1A5 cells. IL-1 alpha mRNA was demonstrated in the PC12 cells, by PCR amplification. Constitutive expression of IL-1 alpha in PC12 cells was demonstrated in all experiments, although the cellular levels of IL-1 alpha-like immunoreactivity varied. The expression of IL-1 alpha, as studied at the mRNA level, was inducible by mouse nerve growth factor (7S NGF), and the gene product level was inducible in a dose- and time-dependent fashion by 7S NGF. The maximum induction corresponds to a 600% increase in IL-1 alpha-like immunoreactivity above the expression level found in noninduced cells and occurred after a 3-day incubation of the cells with NGF at 0.75 micrograms/ml of culture medium. The significance of the ability of NGF to induce IL-1 expression lies in the fact that IL-1 itself also acts as a growth factor that promotes glial proliferation and, even more importantly, IL-1 itself induces the expression of NGF at peripheral nerve injury [Lindholm, D., Heumann, R., Meyer, M. & Thoenen, H. (1987) Nature (London) 330, 658-659].


The effect of aging on contour integration.
Perception of global patterns requires the integration of local orientation information across space. The present study examined whether this integration ability declines in older age. We measured contrast thresholds for discriminating the global orientation of a "C" shaped contour against a blank background in younger and older subjects. Performance of younger subjects improved when the elements composing the "C" were aligned along the contour path, as opposed to being orthogonal to it or of mixed orientations. However, older subjects' performance was not affected by the orientation of the local elements. This indicates an age-related decline in contour integration.


[Aorto-pulmonary windows. Report of fifteen cases (author's transl)].
Fifteen aorto-pulmonary windows have been operated on patients 1,5 months to 6 years old. 6 were associated with other cardiac malformations (ductus arteriosus, VSD, mitral insufficiency, aortic arch atresia). 5 cases died. 3 had other cardiac malformations associated. 10 have an average follow-up of 5 1/2 years. The authors insist on the severity of the cases with high pulmonary pressure, and advise operation during the first year of life.


Coexistence of immune thrombocytopenic purpura and idiopathic membranous glomerulonephritis successfully treated with rituximab.
We describe here coexistence of immune thrombocytopenic purpura (ITP) and idiopathic membranous glomerularnephritis (IMG) in one individual who presented a decade ago after delivering a macerated dead fetus. Investigations performed then revealed clinical, biochemical and histopathological evidence of IMG. A year later she presented with bleeding diathesis and was diagnosed as ITP. Thereafter, she manifested with several episodes of serious bleeding complications especially in the central nervous system with considerable frequency, inspite of receiving treatment with steroids, intravenous immunoglobulin and cyclosporine. Subsequently, she received six courses of rituximab and went into complete remission. To date, after more than 3.5 years of follow up, she is completely symptom free. Co-existence of IMG and ITP has been reported earlier; however, this is the first instance of successful treatment of both these entities with rituximab.


Diurnal Variation in Visual Simple Reaction Time between and within Genders in Young Adults: An Exploratory, Comparative, Pilot Study.
Simple reaction time (SRT) is the minimum time required to respond to a stimulus; it is a measure of processing speed. Our study aimed to determine the variation in visual SRT with time among individuals of the same gender and between genders. We carried out a prospective, parallel group, pilot study involving ten male and ten female medical students aged 18-25 years. After obtaining written informed consent, the participants were familiarized with the procedures, and each completed a single practice session of a computerized visual SRT which was administered using Psychology Experiment Building Language Version 2.0 software. On a predetermined day, the participants completed the exercise at 10 a.m., 1 p.m., and 5 p.m. The results showed no statistically significant difference in SRT based on time of day between genders (χ 2(2) = 4.300, p=0.116) as well as within gender (males (χ 2(2) = 0.600, p=0.741); females (χ 2(2) = 5.000, p=0.082). Our study showed that visual SRT does not change significantly at different times of the day and within and between genders. Intraindividual variations in visual SRT can mask the presence of a small but significant difference; hence, further studies are warranted.


New fluoroprostaglandin F(2alpha) derivatives with prostanoid FP-receptor agonistic activity as potent ocular-hypotensive agents.
To find new prostanoid FP-receptor agonists possessing potent ocular-hypotensive effects with minimal side effects, we evaluated the agonistic activities of newly synthesized prostaglandin F(2alpha) derivatives for the prostanoid FP-receptor both in vitro and in vivo. The iris constrictions induced by the derivatives and their effects on melanin content were examined using cat isolated iris sphincters and cultured B16 melanoma cells, respectively. The effects of derivative ester forms on miosis and intraocular pressure (IOP) were evaluated in cats and cynomolgus monkeys, respectively. Of these derivatives, 6 out of 12 compounds were more potent iris constrictors, with EC(50) values of 0.6 to 9.4 nM, than a carboxylic acid of latanoprost (EC(50)=13.6 nM). A carboxylic acid of latanoprost (100 microM) significantly increased the melanin content of cultured B16 melanoma cells, but some 15,15-difluoro derivatives, such as AFP-157 and AFP-172, did not. Topically applied AFP-168, AFP-169 and AFP-175 (isopropyl ester, methyl ester and ethyl ester forms, respectively, of AFP-172) induced miosis in cats more potently than latanoprost. AFP-168 (0.0005%) reduced IOP to the same extent as 0.005% latanoprost (for at least 8 h). These findings indicate that 15,15-difluoroprostaglandin F(2alpha) derivatives, especially AFP-168, have more potent prostanoid FP-receptor agonistic activities than latanoprost. Hence, AFP-168 may be worthy of further evaluation as an ocular-hypotensive agent.


Growth failure: 'idiopathic' only after a detailed diagnostic evaluation.
The terms 'idiopathic short stature' (ISS) and 'small for gestational age' (SGA) were first used in the 1970s and 1980s. ISS described non-syndromic short children with undefined aetiology who did not have growth hormone (GH) deficiency, chromosomal defects, chronic illness, dysmorphic features or low birth weight. Despite originating in the pre-molecular era, ISS is still used as a diagnostic label today. The term 'SGA' was adopted by paediatric endocrinologists to describe children born with low birth weight and/or length, some of whom may experience lack of catch-up growth and present with short stature. GH treatment was approved by the FDA for short children born SGA in 2001, and by the EMA in 2003, and for the treatment of ISS in the US, but not Europe, in 2003. These approvals strengthened the terms 'SGA' and 'ISS' as clinical entities. While clinical and hormonal diagnostic techniques remain important, it is the emergence of genetic investigations that have led to numerous molecular discoveries in both ISS and SGA subjects. The primary message of this article is that the labels ISS and SGA are not definitive diagnoses. We propose that the three disciplines of clinical evaluation, hormonal investigation and genetic sequencing should have equal status in the hierarchy of short stature assessments and should complement each other to identify the true pathogenesis in poorly growing patients.


Calcium is required in reassembly of bovine papillomavirus in vitro.
Papillomaviruses are small DNA viruses which infect and induce benign warts and sometimes malignant tumours in the epithelium of the skin or mucosa. The viruses do not replicate in conventional tissue culture systems and little is known about the requirements for virus assembly. We investigated the effect of ethylene glycol-bis(aminoethyl ether)-tetraacetic acid (EGTA) and dithiothreitol (DTT) treatment on the stability of bovine papillomavirus type 1 (BPV-1) particles in vitro. Removal of calcium ions by 11 mM EGTA at pH 8.0 together with reduction of disulfide bonds by 15 mM DTT destabilized BPV particles. Electron microscopy examination of treated particles showed that the BPV particles had been disrupted to capsomeres. Addition of exogenous calcium ions to the disruption buffer prevented virus destabilization. Adding calcium to the disrupted BPV particles resulted in the reassembly of disrupted particles. The reassembled particles were morphologically similar to intact BPV virions. We further quantified the efficiency of reassembly by focus formation assay. We recorded 500-fold less infectivity for reassembled BPV and 4-fold less haemagglutination activity compared to untreated BPV, pointing towards a decrease in the amount of reassembled particles recovered.


2003 AHA Environmental Assessment.
The 2003 AHA Environmental Assessment highlights key market indicators that hospital leaders think will have the most influence on the health care climate over the next several years.


Magnetic resonance imaging diagnosis of intervertebral disc disease and myelomalacia in an American black bear (Ursus americanus).
A 23-yr-old black bear (Ursus americanus) was examined because of paralysis of unknown duration. The precise onset of clinical signs was unknown as a result of seasonal torpor. The bear was immobilized and transported to a university veterinary teaching hospital for further evaluation and treatment. Radiography revealed increased mineral opacity and ventral bridging across vertebral segments T8-11. Magnetic resonance imaging demonstrated dorsal and ventral compression of the spinal cord at T8-9. Given the bear's advanced age, the unknown duration of spinal cord compression, unknown presence of deep pain perception, and thus an unknown prognosis for surgical success, euthanasia was elected. Postmortem examination revealed severe spondylosis deformans from T7 to L3 and dorsal extradural extruded disc material in the area of T8-9. Histopathology demonstrated the dorsal horns of the spinal cord at T9 were replaced by foamy macrophages extending into the dorsal and lateral funiculi of the white matter compatible with focal, severe, chronic myelomalacia. This is the first report of intervertebral disc disease and myelomalacia diagnosed using MRI in a large carnivore.


Morphology of the inner structure of the hippocampal formation in Alzheimer disease.
To our knowledge, inner structural alterations of the hippocampus have never been demonstrated because of the lack of contrast between the hippocampus proper and the superficial medullary lamina. We sought to demonstrate the anatomic details of the inner hippocampus and to elucidate its alterations in Alzheimer disease (AD) in vivo. We obtained multishot diffusion- and T2-weighted MR images in 14 healthy control subjects and 26 patients with mild or moderate AD (diagnosis based on Mini-Mental Status Examination scores). We measured the width of the subiculum, CA1 and CA3-4, and the height of CA3-4 on coronal images. The subiculum and hippocampus proper were demonstrated as whirlpool-shaped hyperintense areas, and the superficial medullary lamina was visible as a hypointense structure along the inner margin of the hippocampus proper. Regarding the width of the subiculum and CA1, intergroup analysis revealed significant differences between the control and mild or moderate AD groups. In the width of CA3-4, we found no significant difference between the control and mild AD groups; however, differences between the control and moderate AD groups and between the mild and moderate AD groups were significant. In the height of CA3-4, we observed no significant differences between groups. We clearly visualized the inner structure of the hippocampal formation by using multishot diffusion-weighted imaging. The subiculum and CA1 are the most vulnerable regions in AD, and atrophy of these structures was evident in both mild and moderate AD.


Improvements in HIV care engagement and viral load suppression following enrollment in a comprehensive HIV care coordination program.
Substantial evidence gaps remain regarding human immunodeficiency virus (HIV) intervention strategies that improve engagement in care (EiC) and viral load suppression (VLS). We assessed EiC and VLS before and after enrollment in a comprehensive intervention for persons at risk of poor HIV care outcomes. New York City's Ryan White Part A HIV Care Coordination Program (CCP), launched at 28 agencies in 2009, applies multiple strategies to promote optimal utilization of medical and social services. Using laboratory test records from an HIV surveillance registry, we examined pre-post outcomes among 3641 CCP clients enrolled before April 2011. For the year before and after enrollment, we assessed EiC (defined as ≥2 tests, ≥90 days apart, with ≥1 in each half-year) and VLS (defined as viral load [VL] ≤200 copies/mL on latest VL test in the second half of the year). We estimated relative risks (RRs), comparing pre- and postenrollment proportions achieving EiC and VLS. Among newly diagnosed clients, 90.5% (95% confidence interval [CI], 87.9%-93.2%) and 66.2% (95% CI, 61.9%-70.6%) achieved EiC and VLS, respectively. Among previously diagnosed clients, EiC increased from 73.7% to 91.3% (RR = 1.24; 95% CI, 1.21-1.27) and VLS increased from 32.3% to 50.9% (RR = 1.58; 95% CI, 1.50-1.66). Clients without evidence of HIV care during the 6 months preenrollment contributed most to overall improvements. Pre-post improvements were robust, retaining statistical significance within most sociodemographic and clinical subgroups, and in 89% (EiC) and 75% (VLS) of CCP agencies. Clients in comprehensive HIV care coordination for persons with evident barriers to care showed substantial and consistent improvement in short-term outcomes.


Extending Aging of Beef Longissimus Lumborum From 21 to 84 Days Postmortem Influences Consumer Eating Quality.
Our objective was to determine the effect of extending postmortem aging from 21 to 84 days on consumer eating quality of beef longissimus lumborum. Strip loins were collected from 108 carcasses. The longissimus lumborum muscle was isolated from strip loins and assigned to one of ten postmortem aging periods from 21 to 84 days (7-day increments) and balanced within four anatomical positions within the muscle. Consumer evaluations for tenderness, juiciness, flavor, and overall liking were conducted using untrained consumer sensory panels consisting of 1080 individual consumers, in accordance with the Meat Standards Australia protocols. These scores were then used to calculate an overall eating quality (MQ4) score. Postmortem aging had no effect (P > 0.05) on tenderness, but juiciness, flavor liking, overall liking, and MQ4 declined (P < 0.05) as aging period increased. Samples aged 21 to 42 days were most preferred having greater (P < 0.05) overall liking and greater (P < 0.05) MQ4 scores than samples aged 70 to 84 days postmortem. These results suggest that longissimus lumborum samples should not be wet-aged longer than 63 days to prevent potential negative eating experiences for consumers; however, altering storage conditions, specifically reducing temperature, could potentially allow for longer chilled storage without such negative effects on flavor and overall liking.


Performance and approval procedures for active personal dosemeters.
Active personal dosemeters (APDs) are well accepted as useful and reliable instruments for individual dosimetry measurements. The increasing concern about studying the behaviour of APDs in pulsed fields is illustrated through revision of the results of the most representative studies on the performance of APDs in the last 5 y. The deficiencies of APDs in pulsed fields are discussed together with proposals to overcome them. Although there are no legal constraints or technical limitations for recognising APDs for legal dosimetry in facilities with continuous radiation fields, APDs continue to be mainly used as operational dosemeters. The approval procedures applicable to APDs, especially the approach undertaken by Germany, are presented. Finally, some trends in the developments and use of APDs are summarised.


[Biochemical parameters for determination of graft viability during the early postoperative period (author's transl)].
In 54 patients with graft failure the changes of urine sodium concentration and of urinary enzyme activities (alanine aminopeptidase, AAP) were investigated. It was found that: (1) the kidneys with irreversible acute tubular necrosis are characterised by high urine sodium level, and low AAP activities. These changes correspond to the end stage of renal insufficiency. (2) Low concentration of sodium and extremely high AAP excretion are characteristic in grafts with severe rejection episodes. (3) If kidneys lost their function due to irreversible rejection, the biochemical variables showed the same changes as in the first group. We concluded that by continuous determination of sodium levels and enzyme activities in urine and by their correlation it is possible to detect the non-functioning grafts in the early posttransplantation period.


Understanding the Burden on Caregivers of People with Parkinson's: A Scoping Review of the Literature.
Caregivers are healthcare assets because they care for patients at home; however, when clinicians focus solely on patients, caregivers' needs may not be recognized. The purpose of this scoping literature review is to identify the burdens on caregivers of people with Parkinson's disease. CINAHL and PubMed databases were searched to locate thirteen original articles, one systematic review, and one meta-analysis within the last five years that highlighted caregivers' burdens. Results indicate the need to identify practical interventions that decrease caregivers' physical, psychological, and socioeconomic burdens. Correlates of Parkinson's caregiver burdens are not clearly available. Caregivers' contextual demographic information is missing, as is an understanding of how caregivers negotiate day-to-day caregiving activities. Gaps exist about how caregivers reconcile multiple medications and manage rehabilitation needs of the patient at home. A recommendation for practice is a systematic evaluation of the caregivers' capacity at the time of clinic visit.


Psychiatric problems and trauma exposure in nondetained delinquent and nondelinquent adolescents.
This study examined the prevalence of and associations between specific psychiatric disorders, substance use problems, and trauma exposure in a sample of delinquent and nondelinquent adolescents. A nationally representative sample of adolescents (n = 3,614; M age = 14.5 years, SD = 1.7; 51% male; 71% White, non-Hispanic, 13.3% African American, non-Hispanic, 10.7% Hispanic) was interviewed via telephone about engagement in delinquent acts and their experience of posttraumatic stress disorder, major depressive episode, substance use, interpersonal violence, and other forms of trauma exposure. Delinquent adolescents were more likely than nondelinquent adolescents to experience trauma; they were also more likely to report past-year posttraumatic stress disorder, major depressive episode, alcohol abuse, and nonexperimental drug use. After accounting for the effects of demographics and trauma exposure, delinquency was associated with increased likelihood of posttraumatic stress disorder and problematic substance use in both genders and increased likelihood of major depressive episode in girls. Findings highlight substantial overlap among delinquency, trauma exposure, posttraumatic stress disorder, and major depressive episode in adolescents and the need for interventions that address these varied clinical problems. Future work should examine the factors underlying the development of these relations over time.


[Taxonomy of the Sokuluk virus (SOKV) (Flaviviridae, Flavivirus, Entebbe bat virus group) isolated from bats (Vespertilio pipistrellus Schreber, 1774), ticks (Argasidae Koch, 1844), and birds in Kyrgyzstan].
Complete genome sequencing of the Sokuluk virus (SOKV) isolated in Kyrgyzstan from bats Vespertilio pipistrellus and their obligatory parasites--Argasidae Koch, 1844, ticks was carried out. SOKV was classified as attributed to the Flaviviridae family, Flavivirus genus. The maximum homology (71% for nucleotide and 79% for amino acid sequences) was detected with respect to the Entebbe bat virus (ENTV). ENTV and SOKV form a group joining to the yellow fever virus (YFV) within the limits of the mosquito flavivirus branch. Close relation of SOKV with bat covers and human housings permits to assume SOKV potentially patogenic to human health.


Structural Characterization of Glaucoma Patients with Low Ocular Blood Flow.
Purpose: There is an unclear relationship between ocular blood flow (OBF) and the structural characteristics of the optic nerve head (ONH) in glaucoma, a multifactorial disease. This study used laser speckle flowgraphy (LSFG) to identify low-OBF glaucoma patients and investigated the ONH in these patients. Materials and Methods: In 533 eyes with glaucoma, we determined confounding factors for LSFG-measured OBF (tissue-area mean blur rate: MT) and corrected MT with a linear mixed-effects model (LMM). Structural ONH data (from fundus stereo photography), OCT data, and clinical characteristics were then compared in patients with corrected MT in the upper and lower quartiles using the LMM. Results: Single regression showed significant correlations between MT and age, spherical equivalent (SE), central corneal thickness (CCT), and a weighted count of retinal ganglion cells (wRGC), but not axial length or systemic blood pressure. Gender also significantly influenced MT; MT was corrected for these correlated factors and also glaucoma type with the LMM. The lower-quartile MT group had a significantly larger cup area and cup-disc area ratio and lower temporal quadrant circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and macular ganglion cell complex (GCC) than the upper-quartile group. Conclusions: Low-OBF glaucoma patients were characterized by a larger cup-disc ratio, and higher susceptibility to damage in the temporal disc and the macular area.


Rat serum contains a developmentally regulated cholinergic inducing activity.
Sympathetic neurons cultured in defined medium do not develop the ability to produce acetylcholine, as do neurons grown with serum supplementation (lacovitti, L., M. I. Johnson, T. H. Joh, and R. P. Bunge (1982) Neuroscience 7:2225-2239; Wolinsky, E. J., S. C. Landis, and P. H. Patterson (1985) J. Neurosci. 5: 1497-1508). The implication that rat serum contains cholinergic inducing activity is further explored here. Dependence of cholinergic induction on serum concentration is demonstrated, and the activity is shown to reside in a macromolecular fraction. Very little cholinergic inducing activity is present in serum obtained from animals younger than 9 postnatal days. This age dependence correlates with the time of transition from noradrenergic to cholinergic transmitter status by the sympathetic innervation of the rat sweat gland in vivo (Landis, S. C., and D. Keefe (1983) Dev. Biol. 98: 349-372).


A continuous heparin infusion does not prevent catheter-related thrombosis in infants after cardiac surgery.
To determine whether a continuous infusion of heparin reduces the rate of catheter-related thrombosis in neonates and infants post cardiac surgery. Central venous and intracardiac catheters are used routinely in postoperative pediatric cardiac patients. Catheter-related thrombosis occurs in 8% to 45% of pediatric patients with central venous catheters. Single-center, randomized, placebo-controlled, double-blinded trial. Cardiovascular intensive care unit, university-affiliated children's hospital. Children <1 yr of age recovering from cardiac surgery. Patients were randomized to receive either continuous heparin at 10 units/kg/hr or placebo. The primary end point was catheter-related thrombosis as assessed by serial ultrasonography. Study enrollment was discontinued early based on results from an interim futility analysis. Ninety subjects were enrolled and received the study drug (heparin, 53; placebo, 37). The catheter-related thrombosis rate in the heparin group, compared with the placebo group, was 15% vs. 16% (p = .89). Subjects in the heparin group had a higher mean partial thromboplastin time (52 secs vs. 42 secs, p = .001), and this difference was greater for those aged <30 days (64 secs vs. 43 secs, p = .008). Catheters in place > or = 7 days had both a greater risk of thrombus formation (odds ratio, 4.3; p = .02) and catheter malfunction (odds ratio, 11.2; p = .008). We observed no significant differences in other outcome measures or in the frequency of adverse events. A continuous infusion of heparin at 10 units/kg/hr was safe but did not reduce catheter-related thrombus formation. Heparin at this dose caused an increase in partial thromboplastin time values, which, unexpectedly, was more pronounced in neonates.


Performance of Future Glomerular Filtration Rate Equation by Race in a Large, Racially Diverse Patient Cohort Undergoing Nephrectomy for Renal Cell Carcinoma.
To examine the performance of the Palacios et al [Aguilar Palacios D, Wilson B, Ascha M, et al. New baseline renal function after radical or partial nephrectomy: a simple and accurate predictive model. J Urol. 2021;205:1310-1320] post-nephrectomy future glomerular function rate (fGFR) equation in a diverse cohort using both the Chronic Kidney Disease Epidemiology (CKD-EPI) 2009 equation with race, used in the creation of the formula, as well as the CKD-EPI 2021 equation without race. Patients who underwent partial or radical nephrectomy for renal cell carcinoma from 2005-2021 were identified in our institutional database. Patients with creatinine values preoperatively and 3-12 months postoperatively were included. Correlation/bias/accuracy/precision of the fGFR equation (fGFR = 35+ [preoperative eGFR × 0.65] - 18 [if radical] - [age × 0.25] + 3 [if tumor >7 cm] - 2 [if diabetes]) with observed postoperative eGFR was determined by both the CKD-EPI-2021 and CKD-EPI 2009 equations. A total of 1443 patients were analyzed. Seventy-one percent (1024) were White and 22.9% (331) were Black. Most underwent radical nephrectomy (60.3%). 40% T3-T4 renal cell carcinoma (RCC), with 14.8% of patients having M1 disease. Median observed vs predicted fGFR was 58.0 vs 58.7 mL/min/1.73 m2 for CKD-EPI 2021 and 56.0 vs 57.5 for CKD-EPI 2009. For the total cohort, the correlation/bias/accuracy/precision of the fGFR equation was 0.805/-0.5/81.7/7.9-9.0 for CKD-EPI 2021 and 0.809/-0.8/81.3/-8.1 to 8 for CKD-EPI 2009. In Black patients, fGFR equation demonstrated >75% accuracy with both CKD-EPI equations; however, accuracy was lower in black patients with the CKD-EPI2021 equation (76.1% vs 83.4%, P = .003). The fGFR equation performed well in our large, diverse cohort, though accuracy was relatively lower when using CKD-EPI 2021 compared to CKD-EPI 2009.


Analysis of Cell-Free DNA to Assess Risk of Tumoremia Following Endoscopic Ultrasound Fine-Needle Aspiration of Pancreatic Adenocarcinomas.
Cellular and nuclear material from tumors disseminates into the bloodstream (tumoremia), but it is not clear whether medical procedures cause release of this material or contribute to formation of metastases. We performed a prospective study of blood samples from patients with pancreatic adenocarcinoma (PDAC) to determine whether endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) associates with markers of tumoremia. We obtained peripheral blood from 104 patients (35 with PDAC) before and after EUS-FNA of primary tumors; blood samples from 69 healthy individuals were used as controls. Plasma concentrations of cell-free DNA (cfDNA) were measured, and cfDNA and primary tumor samples were analyzed to detect activating mutations in KRAS. Potential development of tumoremia was defined by an increase in cfDNA of 2-fold or more, and/or detection of mutant KRAS in samples collected after FNA from patients whose blood samples did not contain detectable mutant KRAS before FNA. Peripheral blood concentrations of cfDNA were 1200 ng/ml (500-3300 ng/ml) before FNA vs 1400 ng/ml (900-4000 ng/ml) after FNA (P = .391). Tumoremia was detected in 10/35 patients (28.6%): 7 patients had a ≥2-fold increase in cfDNA concentration (20.6%) and 3 patients had circulating tumor DNA with KRAS mutations after FNA that were not detected before FNA (8.8%). New distant metastases were detected in 1.3 ± 0.82 patients with tumoremia vs 0.64 ± 0.81 without (P = .0375). Overall mortality did not differ significantly between patients with tumoremia (10/10 deaths, 100%) vs those without (19/25 deaths, 76%) nor did survival times of deceased patients (13.3 months for patients with tumoremia; range, 5.8-14.9 months vs 11.1 months for patients without tumoremia; range, 5.5-14.5 months). However, 6 patients without tumoremia were alive at a mean 23.9 months after EUS-FNA (range, 19.9-25 months after EUS-FNA) vs none of the patients with tumoremia. In patients with PDAC, EUS-FNA associates with increased plasma concentration of cfDNA and increased detection of mutant KRAS after the procedure (markers of tumoremia and possible new distant metastasis). Although levels of cfDNA and activating mutations in KRAS are logical markers of tumoremia, they may not serve as the ideal biomarkers of this process. These findings are preliminary and do not indicate a need to modify current practice, yet further studies are needed.


Gender violence: transgender experiences with violence and discrimination.
There is a pervasive pattern of discrimination and prejudice against transgendered people within society. Both economic discrimination and experiencing violence could be the result of a larger social climate that severely sanctions people for not conforming to society's norms concerning gender; as such, both would be strongly associated with each other. Questionnaires were distributed to people either through events or through volunteers, and made available upon the World Wide Web. A sample of 402 cases was collected over the span of 12 months (April 1996-April 1997). We found that over half the people within this sample experienced some form of harassment or violence within their lifetime, with a quarter experiencing a violent incident. Further investigation found that experiencing economic discrimination because one is transgendered had the strongest association with experiencing a transgender related violent incident. Economic discrimination was related to transgendered people's experience with violence. Therefore, both hate crimes legislation and employment protections are needed for transgendered individuals.


[Radiation carcinogenesis as a general biological problem].
The initial steps of radiation carcinogenesis have been briefly surveyed. Actuality of their further research is shown on the molecular level. There is a discussion going on about the close connection of such research with basic directions in the development of biology, such as: genome destabilization, gene repression and activation, regulation of growth activity factors, the role of biomembranes in the processes, and synergism in the action of factors on live systems.


The treatment of hepatitis C: history, presence and future.
The treatment of chronic hepatitis C has made remarkable progress over the past two decades. For interferon-alpha monotherapy, sustained virological response rates were between 2 and 9% in genotype 1 and between 16 and 23% in genotypes 2 and 3. By adjusting treatment duration up to 48 weeks for genotype 1 and combining regular interferon-alpha with ribavirin, sustained response rates could be improved to 28 to 31% in genotype 1 and around 65% in genotypes 2 and 3. Attempts to further increase efficacy included the addition of amantadine without conclusive evidence up till now. With the recent introduction of long-acting pegylated interferon-alpha in combination with ribavirin, sustained virological response rates of 8o% can be obtained in genotypes 2 and 3. However, sustained virological response rates for patients with either genotype 1, nonresponse to prior treatment, cirrhosis or a combination of these characteristics are still less than 50%. In view of results with daily high-dose interferon-alpha induction in combination with prolongation of treatment duration up to 18 months, such patients might benefit from induction and prolonged PEG-IFN-alpha treatment and should be treated in an experimental setting.


A block mixture model to map eQTLs for gene clustering and networking.
To study how genes function in a cellular and physiological process, a general procedure is to classify gene expression profiles into categories based on their similarity and reconstruct a regulatory network for functional elements. However, this procedure has not been implemented with the genetic mechanisms that underlie the organization of gene clusters and networks, despite much effort made to map expression quantitative trait loci (eQTLs) that affect the expression of individual genes. Here we address this issue by developing a computational approach that integrates gene clustering and network reconstruction with genetic mapping into a unifying framework. The approach can not only identify specific eQTLs that control how genes are clustered and organized toward biological functions, but also enable the investigation of the biological mechanisms that individual eQTLs perturb in a signaling pathway. We applied the new approach to characterize the effects of eQTLs on the structure and organization of gene clusters in Caenorhabditis elegans. This study provides the first characterization, to our knowledge, of the effects of genetic variants on the regulatory network of gene expression. The approach developed can also facilitate the genetic dissection of other dynamic processes, including development, physiology and disease progression in any organisms.


The plasticizer benzyl butyl phthalate (BBP) inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary DNA adduct formation and tumorigenesis.
Although the risk for cancer is multifactorial, a substantial portion of cancer incidence rates is related to environmental factors, including diet and environmental chemicals. The magnitude of the contribution to cancer of the breast from exposure to environmental chemicals remains unclear. The phthalate ester plasticizers are abundantly-produced industrial chemicals that have become widely-dispersed environmental pollutants. The present studies were conducted to determine the effect of the phthalate ester, benzyl butyl phthalate (BBP) on mammary gland carcinogenesis induced in the female rat by the polycyclic aromatic hydrocarbon (PAH) 7,12-dimethylbenz[a]anthracene (DMBA). Exposure to BBP (i.p. injection) at 100 and 500 mg/kg doses for 5 days resulted in a significant 72 and 92% inhibition, respectively, in the in vivo formation of mammary DMBA-DNA adducts, compared to controls. Treatment with BBP (i.g. intubation) for 7 days resulted in a significant (48%) inhibition in mammary DMBA-DNA adduct formation only for those animals receiving the 500 mg/kg dose, compared to controls. Administration of BBP (i.g.) at 500 mg/kg for 7 days also was associated with a significant 8.5-fold increase in the liver activity of 7-ethoxyresorufin-O-deethylase. No change in liver glutathione-S-transferase activity was observed for animals treated with both BBP (i.g.) doses. Treatment with BBP (i.g.) at 250 and 500 mg/kg doses for 7 days prior to DMBA administration resulted in a significant 37% decrease in mammary tumor incidence for both doses, compared to controls. The number of mammary adenocarcinomas per rat was significantly inhibited by 60 and 70% for rats exposed to BBP at the 250 and 500 mg/kg doses, respectively, compared to controls. Therefore, the present studies indicate that BBP acts as a blocking agent toward DMBA-induced rat mammary DNA adduct formation and mammary carcinogenesis. This effect partly may be due to increased metabolism of BBP in the liver. These results underscore the need to further examine the effect of BBP and other phthalates on the various stages of mammary carcinogenesis, as well as on the metabolism of mammary carcinogens.


The Influence of Acanthamoeba-Legionella Interaction in the Virulence of Two Different Legionella Species.
The genus Legionella comprises more than 60 species, and about half are associated with infection. Legionella pneumophila is the most commonly associated with these infections and by far the most studied, but L. non-pneumophila species, such as L. feeleii, L. anisa, etc., may also present clinical importance. Free-living amoebae are their preferred environmental host, where these bacteria not only survive but also succeed in multiplying, and this relationship can lead to an increase in bacterial virulence. The goal of this study was to evaluate the alterations of Legionella pathogenicity due to its interaction with Acanthamoeba. For this, the expression of protein effectors SdhA, LegK2, and SidK were evaluated in L. pneumophila and L. feeleii, before and after infecting Acanthamoeba. Additionally, the host response was evaluated by measuring the production of IL-6, IL-8, and IFN-γ in infected macrophages. Regarding the virulence factors, an increase in SdhA expression was observed after these bacteria infected Acanthamoeba, with a higher increase in the macrophage cultures infected with L. feeleii. Also, an increase in the expression of LegK2 was observed after infecting Acanthamoeba, but it was more intense in the cultures infected with L. pneumophila. With regard to SidK, it was increased in L. feeleii after infecting Acanthamoeba, however the same effect was not observed for L. pneumophila. In cytokine production, the effect on IL-6 and IL-8 was similar for both cytokines, increasing their concentration, but higher production was observed in the cultures infected with L. feeleii, even though it demonstrated slightly lower production with the inoculum obtained from Acanthamoeba. Concerning IFN-γ, induction was observed in both species but higher in the infection by L. pneumophila. Nevertheless, it is not known if this induction is enough to promote an efficient immune response against either L. pneumophila or L. feeleii. Altogether, these alterations seem to increase L. feeleii virulence after infecting Acanthamoeba. However, this increase does not seem to turn L. feeleii as virulent as L. pneumophila. More studies are necessary to understand the aspects influenced in these bacteria by their interaction with Acanthamoeba and, thus, identify targets to be used in future therapeutic approaches.


Soil sulfur amendments suppress selenium uptake by alfalfa and Western wheatgrass.
Selenium (Se) is a potential soil contaminant in many parts of the world where it can pose a health risk to livestock and wildlife. Phosphate ore mining in Southeast Idaho has resulted in numerous waste rock dumps revegetated with forages to stabilize the dumps and support grazing. Alfalfa (Medicago sativa L.), smooth brome (Bromus inermis Leyss.), and western wheat grass [Pascopyrum smithii (Rydb.) A. Löve] are the dominant forage species on these lands. To demonstrate the feasibility of using sulfur (S) as a soil amendment to restrict plant Se uptake, 3 kg pots containing 50:50 w/w soil and waste shale were uniformly mixed with 0, 0.5, 1.0, or 2.0 Mg ha(-1) S as either elemental S or gypsum. Pots were seeded with alfalfa or western wheat grass. Dry mass and tissue Se were monitored over several clippings. Soils were sampled at the conclusion of the study and analyzed for water-soluble, oxalate-extractable, and total Se. Sulfur amendments as either elemental S or gypsum at 1.0 Mg ha(-1) or greater equally suppressed Se uptake over 60% in both forage species. Alfalfa accumulated more Se than western wheat grass. Plant removal via successive clippings resulted in lower tissue Se accumulation over time than the use of S soil amendments alone. Alfalfa-planted soils contained lower water-soluble and oxalate-extractable Se than did the non-planted controls while western wheat grass-planted soils contained lower water-soluble Se. Applying S to these shale-based soils may be an economically viable option for treating Se-impacted, revegetated lands.


Development and Effects of a Virtual Reality Simulation Nursing Education Program Combined With Clinical Practice Based on an Information Processing Model.
The need to strengthen patient human rights and create a patient-centered healthcare environment is growing. Also as science and technology develop, new educational methods using virtual reality in nursing education are emerging. This study aimed to develop a virtual reality simulation nursing education program related to postoperative patient nursing based on an information processing model and to verify its effectiveness. Clinical practice-linked virtual reality simulation nursing education was conducted for a total of 4 weeks. Nursing students were divided into an experimental group (n = 22) experiencing virtual reality simulation combined with clinical practice and a control group (n = 22) having routine clinical practice. The analytical results of this study indicated that the information processing model-based virtual reality simulation nursing education program was effective in improving nursing students' performance confidence and clinical decision-making ability. Therefore, the virtual reality simulation program developed in this study can provide basic data for the development of a simulation curriculum in the future and can contribute to the development of clinical competency as a professional nurse by improving the performance confidence and clinical decision-making ability of nursing students.


Dissociation of methane into hydrocarbons at extreme (planetary) pressure and temperature.
Constant-pressure, first-principles molecular dynamic simulations were used to investigate the behavior of methane at high pressure and temperature. Contrary to the current interpretation of shock-wave experiments, the simulations suggest that, below 100 gigapascals, methane dissociates into a mixture of hydrocarbons, and it separates into hydrogen and carbon only above 300 gigapascals. The simulation conditions (100 to 300 gigapascals; 4000 to 5000 kelvin) were chosen to follow the isentrope in the middle ice layers of Neptune and Uranus. Implications on the physics of these planets are discussed.


Training physicians to be doctors--teachers and healers, problem-solvers and decision-makers.
With the scientific advances made in medicine during the past 200 years, the training of physicians in America has changed from that of a mentor/apprenticeship relationship to one in which students are part of an impersonal, mass production process. From a historical perspective, it is contended that basic science and rote memorization of medical theory have subsumed the art of medicine. As a result, students are overloaded with irrelevant facts, few of which they carry over in their professional practice of medicine. To alter this teaching approach and, hence, the quality of physicians, medical school curricula should incorporate recommendations found in the General Professional Education of Physicians Report, among other sources. These recommendations, which have been incorporated successfully in the curriculum at the University of New Mexico School of Medicine, for example, include: establishing goals that may be coordinated interdepartmentally; reestablishing the physician/mentor for each student; using a small-group, interactive, problem-solving, clinically oriented approach to teaching; measuring each student's ability to not only retain knowledge but, more importantly, apply such information to actual clinical problem-solving and decision-making situations; admitting liberal arts graduates--not premedical students--to medical schools; and recruiting and training faculty members who have the time to each and the ability to emphasize biomedicine rather than their special discipline. These changes will make students more than physicians. They will be "real doctors," individuals who not only possess knowledge but can apply it in their daily practice of medicine.


An overview of Cistus ectomycorrhizal fungi.
The genus Cistus comprises a group of about 20 shrub species found in wide areas throughout the whole Mediterranean region to the Caucasus. Being one of the main constituents of the Mediterranean-type maquis, this plant genus is peculiar in that it has developed a range of specific adaptations to resist summer drought and frequent disturbance events, such as fire and grazing. In addition, it can form both ectomycorrhizas and arbuscular mycorrhizas. In this paper, we review the information available on the ectomycorrhizal fungi of Cistus across its entire geographic range, as gathered and critically sifted from both published literature sources and personal observations. Although the resulting data matrix was based primarily on accounts of sporocarp inventories in the field, existing knowledge on the features of Cistus natural and synthesized ectomycorrhizas was also included and discussed. In total, more than 200 fungal species belonging to 40 genera have been reported so far to be associated with Cistus. An analysis of the pattern of ectomycorrhizal diversity and host specificity revealed that members of the Cortinariaceae and Russulaceae make the most of both Cistus-aspecific and Cistus-specific mycobionts. Further studies are needed to expand our preliminary knowledge of the mycorrhizal ecology and biology of Cistus and its fungal associates, focusing on topics such as mycobiont diversity, host specificity, fungal succession, mycorrhizal influence on stress tolerance, and impact of disturbances, while comparing the findings with those from other ecosystems.


Reactivity and kinetics of vinyl sulfone-functionalized self-assembled monolayers for bioactive ligand immobilization.
A new vinyl sulfone (VS) disulfide, 1,2-bis(11-(vinyl sulfonyl)undecyl)disulfane, was synthesized to enable the preparation of VS-presenting self-assembled monolayers (VS SAMs) on Au substrates. The VS SAMs were used as a model system to assess the reaction kinetics of bioactive ligands, i.e., glutathione (GSH), N-(5-amino-1-carboxypentyl)iminodiacetic acid (ab-NTA), and mannose, toward the VS groups on the SAM surface. The VS SAMs and the ligand immobilization were characterized by X-ray photoelectron spectroscopy (XPS), contact angle goniometry, and protein-binding experiments using a quartz crystal microbalance (QCM). Kinetic studies showed that the surface VS groups undergo pseudo-first-order reactions with various ligands, with the observed rate constant being 0.057 min(-1) for GSH at pH 7.5, 0.011 min(-1) for ab-NTA at pH 8.5, and 0.009 min(-1) for mannose at pH 10.5. This work advanced our understanding of the reactivity of VS-bearing functional surfaces and further demonstrated the versatile potential of VS chemistry to prepare ligand-immobilized bioactive surfaces.


[Prader-Willi syndrome: medical, emotional and cognitive facets].
Prader-Willi syndrome, first described in 1956, is characterized by marked hypotonia, hyperphagia, severe obesity, short stature, hypogonadism, orthopedic problems, breathing-related sleep disorders, mild to moderate mental retardation and behavioral abnormalities. The incidence of this syndrome, an expression of a genetic imprinting error in chromosome 15, is 1:10,000-1:25,000. We describe the medical, emotional and cognitive parameters of 34 patients in our multidisciplinary clinic for Prader-Willi syndrome. Their ages range from 5 months to 40 years and 20 are males. Excessive weight gain started at the age of 6 years, increasing to 170-370% of that predicted by height and age and short stature started after the age of 12. All males have hypogonadism; 6 patients have scoliosis. Breathing-related sleep disorders have occurred in 15. Children above the age of 8 years underwent neuropsychological assessment: half (9/18) have borderline intelligence while a quarter have low-normal intelligence and the remainder mild to moderate mental retardation. Behavioral and social problems are common, and become more prominent during adolescence. ADHD was diagnosed in 10/18.


Work-related cumulative trauma disorders and interpreters for the deaf.
With the passage of the Americans with Disabilities Act (ADA), increasing numbers of interpreters for the deaf are being employed in education, industry, or other settings. Professional interpreters are at risk for developing cumulative trauma disorders due to the nature of their work which involves rapid repetitive movements of the arms and hands. One hundred forty-five interpreters for the deaf responded to a survey questionnaire designed to identify their work experiences and development of physical pain/discomfort related to work. Incidence and duration of pain/discomfort is positively correlated with hours worked and time of onset. Regardless of age, training, or work experience, 119 (82%) of these respondents experienced disabling pain/discomfort during and following work. Thirty-nine (33%) of the 119 respondents indicated onset of pain or discomfort in the wrist and hand. These data suggest that interpreting for the deaf may result in debilitating pain/discomfort in hands, arms, shoulders, and back if the interpreter is not appropriately prepared to compensate for physical and attentional stresses. Implications include the need to provide periods of rest while working and to provide training for students learning to interpret for the deaf to minimize physical stress while working.


Salivary gland cancer in BRCA-positive families: a retrospective review.
Although an association between breast cancer and salivary gland cancers has been noted for decades, this is the first study, to our knowledge, to evaluate the possible linkage of BRCA gene mutations and this malignant neoplasm. To compare the prevalence of salivary gland cancers in a large BRCA gene mutation database with background rates in the general population. This is a retrospective review (June 1, 2012, through April 31, 2013) of pedigrees from patients with breast cancer in The Clinical Cancer Genetics Program at The Ohio State University Wexner Medical Center. A total of 5754 individuals were identified from 187 pedigrees, and their medical histories were reviewed for diagnoses of salivary gland tumors and BRCA testing. The pedigrees were restricted to provide a cohort of individuals with reasonable accuracy in family history by considering 3 generations of each pedigree, starting with the proband's generation and adding 1 generation above and below. The youngest generation was replaced with another older generation if there were no BRCA-related cancers or BRCA mutations recorded. Nonblood relatives of the proband (ie, stepparents and stepsiblings) were also excluded. The rate of salivary gland cancers in the Clinical Center Genetics Program was compared with background incidence rates. After applying the restrictions to the 187 pedigrees in the database, 5754 individuals were included in the cohort. Two parotid gland cancers, 2 salivary gland cancers not otherwise specified, and 1 adenoid cystic carcinoma were identified. One of these cancers likely did not segregate with the BRCA mutation, and another individual tested negative for the BRCA mutation, resulting in a rate of 3 of 5754 (0.052%).The observed rate of 3 of 5754 cases (0.052%) of head and neck cancers in BRCA-positive probands and likely carriers is significantly higher than the background incidence rate of 3 of 100,000 (0.003%) per year (P < .001). We believe this is a significant observation that, when considered alongside other similarities between salivary glands and breast tissue, warrants further investigation into the nature of a possible linkage between germline BRCA mutations and salivary gland cancer.


Increasing the Efficiency of Prevention Trials by Incorporating Baseline Covariates.
Most randomized efficacy trials of interventions to prevent HIV or other infectious diseases have assessed intervention efficacy by a method that either does not incorporate baseline covariates, or that incorporates them in a non-robust or inefficient way. Yet, it has long been known that randomized treatment effects can be assessed with greater efficiency by incorporating baseline covariates that predict the response variable. Tsiatis et al. (2007) and Zhang et al. (2008) advocated a semiparametric efficient approach, based on the theory of Robins et al. (1994), for consistently estimating randomized treatment effects that optimally incorporates predictive baseline covariates, without any parametric assumptions. They stressed the objectivity of the approach, which is achieved by separating the modeling of baseline predictors from the estimation of the treatment effect. While their work adequately justifies implementation of the method for large Phase 3 trials (because its optimality is in terms of asymptotic properties), its performance for intermediate-sized screening Phase 2b efficacy trials, which are increasing in frequency, is unknown. Furthermore, the past work did not consider a right-censored time-to-event endpoint, which is the usual primary endpoint for a prevention trial. For Phase 2b HIV vaccine efficacy trials, we study finite-sample performance of Zhang et al.'s (2008) method for a dichotomous endpoint, and develop and study an adaptation of this method to a discrete right-censored time-to-event endpoint. We show that, given the predictive capacity of baseline covariates collected in real HIV prevention trials, the methods achieve 5-15% gains in efficiency compared to methods in current use. We apply the methods to the first HIV vaccine efficacy trial. This work supports implementation of the discrete failure time method for prevention trials.


Toward a safer label.
Pharmacy literature has reminded hospital pharmacists that our computer generated intravenous and medication labels often fall short in the area of legibility and usability. A new computer system and Zebra Stripe S-500 printers (Zebra Technologies Corporation, Vernon Hills, IL) allowed Methodist Medical Center to reexamine our labels and to join with nursing to develop a safer, more user friendly set of labels. These new labels have been well received by our nursing staff.


[Duration-outcome relations in nonpharmacological treatment of chronic cardiac failure developed after acute myocardial infarction].
Left-ventricular (LV) systolic-diastolic function and cardiac rhythm variability, the rate of pathological LV remodeling and outcomes of the disease for 18 months were studied in 394 males at the age 35-68 years suffering from chronic cardiac failure (CCF) of NYHA functional class I-II consequent to myocardial infarction occurring 9.6-4.2 months before. It was found that long-term (12-24 weeks) taking sauna, underwater dousch-massage, general effervescent baths and exercise in combination with drug therapy in patients with asymptomatic CCF inhibit the rate of LV remodeling, decrease LV hypertrophy, improve diastolic function of the heart. This results in lowering a cumulative risk of unfavourable outcomes of the disease by 42% (p = 0.006). The best of effect of the combined therapy is not achieved in angina of effort, massive myocardial hypoperfusion zones, no viable myocardium in the zones of the lesion, marked LV hypertrophy.


Oxalate Nephropathy and the Mechanism of Oxalate-Induced Kidney Injury.
Hyperoxaluria is a major cause of oxalate nephropathy, which can lead to impaired renal function presenting as acute kidney injury, acute on chronic kidney disease, or chronic kidney disease. The Chronic Renal Insufficiency Cohort study showed that higher urinary oxalate is associated with renal outcome in patients with chronic kidney disease, supporting the nephrotoxicity of oxalate. Therefore, a better understanding of the role of oxalate in kidney injury is needed. This review describes the metabolism of oxalate and the clinical and pathology presentation of oxalate nephropathy. It also summarizes the available evidence for the underlying pathogenic mechanism and the development of treatments for oxalate-induced kidney injury. Disruption to any key step in the oxalate pathway including abnormal endogenous generation, ingestion of abnormally high dose of oxalate, increased absorption or attenuation of oxalate degradation in the gut, and reduced excretion through the kidney may lead to disrupted oxalate homeostasis. Oxalate nephropathy is mainly caused by hyperoxaluria. Oxalate crystal deposition in the kidney is usually accompanied with tubular toxicity, obstruction, interstitial fibrosis, and tubular atrophy. The mechanism of oxalate-induced renal injury has not been fully clarified. Evidence from both in vivo and in vitro studies shows that NLRP3 inflammasome activation and macrophage infiltration are involved in the processes of crystal adhesion, aggregation, and elimination and promote intrarenal inflammation and renal fibrosis. Novel treatment strategies have been developed and targeted therapies tested for oxalate nephropathy. Prompt diagnosis and management may help to reduce the deposition of calcium oxalate crystals in the kidney. Further studies are needed to clarify the underlying mechanisms to help develop more targeted therapies for oxalate nephropathy.


The use of HIV-1 integrase inhibitors in antiretroviral naive patients.
In this review we will discuss recent findings on the use of inhibitors of the HIV-1 integrase enzyme for the treatment of antiretroviral naive patients. We will also discuss differences between integrase inhibitors, and comment on the use of this class of drugs in the future. Raltegravir when taken twice daily is as effective and well tolerated as efavirenz. Once daily dosing of raltegravir is virologically inferior to raltegravir taken twice daily. A novel nucleoside-free regimen of raltegravir in combination with a once daily ritonavir-boosted protease inhibitor did not produce adequate viral suppression, although raltegravir with a twice daily protease inhibitor yielded better results. Subset analyses have demonstrated a favorable impact of raltegravir on lipid levels and body fat composition. Two once daily integrase inhibitors not yet Food and Drug Administration-approved, elvitegravir and dolutegravir, have completed phase-2 testing and are also virologically noninferior to efavirenz. Integrase inhibitors provide potent antiretroviral activity, little short-term toxicity and excellent tolerability. For patients with preexisting atherosclerosis or cardiac risk factors this class of therapy is a logical preferred treatment choice. Raltegravir is a preferred option for those in whom therapy for hepatitis C virus infection is anticipated.


Bacillus anthracis diversity in Kruger National Park.
The Kruger National Park (KNP), South Africa, has a recorded history of periodic anthrax epidemics causing widespread disease among wild animals. Bacillus anthracis is the causative agent of anthrax, a disease primarily affecting ungulate herbivores. Worldwide there is little diversity among B. anthracis isolates, but examination of variable-number tandem repeat (VNTR) loci has identified six major clones, with the most dissimilar types split into the A and B branches. Both the A and B types are found in southern Africa, giving this region the greatest genetic diversity of B. anthracis worldwide. Consequently, southern Africa has been hypothesized to be the geographic origin of B. anthracis. In this study, we identify the genotypic types of 98 KNP B. anthracis isolates using multiple-locus VNTR analysis. Two major types are evident, the A branch and the B branch. The spatial and temporal distribution of the different genotypes indicates that anthrax epidemic foci are independent, though correlated through environmental cues. Kruger B isolates were found on significantly higher-calcium and higher-pH soils than were Kruger type A. This relationship between genotype and soil chemistry may be due to adaptive differences among divergent anthrax strains. While this association may be simply fortuitous, adaptation of A types to diverse environmental conditions is consistent with their greater geographic dispersal and genetic dissimilarity.


Histidinemia: biochemical parameters for diagnosis.
A highly specific and sensitive procedure for determining histidase activity, with labeled histidine as the substrate, that requires only 1 to 2 mg of stratum corneum epidermidis has been developed. Methods for determining ratios of urocanic acid to histidine (U/H) in stratum corneum epidermidis and for measuring excretion of histidine and its metabolites by thin-layer chromatography were developed. Application of this triad--stratum corneum epidermidis histidase determination, measurement of stratum corneum U/H, and analysis of excretion of histidine metabolites--should facilitate evaluation of the condition of infants and young children with suspected histidinemia. Moreover, differentiation between patients with the classic form and genetic variants of the disorder should now be possible.


Several different upstream promoter elements can potentiate transactivation by the BPV-1 E2 protein.
The enhancer and upstream promoter regions of RNA polymerase II transcribed genes modulate the rate of transcription initiation and establish specific patterns of gene expression. Both types of region consist of clusters of DNA binding sites for nuclear proteins. To determine how efficiently the same factor can activate transcription when acting as an enhancer or promoter factor, we have studied transactivation by the BPV-1 E2 protein, a papillomavirus transcriptional regulator. By cotransfecting a BPV-1 E2 expression vector and a series of reporter plasmids containing well-defined chimeric promoters we have found that whilst E2 can strongly stimulate complex promoters such as that of the HSV tk gene, it does not efficiently activate constructions containing only a TATA box and initiation site. We show that insertion of upstream promoter elements, but not of spacer DNA, between E2 binding sites and the TATA box greatly increases E2 activation. This effect was observed with more than one type of upstream promoter element, is not related to the strength of the promoter and is unlikely to result from co-operative DNA binding by E2 and the transcription factors tested. These results would suggest that E2 has the properties of an enhancer rather than promoter factor and that in certain cases promoter and enhancer factors may affect different steps in the process of transcriptional activation.


A novel human high-risk ependymoma stem cell model reveals the differentiation-inducing potential of the histone deacetylase inhibitor Vorinostat.
Incompletely resectable ependymomas are associated with poor prognosis despite intensive radio- and chemotherapy. Novel treatments have been difficult to develop due to the lack of appropriate models. Here, we report on the generation of a high-risk cytogenetic group 3 and molecular group C ependymoma model (DKFZ-EP1NS) which is based on primary ependymoma cells obtained from a patient with metastatic disease. This model displays stem cell features such as self-renewal capacity, differentiation capacity, and specific marker expression. In vivo transplantation showed high tumorigenic potential of these cells, and xenografts phenotypically recapitulated the original tumor in a niche-dependent manner. DKFZ-EP1NS cells harbor transcriptome plasticity, enabling a shift from a neural stem cell-like program towards a profile of primary ependymoma tumor upon in vivo transplantation. Serial transplantation of DKFZ-EP1NS cells from orthotopic xenografts yielded secondary tumors in half the time compared with the initial transplantation. The cells were resistant to temozolomide, vincristine, and cisplatin, but responded to histone deacetylase inhibitor (HDACi) treatment at therapeutically achievable concentrations. In vitro treatment of DKFZ-EP1NS cells with the HDACi Vorinostat induced neuronal differentiation associated with loss of stem cell-specific properties. In summary, this is the first ependymoma model of a cytogenetic group 3 and molecular subgroup C ependymoma based on a human cell line with stem cell-like properties, which we used to demonstrate the differentiation-inducing therapeutic potential of HDACi.


[P53 under low-intensity inluence of physical and chemical nature (ionizing radiation and antioxidant)].
It was found that low-intensity ionizing radiation and the antioxidant fenozan at a low concentration (10(-14) M) produce opposite effects on the content of protein p53 in the blood serum of mice. Thus, low-intensity gamma-irradiation of AKR mice with a dose of 1.2 cGy (0.6 cGy per day) led to a decrease in the content of p53 and acceleration of leukosis, whereas fenozan, which has membranolytic and radioprotective properties, when injected intramuscularly to F1 mice (CBA + c57 black) increased the content of p53. However, the dynamics of the activation of protein p53 depended on the concentration of fenozan (10(-4) or 10(-14)), which may be due to the difference in its binding to the membrane and the changes in its antioxidative properties depending on concentration.


Sources other than unused sawdust can introduce Klebsiella pneumoniae into dairy herds.
A longitudinal study was carried out to detect intramammary infections caused by Klebsiella pneumoniae and to identify potential sources of this bacterial species in the environment of the cows. The study was performed in 6 well-managed Belgian dairy herds from May 2008 to May 2009. Monthly (n=13), unused and used sawdust bedding samples as well as individual quarter milk and feces samples were collected from 10 randomly selected cohort cows in each herd. Cases of clinical mastitis of all lactating cows in the 6 herds were also sampled (n=64). From the 3,518 collected samples, 153 K. pneumoniae isolates were obtained, of which 2 originated from milk (clinical mastitis cases). In feces (n=728), used bedding (n=73), and unused bedding (n=73), respectively, 125 (17.2%), 20 (27.4%), and 6 (8.2%) isolates were found. The isolates were fingerprinted by means of pulsed field gel electrophoresis. In total, 109 different pulsotypes were differentiated, indicating a high degree of genetic diversity within the isolates. All isolates from unused bedding belonged to pulsotypes other than those from the other sources, suggesting that sources other than unused sawdust may introduce K. pneumoniae into the herd. Only 2 pulsotypes contained isolates originating from different sources. Pulsotype 10 was found in milk and used bedding and pulsotype 21 was found in feces and used bedding. The 2 milk isolates originated from 2 cows in the same herd but they belonged to a different pulsotype. The results indicate that K. pneumoniae can be prevalent in the environment without causing significant mastitis problems. Most cows were shedding K. pneumoniae in feces, substantiating findings under very different conditions (i.e., American dairy herds). Contamination of used bedding in the cubicles with K. pneumoniae from feces was confirmed, whereas unused bedding was not an important source of K. pneumoniae for the environment of the cows.


Alternative Sample Types for HIV-1 Antiretroviral Drug Resistance Testing.
Monitoring human immunodeficiency virus type 1 (HIV-1) drug resistance is critical for assessing ART effectiveness and treatment outcomes for HIV-1-infected individuals, including children, worldwide. Traditionally, testing for HIV-1 drug resistance has primarily been performed on plasma samples, and with commercially available, clinically validated assays that are costly and difficult to access. While plasma is the preferred sample for HIV-1 drug resistance genotyping, plasma analysis requires sophisticated laboratory equipment, personnel, space, and stringent storage conditions for maintenance of sample integrity and transport. With the limitations in feasibility and affordability of providing these ideal conditions for plasma genotyping in resource-constrained settings, the field has gained substantial experience with the dried blood spot (DBS) technique as an alternative. Moreover, DBS analysis can be used to comprehensively monitor the spread of the epidemic with applications to more-sensitive and quantitative technologies to assess HIV-1 globally.


A comparison of two programs for the control of behavioral experiments.
Two of the most widely used programs for the control of behavioral experiments are Med Associates' MedState Notation and Coulbourn Instruments' Graphic State 2. The two systems vary considerably in their approach to programming and data recording, with Graphic State 2 using a point-and-click interface that appeals to non-programmers while MedState Notation requires the typing of programming code. Graphic State 2 provides many data analysis routines, while MedState Notation allows the user to embed simple data analysis within the behavioral protocol. Graphic State 2 is simpler to use, but MedState Notation is more versatile.


Spectral statistics of the two-body random ensemble revisited.
Using longer spectra we reanalyze spectral properties of the two-body random ensemble studied 30 years ago. At the center of the spectra the old results are largely confirmed, and we show that the nonergodicity is essentially due to the variance of the lowest moments of the spectra. The longer spectra allow us to test and reach the limits of validity of French's correction for the number variance. At the edge of the spectra we discuss the problems of unfolding in more detail. With a Gaussian unfolding of each spectrum the nearest-neighbor spacing distribution between ground state and first exited state is shown to be stable. Using such an unfolding the distribution tends toward a semi-Poisson distribution for longer spectra. For comparison with the nuclear table ensemble we could use such unfolding obtaining similar results as in the early papers, but an ensemble with realistic splitting gives reasonable results if we just normalize the spacings in accordance with the procedure used for the data.


Characterisation of the β-lactam resistance enzyme in Acanthamoeba castellanii.
β-Lactams are well known as the best antibiotics for inhibiting the cross-linking between adjacent polysaccharide chains and peptides in the peptidoglycan layer of bacterial cell walls, causing bacterial cell lysis. There are no reports on the action of and resistance mechanisms to β-lactams in protozoa. Acanthamoeba castellanii is a free-living protozoan pathogen capable of causing blinding keratitis and fatal granulomatous encephalitis. When Acanthamoeba is exposed to harsh conditions, it differentiates into the cyst stage to avoid environmental stresses, such as drug treatment. In this study, it was shown that the mature encystation rate of A. castellanii is decreased by treatment with cefotaxime (CTX) and clavulanic acid (CLA); however, the drugs do not kill the amoeba. We hypothesise that β-lactam antibiotics may disturb synthesis of the double cell wall during the encystation process of Acanthamoeba. Interestingly, CTX is considered a powerful β-lactam, whereas CLA is considered a weak β-lactam but an efficient β-lactamase inhibitor. It was demonstrated that Acanthamoeba expresses β-lactamases to prevent inhibition of the encystation process by β-lactams. To reveal the functions of Acanthamoeba β-lactamases, a recombinant Acanthamoeba β-lactamase was produced in Escherichia coli that conferred resistance to β-lactams such as CTX, cefuroxime, penicillin and meropenem. Consequently, we suggest that Acanthamoeba produces enzymes similar to β-lactamases to avoid interference from the environment. Here we provide a new point of view on an important gene responsible for drug resistance and advocate for the development of more efficient treatment against Acanthamoeba infection.


Imaging features of midface injectable fillers and associated complications.
Injectable fillers are increasingly used for midface augmentation, which can be performed for facial rejuvenation and treatment of HIV facial lipoatrophy. A variety of temporary and permanent filler agents has been developed, including calcium hydroxylapatite, collagen, liquid silicone, polytetrafluoroethylene, hyaluronic acid, poly-l-lactic acid, and polyacrylamide gel. Facial fillers are sometimes encountered on radiologic imaging incidentally and should not be mistaken for pathology. Alternatively, patients with facial fillers may undergo imaging specifically to evaluate associated complications, such as infection, overfilling, migration, foreign-body reaction, and scarring. Therefore, it is important to be familiar with the imaging appearances of the various filler materials and their complications.


[Antithrombin III activity in relation to multiple administration of various doses of heparin to normal animals].
Heparin affected the content of antithrombin III and the thrombin time of blood plasma coagulation depending on the dose of the anticoagulant administered (eight intravenous administrations at single doses of 225, 150, 75, 37 or 18 IU/kg of body mass of healthy rats). High doses of heparin decreased more distinctly the content of antithrombin III as compared with low doses. 8 intravenous infusions of small doses of heparin (37 IU/kg) as well as intramuscular administration of the anticoagulant (10 injections) at a dose of 225 IU/kg caused a compensatory increase in content of antithrombin III. After 30 intramuscular administrations the compensatory reaction of antithrombin III disappeared. In this case the content of antithrombin III and the thrombin time of blood plasma coagulation exhibited stability towards the anticoagulant effect.


Plastid phylogenomic insights into the evolution of the Caprifoliaceae s.l. (Dipsacales).
The family Caprifoliaceae s.l. is an asterid angiosperm clade of ca. 960 species, most of which are distributed in temperate regions of the northern hemisphere. Recent studies show that the family comprises seven major clades: Linnaeoideae, Zabelia, Morinoideae, Dipsacoideae, Valerianoideae, Caprifolioideae, and Diervilloideae. However, its phylogeny at the subfamily or genus level remains controversial, and the backbone relationships among subfamilies are incompletely resolved. In this study, we utilized complete plastome sequencing to resolve the relationships among the subfamilies of the Caprifoliaceae s.l. and clarify several long-standing controversies. We generated and analyzed plastomes of 48 accessions of Caprifoliaceae s.l., representing 44 species, six subfamilies and one genus. Combined with available Caprifoliaceae s.l. plastomes on GenBank and 12 outgroups, we analyzed a final dataset of 68 accessions. Genome structure was strongly conserved in general, although the boundaries between the Inverted Repeat were found to have contracted across Caprifoliaceae s.l. to exclude rpl2, rps19, and ycf1, all or parts of which are typically present in the IR of most angiosperms. The ndhF gene was found to have been inverted in all plastomes of Adoxaceae. Phylogenomic analyses of 68 complete plastomes yielded a highly supported topology that strongly supported the monophyly of Zabelia and its sister relationship to Morinoideae. Moreover, a clade of Valerianoideae + Dipsacoideae was recovered as sister to a clade of Linnaeoideae + Zabelia + Morinoideae clade, and Heptacodium was sister to remaining Caprifolioideae. The Diervilloideae and Caprifolioideae were successively sister to all other Caprifoliaceae s.l. Major lineages of Caprifoliaceae s.l. were estimated to have diverged from the Upper Cretaceous to the Eocene (50-100 Ma), whereas within-genus diversification was dated to the Oligocene and later, concomitant with global cooling and drying. Our results demonstrate the power of plastid phylogenomics in improving estimates of phylogeny among genera and subfamilies, and provide new insights into plastome evolution across Caprifoliaceae s.l.


Peer support in adult mental health services: a metasynthesis of qualitative findings.
Peer support involves people in recovery from psychiatric disability offering support to others in the same situation. It is based on the belief that people who have endured and overcome a psychiatric disability can offer useful support, encouragement, and hope to their peers. Although several quantitative reviews on the effectiveness of peer support have been conducted, qualitative studies were excluded. This study aimed to synthesize findings from these studies. A qualitative metasynthesis was conducted, involving examination, critical comparison, and synthesis of 27 published studies. The experiences of peer support workers, their nonpeer colleagues, and the recipients of peer support services were investigated. Peer support workers experiences included nonpeer staff discrimination and prejudice, low pay and hours, and difficulty managing the transition from "patient" to peer support worker. Positive experiences included collegial relationships with nonpeer staff, and other peers; and increased wellness secondary to working. Recipients of peer support services experienced increased social networks and wellness. The findings highlight training, supervision, pay, nonpeer staff/peer staff relationships, as important factors for statutory mental health peer support programs.


Modelling cell lifespan and proliferation: is likelihood to die or to divide independent of age?
In cell lifespan studies the exponential nature of cell survival curves is often interpreted as showing the rate of death is independent of the age of the cells within the population. Here we present an alternative model where cells that die are replaced and the age and lifespan of the population pool is monitored until a steady state is reached. In our model newly generated individual cells are given a determined lifespan drawn from a number of known distributions including the lognormal, which is frequently found in nature. For lognormal lifespans the analytic steady-state survival curve obtained can be well-fit by a single or double exponential, depending on the mean and standard deviation. Thus, experimental evidence for exponential lifespans of one and/or two populations cannot be taken as definitive evidence for time and age independence of cell survival. A related model for a dividing population in steady state is also developed. We propose that the common adoption of age-independent, constant rates of change in biological modelling may be responsible for significant errors, both of interpretation and of mathematical deduction. We suggest that additional mathematical and experimental methods must be used to resolve the relationship between time and behavioural changes by cells that are predominantly unsynchronized.


The 2011 and 2016 iterations of the Ontario Marginalization Index: updates, consistency and a cross-sectional study of health outcome associations.
The Ontario Marginalization Index (ON-Marg) is an area-based measure used widely to measure health inequalities in Ontario. Recently, the index was updated for 2011 and 2016. The loss of the 2011 long-form census required the use of alternative data sources for the 2011 version. This paper describes the update of ON-Marg, assesses consistency in the indices across census years using Dissemination Areas, and examines associations between ON-Marg 2016 and four health and social outcomes to demonstrate its potential to measure health inequalities. ON-Marg was created using factor analysis. Differences in quintile assignment was compared over time to assess whether the use of taxfiler, immigration, property assessment, and health card address data in 2011 affected consistency in measurement of marginalization. Inequalities in rates of overall mortality, gonorrhea incidence, mental health emergency department visits, and alcohol retail locations across quintiles of ON-Marg 2016 were quantified using the Relative Index of Inequality. Depending on the dimension, between 81% and 96% of DAs showed limited or no changes in quintiles of marginalization between 2006, 2011 and 2016. Of the 45-64% of DAs that did not change quintile between 2006 and 2016, 1.8% to 8.8% of DAs in 2011 differed by two or more quintiles. Findings showed significant differences in rates of health and social outcomes across quintiles of ON-Marg 2016, with strength and directionality varying by dimension of ON-Marg. Alternative data sources did not substantially affect the consistency of the 2011 version of ON-Marg. The updated ON-Marg is a comprehensive tool that can be used to study health inequalities in Ontario.


Efficacy of the repellent N,N-diethyl-3-methyl-benzamide (DEET) against tabanid flies on horses evaluated in a field test in Switzerland.
Female tabanid flies (Diptera: Tabanidae) can be a serious nuisance for horses because of their painful bites during blood feeding. They also play a primary role in mechanical transmission of a lentivirus causing Equine Infectious Anemia (EIA), a virus that has spread within Europe in recent years. According to the European law for products intended for use as a repellent on horses (recreational and sport horses), a field test is mandatory to demonstrate sufficient repellency of such a substance against the specific target fly species, but currently no agreed protocols are available for testing of potential repellents. The aim of the present study was to establish a protocol for a field test to investigate the efficacy of N,N-diethyl-3-methyl-benzamide (DEET, Brum®, Huebeli-Stud Horse Care AG) in a 15-17% oil-water emulsion against tabanid flies on horses up to four hours. Between July and August 2015, four horses on three farms each were tested on two consecutive days in a cross-over design. The four horses on Farm A were used in the pre-test as well as in the main test. Two and a half hours after repellent application the horses were lunged until sweating. Tabanid fly infestations were both photographed and directly counted during five minutes 3 and 4h after repellent application on the right side of the horses in the area from the head to the flank, belly and first third of the foreleg. Without repellent application, up to 29 tabanid flies were counted on a horse, whereas the maximum for the repellent treated horses was four. In 50% of the horses treated with DEET there were no Tabanids observed (efficacy 100%), and in all horses the tabanid fly counts were lower than in the control horses with one exemption at 4h. The efficacy of the DEET repellent was at least 80% and 71% respectively, three or four hours after application (with a confidence level of 89%). A fly trap (Horse Pal) revealed the presence of the tabanid species Tabanus brominus and Haematopota pluvialis, but also non-specified arthropods. The design of the present study simulated practical conditions, allowed to quantify the number of tabanids flies and to demonstrate repellency of DEET in horses.


Consumption of Nopal Powder in Adult Women.
Osteoporosis is a chronic disease in adult women caused by menopause and some other factors, which entails deficiency of calcium in diet. Natural products are the best source of nutriments to reduce the risk of chronic diseases. Nopal (Opuntia ficus-indica) is a plant characterized by its nutritional components and benefits to health. Its calcium content increases with maturation process that could be beneficial for consumers. Nopal powder (NP) was elaborated from nopal harvested within 16-24 weeks of maturation, and the nutritional content was determined. An experimental clinical trial was performed to evaluate the effect of NP. A total of 69 women between 40 and 60 years old participated in the study. During 24 weeks, experimental group (n = 56) consumed a daily dose of 5 g of NP and control group (n = 13) continue with habitual diet. Changes in bone mineral density (BMD), body mass index (BMI), body fat percentage and serum calcium were assessed. Between baseline and after 24 weeks of consumption, no significant changes were found in BMD P = .885 experimental group and P = .970 control group, BMI P = .865 experimental group and P = .984 control group, body fat P = .744 experimental group and P = .740 control group and serum calcium P = .282 experimental group and P = .959 control group. These results indicate that advanced maturation NP does not have influence in bone health, BMI, and body composition in adult women.


Dry Powder Inhalers: From Bench to Bedside.
Dry powder inhalers (DPIs) are now widely prescribed and preferred by the majority of patients. These devices have many advantages over the traditional pressurized metered-dose inhaler (pMDI) but they do have disadvantages. The characteristics of the dose emitted from a DPI are affected by the inhalation manoeuvre used by a patient. Each patient is different and the severity of their lung disease varies from mild to very severe. This affects how they use an inhaler and so determines the type of dose they inhale. An understanding of the pharmaceutical science related to DPIs is important to appreciate the relevance of how patients inhale through these devices. Also, each type of DPI has its unique dose preparation routine, and thus it is essential to follow these recommended steps because errors at this stage may result in no dose being inhaled. All issues related to the inhalation manoeuvre and dose preparation are addressed in this chapter. The importance of the inhalation technique is highlighted with a realization of inhale technique training and checking. During routine patient management, devices should not be switched nor doses increased unless the patient has demonstrated that they can and do use their DPI.


Comparing short form and RAND physical and mental health summary scores: results from total hip arthroplasty and high-risk primary-care patients.
Summary physical health scores for the Short Form (SF) measures are computing using positive weights for physical items and negative weights for mental health items. Mental health summary scores use positive weights for mental items and negative weights for physical. The RAND Health Status Inventory (HSI) measures do not use negative weights. Do these different approaches to scoring matter? The objective was to compare summary scores using both the SF and RAND-HSI. SF-36 and the Health Utilities Index Mark 3 (HUI3) were administered to a cohort of patients waiting for elective total hip arthroplasty (THA). SF-12 and HUI3 were administered to a cohort of high-risk primary-care patients. Summary scores were generated and compared. Single-attribute utility scores for emotion in HUI3 were also computed. Canadian and US norms for SF, RAND-HSI, and HUI3 were used to interpret results. For THA patients, mean physical health scores were 28 and 36 for SF and RAND-HSI. Mean mental health scores were 55 and 42. For the primary-care patients, the scores were 34 and 36 for physical and 46 and 40 for mental health. SF and RAND-HSI provided somewhat similar summary scores in the THA study. However, SF and RAND-HSI mental health scores differed in the primary-care patient cohort and results from HUI3 corroborate the mental health deficits identified by the RAND-HSI. It may be wise for investigators to use both SF and RAND-HSI scoring systems.


Defining risks of taxane neuropathy: insights from randomized clinical trials.
Sensory neuropathy is a common but difficult to quantify complication encountered during treatment of various cancers with taxane-containing regimens. Docetaxel, paclitaxel, and its nanoparticle albumin-bound formulation have been extensively studied in randomized clinical trials comparing various dose and schedules for the treatment of breast, lung, and ovarian cancers. This review highlights differences in extent of severe neuropathies encountered in such randomized trials and seeks to draw conclusions in terms of known pharmacologic factors that may lead to neuropathy. This basic knowledge provides an essential background for exploring pharmacogenomic differences among patients in relation to their susceptibility of developing severe manifestations. In addition, the differences highlighted may lead to greater insight into drug and basic host factors (such as age, sex, and ethnicity) contributing to axonal injury from taxanes.


High-order correlation effects on dynamic hyperpolarizabilities and their geometric derivatives: a comparison with density functional results.
Second harmonic generation hyperpolarizabilities and their geometric derivatives have been calculated for HF, HCl, CO, and LiF, using the coupled cluster hierarchies, CCS, CC2, CCSD, CC3, and large correlation-consistent basis sets. The full configuration interaction results have been used to test the accuracy of the coupled cluster results. The CCS and CC2 methods do not improve on the Hartree-Fock results while CCSD is robust and gives significant improvements compared to CCS and CC2. The effects of triples in CC3 are in some cases substantial. Higher order correlation effects are significant for LiF. Including core-valence correlation effects is required only if high accuracy is desired. The coupled cluster results have been used as benchmarks for the results obtained by means of density functional theory using various exchange-correlation functionals. For the hyperpolarizability B3LYP was found to perform best, i.e., to give the results closest to the CC3 ones, while for the geometric derivatives none of the considered functionals was able to give a consistent description for all the considered molecules.


OBESITY IN GENERAL PRACTICE.
Dr Philip Hopkins defines obesity and describes its incidence in his general practice. He stresses the importance of dealing with underlying psychological factors in the treatment of the condition.Dr A A Lewis discusses hormonal influences and advocates a high protein diet as being an acceptable means of achieving weight reduction.Professor John Yudkin shows that a low protein diet is impracticable, and stresses the importance of physical activity in the treatment of obesity. He advocates a low carbohydrate diet with unrestricted fat and protein.


Defining the morphology and mechanism of the hemoglobin transport pathway in Plasmodium falciparum-infected erythrocytes.
Hemoglobin degradation during the asexual cycle of Plasmodium falciparum is an obligate process for parasite development and survival. It is established that hemoglobin is transported from the host erythrocyte to the parasite digestive vacuole (DV), but this biological process is not well characterized. Three-dimensional reconstructions made from serial thin-section electron micrographs of untreated, trophozoite-stage P. falciparum-infected erythrocytes (IRBC) or IRBC treated with different pharmacological agents provide new insight into the organization and regulation of the hemoglobin transport pathway. Hemoglobin internalization commences with the formation of cytostomes from localized, electron-dense collars at the interface of the parasite plasma and parasitophorous vacuolar membranes. The cytostomal collar does not function as a site of vesicle fission but rather serves to stabilize the maturing cytostome. We provide the first evidence that hemoglobin transport to the DV uses an actin-myosin motor system. Short-lived, hemoglobin-filled vesicles form from the distal end of the cytostomes through actin and dynamin-mediated processes. Results obtained with IRBC treated with N-ethylmaleimide (NEM) suggest that fusion of hemoglobin-containing vesicles with the DV may involve a soluble NEM-sensitive factor attachment protein receptor-dependent mechanism. In this report, we identify new key components of the hemoglobin transport pathway and provide a detailed characterization of its morphological organization and regulation.


Canadian Society of Nephrology Commentary on the Kidney Disease Improving Global Outcomes 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.
(1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients. The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD. The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions. We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool. The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews.