Comparison of Program Resources Required for Colonoscopy and Fecal Screening: Findings From 5 Years of the Colorectal Cancer Control Program.
Colonoscopy and guaiac fecal occult blood tests and fecal immunochemical tests (FOBT/FIT) are the most common colorectal cancer screening methods in the United States. However, information is limited on the program resources required over time to use these tests. We collected cost data from 29 Centers for Disease Control and Prevention Colorectal Cancer Control Program (CRCCP) grantees by using a standardized data collection instrument for 5 program years (2009-2014). We created a panel data set with 124 records and assessed differences by screening test used. Forty-four percent of all programs (N = 124) offered colonoscopy (55 of 124), 32% (39 of 124) offered FOBT/FIT, and 24% (30 of 124) offered both. Overall, total cost per person was higher in program year 1 ($3,962), the beginning of CRCCP than in subsequent program years ($1,714). The cost per person was $3,153 for programs using colonoscopy and $1,291 for those using FOBT/FIT with diagnostic colonoscopy. The average clinical cost per person was $1,369 for colonoscopy and $280 for FOBT/FIT during the program (these do not reflect cost of repeated FOBT/FIT screens). Programs serving a large number of people had lower per-person costs than those serving a small volume, probably because of fixed costs related to nonclinical expenses. Colorectal cancer screening programs incur costs in addition to the clinical cost of the screening procedures to support planning and management, contracting with providers, and tracking patients. Because programs can achieve potential economies of scale, partnerships among smaller programs for screening delivery could decrease overall costs.


Clavien classification of complications after the initial series of robot-assisted radical prostatectomy: the Cancer Institute of New Jersey/Robert Wood Johnson Medical School experience.
To study the safety and feasibility of robot-assisted radical prostatectomy (RARP) for the surgical management of localized prostate cancer, we analyzed perioperative parameters and the pattern of complications in our patients who underwent RARP. After the performance of more than 600 RARP over a 4-year period by a single surgeon using the daVinci® robot system at the Cancer Institute of New Jersey/Robert Wood Johnson Medical School, we reviewed the medical records of the first 200 patients retrospectively. All patients were divided into four groups according to the order of case numbers to compare intergroup differences in preoperative characteristics and perioperative parameters. Perioperative complications were determined in all patients, and complications were classified according to the Clavien classification system. The mean operative time was 212 minutes, and the mean blood loss was 189 mL. The mean length of hospital stay was 1.13 days. Overall, 12% (24 men) experienced various perioperative complications among the 200 patients. Of the total 24 patients, 5 (20.8%) men experienced intraoperative complications, and 19 (79.2%) men showed postoperative complications. Rectal injury occurred in two (8.3%) men, and the injury was repaired primarily using two-layer suture techniques without any sequelae. Three (12.5%) patients had femoral neuropathy, and urinary retention developed in 7 (25.0%) patients. Among our 200 patients, no transfusion was needed intraoperatively and postoperatively. There were nine (4.5%) patients in the Clavien grade I complications category, and another 9 (4.5%) men were classified as grade II complications. Six (3.0%) men had grade IIIb complications, and there were no grade IV or V complications. In our initial series of RARP procedures, we experienced low morbidity, with the overall complication rate of 12%. After implementing minor modifications, most of the early complications were prevented. Rectal injuries, if recognized intraoperatively, can be repaired primarily.


Pregnancy-related events associated with subclinical cardiovascular disease burden in late midlife: SWAN.
Reproductive factors are associated with later life CVD in women (e.g., age at first birth, preeclampsia, gestational diabetes), but studies have focused largely on premenopausal women. We examined the relationship of reproductive factors with subclinical CVD burden in late midlife women. We included 964 parous women from the Study of Women's Health Across the Nation (SWAN), who completed a reproductive history questionnaire at the 13th SWAN visit (2011-2012), and a carotid ultrasound and brachial-ankle pulse wave velocity (baPWV) assessment. The primary outcomes were carotid intima-media thickness, plaque, and baPWV; our secondary outcome was a composite subclinical CVD index created using these measures. Linear and logistic regression was performed to examine associations with individual subclinical CVD measures, and multinomial logistic regression was used in analyses of the composite index. Models adjusted for socio-demographics and cardiovascular risk factors. Mean age at subclinical CVD assessment was 60.2 years (SD ± 2.7). History of gestational hypertension/preeclampsia was associated with greater carotid IMT (β: 0.038, p = 0.004). Earlier age at first birth was associated with subclinical CVD, but not when accounting for CVD risk factors. History of gestational diabetes was associated with greater baPWV, but not related to our composite index. Pregnancy history is an important marker of subclinical CVD in late midlife and may impact the vasculature through distinct pathways. Future studies are necessary to evaluate racial/ethnic differences in the observed associations and to assess the benefit of a composite subclinical CVD index for earlier CVD risk modification in midlife women.


Genotype by energy expenditure interaction with metabolic syndrome traits: the Portuguese healthy family study.
Moderate-to-high levels of physical activity are established as preventive factors in metabolic syndrome development. However, there is variability in the phenotypic expression of metabolic syndrome under distinct physical activity conditions. In the present study we applied a Genotype X Environment interaction method to examine the presence of GxEE interaction in the phenotypic expression of metabolic syndrome. A total of 958 subjects, from 294 families of The Portuguese Healthy Family study, were included in the analysis. Total daily energy expenditure was assessed using a 3 day physical activity diary. Six metabolic syndrome related traits, including waist circumference, systolic blood pressure, glucose, HDL cholesterol, total cholesterol and triglycerides, were measured and adjusted for age and sex. GxEE examination was performed on SOLAR 4.3.1. All metabolic syndrome indicators were significantly heritable. The GxEE interaction model fitted the data better than the polygenic model (p<0.001) for waist circumference, systolic blood pressure, glucose, total cholesterol and triglycerides. For waist circumference, glucose, total cholesterol and triglycerides, the significant GxEE interaction was due to rejection of the variance homogeneity hypothesis. For waist circumference and glucose, GxEE was also significant by the rejection of the genetic correlation hypothesis. The results showed that metabolic syndrome traits expression is significantly influenced by the interaction established between total daily energy expenditure and genotypes. Physical activity may be considered an environmental variable that promotes metabolic differences between individuals that are distinctively active.


Targeting the neurological comorbidities of multiple sclerosis: the beneficial effects of VIP and PACAP neuropeptides.
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two widely expressed neuropeptides with important immunomodulatory and neuroprotective properties in the central nervous system (CNS). Both VIP and PACAP have been implicated in several neurological diseases and have shown favourable effects in different animal models of multiple sclerosis (MS). MS is a chronic inflammatory and neurodegenerative disease of the CNS affecting over 2.5 million people worldwide. The disease is characterised by extensive neuroinflammation, demyelination and axonal loss. Currently, there is no cure for MS, with treatment options only displaying partial efficacy. Importantly, epidemiological studies in the MS population have demonstrated that there is a high incidence of neurological and psychological comorbidities such as depression, anxiety, epilepsy and stroke among afflicted people. Hence, given the widespread protective effects of the VIP/PACAP system in the CNS, this review will aim at exploring the beneficial roles of VIP and PACAP in ameliorating some of the most common neurological comorbidities associated with MS. The final scope of the review is to put more emphasis on how targeting the VIP/PACAP system may be an effective therapeutic strategy to modify MS disease course and its associated comorbidities.


The cost of obesity: the Australian perspective.
Obesity is a known risk factor for a number of diseases with serious mortality and morbidity implications. Thus, obesity is an economic burden to communities, since it reduces quality of life and leads to premature mortality; in addition, healthcare resources are used to manage obesity-related disease. It was estimated that in 1989, management of disease due to obesity (defined as body mass index greater than 30) cost A$395 million. This estimate covers the healthcare costs for the management of obesity, non-insulin-dependent diabetes mellitus (NIDDM), gallstones, hypertension, coronary heart disease (CHD), breast cancer (among postmenopausal women), and colon cancer. As this estimate excludes the costs of some disease attributable to obesity, it is an underestimate of the true costs. Nonetheless, the estimated cost of the management of obesity-related conditions represents 86% of the healthcare costs used for the management of alcohol-related diseases in Australia. Healthcare costs attributable to obesity have not yet been estimated for countries elsewhere in Asia and the Pacific. However, it is acknowledged that obesity is a major problem in the Pacific, with exceptionally high prevalence rates and concomitant high rates of diseases for which obesity is a major risk factor, particularly NIDDM and CHD. It would, therefore, be useful to explore the cost of disease attributable to obesity in healthcare systems in these communities, and the potential for preventive programmes to reduce these costs.


Holistic concerns of Chinese stroke survivors during hospitalization and in transition to home.
This article is a report of a study conducted to explore the phenomenon of concerns as experienced by Chinese stroke survivors during hospitalization and in transition to home. Stroke is characterized by its sudden onset and prolonged residual problems, which affect survivors' holistic well-being. Many studies have focused on stroke consequences and their correlates with psychosocial outcomes. Very little is known about holistic concerns of stroke survivors, particularly in the transition from hospital to home. We used purposive sampling of 15 stroke survivors who participated in semi-structured interviews after being discharged from stroke wards of a general hospital in Hong Kong from November 2008 to February 2009. The interviews were transcribed verbatim and analysed using Giorgi's phenomenological techniques. Stroke survivors' physical, psychological, socio-cultural and spiritual concerns in hospital and transition to home emerged from the data analysis. The four major themes identified were: (a) dynamic interplay of holistic concerns, (b) cultural expression of illness experiences, (c) social support 'paradox' and (d) caring gaps in clinical management. Understanding the interwoven holistic concerns for the stroke survivors in hospital and after discharged home can help nurses to identify their health needs and plan for appropriate nursing interventions. The findings provide guidance for the development of culture-sensitive holistic care interventions with family involvement in Chinese stroke populations.


Applying Ecological Positive Youth Development Theory to Address Co-Occurring Health Disparities Among Immigrant Latino Youth.
This article outlines the theory and resulting approach employed in a multilevel, integrated, collaborative community intervention called Adelante, implemented by a university-community partnership in a Latino immigrant community to address co-occurring health disparities of substance abuse, sex risk, and interpersonal violence among youth. The basis for the intervention is a social-ecological interpretation of positive youth development theory, which focuses on changes in the person environment context and community assets as a preventive mechanism. This approach is viewed as appropriate for a community facing multiple barriers to health equity. The article describes the translation of this positive youth development model to practice, including the design of the intervention, intervention components, and the protocol for evaluation. The Adelante intervention is intended to reduce health disparities and, in addition, to add a broader community model to the evidence base.


Aldose-reductase- and protein-glycation-inhibitory principles from the whole plant of Duchesnea chrysantha.
Ellagic acid (1), 3,3'-di-O-methylellagic acid (2), 3,3',4-tri-O-methylellagic acid (3), isovitexin (4), kaempferol 3-O-beta-D-glucuronide methyl ester (5), quercetin 3-O-alpha-L-arabinopyranosyl-(1-->6)-beta-D-galactopyranoside (6), ursolic acid, pomolic acid, tormentic acid, euscaphic acid, euscaphic acid 28-O-beta-D-glucopyranoside, and maslinic acid were isolated from the AcOEt- and BuOH-soluble MeOH extract of Duchesnea chrysantha (whole plant). The isolates were subjected to in vitro bioassays to evaluate their inhibitory activity on rat-lens aldose reductase (RLAR) and formation of advanced glycation end products (AGEs). The ellagic acids and flavonoids, compounds 1-6, exhibited moderate inhibitory effects on RLAR. However, compounds 1 and 4-6 showed excellent inhibitory activities towards the formation of AGEs. This is the first report that 4 and 6 exhibit inhibitory activity towards AR and AGEs formation.


Melatonin inhibits the formation of chemically induced experimental encapsulating peritoneal sclerosis through modulation of T cell differentiation by suppressing of NF-κB activation in dendritic cells.
Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Surgery is a therapeutic strategy for the treatment of complete intestinal obstruction. However, complete intestinal obstruction in long-term PD results in high mortality and morbidity rates after surgery. Immunopathogenesis participates in EPS formation: CD8, Th1, and Th17 cell numbers increased during the formation of EPS. The anti-inflammatory and immunomodulatory effects of melatonin may have beneficial effects on this EPS. In the present study, we determined that melatonin treatment significantly decreases the Th1 and Th17 cell populations in mice with EPS, decreases the production of IL-1β, TNF-α, IL-6, and IFN-γ, and increases the production of IL-10. The suppression of Th1 and Th17 cell differentiation by melatonin occurs through the inhibition of dendritic cell (DC) activation by affecting the initiation of the NF-κB signaling pathway in DCs. Our study suggests that melatonin has preventive potential against the formation of EPS in patients with PD.


Adaptive grid generation in a patient-specific cerebral aneurysm.
Adapting grid density to flow behavior provides the advantage of increasing solution accuracy while decreasing the number of grid elements in the simulation domain, therefore reducing the computational time. One method for grid adaptation requires successive refinement of grid density based on observed solution behavior until the numerical errors between successive grids are negligible. However, such an approach is time consuming and it is often neglected by the researchers. We present a technique to calculate the grid size distribution of an adaptive grid for computational fluid dynamics (CFD) simulations in a complex cerebral aneurysm geometry based on the kinematic curvature and torsion calculated from the velocity field. The relationship between the kinematic characteristics of the flow and the element size of the adaptive grid leads to a mathematical equation to calculate the grid size in different regions of the flow. The adaptive grid density is obtained such that it captures the more complex details of the flow with locally smaller grid size, while less complex flow characteristics are calculated on locally larger grid size. The current study shows that kinematic curvature and torsion calculated from the velocity field in a cerebral aneurysm can be used to find the locations of complex flow where the computational grid needs to be refined in order to obtain an accurate solution. We found that the complexity of the flow can be adequately described by velocity and vorticity and the angle between the two vectors. For example, inside the aneurysm bleb, at the bifurcation, and at the major arterial turns the element size in the lumen needs to be less than 10% of the artery radius, while at the boundary layer, the element size should be smaller than 1% of the artery radius, for accurate results within a 0.5% relative approximation error. This technique of quantifying flow complexity and adaptive remeshing has the potential to improve results accuracy and reduce computational time for patient-specific hemodynamics simulations, which are used to help assess the likelihood of aneurysm rupture using CFD calculated flow patterns.


Review of Current Literature for Prostatic Artery Embolization.
Prostatic artery embolization (PAE) is an emerging, novel interventional technique in the management of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). BPH is a common clinical condition in middle-aged and elderly men resulting in LUTS, including nocturia, urinary frequency, urgency, decreased urinary flow rates, hesitancy, and incomplete bladder emptying. Traditionally, LUTSs have been managed by medical or surgical therapies. Since the initial incidental discovery that selective PAE performed for uncontrolled bleeding secondary to BPH resulted in improved LUTS, the technique has continually evolved with a growing body of evidence supporting its safety and efficacy. However, despite the available data, PAE has yet to be established as a standard-of-care treatment option for patients with LUTS/BPH. In this article, the authors review the history and current state of PAE, including published data from case reports, animal studies, retrospective/prospective cohort studies, and prospective randomized controlled trials.


Enzymic synthesis of N-acetyl-L-phenylalanine in Escherichia coli K12.
1. Cell-free extracts of Escherichia coli K12 catalyse the synthesis of N-acetyl-l-phenylalanine from acetyl-CoA and l-phenylalanine. 2. The acetyl-CoA-l-phenylalanine alpha-N-acetyltransferase was purified 160-fold from cell-free extracts. 3. The enzyme has a pH optimum of 8 and catalyses the acetylation of l-phenylalanine. Other l-amino acids such as histidine and alanine are acetylated at slower rates. 4. A transacylase was also purified from E. coli extracts and its substrate specificity studied. 5. The properties of both these enzymes were compared with those of other known amino acid acetyltransferases and transacylases.


Regulation of TRIF-mediated innate immune response by K27-linked polyubiquitination and deubiquitination.
TIR domain-containing adaptor inducing interferon-β (TRIF) is an essential adaptor protein required for innate immune responses mediated by Toll-like receptor (TLR) 3- and TLR4. Here we identify USP19 as a negative regulator of TLR3/4-mediated signaling. USP19 deficiency increases the production of type I interferons (IFN) and proinflammatory cytokines induced by poly(I:C) or LPS in vitro and in vivo. Usp19-/- mice have more serious inflammation after poly(I:C) or LPS treatment, and are more susceptible to inflammatory damages and death following Salmonella typhimurium infection. Mechanistically, USP19 interacts with TRIF and catalyzes the removal of TRIF K27-linked polyubiquitin moieties, thereby impairing the recruitment of TRIF to TLR3/4. In addition, the RING E3 ubiquitin ligase complex Cullin-3-Rbx1-KCTD10 catalyzes K27-linked polyubiquitination of TRIF at K523, and deficiency of this complex inhibits TLR3/4-mediated innate immune signaling. Our findings thus reveal TRIF K27-linked polyubiquitination and deubiquitination as a critical regulatory mechanism of TLR3/4-mediated innate immune responses.


Preparation, Antimicrobial Properties, and Cytotoxicity of Acrylic Resins Containing Poly(diallyldimethylammonium chloride).
To design and analyze the biologic properties (antibacterial and antifungal, as well as cytotoxicity) of a dental biomaterial based on incorporation of the biocide poly(diallyldimethylammonium chloride) (PDADMAC) into the masses of self- and thermopolymerizable acrylic resins. PDADMAC was diluted into tetrahydrofuran (4 wt%) and incorporated into self- and thermopolymerizable acrylic resins. PDADMAC inclusion was verified by measuring the contact angle with water droplets. Plain resins were used as controls. The antibacterial activity was evaluated against Staphylococcus aureus (ATCC 6538P) and Escherichia coli (ATCC 8739), and the antifungal activity was tested against Candida albicans (ATCC 10231) and Aspergillus niger (ATCC 16404). The cytotoxicity of substances leached from these materials was analyzed in human dental pulp stem cells using MTT reduction assay. Reduction of contact angle confirmed the incorporation of PDADMAC in the resins. Both resins containing PDADMAC were more effective against Gram-positive and Gram-negative bacteria than their controls. The modified resins were also significantly more effective against Candida albicans than controls, but no resin was effective against Aspergillus niger. The cell viability of cultures submitted to substances leached from the PDADMAC resins was similar to that of cells cultured under ideal conditions. The incorporation of PDADMAC into the acrylic resins achieved the desired antibacterial effect, with no changes in the biocompatibility properties of the resins. Moreover, the modified resins were effective against Candida albicans, the most common fungus in the oral cavity. Thus, the incorporation of PDADMAC in biomaterials seems to be promising in dentistry.


Deletion of cis-regulatory Element in FOXL2 Promoter in a Chinese Family of Type II Blepharophimosis-ptosis-epicanthus Inversus Syndrome with Polydactyly.
Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a relatively uncommon autosomal-dominant genetic disorder, primarily attributed to mutations in the forkhead box L2 (FOXL2) gene. Albeit the involvement of protein-coding regions of FOXL2 has been observed in the majority of BPES cases, whether deficiencies in regulatory elements lead to the pathogenesis remains poorly understood. Herein, an autosomal-dominant BPES type II family was included. Peripheral venous blood has been collected, and genomic DNA has been extracted from leukocytes. A whole exome sequencing analysis has been performed and analyzed (Deposited in NODE database: OER422653). The promoter region of FOXL2 was amplified using polymerase chain reaction (PCR). The luciferase reporter assay was performed to identify the activity of this region. In this study, we present a Chinese family diagnosed with type II BPES, characterized by the presence of small palpebral fissures, ptosis, telecanthus, and epicanthus inversus. Notably, all male individuals within the family display polydactyly. A 225-bp deletion in the 556-bp 5'-upstream to transcription start site of FOXL2, decorated by multiple histone modifications, was identified in affected members of the family. This deletion significantly decreased FOXL2 promoter activity, as measured by the luciferase assay. Conclusively, a novel 255-bp-deletion of the FOXL2 promoter was identified in Chinese families with BPES. Our results expand the spectrum of known FOXL2 mutations and provide additional insight into the genotype-phenotype relationships of the BPES pathogenesis. In addition, this study indicates the important role of genetic screening of cis-regulatory elements in testing heritable diseases.


Woody plants: changes in survival in response to long-term (8 years) chronic gamma irradiation.
The number of plant deaths which occurred over 8 years of chronic gamma irradiation (20 hours/day) of 11 species of woody plants indicated a decline in the rate of death with increasing exposure time. This suggests that a highly effective repair system may develop, at least in the range of exposure which reduces survival by 50 percent. The inverse relationship previously found between interphase chromosome volume and radiosensitivity for single 16-hour exposures was confirmed for chronic exposures by construction of appropriate regressions. Radiosensitivity of a species can be predicted from these regressions if the interphase chromosome volume is known. The distributions of interphase chromosome volumes and predicted sensitivities are given for 215 species of woody plants.


Microsatellite loci for the invasive colonial hydrozoan Cordylophora caspia.
Cordylophora caspia, a colonial hydrozoan native to the Ponto-Caspian region, has become a common invader of both fresh and brackish water ecosystems of North America and Europe. We describe 11 polymorphic microsatellite loci for this species. Preliminary analyses indicate that population substructure may contribute to departures from Hardy-Weinberg equilibrium. In addition, new loci failed to consistently amplify Cordylophora samples known to be genetically distant from those utilized in this study, indicating the presence of cryptic diversity within the taxon.


Midterm Outcome of Femoral Artery Stenting and Factors Affecting Patency.
The purpose of this study was to evaluate the early and midterm results of superficial femoral artery (SFA) stenting with self-expanding nitinol stents and to identify the factors affecting patency. SFA stenting was performed in 165 limbs of 117 patients from January 2009 to December 2013. Patients were followed-up for the first occurrence of occlusion or stenosis based on computed tomography and duplex scan results and a decrease in ankle brachial index of >15%. During the follow-up period (mean, 15.3±3.2 months), no early thrombotic reocclusions occurred within 30 days, but in-stent restenosis developed in 78 limbs. The primary patency rates at 6, 12, 18, and 24 months were 78%, 66%, 42%, and 22%, respectively, and the secondary patency rates were 85%, 72%, 58%, and 58%, respectively. TASC II C or D lesions, stent length >8 cm, number of patent tibial arteries and diabetes were significantly associated with reintervention. The midterm results of stenting for SFA occlusive disease were disappointing because the primary and secondary patency rates at two years were 22% and 58%, respectively. Reintervention after SFA stenting remains a major problem, particularly in patients with diabetes mellitus or long TASC II C or D lesions.


Prostatitis, a rare presentation of granulomatosis with polyangiitis, successfully treated with rituximab and prednisone.
A previously healthy 21-year-old man presented with an 8-month history of weight loss, lethargy and dysuria unresponsive to empiric antibiotics and paraurethral drainage of a prostatic abscess. Urinalysis showed pyuria, but cultures failed to grow any organisms. Additionally, he developed new onset sensorineural hearing loss. CT of the chest showed two right-sided cavitary lesions. CT of the abdomen and pelvis demonstrated a prostatic abscess. A prostate biopsy demonstrated necrotising granulomatous prostatitis. A lung biopsy showed necrotising granulomatous inflammation. He was diagnosed with granulomatosis with polyangiitis (GPA). He was successfully treated with rituximab and prednisone. At 6-month follow-up, he continued to be in remission with resolution of his symptoms. This case demonstrates a rare presentation of prostatitis as the presenting symptom of GPA. As far as we know, this case is the first documented report of rituximab and prednisone as successful therapy for prostatitis secondary to GPA.


Selection of planning unit size in dynamic management strategies to reduce human-wildlife conflict.
Conservation planning traditionally relies upon static reserves, however there is increasing emphasis on dynamic management (DM) strategies that are flexible in space and time. Due to its novelty, the field of DM lacks best practices to guide design and implementation. We assess the effect of planning unit (PU) size within the context of an applied DM tool designed to reduce entanglements of protected whales in a lucrative U.S. crab fishery. We find that smaller PUs avoided up to $47M of revenue loss and reduced entanglement risk by up to 25% compared to the large PUs currently in use by avoiding the incidental closure of lose-lose areas with low biodiversity value and high fisheries revenue. However, larger PUs were more buffered against the effects of an unprecedented marine heatwave in 2014-16, and were less affected by delays in data availability. Our findings suggest that novel and adaptive management solutions - rather than a one-size-fits-all approach - are needed to separate wildlife from their threats under a changing climate. This article is protected by copyright. All rights reserved.


[Prevention and prognosis of cardiac complications in patients following reconstruction of terminal aorta or lower limb arteries for atherosclerotic lesions].
The paper analyses several risk factors of cardiac postoperative complications in 284 patients with atherosclerosis of terminal aorta or lower limb arteries and correlation between preoperative management and intervention outcomes. Results of preoperative functional examination (transesophageal electric stimulation, echocardiography) and intraoperative monitoring of central hemodynamics were highly prognostic for cardiac complications. Causative analysis of cardiac complications enabled to develop a preventive strategy that has decreased the complication rate in 1.8 times.


Predictable visual responses to increasing age.
Some loss of visual efficiency with age is universal. Such visual impairment probably is more disabling than most young eye practitioners tend to realize because the visual loss that attends uncomplicated aging impacts only slightly the common clinical tests of vision. Nevertheless, visual impairment associated with aging can interfere significantly with one's ability to perform certain types of visual tasks efficiently. This becomes a problems particularly when these tasks must be carried out under less than optimal viewing conditions.


Alcohol use disorders in geriatrics.
Alcohol use disorders cause significant morbidity and mortality in the geriatric population. This review article begins with a hypothetical case for illustration, asking what the primary care physician could do for a geriatric patient with alcohol abuse over a course of four office visits. Various aspects of alcohol use disorders in the geriatric population are reviewed, such as range of alcohol use, epidemiology, medical/psychiatric impact, detection, comprehensive treatment planning, modalities of psychotherapy, medication management, and resources for clinicians/patients.


A study of magnesium deficiency in human and experimental pulmonary hypertension.
Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure above 25 mmHg. Pulmonary vasoconstriction, cellular proliferation, inflammation, and oxidative stress are involved in the pathophysiology of PH. Since hypomagnesemia was reported to promote endothelial cell dysfunction leading to inflammation and oxidative stress, we investigated the potential involvement of magnesium (Mg) deficiency in experimental and human PH. Our results indicate that Mg deficiency has no impact on hypoxia-induced PH development or severity, and that no reduction in Mg plasma concentration was observed in patients with severe pulmonary arterial hypertension. Thus, hypomagnesemia does not appear to play a role in the pathophysiology of experimental and human pulmonary hypertension.


The immune response of rabbits tolerant to bovine serum albumin to the injection of other heterologous serum albumins.
Immunological tolerance produced in rabbits by neonatal injections of BSA can be terminated by a series of injections of certain heterologous serum albumins which cross-react with BSA. Injections of albumins distantly related to BSA were more effective in terminating the tolerant state than injections of albumins closely related to BSA. It was concluded from results obtained with several heterologous albumins that immunological tolerance to BSA is directed to both the over-all antigenic or physical-chemical composition of the protein and the individual determinant groups present on the protein. Several possible mechanisms were given to explain the ability of cross-reacting albumins to terminate the tolerant state of BSA-tolerant rabbits. A possible relationship between the termination of tolerance in BSA-tolerant rabbits injected with cross-reacting albumins and autoimmunily was discussed. It was also suggested that the relative ease with which tolerance could be established to heterologous serum proteins in comparison to bacterial antigens is the result of the close serological and physical-chemical relationship of the heterologous serum proteins to the serum proteins of the rabbit. Rabbits injected with 500 mg of BSA during the first 5 days of life failed to form antibody capable of either eliciting an immune elimination of an injection of I* BSA given 3 to 4 months later or complexing with the circulating I* BSA.


Neuroendoscopy combined with frameless neuronavigation.
Minimal invasive neurosurgery is becoming more and more standard in neurosurgical procedures. Several types of lesions are now approached endoscopically. The surgical planning and intraoperative orientation during endoscopic surgical procedures are sometimes difficult. To solve this problem, a combination of the endoscopic procedure with a frameless, armless neuronavigation system is used in our service. The combination of the endoscope and the frameless navigation system was used in tumour surgery, ventriculostomies and arachnoid cyst operations. All procedures were performed successfully. The combination of both systems has proved to be advantageous because of safe surgical planning using the frameless stereotactic technique and the possibility of real time orientation of the endoscope. This technique is very useful in removing intraventricular and large brain mass lesions.


Effects of oestrogen on the extracellular matrix in the endometrium of postmenopausal women.
To obtain insight into the effects of oestrogen on extracellular matrix (ECM) in the postmenopausal endometrium. The distribution of the components of the ECM, including collagen types I, III, IV, and VI, and laminin, was investigated in the human postmenopausal endometrium by an indirect immunofluorescence method with specific monoclonal antibodies and a polyclonal antibody. Collagens were also extracted from the endometrial tissues of postmenopausal women who had or had not been treated with oestrogen for three weeks. Immunohistochemical studies demonstrated that type I collagen was the predominant interstitial collagen, and that types III and VI collagens were absent or very sparsely distributed in the stroma of the postmenopausal endometrium. However, types I, III, and VI collagens were diffusely localised in the stroma of the postmenopausal endometrium after administration of oestrogen. Even though type IV collagen was not seen in the basement membrane of the endometrial glands in the endometrium of postmenopausal women in the absence of oestrogen treatment, both type IV collagen and laminin were localised exclusively in the basement membrane of the endometrial glands in the postmenopausal endometrium after three weeks of oestrogen treatment. The level of type III collagen relative to that of type I collagen was significantly increased (p < 0.01) in the endometrium of oestrogen treated postmenopausal women compared with non-treated postmenopausal women. Conjugated equine oestrogen might induce changes in the distribution of components and in the composition of the ECM in the endometrium of postmenopausal women.


The proof is in the eating: subjective peer norms are associated with adolescents' eating behaviour.
To investigate associations of self-perceived eating-related peer norms (called 'subjective peer norms') with adolescents' healthy eating intentions and intake of healthy and unhealthy food. Cross-sectional data were collected in a large international survey. Two types of subjective peer norms were assessed: perceived peer encouragement of healthy eating and perceived peer discouragement of unhealthy eating. Outcome variables were healthy eating intentions, intake of healthy food (fruits and vegetables) and intake of unhealthy food (snacks and soft drinks). Over 2500 European (pre-)adolescents aged between 10 and 17 years participated. Subjective peer norms were associated with all three outcome variables. While both perceived encouragement of healthy eating and perceived discouragement of unhealthy eating were related to intentions, only peer encouragement of healthy eating was related to intakes of both healthy and unhealthy food. Subjective peer norms play a role in adolescent eating behaviour and as such are an important target for health promotion. Addressing norms that encourage healthy eating may be more promising in changing behaviour than norms that discourage unhealthy eating.


The future of anesthesiology: implications of the changing healthcare environment.
Anesthesiology is at a crossroad, particularly in the USA. We explore the changing and future roles for anesthesiologists, including the implication of new models of care such as the perioperative surgical home, changes in payment methodology, and the impact other refinements in healthcare delivery will have on practice opportunities and training requirements for anesthesiologists. The advances in the practice of anesthesiology are having a significant impact on patient care, allowing a more diverse and complex patient population to benefit from the knowledge, skills and expertise of anesthesiologists. Expanded clinical opportunities, increased utilization of technology and expansion in telemedicine will provide the foundation to care for more patients in diverse settings and to better monitor patients remotely while ensuring immediate intervention as needed. Although the roles of anesthesiologists have been diverse, the scope of practice varies from one country to another. The changing healthcare needs in the USA in particular are creating new opportunities for American anesthesiologists to define expanded roles in healthcare delivery. To fulfill these evolving needs of patients and health systems, resident training, ongoing education and methods to ensure continued competency must incorporate new approaches of education and continued certification to ensure that each anesthesiologist has the full breadth and depth of clinical skills needed to support patient and health system needs. The scope of anesthesia practice has expanded globally, providing anesthesiologists, particularly those in the USA, with unique new opportunities to assume a broader role in perioperative care of surgical patients.


Non-co-ordinate development of beta-adrenergic receptors and adenylate cyclase in chick heart.
We have studied the properties of beta-adrenergic receptors and of their interaction with adenylate cyclase in the chick myocardium during embryogenesis. Between 4.5 and 7.5 days in ovo the number of receptors determined by (-)-[3H]dihydroalprenolol ([3H]DHA) binding is constant at approx. 0.36 pmol of receptor/mg of protein. By day 9 the density decreases significantly to 0.22 pmol of receptor/mg of protein. At day 12.5--13.5 the number was 0.14--0.18 pmol of receptor/mg of protein. This number did not change further up to day 16. The same results were obtained with guanosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppG) added to the assay mixtures. There was no significant change in receptor affinity for the antagonist [3H]DHA between days 5.5 and 13. Despite the decrease in numbers of beta-adrenergic receptors, there was no change in basal, p[NH]ppG-, isoprenaline- or isoprenaline-plus-p[NH]ppG-stimulated adenylate cyclase activity between days 3 and 12 of development. We conclude that beta-adrenergic receptors and adenylate cyclase are not co-ordinately regulated during early embryonic development of the chick heart. Some of the beta-adrenergic receptors present very early in the ontogeny of cardiac tissue appear not to be coupled to adenylate cyclase since their loss is not reflected in decreased activation of the enzyme.


Action of chelators in iron-loaded cardiac cells: Accessibility to intracellular labile iron and functional consequences.
Labile iron in hemosiderotic plasma and tissue are sources of iron toxicity. We compared the iron chelators deferoxamine, deferiprone, and deferasirox as scavengers of labile iron in plasma and cardiomyocytes at therapeutic concentrations. This comprised chelation of labile plasma iron (LPI) in samples from thalassemia patients; extraction of total cellular iron; accessing labile iron accumulated in organelles and preventing formation of reactive-oxidant species; and restoring impaired cardiac contractility. Neonatal rat cardiomyocytes were used for monitoring chelator extraction of LCI (labile cell iron) as 59Fe; assessing in situ cell iron chelation by epifluorescence microscope imaging using novel fluorescent sensors for iron and reactive oxygen species (ROS) selectively targeted to organelles, and monitoring contractility by time-lapse microscopy. At plasma concentrations attained therapeutically, all 3 chelators eliminated LPI but the orally active chelators rapidly gained access to the LCI pools of cardiomyocytes, bound labile iron, attenuated ROS formation, extracted accumulated iron, and restored contractility impaired by iron overload. The effect of deferoxamine at therapeutically relevant concentrations was primarily by elimination of LPI. The rapid accessibility of the oral chelators deferasirox and deferiprone to intracellular labile iron compartments renders them potentially efficacious for protection from and possibly reversal of cardiac damage induced by iron overload.


The influence of chromosome content on the size and shape of sperm heads in Drosophila melanogaster and the demonstration of chromosome loss during spermiogenesis.
The volumes of sperm heads were estimated from three-dimensional reconstructions of serially sectioned bundles of nearly mature spermatid nuclei. Cysts from males in which all sperm are expected to have comparable amounts of chromatin (X/Y and 1n(3LR)/+) show unimodal frequency distributions of nuclear volumes, whereas cysts from males in which meiotic segregation is expected to deliver unequal amounts of chromatin material to spermatid nuclei show two (XY/O and XY/Y) or more (T(2;3)/+ ANd C(2L);C(2R)) modes. The mean volumes of the subpopulations in these cases are related in the same proportions as the metaphase lengths of their chromosomal complements. Thus the volumes of sperm nuclei are proportional to their DNA content. Sperm head shape, on the other hand, does not appear to be very sensitive to chromosomal constitution, as heads of different size do not vary greatly in shape.----The numbers of sperm heads in the various size classes in a cyst depart from mendelian expectations; these departures are caused by the elimination, during individualization, of chromosomes contained within micronuclei that are formed in spermatids at the end of the second meiotic division. The effect of this chromosome loss is to increase the proportion of nullosomic gametes in the sperm pool.----The relative frequencies of XY-bearing and nullo-X, nullo-Y sperm in XY/O males were estimated from the volume measurements. Taking this estimate as a measure of the fertilizing population, it is possible to infer from the change in sex ratio over time following insemination, that XY-bearing sperm have an advantage of 1.5 over nullo-X, nullo-Y sperm in leaving the seminal receptacle of the female for fertilization of ova.


Expanding practice to include i.v. cannulation.
Peripheral i.v. cannulation is one of the most common procedures performed in hospitals. Expanding the nursing role to include i.v. cannulation has the potential to improve care. The individual practitioner is responsible for maintaining and updating such skills.


Eliminating the solvent blocking requirement of interconnection layers in polymer tandem solar cells by thin-film transfer technique.
Interconnection layers (ICLs) for polymer tandem solar cells reported so far are limited in materials' choice and layer structure, because of a requirement that the ICLs must prevent the penetration of solvents used for the top cells. In this research, it is demonstrated that depositing the active layer of the top subcell using a dry thin-film transfer technique allows for incorporation of an ICL composed of vacuum deposited materials in a polymer tandem cell, providing a large degree of freedom in ICL design. Specifically, a polymer tandem solar cell was fabricated using an ICL composed of bathocuproine:silver/silver islands/1,4,5,8,9,11-hexaazatriphenylene hexacarbonitrile (BCP:Ag/Ag islands/HAT-CN), where the thicknesses of the BCP:Ag and Ag island layers are precisely controlled at the nanoscale to facilitate the transport of electrons generated in the bottom subcell and to ensure their efficient recombination with holes generated in the top subcell. Consequently, the tandem device featuring the optimized ICL, whose active layers are composed of poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PC61BM) and poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)]:[6,6]-phenyl-C71-butyric acid methyl ester (PCPDTBT:PC71BM), exhibits an open-circuit voltage of 1.20 V, which is equal to the sum of the open-circuit voltages of the two subcells, with a fill factor (FF) of 0.60 almost identical to the FFs of the subcells.


Lifetime-resolved Photoacoustic (LPA) Spectroscopy for monitoring Oxygen change and Photodynamic Therapy (PDT).
The Methylene Blue loaded Polyacrylamide Nanoparticles (MB-PAA NPs) are used for oxygen sensing and Photodynamic therapy (PDT), a promising therapeutic modality employed for various tumors, with distinct advantages of delivery of biomedical agents and protection from other bio-molecules overcoming inherent limitations of molecular dyes. Lifetime-resolved photoacoustic spectroscopy using quenched-phosphorescence method is applied with MB-PAA NPs so as to sense oxygen, while the same light source is used for PDT. The dye is excited by absorbing 650 nm wavelength light from a pump laser to reach triplet state. The probe laser at 810 nm wavelength is used to excite the first triplet state at certain delayed time to measure the dye lifetime which indicates oxygen concentration. The 9L cells (106 cells/ml) incubated with MB-PAA NP solution are used for monitoring oxygen level change during PDT in situ test. The oxygen level and PDT efficacy are confirmed with a commercial oximeter, and fluorescence microscope imaging and flow cytometry results. This technique with the MB-PAA NPs allowed us to demonstrate a potential non-invasive theragnostic operation, by monitoring oxygen depletion during PDT in situ, without the addition of secondary probes. Here, we demonstrate this theragnostic operation, in vitro, performing PDT while monitoring oxygen depletion. We also show the correlation between O2 depletion and cell death.


Coexpression network analysis identifies transcriptional modules related to proastrocytic differentiation and sprouty signaling in glioma.
Gliomas are primary brain tumors with high mortality and heterogeneous biology that is insufficiently understood. In this study, we performed a systematic analysis of the intrinsic organization of complex glioma transcriptome to gain deeper knowledge of the tumor biology. Gene coexpression relationships were explored in 790 glioma samples from 5 published patient cohorts treated at different institutions. We identified 20 coexpression modules that were common to all the data sets and associated with proliferation, angiogenesis, hypoxia, immune response, genomic alterations, cell differentiation phenotypes, and other features inherent to glial tumors. A collection of high-quality signatures for the respective processes was obtained using cross-data set summarization of the modules' gene composition. Individual modules were found to be organized into higher order coexpression groups, the two largest of them associated with glioblastoma and oligodendroglioma, respectively. We identified a novel prognostic gene expression signature (185 genes) linked to a proastrocytic pattern of tumor cell differentiation. This "proastrocytic" signature was associated with long survival and defined a subgroup of the previously established "proneural" class of gliomas. A strong negative correlation between proastrocytic and proneural markers across differentiated tumors underscored the distinction between these subtypes of glioma. Interestingly, one further novel signature in glioma was identified that was associated with EGFR (epidermal growth factor receptor) gene amplification and suggested that EGF signaling in glioma may be a subject to regulation by Sprouty family proteins. In summary, this integrated analysis of the glioma transcriptome provided several novel insights into molecular heterogeneity and pathogenesis of glial tumors.


[Tonographic follow-up after laser trabeculoplasty].
On 62 eyes with open-angle glaucoma the authors performed tonography one month before and after laser trabeculoplasty. While, generally speaking, there was no significant influence on outflow facility, the eyes with preoperative pathologic outflow facility reacted better after the laser trabeculoplasty, at least tomographically, than the eyes with initially normal tonography results. The possible significance of these results with regard to indication for laser trabeculoplasty is discussed.


Immunoglobulin G4-related disease (IgG4-RD) in the orbit: mucosa-associated lymphoid tissue (MALT)-type lymphomas.
MALT lymphomas were classified for differential diagnostics of IgG4-dependent disease due to their exceptional predilection to intraorbital localization. Therefore, the goal of our studies was large retrospective analysis of patients diagnosed with MALT lymphomas within the orbital tissues, since no such studies have been conducted in Poland. The starting study population consisted of 167 patients with isolated infiltrative tumor diseases within the orbital region treated at the Department of Otolaryngology, Head and Neck Surgery of the Medical College Jagiellonian University in Cracow. The immunohistochemical assays using anti-IgG, anti-IgG4 and anti-CD138 antibodies were used to estimate the IgG4+/CD138+ and IgG4+/IgG+ ratios. Of all the studied and analyzed patients, a final group of 19 patients with orbital MALT lymphomas was selected to undergo diagnostic examinations for IgG4-related disease. Detailed analysis and diagnostic screening for IgG4-related disease was performed and results meeting the criteria of IgG4-dependent disease were obtained in 10 out of 19 patients with the diagnosis of MALT tumor established on the basis of immunohistochemical assays. MALT lymphomas are the most common of all lymphomas occurring within orbital tissues. In this study, results consistent with the criteria of IgG4-related disease were obtained in approximately 50% patients with immunohistochemical diagnosis of orbital MALT lymphoma.


Wiring the Vascular Network with Neural Cues: A CNS Perspective.
The vascular and the nervous system are responsible for oxygen, nutrient, and information transfer and thereby constitute highly important communication systems in higher organisms. These functional similarities are reflected at the anatomical, cellular, and molecular levels, where common developmental principles and mutual crosstalks have evolved to coordinate their action. This resemblance of the two systems at different levels of complexity has been termed the "neurovascular link." Most of the evidence demonstrating neurovascular interactions derives from studies outside the CNS and from the CNS tissue of the retina. However, little is known about the specific properties of the neurovascular link in the brain. Here, we focus on regulatory effects of molecules involved in the neurovascular link on angiogenesis in the periphery and in the brain and distinguish between general and CNS-specific cues for angiogenesis. Moreover, we discuss the emerging molecular interactions of these angiogenic cues with the VEGF-VEGFR-Delta-like ligand 4 (Dll4)-Jagged-Notch pathway.


Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons.
Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after traumatic brain injury (TBI). Inhibiting the excessive inflammatory response is essential for improving the neurologic outcome. To clarify the regulatory mechanism of microglial exosomes on neuronal inflammation in TBI, we focused on studying the impact of microglial exosomal miRNAs on injured neurons in this research. We used a repetitive (r)TBI mouse model and harvested the injured brain extracts from the acute to the chronic phase of TBI to treat cultured BV2 microglia in vitro The microglial exosomes were collected for miRNA microarray analysis, which showed that the expression level of miR-124-3p increased most apparently in the miRNAs. We found that miR-124-3p promoted the anti-inflamed M2 polarization in microglia, and microglial exosomal miR-124-3p inhibited neuronal inflammation in scratch-injured neurons. Further, the mammalian target of rapamycin (mTOR) signaling was implicated as being involved in the regulation of miR-124-3p by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Using the mTOR activator MHY1485 we confirmed that the inhibitory effect of exosomal miR-124-3p on neuronal inflammation was exerted by suppressing the activity of mTOR signaling. PDE4B was predicted to be the target gene of miR-124-3p by pathway analysis. We proved that it was directly targeted by miR-124-3p with a luciferase reporter assay. Using a PDE4B overexpressed lentivirus transfection system, we suggested that miR-124-3p suppressed the activity of mTOR signaling mainly through inhibiting the expression of PDE4B. In addition, exosomal miR-124-3p promoted neurite outgrowth after scratch injury, characterized by an increase on the number of neurite branches and total neurite length, and a decreased expression on RhoA and neurodegenerative proteins [Aβ-peptide and p-Tau]. It also improved the neurologic outcome and inhibited neuroinflammation in mice with rTBI. Taken together, increased miR-124-3p in microglial exosomes after TBI can inhibit neuronal inflammation and contribute to neurite outgrowth via their transfer into neurons. miR-124-3p exerted these effects by targeting PDE4B, thus inhibiting the activity of mTOR signaling. Therefore, miR-124-3p could be a promising therapeutic target for interventions of neuronal inflammation after TBI. miRNAs manipulated microglial exosomes may provide a novel therapy for TBI and other neurologic diseases.-Huang, S., Ge, X., Yu, J., Han, Z., Yin, Z., Li, Y., Chen, F., Wang, H., Zhang, J., Lei, P. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons.


What are the benefits and drawbacks of statins in carotid artery disease? A perspective review.
The prevalence of carotid artery stenosis in the general population is approximately 3%, but approximately 20% among people with acute ischemic stroke. Statins are recommended by multiple international guidelines as the drug of choice for lipid control in people with asymptomatic or symptomatic carotid artery stenosis due to their lipid-lowering and other pleiotropic effects. This review discusses the guidelines for statin usage as a cornerstone in the prevention and management of atherosclerotic carotid artery disease and the impact of statins on stroke incidence and mortality. Statin side effects, alternative therapy, and genetic polymorphisms are reviewed. Statin therapy is associated with a decreased incidence of stroke and mortality as well as improved outcomes for patients treated with carotid revascularization. Statins are a safe and effective class of medications, but the initiation of therapy warrants close monitoring to avoid rare and potentially serious side effects. Lack of clinical efficacy or the presence of side effects suggests a need for treatment with an alternative therapy such as PCSK9 inhibitors. Understanding the interplay between the mechanisms of statins and PCSK9 inhibition therapies will allow optimal benefits while minimizing risks. Future research into genetic polymorphisms may improve patient selection for personalized therapy.


California's historic effort to reduce the stigma of mental illness: the Mental Health Services Act.
In a historic effort to reduce the stigma of mental illness, California voters approved the Mental Health Services Act in 2004. The law funds a comprehensive statewide prevention initiative that places stigma and discrimination reduction at its center, with 25 projects providing interventions at the institutional, societal, and individual levels. Stakeholders selected specific strategies from the research-based California Strategic Plan on Reducing Stigma and Discrimination. Strategies range from social marketing to increase public knowledge to capacity building at the local level, including training that emphasizes participation by consumers of mental health services and cultural competence. Collectively, these strategies aim to foster permanent change in the public perception of mental illness and in the individual experience of stigma. We examined the context, planning, programming, and evaluation of this effort.


Evaluation of tooth wear and associated risk factors: A matched case-Control study.
The aim of this case-control study was to compare the associated risk factors between adults with tooth wear (TW) and age- and sex-matched controls without TW. Fifty participants with TW and 50 age- and sex-matched controls participated in this study. A questionnaire was prepared to assess oral healthcare and consumption of erosive food and drinks. All participants completed the diet analysis forms. Saliva characteristics were evaluated with GC Saliva-Check BUFFER test. Examiners measured the TW of case patients, using the TW index. Data were statistically analyzed using Chi-square and Mann-Whitney U-tests (P < 0.05). Individuals in the case group brush their teeth more often (P < 0.05). The difference in erosive food consumption between the case and control groups was significant (P < 0.05). There was no erosive effect of acidic food when consumed as a main meal or a snack (P > 0.05). Although there was no difference between stimulated saliva flow rate and buffering capacity between groups, the difference between the resting saliva flow rates and pH values was significant (P < 0.05). Although some wear was seen on buccal/labial surfaces of teeth, cervical and occlusal/incisal surfaces were scored higher. No TW was observed on palatal/lingual surfaces. The cervical surfaces of mandibular premolars and incisal surfaces of anterior teeth were most affected. Of the factors investigated, TW in the case group was correlated with consumption of acidic foods, lower salivary flow rate, and pH.


The association of blood lead level and cancer mortality among whites in the United States.
Lead is classified as a possible carcinogen in humans. We studied the relationship of blood lead level and all cancer mortality in the general population of the United States using data from the National Health and Nutrition Examination Survey II (NHANES II) Mortality Study, 1992, consisting of a total of 203 cancer deaths (117 men and 86 women) among 3,592 whites (1,702 men and 1,890 women) with average of 13.3 years of follow-up. We used Cox proportional hazard regression models to estimate the dose-response relationship between blood lead and all cancer mortality. Log-transformed blood lead was either categorized into quartiles or treated as a continuous variable in a cubic regression spline. Relative risks (RRs) were estimated for site-specific cancers by categorizing lead above and below the median. Among men and women combined, dose-response relationship between quartile of blood lead and all cancer mortality was not significant (ptrend = 0.16), with RRs of 1.24 [95% percent confidence interval (CI), 0.66-2.33], 1.33 (95% CI, 0.57-3.09), and 1.50 (95% CI, 0.75-3.01) for the second, third, and fourth quartiles, respectively, compared with the first quartile. Spline analyses found no dose response (p = 0.29), and none of the site-specific cancer RRs were significant. Among men, no significant dose-response relationships were found for quartile or spline analyses (p trend = 0.57 and p = 0.38, respectively). Among women, no dose-response relationship was found for quartile analysis (ptrend = 0.22). However, the spline dose-response results were significant (p = 0.001), showing a threshold effect at the 94th percentile of blood lead or a lead concentration of 24 microg/dL, with an RR of 2.4 (95% CI, 1.1-5.2) compared with the risk at 12.5 percentile. Because the dose-response relationship found in women was not found in men, occurred at only the highest levels of lead, and has no clear biologic explanation, further replication of this relationship is needed before it can be considered believable. In conclusion, individuals with blood lead levels in the range of NHANES II do not appear to have increased risk of cancer mortality.


Anatomy, histology and immunohistochemistry of normal human skin.
The skin is the largest organ of the body, accounting for about 15% of the total body weight in adult humans. It exerts multiple vital protective functions against environmental aggressions, rendered possible thanks to an elaborate structure, associating various tissues of ectodermal and mesodermal origin, arranged in three layers, including (from top to bottom) the epidermis (and its appendages), the dermis and the hypodermis. This article reviews the main data concerning the anatomy, histology and immunohistochemistry of normal human skin.


Pathogenicity and selective constraint on variation near splice sites.
Mutations that perturb normal pre-mRNA splicing are significant contributors to human disease. We used exome sequencing data from 7833 probands with developmental disorders (DDs) and their unaffected parents, as well as more than 60,000 aggregated exomes from the Exome Aggregation Consortium, to investigate selection around the splice sites and quantify the contribution of splicing mutations to DDs. Patterns of purifying selection, a deficit of variants in highly constrained genes in healthy subjects, and excess de novo mutations in patients highlighted particular positions within and around the consensus splice site of greater functional relevance. By using mutational burden analyses in this large cohort of proband-parent trios, we could estimate in an unbiased manner the relative contributions of mutations at canonical dinucleotides (73%) and flanking noncanonical positions (27%), and calculate the positive predictive value of pathogenicity for different classes of mutations. We identified 18 patients with likely diagnostic de novo mutations in dominant DD-associated genes at noncanonical positions in splice sites. We estimate 35%-40% of pathogenic variants in noncanonical splice site positions are missing from public databases.


Carpal tunnel syndrome in pediatric mucopolysaccharidoses. Report of four cases.
Four pediatric patients with mucopolysaccharidoses and an associated carpal tunnel syndrome are presented. Findings in these cases were typical of the adult form of median nerve compression at the wrist, but the patients had minimal symptoms in view of these findings. The importance of careful clinical eximination and early surgical decompression is emphasized.


Outcomes of lateral femoral sliding osteotomy in primary total knee arthroplasty for type two fixed valgus deformity.
The aim of our study was to determine the surgical outcomes of patients who underwent lateral femoral sliding osteotomy (LFSO) with total knee arthroplasty (TKA) for Ranawat's type 2 fixed valgus deformity. The consecutive patients who underwent primary TKA with posterior-stabilized implant and LFSO for fixed valgus deformity were reviewed. The radiological parameters analyzed were pre- and postoperative hip-knee-ankle (HKA) angle and tibio-femoral angle in varus-valgus stress views. The clinical outcome was measured by Oxford knee score (OKS), knee society score (KSS), and functional score (KSS-F). The complications and any reoperation were noted in the follow-up. There were total 28 patients included with an average follow-up time of 47.2 ± 24.9 months. The average arc of motion was 101.3 ± 23.8° preoperatively and 102.7 ± 11.8° postoperatively (p > 0.05). The average deformity in varus and valgus stress views was 196.6 ± 4.8 and 207.8 ± 7.4°, respectively. There was significant improvement in HKA from 205.2 ± 8.3° preoperatively to 181.9 ± 3.7° postoperatively (p < 0.05). At the final follow-up, bony union of the osteotomy fragment was noted in all the patients. There was significant improvement in OKS, KSS, and KSS-F score from a preoperative 15.1 ± 3.9, 35.1 ± 10.6, and 26.6 ± 12.6 to 40.3 ± 2.9, 85.6 ± 4.8, and 89.4 ± 7.7, postoperatively (p < 0.05), respectively. One patient had acute periprosthetic joint infection that was managed with debridement and polyethylene insert exchange. Lateral femoral sliding osteotomy is an effective technique for optimal soft tissue balance in fixed valgus deformity. It provides satisfactory clinical outcome with restoration of knee alignment without using the constrained implants.


The Assessment of Circadian Rhythms Within the Immune System.
In recent years, circadian rhythms have been observed in many aspects of the immune system, both for the innate immunity (the first line of defense against pathogens) and the adaptive immunity (a more specific set of responses, which lead to immune memory). Here, to illustrate principles to be taken into account when working on circadian rhythms in immunology experiments, two protocols will be presented. The first one aims to analyze immune parameters in blood sampled from human subjects at different times over the day: counts of different cell types among the peripheral blood mononuclear cells and cytokine secretion by monocytes and T cells after ex vivo stimulation. The second protocol describes how to follow the response of CD8+ T cells after immunization of mice with antigen presenting cells loaded with a peptide antigen. These two protocols are optimized for circadian experiments, and outcome measures are mainly based on flow cytometry, which allows analysis of different parameters in the same cells.


Aortic dissection in young adults who abuse amphetamines.
Case reports suggest a relationship between amphetamine abuse/dependence and aortic dissection, but no population-based epidemiologic studies have examined this link. Our objective was to test the hypothesis that young adults with a diagnosis of amphetamine abuse/dependence would be at higher risk for aortic dissection after accounting for known risk factors. In this population-based case-control study of 30,922,098 discharges from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1995 to 2007, among persons aged 18 to 49 years, we identified 3,116 thoracic and thoracoabdominal aortic dissections using International Classification of Disease, Ninth Edition, Clinical Modification codes 441.01 and 441.03. The SURVEYLOGISTIC procedure in SAS 9.2 (SAS Institute, Cary, NC) was used to account for the Nationwide Inpatient Sample sampling methodology. In a multiple logistic regression analysis, while controlling for known risk factors, amphetamine abuse/dependence was significantly associated with aortic dissection (adjusted odds ratio = 3.33, 95% CI = 2.37-4.69, P < .0001). This statistically significant association suggests that amphetamine abuse/dependence may play a role in aortic dissection in young adults in the United States.


Live recombinant vectors for AIDS vaccine development.
Live recombinant vectors entered the AIDS vaccine field with the realization that live attenuated HIV vaccines posed too great a safety risk, and that subunit vaccines elicited antibodies which lacked the breadth or potency needed to induce sterilizing immunity. Vectored vaccines provided a means to bring the cellular arm of the immune system into play by mimicking natural viral infection. By delivering antigens within host cells, processing and presentation could occur for induction of cellular immune responses. This recombinant vector approach, either alone or combined with other strategies, has produced impressive results. Recombinants have been generated from DNA and RNA viruses and bacteria. With few exceptions, each vector poses some risk, yet each possesses unique features that make it attractive. In addition to safety, key considerations in vector selection have included previous success as a vaccine against the wild-type agent or other pathogens; ability to induce potent, persistent immune responses; ability to target mucosal inductive sites and antigen presenting cells; lack of integration into the host genome; presence of pre-existing immunity in people; ease of mucosal administration; cloning capacity; ease of engineering and production; and stability of the final product. Here we up-date the status of several live recombinant vectors that have shown good potential in pre-clinical studies. Some have progressed to human clinical trials, and others will shortly. The abundance of vectors, coupled with the complexity arising from use of combination regimens with other vaccine types and heterologous vectors, will necessitate selection of the most promising candidates for large-scale efficacy trials in people. The sooner comparative studies can be designed and implemented in which live recombinant vectors containing the same inserted genes are evaluated head-to-head, the closer we will be to an eventual vaccine.


Glycinergic tonic inhibition of hippocampal neurons with depolarizing GABAergic transmission elicits histopathological signs of temporal lobe epilepsy.
An increasing number of epilepsy patients are afflicted with drug-resistant temporal lobe epilepsy (TLE) and require alternative therapeutic approaches. High-affinity glycine receptors (haGlyRs) are functionally adapted to tonic inhibition due to their response to hippocampal ambient glycine, and their synthesis is activity-dependent. Therefore, in our study, we scanned TLE hippocampectomies for expression of haGlyRs and characterized the effects mediated by these receptors using primary hippocampal neurons. Increased haGlyR expression occurred in TLE hippocampi obtained from patients with a severe course of disease. Furthermore, in TLE patients, haGlyR and potassium chloride cotransporter 2 (KCC2) expressions were inversely regulated. To examine this potential causal relationship with respect to TLE histopathology, we established a hippocampal cell culture system utilising tonic inhibition mediated by haGlyRs in response to hippocam-pal ambient glycine and in the context of a high Cl equilibrium potential, as is the case in TLE hippocampal neurons. We showed that hypoactive neurons increase their ratio between glutamatergic and GABAergic synapses, reduce their dendrite length and finally undergo excitotoxicity. Pharmacological dissection of the underlying processes revealed ionotropic glutamate and TrkB receptors as critical mediators between neuronal hypoactivity and the emergence of these TLE-characteristic histopathological signs. Moreover, our results indicate a beneficial role for KCC2, because decreasing the Cl- equilibrium potential by KCC2 expression also rescued hypoactive hippocampal neurons. Thus, our data support a causal relationship between increased haGlyR expression and the emergence of histopathological TLE-characteristic signs, and they establish a pathophysiological role for neuronal hypoactivity in the context of a high Cl- equilibrium potential.


Long-term follow-up of newborn screening patients.
New technology in newborn screening permits clinicians to approach strategies for defining optimal treatments for newborn-screened conditions. The Health Resources and Services Administration Maternal and Child Health Bureau, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Centers for Disease Control and Prevention have all established initiatives for long-term follow-up assessment of children identified after newborn screening. In October 2008, an inaugural meeting of the National Institute of Child Health and Human Development-sponsored National Coordinating Center Long-Term Follow-Up Data Collection Work Group brought together partners from Health Resources and Services Administration-sponsored Regional Genetics Collaboratives to review pilot projects undertaken to promote systematic long-term follow-up for children with inborn errors of metabolism identified by newborn bloodspot screening. Beginning with these projects, the goal of this meeting was to provide a foundation for national planning for a common data set to be used for long-term follow-up. This supplement summarizes these initial projects.


Neuromyotonia: a skin-deep problem.
A 45-year-old woman was evaluated for right-sided hemicorporal scar-like skin lesions on her arm and thoracic and inguinal areas that appeared shortly after reduction mammoplasty. Five years later, she developed spontaneous cramps and involuntary abnormal, painful, twitching movements in the same areas. With time, the cramps worsened and disabled the patient. The use of her right arm triggered contractures of muscles and abnormal movements. A diagnosis of neuromyotonia (NMT) was established on the basis of clinical findings and on electromyographic findings of a burst of high-frequency motor unit potentials recorded in the right triceps in the area of skin lesions. The results of medullary, encephalic MRI as well as a comprehensive metabolic panel were normal. She was positive for antinuclear antibodies without specificity. Neither antineural antibodies nor antivoltage-gated potassium channel complex antibodies (specifically, leucine-rich glioma inactivated protein 1 and contactin-associated protein-like-2) were detected. Her skin lesions were diagnosed as morphea. Two combined strategies of treatment were initiated: antiepileptic drugs for NMT and corticosteroids and methotrexate for morphea. NMT is a rare, debilitating neurological complication of morphea.


Cerebrovascular disease in patients with cognitive impairment: A white paper from the ESO dementia committee - A practical point of view with suggestions for the management of cerebrovascular diseases in memory clinics.
Practical suggestions on clinical decisions about vascular disease management in patients with cognitive impairment are proposed. The document was produced by the Dementia Committee of the European Stroke Organisation (ESO) based on the evidence from the literature where available and on the clinical experience of the Committee members. This paper was endorsed by the ESO. Vascular risk factors and cerebrovascular disease are frequent in patients with cognitive impairment. While acute stroke treatment has evolved substantially in last decades, evidence of management of cerebrovascular pathology beyond stroke in patients with cognitive impairment and dementia is quite limited. Additionally, trials to test some daily-life clinical decisions are likely to be complex, difficult to undertake and take many years to provide sufficient evidence to produce recommendations. This document was conceived to provide some suggestions until data from field trials are available. It was conceived for the use of clinicians from memory clinics or involved specifically in cognitive disorders, addressing practical aspects on diagnostic tools, vascular risk management and suggestions on some therapeutic options. The authors did not aim to do an exhaustive or systematic review or to cover all current evidence. The document approach in a very practical way frequent issues concerning cerebrovascular disease in patients with known cognitive impairment.


Quantitative risk assessment of human campylobacteriosis associated with thermophilic Campylobacter species in chickens.
A quantitative risk assessment comprising the elements hazard identification, hazard characterization, exposure assessment, and risk characterization has been prepared to assess the effect of different mitigation strategies on the number of human cases in Denmark associated with thermophilic Campylobacter spp. in chickens. To estimate the human exposure to Campylobacter from a chicken meal and the number of human cases associated with this exposure, a mathematical risk model was developed. The model details the spread and transfer of Campylobacter in chickens from slaughter to consumption and the relationship between ingested dose and the probability of developing campylobacteriosis. Human exposure was estimated in two successive mathematical modules. Module 1 addresses changes in prevalence and numbers of Campylobacter on chicken carcasses throughout the processing steps of a slaughterhouse. Module 2 covers the transfer of Campylobacter during food handling in private kitchens. The age and sex of consumers were included in this module to introduce variable hygiene levels during food preparation and variable sizes and compositions of meals. Finally, the outcome of the exposure assessment modules was integrated with a Beta-Poisson dose-response model to provide a risk estimate. Simulations designed to predict the effect of different mitigation strategies showed that the incidence of campylobacteriosis associated with consumption of chicken meals could be reduced 30 times by introducing a 2 log reduction of the number of Campylobacter on the chicken carcasses. To obtain a similar reduction of the incidence, the flock prevalence should be reduced approximately 30 times or the kitchen hygiene improved approximately 30 times. Cross-contamination from positive to negative flocks during slaughter had almost no effect on the human Campylobacter incidence, which indicates that implementation of logistic slaughter will only have a minor influence on the risk. Finally, the simulations showed that people in the age of 18-29 years had the highest risk of developing campylobacteriosis.


The dimeric platelet collagen receptor GPVI-Fc reduces platelet adhesion to activated endothelium and preserves myocardial function after transient ischemia in mice.
Platelets play a critical role in the pathophysiology of reperfusion, sepsis, and cardiovascular diseases. In a multiple step process, they adhere to activated endothelium and release proinflammatory cytokines thereby promoting the inflammatory process. Glycoprotein VI (GPVI) is the major collagen receptor on the platelet surface and triggers platelet activation and primary hemostasis. Activation of GPVI leads to stable platelet adhesion and degranulation of platelet granules. However, GPVI is critically involved in platelet adhesion to activated endothelium without exposure of subendothelial matrix. Earlier studies show that the soluble GPVI-Fc binds to collagen and protects mice from atherosclerosis and decreases neointima proliferation after arterial injury. Here, we show for the first time that recombinant GPVI-Fc binds to activated endothelium mainly via vitronectin and prevents platelet/endothelial interaction. Administration of GPVI-Fc reduced infarct size and preserved cardiac function in a mouse model of myocardial infarction. This process was associated with reduced GPVI-induced platelet degranulation and release of proinflammatory cytokines in vitro and in vivo. Taken together, administration of GPVI-Fc offers a novel strategy to control platelet-mediated inflammation and to preserve myocardial function following myocardial infarction.


[Degenerative adult scoliosis].
Adult scoliosis is a complex three-dimensional rotational deformity of the spine, resulting from the progressive degeneration of the vertebral elements in middle age, in a previously straight spine; a Cobb angle greater than 10° in the coronal plane, which also alters the sagittal and axial planes. It originates an asymmetrical degenerative disc and facet joint, creating asymmetrical loads and subsequently deformity. The main symptom is axial, radicular pain and neurological deficit. Conservative treatment includes drugs and physical therapy. The epidural injections and facet for selectively blocking nerve roots improves short-term pain. Surgical treatment is reserved for patients with intractable pain, radiculopathy and/ or neurological deficits. There is no consensus for surgical indications, however, it must have a clear understanding of the symptoms and clinical signs. The goal of surgery is to decompress neural elements with restoration, modification of the three-dimensional shape deformity and stabilize the coronal and sagittal balance.


Olive oil consumption and risk of CHD and/or stroke: a meta-analysis of case-control, cohort and intervention studies.
Increasing evidence suggests that the Mediterranean diet can reduce the risk of CVD. Olive oil is the hallmark of this dietary pattern. We conducted a meta-analysis of case-control, prospective cohort studies and a randomised controlled trial investigating the specific association between olive oil consumption and the risk of CHD (101,460 participants) or stroke (38,673 participants). The results of all observational studies were adjusted for total energy intake. The random-effects model assessing CHD as an outcome showed a relative risk (RR) of 0.73 (95% CI 0.44, 1.21) in case-control studies and 0.96 (95% CI 0.78, 1.18) in cohort studies for a 25 g increase in olive oil consumption. In cohort studies, the random-effects model assessing stroke showed a RR of 0.74 (95% CI 0.60, 0.92). The random-effects model combining all cardiovascular events (CHD and stroke) showed a RR of 0.82 (95% CI 0.70, 0.96). Evidence of heterogeneity was apparent for CHD, but not for stroke. Both the Egger test (P= 0.06) and the funnel plot suggested small-study effects. Available studies support an inverse association of olive oil consumption with stroke (and with stroke and CHD combined), but no significant association with CHD. This finding is in agreement with the recent successful results of the PREDIMED randomised controlled trial.


Cellulose microfibril deposition: coordinated activity at the plant plasma membrane.
Plant cell wall production is a membrane-bound process. Cell walls are composed of cellulose microfibrils, embedded inside a matrix of other polysaccharides and glycoproteins. The cell wall matrix is extruded into the existing cell wall by exocytosis. This same process also inserts the cellulose synthase complexes into the plasma membrane. These complexes, the nanomachines that produce the cellulose microfibrils, move inside the plasma membrane leaving the cellulose microfibrils in their wake. Cellulose microfibril angle is an important determinant of cell development and of tissue properties and as such relevant for the industrial use of plant material. Here, we provide an integrated view of the events taking place in the not more than 100 nm deep area in and around the plasma membrane, correlating recent results provided by the distinct field of plant cell biology. We discuss the coordinated activities of exocytosis, endocytosis, and movement of cellulose synthase complexes while producing cellulose microfibrils and the link of these processes to the cortical microtubules.


Effects of feeding different proportions of silver leaf desmodium (Desmodium uncinatum) with banana (Musa paradisiaca) leaf on nutrient utilization in Horro sheep fed a basal diet of natural grass hay.
The objective was to evaluate feed intake, digestibility, body weight change and carcass characteristics of sheep fed a basal diet of hay supplemented with banana leaves and silver leaf desmodium. Thirty yearling lambs with an average initial body weight of 15.85±1.6 kg were grouped into six blocks of five rams in each block. The treatments were: hay alone (T1), hay+ 100% banana leaf (T2), hay+67% banana leaf+33% desmodium leaf (T3), hay+33% banana leaf+67% desmodium leaf (T4), andhay+100% desmodium leaf (T5). Three hundred grams of treatment diets were offered daily on as fed basis. The feeding and digestibility trials lasted for 84 and 7 days, respectively, followed by carcass evaluation. The total dry matter (DM) intake for T3, T4, and T5 were greater (p<0.05) than those fed T1 and T2 diets. The lowest (p<0.05) organic matter (OM) intake was recorded in rams reared on T1 diet. The total crude protein (CP) intake was in the following order: T5> T4>T3>T2>T1. Ram lambs receiving supplementary diets had higher (p<0.05) DM, OM, CP, neutral detergent fiber and acid detergent fiber digestibility compared with the control diet. The empty body weight and slaughter weight was highest (p<0.05) in rams receiving T3, T4, and T5 diets. The average daily gain and feed conversion efficiency was highest (p< 0.05) in rams receiving the supplementary diets. The dressing percentage on the basis of hot carcass weight linearly increased with increasing levels of desmodium. Rams reared on supplementary diet had higher (p<0.05) rib eye area compared with the control diet. In conclusion, when banana leaf is used as a supplement to poor quality grass, better body weight gain was obtained when fed in combination with desmodium.


Pharmacological STING Activation Is a Potential Alternative to Overcome Drug-Resistance in Melanoma.
Melanoma is the most aggressive type of skin cancer and resistance to the conventional chemotherapy is the major cause for its poor prognosis. Metabolic perturbations leading to increased production of reactive oxygen species activate NRF2-dependent anti-oxidative responses to survive oxidative stress. This protective function of NRF2 is the primary cause for therapy resistance in cancer as anti-cancer agents such as BRAF inhibitors also induce NRF2-dependent antioxidative response. We had reported that type I interferons produced upon activation of STING, abrogates NRF2 function. Therefore, we investigated if STING agonists such as the newly developed dimeric aminobenzimidazole (diABZI) could sensitize melanoma cells to the clinically used BRAF inhibitors. Our results reveal that pharmacological activation of STING by diABZI, down regulates NRF2-dependent anti-oxidative responses and potentiates cell-death in melanoma cells when used in combination with BRAF inhibitors.


First-principles elastic and thermal properties of TiO2: a phonon approach.
Elastic and thermal properties of the TiO(2) lattice in anatase and rutile phases were studied in the framework of density functional perturbation theory within the local density approximation (LDA) and generalized-gradient approximation (GGA). The full elastic constant tensors of the polymorphs were calculated by linear fits to the acoustic branches of the phonon band structure near the center of the first Brillouin zone in symmetry directions of the crystals. It was observed that the elastic constants within the GGA are in better agreement with experiment. In addition, the Born effective charges, dielectric tensor, heat capacity, mean sound velocity and Debye temperature were calculated. The heat capacity at room temperature and the Debye temperature within the LDA are in better agreement with the experimental results. Therefore, using the phonon band structure and the density of states, one can obtain the important mechanical and thermal properties of materials.


Minimum qualifications for clinical pharmacy practice faculty.
The American College of Clinical Pharmacy 2013 Educational Affairs Committee was charged with developing recommendations for the minimum qualifications required for clinical pharmacy practice faculty in United States colleges and schools of pharmacy with respect to education, postgraduate training, board certification, and other experiences. From a review of the literature, the committee recommends that clinical pharmacy practice faculty possess the following minimum qualifications, noting that, for some positions, additional qualifications may be necessary. Clinical pharmacy practice faculty should possess the Doctor of Pharmacy degree from an Accreditation Council for Pharmacy Education–accredited institution. In addition, faculty should have completed a postgraduate year one (PGY1) residency or possess at least 3 years of direct patient care experience. Faculty who practice in identified areas of pharmacotherapy specialization, as identified by American Society of Health-System Pharmacists postgraduate year two (PGY2) residency guidelines, should have completed a PGY2 residency in that area of specialty practice. Alternatively, faculty should have completed a minimum of a PGY1 residency and 1 additional year of practice, with at least 50% of time spent in their area of specialization, which is documented in a portfolio, or 4 years of direct patient care in their area of specialization, which is documented in a portfolio. Fellowship training or a graduate degree (e.g., Ph.D.) should be required for research-intensive clinical faculty positions. All faculty should obtain structured teaching experience during or after postgraduate training, preferably through a formal teaching certificate program or through activities documented in a teaching portfolio. A baseline record of scholarship should be obtained before hire as clinical pharmacy practice faculty through exposure in postgraduate programs or previous employment. Faculty should be board certified before hire or attain board certification within 2 years of hire through the Board of Pharmacy Specialties (BPS) or, if appropriate for the practice area, through a nonBPS-certifying agency. If no certification exists in the area of specialty, the faculty member should develop a portfolio with evidence of excellence in clinical practice, teaching, and scholarship.


[Continuous spike-wave activity during sleep. Electroencephalographic and clinical features].
Seventeen children were retrospectively evaluated. They exhibited continuous spike-wave activity during slow wave sleep (CSWS). Five of these had only speech problems and seizures (Landau-Kleffner syndrome) (group 1). The other cases had developmental milestones acquisition delay and/or mental retardation (group 2). Epileptic seizures were present in 11 of these, tetraparesis was observed in 5, hemiparesis in 2, microcephaly in 2 and behavior disturbances in 4 cases. The electroencephalogram showed in all cases diffuse CSWS. Group 1 showed diffuse activity, at times accentuated in the centrotemporal region (4/5). Group 2 had widespread discharges, including multifocal activity (5/12), sometimes with anterior predominance (7/12). We concluded that CSWS is a non specific electrographic pattern observed in some types of epilepsy in childhood that have different clinical presentation. It has however some topographic differentiation, depending upon the lesional sites.


Characterization of hepatitis C RNA-containing particles from human liver by density and size.
Hepatitis C virus (HCV) particles found in vivo are heterogeneous in density and size, but their detailed characterization has been restricted by the low titre of HCV in human serum. Previously, our group has found that HCV circulates in blood in association with very-low-density lipoprotein (VLDL). Our aim in this study was to characterize HCV RNA-containing membranes and particles in human liver by both density and size and to identify the subcellular compartment(s) where the association with VLDL occurs. HCV was purified by density using iodixanol gradients and by size using gel filtration. Both positive-strand HCV RNA (present in virus particles) and negative-strand HCV RNA (an intermediate in virus replication) were found with densities below 1.08 g ml(-1). Viral structural and non-structural proteins, host proteins ApoB, ApoE and caveolin-2, as well as cholesterol, triglyceride and phospholipids were also detected in these low density fractions. After fractionation by size with Superose gel filtration, HCV RNA and viral proteins co-fractionated with endoplasmic reticulum proteins and VLDL. Fractionation on Toyopearl, which separates particles with diameters up to 200 nm, showed that 78 % of HCV RNA from liver was >100 nm in size, with a positive-/negative-strand ratio of 6 : 1. Also, 8 % of HCV RNA was found in particles with diameters between 40 nm and 70 nm and a positive-/negative-strand ratio of 45 : 1. This HCV was associated with ApoB, ApoE and viral glycoprotein E2, similar to viral particles circulating in serum. Our results indicate that the association between HCV and VLDL occurs in the liver.


Planck spectroscopy and quantum noise of microwave beam splitters.
We use a correlation function analysis of the field quadratures to characterize both the blackbody radiation emitted by a 50 Ω load resistor and the quantum properties of two types of beam splitters in the microwave regime. To this end, we first study vacuum fluctuations as a function of frequency in a Planck spectroscopy experiment and then measure the covariance matrix of weak thermal states. Our results provide direct experimental evidence that vacuum fluctuations represent the fundamental minimum quantum noise added by a beam splitter to any given input signal.


Sphingobacterium yanglingense sp. nov., isolated from the nodule surface of soybean.
A Gram-staining-negative, non-motile, catalase- and oxidase-positive strain, designated CCNWSP36-1(T), was isolated from the nodule surface of soybean [Glycine max (L.) Merrill] cultivar Zhonghuang 13. The 16S rRNA gene sequence analysis clearly showed that the isolate represented a member of the genus Sphingobacterium. On the basis of pairwise comparisons of 16S rRNA gene sequences, strain CCNWSP36-1(T) showed 96.8% similarity to Sphingobacterium nematocida CCTCC AB 2010390(T) and less than 95.2% similarity to other members of the genus Sphingobacterium. Growth of strain CCNWSP36-1(T) occurred at 10-40 °C and at pH 5.0-9.0. The NaCl range (w/v) for growth was 0-4%. The predominant isoprenoid quinone was MK-7. The polar lipids were phosphatidylethanolamine and several unidentified polar lipids. Sphingolipid was present. The major fatty acids were iso-C(15:0) and summed feature 3 (comprising C(16:1)ω6c and/or C(16:1)ω7c). The G+C content of the genomic DNA was 41.1 mol%. As the physiological and biochemical characteristics of strain CCNWSP36-1(T) and the type strains of its closest phylogenetic neighbours showed clear differences, a novel species, Sphingobacterium yanglingense, is proposed. The type strain is CCNWSP36-1(T) ( =ACCC 19328(T) =JCM 30166(T)).


Correlation between depth perception by three-rods test and stereoacuity by distance Randot Stereotest.
The examination of depth perception with three-rods test, in addition to visual acuity testing, is required to obtain motor vehicle license to drive taxies and trucks, according to the Road Traffic Act in Japan. The aim of this study was to examine whether the results of the three-rods test would correlate with the results of static stereopsis tests, used in ophthalmic practice. This study involved 54 normal subjects, 9 women and 45 men, with ages ranging from 18 to 25 (mean, 20.8) years. All had visual acuity of 0.8 or better with or without glasses or contact lenses correction and had no strabismus at the distant (5 m) or near (0.3 m) fixation. TNO Stereotest and Titmus Stereotest were examined at 40 cm while Distance Randot Stereotest was at 3 m. At three-rods test, a central rod was moved at the speed of 50 mm/sec forward and backward automatically against two laterally located fixed rods, placed inside the illuminated box. An examinee at the distance of 2.5 m observed the rods inside the box from a small viewing window and pushed a button to stop the central rod in alignment with the fixed rods. Erred distance (mm) of the central rod from the fixed rods as a mean of 4 measurements was correlated with stereoacuity in second of arc, measured by three kinds of the stereopsis tests. The erred distance of three-rods test was positively correlated with static stereoacuity at distance measured with Distance Randot Stereotest (ρ=0.418, p=0.0023, Spearman rank correlation test) and also with the other stereopsis tests at near fixation. The stereoacuity at near fixation, measured by TNO Stereotest and Titmus Stereotest, was positively correlated with each other (ρ=0.431, p=0.0017). Three-rods test, examining depth perception, together with the response by eye-hand coordination, gave consistent results with distant static stereoacuity when measured with Distance Randot Stereotest.