Evaluation of clinical pharmacy services in a hematology/oncology outpatient setting.
The Veterans Affairs North Texas Health Care System in Dallas, TX, provides a unique opportunity for clinical pharmacists to work as providers. Even though clinical pharmacists are actively involved in patient care, many of their efforts remain undocumented, resulting in an underestimation of the importance of their services and missed opportunities for improvements and new directions. To document and evaluate the services of a hematology/oncology clinical pharmacy in the outpatient setting. Pendragon Forms 3.2 software was used to design the documentation template. The template was designed to collect diagnoses, supportive care issues, drug-specific interventions, and prescriptions written. This template was uploaded to the personal digital assistant (PDA) for documentation. Patient-specific information was documented in a password-protected PDA. Data collected from November 1, 2002, to October 31, 2003, were retrospectively analyzed. Clinical pharmacists were involved in 423 patient visits for chemotherapy follow-up or disease management. Cancer diagnoses included colorectal (n = 99), multiple myeloma (59), non-small cell lung (56), chronic lymphocytic leukemia (44), myelodysplastic syndromes (22), and chronic myelogenous leukemia (19). During the 423 patient visits, 342 supportive care issues were addressed including anemia (34%), pain management (22%), constipation/diarrhea (15%), and nausea/vomiting (8%). Major drug-specific interventions included drug addition (41%), discontinuation (23%), and adjustment (21%). Four hundred forty-five prescriptions were filled, of which 181 were new and 150 were refilled. This is the first study, as of July 25, 2006, to document considerable contribution of an outpatient clinical pharmacist in direct cancer patient care. Although the disease management and supportive care issues addressed here may differ based on institution and patient population, the results of our study show that clinical pharmacists have ever-growing roles in the management of these patients.


[The trends of ultrasound-guided neuraxial block].
Ultrasound-guided neuraxial block has provided safe and accurate analgesia. Although the classic anatomical landmark technique is still standard for completing epidural or subarachnoid puncture, it is difficult to identify the anatomical structure in some cases such as pregnant women, obese patients and patients with spinal deformity. Preparatory ultrasound scanning enables to identify the midline and determine the point of insertion, which reduces the number of puncture attempts and failure rate of procedure. Moreover, there are reports about the efficacy of ultrasound guidance in children. Usually, neuraxial block for children is performed under general anesthesia which has some risk for nerve injury and inadequate catheterization. Visualization of epidural and subarachnoid space facilitates an appropriate insertion. Additionally, the utility of ultrasound-guided lumbar puncture has also been reported in emergency department. Cerebrospinal puncture is an important procedure for diagnosis of some critical conditions such as subarachnoid hemorrhage and central nervous system infections. Ultrasound imaging contributes to smooth procedure and fewer complications. This review summarizes the basic ultrasound-guided technique for expected difficult neuraxial block patients, presenting recent findings.


[Chronic brain edema in neurocysticercosis].
In a retrospective study, we report the clinical characteristics of chronic brain oedema (CBO) in 34 patients with neurocysticercosis (NCC) who presented diffuse brain oedema upon computed tomography (CT) as a common point. All patients received dextrochlorpheniramine, and, 94.1% of them also albendazole. A predominance of females (73.5%) aged 11-40 years (92.3%) was seen. Headache occurred in 94.1% of patients, nausea/vomiting in 47.1%, epileptic manifestations in 41.1% and psychiatric disorders in 38.2%. Hyperreflexia was obtained in 82.3% of patients, papilloedema in 58.8% and normal neurological examination in 11.8%. The CT scan of the brain showed an association of oedema with calcifications in 61.8% of cases. The cerebrospinal fluid (CSF) pressure was higher before than after treatment (p < 0.05). At the last visit, 79.4% of patients were currently asymptomatic (57.1% of them without medication). It is pointed out that CBO may be an antigenic manifestation in NCC without the concomitant presence of parasitic cysts and may represent an additional clinical condition associated with benign intracranial hypertension.


[Mothers' knowledge about exclusive breastfeeding].
This is a descriptive study, with a qualitative approach, aimed to identify the knowledge of puerperal women on exclusive breastfeeding. Data were collected between September-October 2011, through semi-structured interview. Thirteen puerperal women, interned in a rooming unit of a public institution in the city of Caxias do Sul-RS, participated in the study. Data analysis was performed using thematic analysis. From the interpretation of information three categories emerged: the knowledge about exclusive breastfeeding, the breastfeeding process and the influences of received information. Even getting information from health professionals in the prenatal period, it is possible to understand that there is a need to improve communication and monitoring of mothers, as a continuity of professional care in the postpartum period, and also later, in the remote.


Maximum gene-support tree.
Genomes and genes diversify during evolution; however, it is unclear to what extent genes still retain the relationship among species. Model species for molecular phylogenetic studies include yeasts and viruses whose genomes were sequenced as well as plants that have the fossil-supported true phylogenetic trees available. In this study, we generated single gene trees of seven yeast species as well as single gene trees of nine baculovirus species using all the orthologous genes among the species compared. Homologous genes among seven known plants were used for validation of the finding. Four algorithms-maximum parsimony (MP), minimum evolution (ME), maximum likelihood (ML), and neighbor-joining (NJ)-were used. Trees were reconstructed before and after weighting the DNA and protein sequence lengths among genes. Rarely a gene can always generate the "true tree" by all the four algorithms. However, the most frequent gene tree, termed "maximum gene-support tree" (MGS tree, or WMGS tree for the weighted one), in yeasts, baculoviruses, or plants was consistently found to be the "true tree" among the species. The results provide insights into the overall degree of divergence of orthologous genes of the genomes analyzed and suggest the following: 1) The true tree relationship among the species studied is still maintained by the largest group of orthologous genes; 2) There are usually more orthologous genes with higher similarities between genetically closer species than between genetically more distant ones; and 3) The maximum gene-support tree reflects the phylogenetic relationship among species in comparison.


An integral approach to compliance.
Financial managers of managed care organizations should structure their compliance plans to conform with requirements shaped by forces such as judicial decisions and extralegal standards for managed care operations, in addition to state and Federal laws and regulations. In addition to researching the law and training employees, an integral compliance plan should include monitoring organizational systems that can encourage or impede compliance, measuring employees' motivation to adhere to compliance standards, and modifying corporate culture to support compliance goals. Managed care organizations should empower compliance officers with a broad range of tools to assess and improve compliance efforts, or risk having organizational decisions examined externally through the lens of an onerous, dynamic system of laws and judicial decisions.


An innovative experimental setup for the measurement of sputtering yield induced by keV energy ions.
An innovative experimental equipment allowing to study the sputtering induced by ion beam irradiation is presented. The sputtered particles are collected on a catcher which is analyzed in situ by Auger electron spectroscopy without breaking the ultra high vacuum (less than 10(-9) mbar), avoiding thus any problem linked to possible contamination. This method allows to measure the angular distribution of sputtering yield. It is now possible to study the sputtering of many elements such as carbon based materials. Preliminary results are presented in the case of highly oriented pyrolytic graphite and tungsten irradiated by an Ar(+) beam at 2.8 keV and 7 keV, respectively.


Self-care in adults with sickle cell disease.
This article summarizes the psychometric evaluation of the Chronic Illness Assessment Interview for Sickle Cell Disease (CIAI-SCD), an instrument based on a model of self-care for adult patients with chronic medical conditions. The CIAI-SCD was administered to 104 adults with sickle cell disease. A factor analysis identified three factors that reflected the psychological constructs of Personal Satisfaction and Perceived Control (Factor 1), Feeling Concerned and Worried (Factor 2), and Feeling Supported (Factor 3). Preliminary evidence for the internal consistency, test-retest reliability content validity, and construct validity of the CIAI-SCD was obtained. After further refinement and validation, the CIAI-SCD may be a useful tool for assessing factors related to self-care skills among adults with sickle cell disease.


High Lifetime Blast Exposure Using the Blast Exposure Threshold Survey Is Associated With Worse Warfighter Brain Health Following Mild Traumatic Brain Injury.
The purpose of this study was to extend previous research by examining the relationship between lifetime blast exposure and neurobehavioral functioning after mild TBI (MTBI) by (a) using a comprehensive measure of lifetime blast exposure, and (b) controlling for the influence of post-traumatic stress disorder (PTSD). Participants were 103 United States service members and veterans (SMVs) with a medically documented diagnosis of MTBI, recruited from three military treatment facilities (74.8%) and community-based recruitment initiatives (25.2%, e.g., social media, flyers). Participants completed a battery of neurobehavioral measures 12 or more months post-injury (Neurobehavioral Symptom Inventory, PTSD-Checklist PCLC, TBI-Quality of Life), including the Blast Exposure Threshold Survey (BETS). The sample was classified into two lifetime blast exposure (LBE) groups: High (n = 57) and Low (n = 46) LBE. In addition, the sample was classified into four LBE/PTSD subgroups: High PTSD/High LBE (n = 38); High PTSD/Low LBE (n = 19); Low PTSD/High LBE (n = 19); and Low PTSD/Low LBE (n = 27). The High LBE group had consistently worse scores on all neurobehavioral measures compared with the Low LBE group. When controlling for the influence of PTSD (using ANCOVA), however, only a handful of group differences remained. When comparing measures across the four LBE/PTSD subgroups, in the absence of clinically meaningful PTSD symptoms (i.e., Low PTSD), participants with High LBE had worse scores on the majority of neurobehavioral measures (e.g., post-concussion symptoms, sleep, fatigue). When examining the total number of clinically elevated measures, the High LBE subgroup consistently had a greater number of clinically elevated scores compared with the Low LBE subgroup for the majority of comparisons (i.e., four to 15 or more elevated symptoms). In contrast, in the presence of clinically meaningful PTSD symptoms (i.e., High PTSD), there were no differences between High versus Low LBE subgroups for all measures. When examining the total number of clinically elevated measures, however, there were meaningful differences between High versus Low LBE subgroups for those comparisons that included a high number of clinically elevated scores (i.e., six to 10 or more), but not for a low number of clinically elevated scores (i.e., one to five or more). High LBE, as quantified using a more comprehensive measure than utilized in past research (i.e., BETS), was associated with worse overall neurobehavioral functioning after MTBI. This study extends existing literature showing that lifetime blast exposure, that is largely subconcussive, may negatively impact warfighter brain health and readiness beyond diagnosable brain injury.


Congenital hyperinsulinism and mosaic abnormalities of the ploidy.
Congenital hyperinsulinism and Beckwith-Wiedemann syndrome both lead to beta islet hyperplasia and neonatal hypoglycaemia. They may be related to complex genetic/epigenetic abnormalities of the imprinted 11p15 region. The possibility of common pathophysiological determinants has not been thoroughly investigated. To report abnormalities of the ploidy in two unrelated patients with congenital hyperinsulinism. Two patients with severe congenital hyperinsulinism, one overlapping with Beckwith-Wiedemann syndrome, had pancreatic histology, ex vivo potassium channel electrophysiological studies, and mutation detection of the encoding genes. The parental genetic contribution was explored using genome-wide polymorphism, fluorescent in situ hybridisation (FISH), and blood group typing studies. Histological findings diverged from those described in focal congenital hyperinsulinism or Beckwith-Wiedemann syndrome. No potassium channel dysfunction and no mutation of its encoding genes (SUR1, KIR6.2) were detected. In patient 1 with congenital hyperinsulinism and Beckwith-Wiedemann syndrome, paternal isodisomy for the whole haploid set was homogeneous in the pancreatic lesion, and mosaic in the leucocytes and skin fibroblasts (hemihypertrophic segment). Blood group typing confirmed the presence of two erythroid populations (bi-parental v paternal only contribution). Patient 2 had two pancreatic lesions, both revealing triploidy with paternal heterodisomy. Karyotype and FISH analyses done on the fibroblasts and leucocytes of both patients were unremarkable (diploidy). Diploid (biparental/paternal-only) mosaicism and diploid/triploid mosaicism were present in two distinct patients with congenital hyperinsulinism. These chromosomal abnormalities led to paternal disomy for the whole haploid set in pancreatic lesions (with isodisomy or heterodisomy), thereby extending the range and complexity of the mechanisms underlying congenital hyperinsulinism, associated or not with Beckwith-Wiedemann syndrome.


Photooxidation of 2,4-dichlorophenoxyacetic acid by ferrous oxalate-mediated system.
The photodegradation of a herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) by ferrous oxalate/UV/H2O2 was studied. Ferrous oxalate, the more photoactive and reactive species, was found to react faster with hydrogen peroxide for hydroxyl radical production than ferrous ions under UV irradiation. About 2.9 times greater rate enhancement was found with the addition of 0.3 mM oxalate than that of a solution containing 0.1 mM Fe2+ and 1 mM H2O2 in the presence of UV light at 253.7 nm. The kinetics dependence of hydrogen peroxide concentration and initial solution pH were also investigated. A threefold increase in peroxide concentration could accelerate the removal of 2,4-D and nearly complete the reaction in 30 min of illumination. The initial decay rate of 2,4-D treated by ferrous oxalate/UV/H2O2 accelerated from 0.0029 to 0.0034 s(-1) and the overall removal of the starting material increased from 78% to 99.9%. The 2,4-D transformation at lower initial pH had higher reaction rates than that at higher pH and different reaction mechanisms were identified. The efficiency of the herbicide decomposition was retarded 2.6 times and 9.6 times as initial pH increased from 2.8 to 5.1 and 9.0, respectively.


A phase III study of surgical resection and paclitaxel/carboplatin chemotherapy with or without adjuvant radiation therapy for resected stage III non-small-cell lung cancer: Cancer and Leukemia Group B 9734.
Patients with completely resected stage IIIA (N2) non-small-cell lung cancer (NSCLC) are at substantial risk for locoregional and systemic recurrence. Adjuvant chemotherapy has recently improved overall control for these patients. We added adjuvant chemotherapy to control presumed micrometastatic disease and then randomized patients to receive radiation therapy (RT) or observation to determine the benefit of local radiation consolidation. Patient eligibility required histologically documented stage IIIA (radiographically occult N2) NSCLC that was completely resected, with no known residual disease, surgical staging per protocol requirements, Cancer and Leukemia Group B performance status of 0/1, no previous chemotherapy or RT, and minimal laboratory values. All eligible patients received 4 cycles of paclitaxel 200 mg/m2 over 3 hours with carboplatin at an area under the curve of 6 on days 1, 22, 43, and 64 beginning 4-8 weeks after surgery. Two to 4 weeks after chemotherapy, patients were randomized to receive RT as 5000 cGy in 25 fractions over 5 weeks or observation. The study closed after 2 years because of slow accrual. Forty-four patients entered the study; 2 were ineligible, and 5 were not randomized because of progression, adverse reaction, or patient withdrawal. Thirty-seven patients were the basis of this analysis. Median failure-free survival was 16.8 months on the observation arm and 33.7 months on the RT arm, with a 1-year survival rate of 72% on the observation arm and 74% on the RT arm. There were no statistical differences between the observation and RT arms for failure-free survival or overall survival. In this small study, consolidation RT after complete resection and adjuvant chemotherapy in stage IIIA NSCLC did not significantly improve outcome for this high-risk population.


Trends in Locoregional Therapy in Older Women with Early-Stage Hormone Receptor-Positive Breast Cancer by Frailty and Life Expectancy.
In women ≥ 70 years of age with T1N0 hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, breast surgery type and omission of axillary surgery or radiation therapy (RT) do not impact overall survival. Although frailty and life expectancy ideally factor into therapy decisions, their impact on therapy receipt is unclear. We sought to identify trends in and factors associated with locoregional therapy type by frailty and life expectancy. Women ≥ 70 years of age with T1N0 HR+/HER2- breast cancer diagnosed in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 2010 and 2015 were stratified by validated claims-based frailty and life expectancy measures. Therapy trends over time by regimen intensity ('high intensity': lumpectomy + axillary surgery + RT, or mastectomy + axillary surgery; 'moderate intensity': lumpectomy + RT, lumpectomy + axillary surgery, or mastectomy only; or 'low intensity': lumpectomy only) were analyzed. Factors associated with therapy type were identified using generalized linear mixed models. Of 16,188 women, 21.8% were frail, 22.2% had a life expectancy < 5 years, and only 12.3% fulfilled both criteria. In frail women with a life expectancy < 5 years, high-intensity regimens decreased significantly (48.8-31.2%; p < 0.001) over the study period, although in 2015, 30% still received a high-intensity regimen. In adjusted analyses, frailty and life expectancy < 5 years were not associated with breast surgery type but were associated with a lower likelihood of axillary surgery (frailty: odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76-0.96; life expectancy < 5 years: OR 0.22, 95% CI 0.20-0.25). Life expectancy < 5 years was also associated with a lower likelihood of RT receipt in breast-conserving surgery patients (OR 0.30, 95% CI 0.27-0.34). Rates of high-intensity therapy are decreasing but overtreatment persists in this population. Continued efforts aimed at appropriate de-escalation of locoregional therapy are needed.


The Hormonal Fingerprints and BMI: Implications for Risk Factors in Dental Caries and Malocclusion.
The hormonal fingerprint is the ratio between 2(nd) and 4(th) digit lengths. It was evidenced in the medical scenario that it can be used as an indirect marker in many diseases like Coronary Heart Disease (CHD) and metabolic syndromes. As far as dentistry is concerned very few studies in the literature have been done to evaluate the influence of hormonal fingerprint on oral health, thus provoking us to formulate new method for predicting dental caries and malocclusion and its association with Body Mass Index (BMI). The purpose of this retrospective study was to highlight the role of new biological marker-Hormonal fingerprints in the early detection of malocclusion, caries, the influence of BMI on malocclusion and caries. We also attempted to study the correlation of BMI with hormonal fingerprints. A total of 300 children were randomly selected from both sexes of age group 10-15 years. The hormonal fingerprint was made by measuring the length ratio of the index and ring finger with the help of digital Vernier caliper. Anthropometric measures (weight in kilograms and height in metres) for the calculation of BMI were recorded. Caries assessment was done using standard mouth mirrors and Community Periodontal Index probes. DMFT index was followed for assessment of caries according to the WHO assessment form, 1997. Occlusal characteristics of the children evaluated were molar relation, anterior and posterior cross bite, open bite, deep bite, lower anterior crowding. All the factors were recorded by two investigators. The results of the study showed that majority of the children among study population were having 2D:4D <1. The rate of occurrence of malocclusion was increasing with increase in the value of 2D:4D ratio with a statistically significant p-value of <0.001. Higher BMI values were associated with normal occlusal conditions (p= 0.041) and lower 2D:4D ratio (p= 0.037). High caries experience was noticed in children with malocclusion (p= 0.027) which further influences the caries susceptibility. Pearson's correlation test, t-test and ANOVA were used in the study for statistical analysis using SPSS software. This study confirms the impact of hormones on incidence of malocclusion, BMI which in turn influences the caries index and could be used as an early predictor.


A review of the Malaria Eradication Programme in the Solomon Islands 1975-1976.
The review outlines the developments in the Solomon Islands Malaria Eradication Programme (MEP) during the period 1975 - 1976. In most of the islands of the Solomons group MEP continues to be successful, but overall progress is hindered by persistent foci in areas of high malaria endemicity in north Guadalcanal. Some changes in the operational methodology are described, together with a report on supplementary measures carried out in the 'problem area' of north Guadalcanal.


Costs of treating and preventing nausea and vomiting in patients receiving chemotherapy.
To evaluate the effect of ondansetron availability on the costs of managing nausea and vomiting. We retrospectively assessed antiemetic costs (drug costs, nursing time, pharmacy time, physician's time, supplies, and facility "hotel" costs, in 1991 Canadian dollars) for all patients who received moderately or highly emetogenic chemotherapy from 6 months before to 6 months after ondansetron became commercially available in September 1991. We compared the costs for treating patients who received ondansetron versus those who received other antiemetic regimens, the costs for treating patients in the 6 months before versus the 6 months after ondansetron commercial availability, and the costs for treating patients in the first 4 months versus the last 4 months of the study period. We found no cost differences for patients treated with ondansetron versus other antiemetic regimens. However, there was a significant reduction in emesis management costs for patients treated after versus before the availability of ondansetron: for patients treated in the last third versus first third of the study period, there was a decrease in cost per patient per month of treatment of $374 (95% confidence interval, $243 to $505). These savings were achieved through a reduction in hospital bed days and other costs associated with the prevention and more effective management of nausea and vomiting. At the same time, the number of patients who received emetogenic chemotherapy and their average age increased, presumably because of the better control of gastrointestinal toxicity. Ondansetron availability has been associated with changes in the clinical management of cancer patients receiving chemotherapy and with overall cost savings compared with previously available antiemetic therapy.


β-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes.
Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters were derived from established mathematical models yielding β-cell glucose sensitivity (βCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT-βCGS to the 2-h hyperglycemic clamp-βCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, βCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia.


Pediatric Ingestions: Emergency Department Management.
Pediatric ingestions present a common challenge for emergency clinicians. Each year, more than 50,000 children aged less than 5 years present to emergency departments with concern for unintentional medication exposure, and nearly half of all calls to poison centers are for children aged less than 6 years. Ingestion of magnetic objects and button batteries has also become an increasing source of morbidity and mortality. Although fatal pediatric ingestions are rare, the prescription medications most responsible for injury and fatality in children include opioids, sedative/hypnotics, and cardiovascular drugs. Evidence regarding the evaluation and management of common pediatric ingestions is comprised largely of case reports and retrospective studies. This issue provides a review of these studies as well as consensus guidelines addressing the initial resuscitation, diagnosis, and treatment of common pediatric ingestions. Also discussed are current recommendations for decontamination, administration of antidotes for specific toxins, and management of ingested foreign bodies.


[Evaluation of the consultants to a urology service at hospital level].
The main objectives of this study were to value the quality of the contained information, the characteristics of the consultants (IC) and as well as to know the performance carried out by the service of Urology in our hospital. It was carried out an observational descriptive study where the documents of IC picked up by the service of Urology during 8 months were analyzed. Previously defined approaches of quality were used by Irazábal et al (changed) and Batista Miranda JE et al. They were picked up a total of 411 IC, arrivals to the service in a serial way. Coming from 27 hospital services. 82.2% of the derivatived patients were male. The half age of the patients was of 63, 25 years. 192 patients had personal urological records of interest (47%). The IC grouped in 27 different reasons. The reason of more frequent consultation was the incidentaloma with 21.5%. Regarding the grade of execution of the document of IC: there was perseverance of filiation data (96.3%), a description of the symptoms was in 68.2% and the physical examination appeared reflected in 8.8% of the total of the IC. They were requested as normal IC 63.4%, preferent 25% and urgent 11.7%. The days of answer to the IC it was of stocking of 1,45 days with typical deviation of 1,65 days. According to the established approaches, to classify the documents for adaptation level, they were classified as inappropriate to 32.9% of the IC (n = 135). They were classified in grade 1 the 44.6% (n = 183), grade 2 20% (n = 82) and grade 3 2.4% (n = 10). The attitude that was taken: it was remitted to External Consultations of Urology to 10.5% of the total of the IC, to the Center of Specialized Attention to 7.8%, it was requested complementary tests to 7.8%, it was remitted to the functional Tests of Urology, for the realization of some complementary test to 61 patients (14.9%), it was presented in Clinical Session of Urology to 5,6% of the patients, he/she moved to the Service of Urology to 2 patients (0.5%) and he/she took some other therapeutic attitude in 19.6%, these results had a p = 0.000 significance. In our study, we observe a high percentage as for the perseverance of the data of lightly inferior filiation in the description of the symptoms and considered low in the physical exploration. A high percentage of inappropriate considered IC. Regarding the attitude that took the Service of Urology, maybe had a low used of the Functional Unit. Until the moment and under our knowledge a study carried out in the environment from the realized IC to the Service of Urology in a Hospital of third level only exists and we believe that the realization of studies would improve the quality from the attendance to our patients.


Repetition priming effects for famous faces through dynamic causal modelling of latency-corrected event-related brain potentials.
Repetition priming, that is, the repeated processing of a stimulus, facilitates performance. However, the neural underpinnings of repetition priming for famous faces in terms of effective connectivity are not known. Here we investigated this problem using dynamic causal modelling of latency-corrected event-related brain potentials (RERPs). Source waveforms of RERP-derived sources in the Occipital Lobe, Fusiform Gyrus, Mediotemporal Lobe, Prefrontal Cortex and Anterotemporal Lobe of each hemisphere entered into models with only forward (F) or also with backward (FB) connections. Based on the framework of predictive coding formulated for repetition suppression, modulations of F and FB connections were expected for sources that displayed priming effects in their source waveforms. Hence, neural sources in each hemisphere were fitted with either F or FB connections. Inter-hemispheric connections were considered between homologous areas and were allowed to be modulated in an incremental manner resulting in a model space that comprised of 24 models. Bayesian model averaging across models revealed effective bidirectional connectivity between the Fusiform Gyrus (face perception) and Prefrontal Cortex (decision-making) in both hemispheres to be modulated by priming. In the left hemisphere, there is also a substantial involvement from the Mediotemporal Lobe, indicating the facilitation of automatic retrieval of the famous person's name. Furthermore, there is evidence that the priming is supported by connections from the right to the left Fusiform Gyri possibly in the service of inter-hemispheric cooperation. Altogether, the study indicates that along with top-down modulations, efficient processing within and across the two hemispheres is crucial for famous face priming.


Transport through graphene on SrTiO3.
We report transport measurements through graphene on SrTiO(3) substrates as a function of magnetic field B, carrier density n, and temperature T. The large dielectric constant of SrTiO(3) very effectively screens long-range electron-electron interactions and potential fluctuations, making Dirac electrons in graphene virtually noninteracting. The absence of interactions results in an unexpected behavior of the longitudinal resistance in the N=0 Landau level and in a large suppression of the transport gap in nanoribbons. The "bulk" transport properties of graphene at B=0 T, on the contrary, are completely unaffected by the substrate dielectric constant.


Mouse Models for HTLV-1 Infection and Adult T Cell Leukemia.
Adult T cell leukemia (ATL) is an aggressive hematologic disease caused by human T cell leukemia virus type 1 (HTLV-1) infection. Various animal models of HTLV-1 infection/ATL have been established to elucidate the pathogenesis of ATL and develop appropriate treatments. For analyses employing murine models, transgenic and immunodeficient mice are used because of the low infectivity of HTLV-1 in mice. Each mouse model has different characteristics that must be considered before use for different HTLV-1 research purposes. HTLV-1 Tax and HBZ transgenic mice spontaneously develop tumors, and the roles of both Tax and HBZ in cell transformation and tumor growth have been established. Severely immunodeficient mice were able to be engrafted with ATL cell lines and have been used in preclinical studies of candidate molecules for the treatment of ATL. HTLV-1-infected humanized mice with an established human immune system are a suitable model to characterize cells in the early stages of HTLV-1 infection. This review outlines the characteristics of mouse models of HTLV-1 infection/ATL and describes progress made in elucidating the pathogenesis of ATL and developing related therapies using these mice.


[Intracranial hypertension in the acute stage of a stroke (spinal fluid dynamic and computer-tomographic studies)].
The given study aimed to answer the question about the realization in clinical practice of the possibility of the timely identification of the degree of intracranial hypertension in patients with cerebral stroke under continuous monitoring of the intracranial volume/pressure ratios by means of examination of CSF changes and CT of the head. On the basis of an analysis of the interrelationship between the severity of neurologic deficit, findings of CT of the head and the results of examination of the cerebral hemodynamics the authors evaluated the informativeness of the main parameters of monitoring the intracranial volume/pressure ratios in the acute stage of cerebral stroke. It has been found that only prolonged registration of the mean and pulse pressure of the CSF in combination with "testing the reserve of the intracranial volume" may ensure the timely detection of disorders of the homeostasis of the craniospinal reservoir and the selection of the most effective means of their correction.


Intermediate trophoblast: further immunocytochemical characterization.
Intermediate trophoblast has been recently described as a distinctive subpopulation of trophoblast. Previous immunocytochemical studies demonstrated that these cells react with antibodies against human placental lactogen (hPL) but fail to react with antibodies against beta-human chorionic gonadotropin (beta-hCG). To further characterize the immunocytochemical features of intermediate trophoblast and to possibly identify a more sensitive marker, we studied 88 placentas and implantation sites ranging from 4 to 40 wk gestation with a panel of antibodies that included keratin, epithelial membrane antigen (EMA), placental alkaline phosphatase (PLAP), alpha-hCG, and prolactin. Keratin was found in all intermediate trophoblast cells throughout gestation, and EMA was present in intermediate trophoblast in the second and third trimesters but was less consistently expressed than keratin. Comparison with the distribution of hPL revealed that keratin and EMA were present in intermediate trophoblast cells that were hPL-positive as well as many that were hPL-negative. alpha-hCG showed reactivity in intermediate trophoblast in the first and second trimester. PLAP and prolactin showed little or no reactivity in intermediate trophoblast. Decidual cells, which may be difficult to distinguish from intermediate trophoblast at the implantation site, failed to react with any of the antibodies tested. Cytotrophoblast and syncytiotrophoblast were positive for keratin throughout gestation, but EMA was negative in cytotrophoblast and inconsistently expressed in syncytiotrophoblast. Thus, antibodies against keratin and EMA are more sensitive than those directed against hPL in identifying intermediate trophoblast and are therefore useful in distinguishing intermediate trophoblast from decidua.


The Prognostic Value of Estrogen Receptor β Isoform With Correlation of Estrogen Receptor α Among Sudanese Breast Cancer Patients.
Two estrogen receptor isoforms (ERα and ERβ) have been characterized with variable and sometimes contrasting responses to estrogens, partially explained by different receptor signaling pathways in estrogen-sensitive tissues. This is a retrospective, descriptive, cross-sectional study, aiming to evaluate the expression pattern of ERβ, employing immunohistochemical techniques using specific monoclonal antibody for ERβ, to correlate its expression with that of ERα in a Sudanese population. Two-hundred and fifty formalin-fixed paraffin-wax-embedded breast tissue blocks were used in this study. Of these, 200 were taken from breast cancer patients ascertained as study cases, and the remaining 50 were noninvolved surgical margin considered as normal breast tissue. Receptor expression was demonstrated using immunohistochemical techniques. The immune expression of ERβ was detected in 57.5% of breast cancers. It was differentially expressed in breast tissues encompassing normal, noninvasive, as well as invasive carcinoma (P = .02). There was no evidence of a significant relationship between ERβ and ERα expression. Among the ERα-negative tumor, 60.4% expressed ERβ. The expression of ERβ among this subgroup was significantly associated with good clinicopathological parameters such as negative Her2/neu, lower grade, and negative lymph node metastasis (P = .002). This study concludes that ERβ was commonly expressed among Sudanese patients with breast cancer, either co-expressed with ERα or expressed alone. In the ERα-negative subgroup, it was associated with better tumor outcomes suggesting ERβ should be included in the diagnostic protocol as an independent marker for favorable prognosis.


Perfusate Proteomes Provide Biological Insight Into Oxygenated Versus Standard Hypothermic Machine Perfusion in Kidney Transplantation.
To provide mechanistic insight into key biological alterations in donation after circulatory death kidneys during continuous pefusion we performed mass spectrometry profiling of perfusate samples collected during a phase 3 randomized double-blind paired clinical trial of hypothermic machine perfusion with and without oxygen (COMPARE). Despite the clinical benefits of novel perfusion technologies aiming to better preserve donor organs, biological processes that may be altered during perfusion have remained largely unexplored. The collection of serial perfusate samples during the COMPARE clinical trial provided a unique resource to study perfusate proteomic profiles, with the hypothesis that in-depth profiling may reveal biologically meaningful information on how donor kidneys benefit from this intervention. Multiplexed liquid chromatography-tandem mass spectrometry was used to obtain a proteome profile of 210 perfusate samples. Partial least squares discriminant analysis and multivariate analysis involving clinical and perfusion parameters were used to identify associations between profiles and clinical outcomes. Identification and quantitation of 1716 proteins indicated that proteins released during perfusion originate from the kidney tissue and blood, with blood-based proteins being the majority. Data show that the overall hypothermic machine perfusion duration is associated with increasing levels of a subgroup of proteins. Notably, high-density lipoprotein and complement cascade proteins are associated with 12-month outcomes, and blood-derived proteins are enriched in the perfusate of kidneys that developed acute rejection. Perfusate profiling by mass spectrometry was informative and revealed proteomic changes that are biologically meaningful and, in part, explain the clinical observations of the COMPARE trial.


Disturbed development of the preimplantation embryo in the insulin-dependent diabetic BB/E rat.
Although improved regulation of maternal IDDM during pregnancy has resulted in a major fall in the stillbirth rate, the rates for other problems, such as spontaneous preterm labor, fetuses small for gestational age, congenital malformation, and the incidence of large placentas, remain raised. This has suggested the possibility that the damaging effect of conventionally treated but poorly regulated IDDM may operate primarily at the earliest stages of gestation, even before the diagnosis of pregnancy has been made. This study shows that spontaneous autoimmune IDDM in the Bio Breeding/Edinburgh (BB/E) rat is associated with severe disturbance in the development of the preimplantation embryo in a majority of pregnancies, as indicated by a fivefold increase in the incidence of degenerate fragmented embryos and a 33% reduction in the number of expanded blastocysts and in those blastocysts that reach the expanded stage a 20% cellular deficit in the inner-cell mass without any change in trophectoderm cell number. In addition, we find that blastocysts removed from diabetic rats and cultured in vitro for 24 h show no sign of "catch-up" growth of the inner-cell mass, although under these conditions, the trophectoderm exhibits a 25% cellular accretion. It is tempting to speculate that these phenomena are a presage of the characteristic combination of fetal growth retardation and large placentas, which are a feature of both BB/E rat and human IDDM pregnancy.


IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV-coinfected patients.
Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate(®) assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n = 65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P = 0.024), as well as the subgroups of patients with significant fibrosis (P = 0.047) and infected with HCV genotype 3 (P = 0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR) = 2.02; P = 0.034), in patients with significant fibrosis (aOR = 2.86; P = 0.039) and HCV genotype 3 patients (aOR = 4.89; P = 0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.


The Physician Quality Improvement Initiative: Engaging Physicians in Quality Improvement, Patient Safety, Accountability and their Provision of High-Quality Patient Care.
University Health Network has been working to become a high-reliability organization, with a focus on safe, quality patient care. In response, the Medical Affairs Department has implemented several strategic initiatives to drive accountability, quality improvement and engagement with our physician population. One of these initiatives, the Physician Quality Improvement Initiative (PQII) is a physician-led project designed to provide active medical staff, in collaboration with their physician department chiefs, a comprehensive approach to focused and practical quality improvement in their practice. In this document, we outline the project, including its implementation strategy, logic model and outcomes, and provide discussion on how it fits into UHN's global strategy to provide safe, quality patient care.


Adaptive Sampling Methods for Molecular Dynamics in the Era of Machine Learning.
Molecular dynamics (MD) simulations are fundamental computational tools for the study of proteins and their free energy landscapes. However, sampling protein conformational changes through MD simulations is challenging due to the relatively long time scales of these processes. Many enhanced sampling approaches have emerged to tackle this problem, including biased sampling and path-sampling methods. In this Perspective, we focus on adaptive sampling algorithms. These techniques differ from other approaches because the thermodynamic ensemble is preserved and the sampling is enhanced solely by restarting MD trajectories at particularly chosen seeds rather than introducing biasing forces. We begin our treatment with an overview of theoretically transparent methods, where we discuss principles and guidelines for adaptive sampling. Then, we present a brief summary of select methods that have been applied to realistic systems in the past. Finally, we discuss recent advances in adaptive sampling methodology powered by deep learning techniques, as well as their shortcomings.


A noise-robust data assimilation method for crystal structure determination using powder diffraction intensity.
Crystal structure prediction for a given chemical composition has long been a challenge in condensed-matter science. We have recently shown that experimental powder x-ray diffraction (XRD) data are helpful in a crystal structure search using simulated annealing, even when they are insufficient for structure determination by themselves [Tsujimoto et al., Phys. Rev. Mater. 2, 053801 (2018)]. In the method, the XRD data are assimilated into the simulation by adding a penalty function to the physical potential energy, where a crystallinity-type penalty function, defined by the difference between experimental and simulated diffraction angles was used. To improve the success rate and noise robustness, we introduce a correlation-coefficient-type penalty function adaptable to XRD data with significant experimental noise. We apply the new penalty function to SiO2 coesite and ɛ-Zn(OH)2 to determine its effectiveness in the data assimilation method.


Recent advances in the treatment of thromboembolic diseases: venous thromboembolism.
Venous thromboembolic diseases are the major concern of rising cost of healthcare and are commonest health problem across the globe. Both genetic and acquired risk factors are believed to be strongly linked with these diseases. Commonly encountered problems to the therapy include dose fixing and routine monitoring, yet some serious problems of bleeding also necessitate the immediate need to develop new agents. The review is primarily concerned with the new developments in the treatment of thromboembolic diseases. Therapeutic applications of anticoagulants, antiplatelets, and thrombolytics have been discussed in enough detail.


Isolated optic nerve sarcoidosis.
Objective: To report three cases of sarcoidosis confined to the optic nerve. Methods: Chart review of clinical, laboratory, imaging, and optic nerve biopsy findings and a review of the literature. Results: All three cases presented with progressive visual loss and showed enhancement of the intraorbital optic nerve on magnetic resonance imaging. There was no evidence for systemic disease, including a negative workup for sarcoidosis or other infiltrative pathologies. Optic nerve biopsy in each case showed non-caseating granulomas consistent with sarcoidosis. Conclusions: Sarcoidosis confined to the optic nerve is a rare phenomenon but should still be considered in the differential diagnosis of progressive optic neuropathy, even in the absence of systemic disease. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 179-183).


Mobile Technology Application for Improved Urine Concentration Measurement Pilot Study.
Objectives: Low hydration has a deleterious effect on many conditions. In the absence of a urine concentrating defect, urine concentration is a marker of hydration status. However, markers to evaluate hydration status have not been well studied in children. The objectives of this paper are to compare measures of thirst and urine concentration in children and to develop a novel mobile technology application to measure urine concentration. Study Design: Children age 12-17 years were selected (n = 21) for this pilot study. Thirst perception, specific gravity (automated dipstick analysis and refractometer), and urine color scale results were correlated to urine osmolality. The technology department developed a mobile technology camera application to measure light penetrance into urine which was tested on 25 random anonymized urine samples. Results: The patients' thirst perception and color scale as well as two researchers color scale did not significantly correlate with osmolality. Correlation between osmolality and hydration markers resulted in the following Pearson coefficients: SG automated dipstick, 0.61 (P 0.003); SG refractometer, 0.98 (P < 0.0001); urine color scale (patient), 0.37 (P 0.10), and light penetrance, -0.77 (P < 0.0001). The correlation of light penetrance with osmolality was stronger than all measures except SG by refractometer and osmolality. Conclusion: The mobile technology application may be a more accurate tool for urine concentration measurement than specific gravity by automated dipstick, subjective thirst, and urine color scale, but lags behind specific gravity measured by refractometer. The mobile technology application is a step toward patient oriented hydration strategies.


[Experimental evaluation of the bacteriotoxic phototherapy of inflammatory diseases of the oral cavity].
The combined use of laser radiation and Radachlorine revealed the presence of correlation between the number of viable Streptococcus pyogenes cells and the concentration of photosensitizer (r=-0.62), time of irradiation (r=-0.75), as well as energy density (r=-0.80). The death of 100% of suspended S. pyogenes cells was observed at the concentration of Radachlorine reaching 14.4 mM and radiation power reaching 1 W, irrespective of energy density. Pulse and superpulse laser radiation, carried out simultaneously with the use of Radachlorine at a concentration of 1.8 microM, resulted in the death of 100% of S. pyogenes cells in vitro. On the experimental model of inflammation the application of 0.1% Radachlorine gel demonstrated higher effectiveness (in comparison with 0.35% Radachlorine solution) when used simultaneously with laser radiation, both continuous and superpulse (with energy density being 400 j/cm2 and power being 1 W). The use of these parameters in the treatment of the experimental foci of inflammation in the animals led to the complete elimination of S. pyogenes from infected tissues.


Emo-regulator: An emotion-regulation training system fusing virtual reality and EEG-based neurofeedback.
Good emotion-regulation ability (ERA) is a vital sign of psychological health; conversely, emotion dysregulation may lead to mental or neurological disorders, such as anxiety disorders and depression. This study developed an emotion-regulation training system, Emo-regulator, fusing virtual reality (VR) and EEG-based neurofeedback to enhance subjects' ability to down-regulate negative emotions. Emo-regulator first elicited negative emotions in subjects through VR scenarios and then asked them to regulate emotions using cognitive reappraisal to change the emotional responses elicited by the VRs. Meanwhile, EEG signals from the subjects were collected and analyzed in real time by machine learning to predict the emotional states of the subjects (negative or positive). Emo-regulator changed the VR scenarios according to the prediction results and completed the feedback. Eight subjects used Emo-regulator for two weeks, and the results showed it could help the subjects improve their emotion regulation, and its usability is above average.Clinical Relevance-Emo-regulator can help subjects improve their ability to down-regulate negative emotions and increase the frequency of cognitive reappraisal use during emotion regulation.


Thermoregulation and the menstrual cycle.
Four women, aged 20-35 years, exercised at approximately 30% VO2 max in three environments (28 degrees C, 12.6 torr vp; 35 degrees C, 28.0 torr vp; 48 degrees C, 8.7 torr vp) during three stages at the menstrual cycle: ovulation, luteal phase, and flow. Cycle phase was confirmed by hormone analysis for estradiol-17B and progesterone in venous blood samples. Although pre-exposure care temperature and oxygen uptake were higher in the luteal phase, these differences disappeared under the combined influence of exercise and heat stress. Exercise heart rate, care temperature, and sweat rate were similar in all cycle phases. Oxygen uptake, ventilatory volume, cardiac output, stroke volume, blood electrolytes, blood pressure, body weight, and tolerance time were unaffected by cycle phase. In the 28 degrees C environment, mean skin temperature and forearm blood flow were lower in the luteal phase than during flow, but this difference was not observed in 35 degrees C or 48 degrees C. A greater relative decrease in plasma volume was observed in the luteal phase following exercise in 48 degrees C than during flow. However, the overall response of women to exercise and heat stress during three phases of the menstrual cycle suggest that minor cyclic alterations in physiological systems apparent at rest are masked by the demands of the activity and the environment.


A Quality Improvement Bundle to Improve Outcomes in Extremely Preterm Infants in the First Week.
Our objective with this quality improvement initiative was to reduce rates of severe intracranial hemorrhage (ICH) or death in the first week after birth among extremely preterm infants. The quality improvement initiative was conducted from April 2014 to September 2020 at the University of Alabama at Birmingham's NICU. All actively treated inborn extremely preterm infants without congenital anomalies from 22 + 0/7 to 27 + 6/7 weeks' gestation with a birth weight ≥400 g were included. The primary outcome was severe ICH or death in the first 7 days after birth. Balancing measures included rates of acute kidney injury and spontaneous intestinal perforation. Outcome and process measure data were analyzed by using p-charts. We studied 820 infants with a mean gestational age of 25 + 3/7 weeks and median birth weight of 744 g. The rate of severe ICH or death in the first week after birth decreased from the baseline rate of 27.4% to 15.0%. The rate of severe ICH decreased from a baseline rate of 16.4% to 10.0%. Special cause variation in the rate of severe ICH or death in the first week after birth was observed corresponding with improvement in carbon dioxide and pH targeting, compliance with delayed cord clamping, and expanded use of indomethacin prophylaxis. Implementation of a bundle of evidence-based potentially better practices by using specific electronic order sets was associated with a lower rate of severe ICH or death in the first week among extremely preterm infants.


Ethanol stimulates [3H]5-HT high-affinity uptake by rat forebrain synaptosomes: role of 5-HT receptors and voltage channel blockers.
We examined ethanol's interactions with serotonin (5-HT) receptor-mediated [3H]5-HT high-affinity uptake by adult rat forebrain synaptosomes. The serotonergic transport mechanism was chosen because ethanol consumption patterns can be manipulated by serotonin receptors and uptake blockers. We report that a dose of ethanol which causes general anesthesia in humans (54 mM) applied in vitro enhanced rat synaptosomal [3H]5-HT uptake after 5 min at 37 degrees C. Similar levels of stimulation by 54 mM ethanol were seen in hippocampal, cerebral cortex and brainstem synaptosomes. Significant inhibition of uptake was not detected until concentrations of ethanol reached 2.1 M, which is lethal in vivo. Ryanodine and the 5-HT2 agonist, DOI, are believed to cause an increase in intracellular Ca2+ levels. We observed that they also caused an elevation of [3H]5-HT uptake, and this stimulation was less than additive with the ethanol-induced increase. Inhibition of the 5-HT3, receptor-mediated Na+ channel with the antagonist ICS 205930, partially reversed ethanol's stimulatory effects on [3H]5-HT uptake. Blockade of voltage-dependent Na+ flux with tetrodotoxin and lidocaine, however, had no effect on the stimulation by ethanol. But tetraethylammonium, which blocks voltage-dependent K+ channels, partially counteracted ethanol's action on [3H]5-HT uptake. These compounds had no effect on uptake by themselves. These results indicate that ethanol's stimulation of [3H]5-HT uptake involves a rise in [Ca2+]i which is sensitive to voltage-dependent K+ flux and 5-HT3 receptor-mediated Na+ flux, and would decrease the availability of synaptic 5-HT.


Multilayer Aggregation with Statistical Validation: Application to Investor Networks.
Multilayer networks are attracting growing attention in many fields, including finance. In this paper, we develop a new tractable procedure for multilayer aggregation based on statistical validation, which we apply to investor networks. Moreover, we propose two other improvements to their analysis: transaction bootstrapping and investor categorization. The aggregation procedure can be used to integrate security-wise and time-wise information about investor trading networks, but it is not limited to finance. In fact, it can be used for different applications, such as gene, transportation, and social networks, were they inferred or observable. Additionally, in the investor network inference, we use transaction bootstrapping for better statistical validation. Investor categorization allows for constant size networks and having more observations for each node, which is important in the inference especially for less liquid securities. Furthermore, we observe that the window size used for averaging has a substantial effect on the number of inferred relationships. We apply this procedure by analyzing a unique data set of Finnish shareholders during the period 2004-2009. We find that households in the capital have high centrality in investor networks, which, under the theory of information channels in investor networks suggests that they are well-informed investors.


Clonal propagation of Phyllanthus amarus: A hepatoprotector.
The micropropagation protocol for Phyllanthus amarus, an important medicinal herb used widely for the treatment of hepatitis in ethnomedicinal systems, was standardized with shoot tip and single node explants. The micropropagation was carried out for the hyperproducing ecotype (phyllanthin content 463.828 ppm; hypophyllanthin content: 75.469 ppm) collected from Aanaikatti, Coimbatore, and grown in mist chamber, CPMB, TNAU. For micropropagation studies, the leaves were trimmed off and the shoot tips (6 mm long) and nodal segments (single node) were used for initiation. Shoot tips and single node explants gave a maximum of 6.00 and 7.00 multiple shoots per explant with Benzyl Amino Purine (BAP) (1.0mg/L mg/L). Upon subculturing, a shoot length of around 7 cm with an average of eight internodes per shoot was observed after 20 days in the elongation medium supplemented with BAP (0.2 mg/Lmg/L) and Indole Acetic Acid (IAA) (2.0 mg/L). Seven to ten adventitious roots developed when the elongated microshoots were cultured in half strength MS medium with Indole Butyric Acid (IBA) (2.0 mg/Lmg/L) and NAA (1.0 mg/L mg/L) in 15-20 days after transfer. The rooted shoots acclimatized successfully to field conditions. A method for successful micropropagation of the valuable medicinal plant was established which will provide a better source for continuous supply of plants for manufacturing drugs.


Advanced Surgical Skills for Exposure in Trauma (ASSET): the first 25 courses.
The Advanced Surgical Skills for Exposure in Trauma (ASSET) course was developed to address limited experience of residents and practicing surgeons (PS) in rapid exposure of major blood vessels for trauma. This one day, case based, scenario driven, fresh cadaver dissection course emphasizes rapid surgical exposure of the vasculature of the neck, chest, abdomen, pelvis and extremities with additional focus on fasciotomies and pelvic packing. Contained herein are the results of the first 25 courses. Data collected from 25 ASSET courses conducted between September 2010 and February 2012 included self-reported comfort level (5 point Likert scale) with each of 25 specific skills before and upon completion of the course, and evaluation of the course content. Statistical analysis was accomplished using the Student t-test with α set at P < 0.05. Ninety-one surgical trainees and 123 PS were taught at 11 ASSET sites. Self-assessed comfort levels for all 25 queried skills and exposures improved significantly over baseline with P values ranging from 1.6 × 10(-7) to 3.9 × 10(-41). Participants gained new knowledge (4.83 on 5 point scale); learned new techniques (4.83), felt better prepared to expose traumatically injured vessels (4.88), and would recommend the course to a colleague (4.92). The ASSET course was well received and significantly improved self-reported confidence in the exposures needed to care for trauma in both surgical trainees and PS. Ongoing experience with this course will enable more comprehensive psychometric analysis and further validation of this curriculum.


Psychrometry in the thermal comfort diagnosis of production animals: a combination of the systematic review and methodological proposal.
Animal welfare and productive performance are compromised when animals are housed in environments which place them outside their thermal comfort zone. However, the identification of thermal stress, when based on air properties, suggests the use of outdated and generic indices. The objective of this work was to develop and validate a methodology for classifying and diagnosing heat stress in production animals based on psychrometric air relations. The model was created for broilers, pigs, dairy cattle, and laying birds, categorized into a total of 21 breeding phases. For each phase, a bibliographic search was carried out for the psychrometric parameters of the air-dry bulb temperature (AT) and relative humidity (RH)-that satisfied the animals' critical and ideal thermoneutral zones. Adding the local atmospheric pressure (AP), the parameters were used to calculate the enthalpy (h), resulting in five comfort ranges. Based on this, a decision tree was elaborated, consisting of three attributes (AT, RH, and h) and seven diagnostic classes, based on the psychrometric principles of air. The proposed methodology was used in a case study, with a database extracted from an individual shelter for calves. For the evaluation of the decision tree, two induction algorithms, ID3 and c4.5, were compared, both of which presented high accuracy and proposed simpler tree models than the one theoretically developed for the methodology. In conclusion, the methodology represents a great potential to characterize the thermal comfort of the animals, diagnose the causes of stress, and recommend possible corrective actions. The study revealed that decision trees can be adapted and simplified for each creation phase.


Structure-function correlations in the human medial rectus extraocular muscle pulleys.
Fibroelastic pulleys function like the trochlea to fix the position and pulling direction of the recti extraocular muscles within the orbit. This study characterized the fine structure of the human medial rectus muscle pulley. Human medial rectus muscle pulley tissue was dissected at autopsy, immersed in aldehyde fixative solution, and processed for and examined with light and electron microscopy. Pulley structure were located within posterior Tenon's fascia, closely surrounding the medial rectus muscle. Pulleys were comprised of a dense collagen matrix with alternating bands of collagen fibers precisely arranged at right angles to one another. This three-dimensional organization most likely confers high tensile strength to the pulley. Elastin fibrils were interspersed in the collagen matrix. Fibroblasts and mast cells were scattered throughout the relatively acellular and avascular collagen latticework. Connective tissue and smooth muscle bundles suspended the pulley from the periorbita. Smooth muscle was distributed in small, discrete bundles attached deeply into the dense pulley tissue. Fine structural observations confirm the existence and substantial structure of a pulley system in association with the medial rectus extraocular muscle. The presence of pulleys must be considered in models of the oculomotor plant. The cytoarchitecture and placement of pulleys suggest that they are internally rigid structures and are consistent with the idea that they determine functional origins for the extraocular muscles. However, the nature of the connective tissue-smooth muscle struts suspending the pulley system to the orbit supports the notion that the pulley position, and thus the vector force of the eye muscles, may be adjustable.


Functional variants of POC5 identified in patients with idiopathic scoliosis.
Idiopathic scoliosis (IS) is a spine deformity that affects approximately 3% of the population. The underlying causes of IS are not well understood, although there is clear evidence that there is a genetic component to the disease. Genetic mapping studies suggest high genetic heterogeneity, but no IS disease-causing gene has yet been identified. Here, genetic linkage analyses combined with exome sequencing identified a rare missense variant (p.A446T) in the centriolar protein gene POC5 that cosegregated with the disease in a large family with multiple members affected with IS. Subsequently, the p.A446T variant was found in an additional set of families with IS and in an additional 3 cases of IS. Moreover, POC5 variant p.A455P was present and linked to IS in one family and another rare POC5 variant (p.A429V) was identified in an additional 5 cases of IS. In a zebrafish model, expression of any of the 3 human IS-associated POC5 variant mRNAs resulted in spine deformity, without affecting other skeletal structures. Together, these findings indicate that mutations in the POC5 gene contribute to the occurrence of IS.


Vincristine-loaded liposomes prepared by ion-paring techniques: Effect of lipid, pH and antioxidant on chemical stability.
In the present study, vincristine (VCR)-loaded liposomes were designed by ion-pairing techniques and the model could be applied to investigate the effect of lipids on the degradation of vinca alkaloids, and how to weaken their influence by adjusting pH and adding antioxidants. It was found that there was a positive correlation between degree of degradation and the unsaturation extent of the phospholipids. In the phospholipid with the lowest oxidation index, only 6% of VCR was degraded in 6days at 37°C, whereas for the phospholipids with highest oxidation index, the degradation reached above 95% over the same time. At pH6.8 and 7.4, the degradation rate of VCR in the lipid membrane was significantly faster than that in aqueous solution, instead, at pH5.0. After the addition of butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), tocopherol, ascorbate and tocopherol with ascorbate, the residual content of VCR after 6days was 79.9%, 78.1%, 7.1%, 89.6% and 94.6% respectively. It was speculated that VCR could be oxidized by hydrated peroxyl radicals, which formed from lipid peroxidation as well as nucleophilic substitution with peroxyl radicals in the dry state. Also, the antioxidants were shown to have different eliminating capacity on the peroxyl radicals whether hydrated or not, and the phenoxyl radicals generated from fat-soluble antioxidants may be potentially destabilizing to VCR. Therefore, for these two crucial reasons, the degradation of VCR was quite different when used with a combination of water and fat-soluble antioxidants, and thus provides the best protection for VCR.


Characterization of comorbidity heterogeneity among 13,667 patients with hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by recurrent abscesses in the groin and flexural areas. HS is associated with a wide range of comorbidities that complicate the disease course. Although these comorbidities have been well described, it remains unclear how these comorbidities coassociate and whether comorbidity profiles affect disease trajectory. In addition, it is unknown how comorbidity associations are modulated by race and sex. In this comprehensive analysis of 77 million patients in a large US population-based cohort, we examined coassociation patterns among HS comorbidities and identified clinically relevant phenotypic subtypes within HS. We demonstrated that these subtypes not only differed among races, but also influenced clinical outcomes as measured by HS-related emergency department visits and cellulitis. Taken together, our findings provide key insights that elucidate the unique disease trajectories experienced by patients with HS and equip clinicians with a framework for risk stratification and improved targeted care in HS.


Management of late biliary complications in patients with gallbladder stones in situ after endoscopic papillary balloon dilation.
Patients with untreated gallbladder stones in situ are at high risk for late biliary complications after endoscopic papillary balloon dilation (EPBD) and bile duct stone extraction. Few data exist on the short-term and long-term results in these patients after the recurrence of bile duct stones and acute cholecystitis. The aim of this study was to evaluate the outcome of late biliary complications in patients with gallbladder stones in situ after EPBD. Fifty-six patients who developed late biliary complications, including bile duct stone recurrence (n=43) and acute cholecystitis (n=13), were managed at our institutions. We investigated the short-term and long-term outcomes after the management of late biliary complications. Complete removal of recurrent bile duct stones was achieved in 38 of 43 patients (88%) by repeated EPBD alone. Pancreatitis after repeated EPBD occurred in two patients (5%). After successful bile duct stone extraction by EPBD, none of the 16 patients who underwent cholecystectomy developed late biliary complications (mean follow-up period of 5.2 years), wheras re-recurrent bile duct stones occurred in three of the 21 patients (14%) with gallbladder stones left in situ (mean follow-up period of 4.4 years)(P=0.1148). Re-recurrent bile duct stones were successfully treated endoscopically. One of the eight patients who did not undergo cholecystectomy for acute cholecystitis had a recurrence of cholecystitis, which was managed conservatively. The long-term outcomes of late biliary complications are favorable when patients with concomitant gallbladder stones undergo cholecystectomy. Re-recurrent bile duct stones are considerable when gallbladder stones are left in situ, but should be treated endoscopically.


A closed-form solution to tensor voting: theory and applications.
We prove a closed-form solution to tensor voting (CFTV): Given a point set in any dimensions, our closed-form solution provides an exact, continuous, and efficient algorithm for computing a structure-aware tensor that simultaneously achieves salient structure detection and outlier attenuation. Using CFTV, we prove the convergence of tensor voting on a Markov random field (MRF), thus termed as MRFTV, where the structure-aware tensor at each input site reaches a stationary state upon convergence in structure propagation. We then embed structure-aware tensor into expectation maximization (EM) for optimizing a single linear structure to achieve efficient and robust parameter estimation. Specifically, our EMTV algorithm optimizes both the tensor and fitting parameters and does not require random sampling consensus typically used in existing robust statistical techniques. We performed quantitative evaluation on its accuracy and robustness, showing that EMTV performs better than the original TV and other state-of-the-art techniques in fundamental matrix estimation for multiview stereo matching. The extensions of CFTV and EMTV for extracting multiple and nonlinear structures are underway.


Mechanism for the separation of large molecules based on radial migration in capillary electrophoresis.
We demonstrate a novel separation mechanism for large molecules based on their radial migration in capillary electrophoresis with applied hydrodynamic flow (HDF). The direction of radial migration depends on the direction of the applied HDF relative to the electric field. The radial migration velocities are size-dependent, which could be attributed to the different degree of deformation under shear flow. Analytical separation was demonstrated on a sample plug containing lambda DNA (48 502 bp) and phiX174 RF DNA (5386 bp) with baseline separation. Alternatively, this separation mode can be performed continuously and is thus applicable to preparative separations. Without the need for gel/polymer or complex instrumentation, this separation technique is complementary to capillary gel electrophoresis and field-flow fractionation. Although large DNA molecules were used to demonstrate the separation mechanism here, these protocols could also be applied to the separation of proteins, cells, or particles based on size, shape, or deformability.


Catastrophic cascade of failures in interdependent networks.
Complex networks have been studied intensively for a decade, but research still focuses on the limited case of a single, non-interacting network. Modern systems are coupled together and therefore should be modelled as interdependent networks. A fundamental property of interdependent networks is that failure of nodes in one network may lead to failure of dependent nodes in other networks. This may happen recursively and can lead to a cascade of failures. In fact, a failure of a very small fraction of nodes in one network may lead to the complete fragmentation of a system of several interdependent networks. A dramatic real-world example of a cascade of failures ('concurrent malfunction') is the electrical blackout that affected much of Italy on 28 September 2003: the shutdown of power stations directly led to the failure of nodes in the Internet communication network, which in turn caused further breakdown of power stations. Here we develop a framework for understanding the robustness of interacting networks subject to such cascading failures. We present exact analytical solutions for the critical fraction of nodes that, on removal, will lead to a failure cascade and to a complete fragmentation of two interdependent networks. Surprisingly, a broader degree distribution increases the vulnerability of interdependent networks to random failure, which is opposite to how a single network behaves. Our findings highlight the need to consider interdependent network properties in designing robust networks.


Disability and health-related quality of life in long-term survivors of cancer in childhood in Brazil.
There is limited experience with patient-reported measurements of health status and health-related quality of life (HRQL) in survivors of cancer in childhood in low-income countries. The purposes of this study were to collect such measurements in Brazil, to test hypotheses about differences among diagnostic groups, and to compare results with those from other countries. Survivors were eligible if diagnosed with cancer in childhood, attending a long-term follow-up clinic, cancer free, literate, and at least 13 years of age. Health status measurements were collected using a Brazilian Portuguese Health Utilities Index questionnaire. Questionnaire responses were converted to scores for morbidity in individual health attributes and for overall HRQL. More than one-third of the 138 consecutive survivors who participated reported some cognitive disability or pain. Approximately one-quarter reported problems with vision, speech, or emotion. Mean HRQL was similar (P>0.05) among countries for survivors of acute lymphoblastic leukemia and Hodgkin disease. The results support the hypotheses that Brazilian survivors of cancer in childhood experience a wide range of disabilities and impaired HRQL, are similar to those in other countries, and should be assessed in long-term follow-up clinics.


Pleasant for some and unpleasant for others: a protocol analysis of the cognitive factors that influence affective responses to exercise.
At exercise intensities around ventilatory threshold (VT), the extent to which individuals experience pleasure or displeasure from the exercise varies between individuals. One source of this variability is proposed to be the cognitive appraisal that occurs during the exercise which influences the generation of the affective response. When individuals self-select their own intensity they choose to exercise around VT and experience more positive affective responses, again the explanation being that cognitive appraisal processes influence the choice of intensity and resulting affective response. However, the specific factors that comprise this appraisal process have not been thoroughly explored. In addition, it is not clear if activity status influences this appraisal and different cognitive factors play a role in the generation of affective responses. Therefore, the purpose of this study was to explore the cognitive factors that influence the affective response experienced during prescribed and self-selected intensity exercise in low-active and high-active women. Seventeen low-active and 15 high-active women (M age = 45 years, SD = 10) completed a graded exercise test and two 30 min bouts of treadmill exercise, one at a self-selected intensity and one prescribed at an intensity around VT. Using 'think aloud' procedures, every five min, the women were asked to provide an affective response and explain the thought processes that caused them to report that affective response. Using inductive content analysis, the verbal reports provided by the women were analysed for key themes and categories that emerged as explaining the factors that underpinned the generation of the affective response. Data from the low-active and high-active women were analysed separately. Concepts relating to pre-exercise affective state, perceptions of ability, immediate and anticipated outcomes, attentional focus and perceptions of control emerged. The physiological demands of the exercise stimulus influenced affective responses through themes related to the interpretation of physiological symptoms and the physiological state of the body. No thematic differences emerged between high-active and low-active women. Results highlight the complex interaction of psychological and physiological influences in producing an affective response to exercise and provide insight into how exercise can be structured to elicit positive affective responses.


Enhancing Multichannel Laser-Doppler Vibrometry Signals with Application to (Carotid-Femoral) Pulse Transit Time Estimation.
Pulse-wave velocity (PWV) can be used to quantify arterial stiffness, allowing for a diagnosis of this condition. Multi-beam laser-doppler vibrometry offers a cheap, non-invasive and user-friendly alternative to measuring PWV, and its feasibility has been previously demonstrated in the H2020 project CARDIS. The two handpieces of the prototype CARDIS device measure skin displacement above main arteries at two different sites, yielding an estimate of the pulse-transit time (PTT) and, consequently, PWV. The presence of multiple beams (channels) on each handpiece can be used to enhance the underlying signal, improving the quality of the signal for PTT estimation and further analysis. We propose two methods for multi-channel LDV data processing: beamforming and beamforming-driven ICA. Beamforming is done by an SNR-weighted linear combination of the time-aligned channels, where the SNR is blindly estimated from the signal statistics. ICA uses the beamformer to resolve its inherent permutation and scale ambiguities. Both methods yield a single enhanced signal at each handpiece, where spurious peaks in the individual channels as well as stochastic noise are well suppressed in the output. Using the enhanced signals yields individual PTT estimates with a low spread compared to the baseline approach. While the enhancement is introduced in the context of PTT estimation, the approaches can be used to enhance signals in other biomedical applications of multi-channel LDV as well.


Computerized whole slide quantification shows increased microvascular density in pT2 prostate cancer as compared to normal prostate tissue.
Contrast enhanced imaging enables powerful, non-invasive diagnostics, important for detection and staging of early prostate cancer. The uptake of contrast agent is increased in prostate cancer as compared to normal prostate tissue. To reveal the underlying physiological mechanisms, quantification of tissue components in pathology specimens may yield important information. Aim of this study was to investigate whether microvascularity is increased in prostate confined cancer (pT2). Radical prostatectomy specimens of 26 patients were selected for organ confined peripheral zone tumors which were restricted to one side of the prostate. Microvessels were visualized by immunohistochemistry against CD31. Specimens were scanned using a computer controlled microscope and scanning stage and vessels were recognized automatically. Pseudocolor mappings were produced showing number of vascular profiles (MVD), vascular area (MVA) and perimeter (MVP) in an overview of the entire prostate transection. MVD is a common measure for vascularity, whereas MVA represents the 3D vascular volume and MVP the perfused surface area. Mean, coefficient of variation and 75th percentile of these parameters were calculated automatically in manually indicated areas, consisting of the entire tumor area and the corresponding normal area in the contra lateral side of the prostate. The mappings clearly indicate areas of increased vascularity in prostate transections. In tumor tissue an increase was found compared to normal tissue of 81%, 49%, and 62% for mean MVD, mean MVA and mean MVP, respectively (P < 0.001 for all comparisons). In contrast, the heterogeneity in tumor vasculature was significantly decreased as compared to normal prostate (P < 0.001). Characteristics of microvasculature deviated significantly in pT2 prostate tumor as compared to normal tissue.


The brain of teleost fish, a source, and a target of sexual steroids.
Neurosteroids are defined as steroids de novo synthesized in the central nervous system. While the production of neurosteroids is well documented in mammals and amphibians, there is less information about teleosts, the largest group of fish. Teleosts have long been known for their high brain aromatase and 5α-reductase activities, but recent data now document the capacity of the fish brain to produce a large variety of sex steroids. This article aims at reviewing the available information regarding expression and/or activity of the main steroidogenic enzymes in the brain of fish. In addition, the distribution of estrogen, androgen, and progesterone nuclear receptors is documented in relation with the potential sites of production of neurosteroids. Interestingly, radial glial cells acting as neuronal progenitors, appear to be a potential source of neurosteroids, but also a target for centrally and/or peripherally produced steroids.


Expression and functional significance of NADPH oxidase 5 (Nox5) and its splice variants in human blood vessels.
The expression and functional significance of NADPH oxidase 5 (Nox5) and its five isoforms in vascular cells is poorly understood. The goal of this study was to determine whether Nox5-α, -β, -δ, -γ, and -ε (short) are expressed in human blood vessels and evaluate their respective functions. Nox5 mRNA and protein were detected in human blood vessels, cultured human vascular smooth muscle (HVSMC) and endothelium, but not fibroblasts. The most abundant isoforms were α and β, whereas δ and γ were not detected. Nox5-α and -β produced reactive oxygen species (ROS), but -δ, -γ, and -ε were not catalytically active. Coexpression of the active Nox5 isoforms with inactive Nox5 variants suppressed ROS production, and coimmunoprecipitation revealed that Nox5-β binds the inactive ε variant, which may account for reduced ROS production. In HVSMC, angiotensin II, endothelin-1 and TNF-α increased endogenous Nox5 mRNA levels, while adenovirus-mediated overexpression of Nox5 promoted p38 MAPK, JAK2, JNK, and ERK1/2 phosphorylation in endothelial cells (EC), but only increased ERK1/2 phosphorylation in HVSMC. At higher levels of Nox5, there was evidence of increased apoptosis in EC, but not in HVSMC, as detected by the presence of cleaved caspase-3 and cleaved poly(ADP-ribose)polymerase. Although catalytically inactive, Nox5-ε potently activated ERK in HVSMC, and increased expression of Nox5-ε promoted HVSMC proliferation. Nox5 is expressed in human blood vessels. The Nox5-α and -β splice variants are the major isoforms that are expressed and the only variants capable of ROS production. Nox5-ε can inhibit Nox5 activity and activate ERK and HVSMC proliferation.


Can Machine Learning Methods Produce Accurate and Easy-to-use Prediction Models of 30-day Complications and Mortality After Knee or Hip Arthroplasty?
Existing universal and procedure-specific surgical risk prediction models of death and major complications after elective total joint arthroplasty (TJA) have limitations including poor transparency, poor to modest accuracy, and insufficient validation to establish performance across diverse settings. Thus, the need remains for accurate and validated prediction models for use in preoperative management, informed consent, shared decision-making, and risk adjustment for reimbursement. The purpose of this study was to use machine learning methods and large national databases to develop and validate (both internally and externally) parsimonious risk-prediction models for mortality and complications after TJA. Preoperative demographic and clinical variables from all 107,792 nonemergent primary THAs and TKAs in the 2013 to 2014 American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) were evaluated as predictors of 30-day death and major complications. The NSQIP database was chosen for its high-quality data on important outcomes and rich characterization of preoperative demographic and clinical predictors for demographically and geographically diverse patients. Least absolute shrinkage and selection operator (LASSO) regression, a type of machine learning that optimizes accuracy and parsimony, was used for model development. Tenfold validation was used to produce C-statistics, a measure of how well models discriminate patients who experience an outcome from those who do not. External validation, which evaluates the generalizability of the models to new data sources and patient groups, was accomplished using data from the Veterans Affairs Surgical Quality Improvement Program (VASQIP). Models previously developed from VASQIP data were also externally validated using NSQIP data to examine the generalizability of their performance with a different group of patients outside the VASQIP context. The models, developed using LASSO regression with diverse clinical (for example, American Society of Anesthesiologists classification, comorbidities) and demographic (for example, age, gender) inputs, had good accuracy in terms of discriminating the likelihood a patient would experience, within 30 days of arthroplasty, a renal complication (C-statistic, 0.78; 95% confidence interval [CI], 0.76-0.80), death (0.73; 95% CI, 0.70-0.76), or a cardiac complication (0.73; 95% CI, 0.71-0.75) from one who would not. By contrast, the models demonstrated poor accuracy for venous thromboembolism (C-statistic, 0.61; 95% CI, 0.60-0.62) and any complication (C-statistic, 0.64; 95% CI, 0.63-0.65). External validation of the NSQIP- derived models using VASQIP data found them to be robust in terms of predictions about mortality and cardiac complications, but not for predicting renal complications. Models previously developed with VASQIP data had poor accuracy when externally validated with NSQIP data, suggesting they should not be used outside the context of the Veterans Health Administration. Moderately accurate predictive models of 30-day mortality and cardiac complications after elective primary TJA were developed as well as internally and externally validated. To our knowledge, these are the most accurate and rigorously validated TJA-specific prediction models currently available (http://med.stanford.edu/s-spire/Resources/clinical-tools-.html). Methods to improve these models, including the addition of nonstandard inputs such as natural language processing of preoperative clinical progress notes or radiographs, should be pursued as should the development and validation of models to predict longer term improvements in pain and function. Level III, diagnostic study.


Colorimetric peroxidase mimetic assay for uranyl detection in sea water.
Uranyl (UO2(2+)) is a form of uranium in aqueous solution that represents the greatest risk to human health because of its bioavailability. Different sensing techniques have been used with very sensitive detection limits especially the recently reported uranyl-specific DNAzymes systems. However, to the best of our knowledge, few efficient detection methods have been reported for uranyl sensing in seawater. Herein, gold nanoclusters (AuNCs) are employed in an efficient spectroscopic method to detect uranyl ion (UO2(2+)) with a detection limit of 1.86 μM. In the absence of UO2(2+), the BSA-stabilized AuNCs (BSA-AuNCs) showed an intrinsic peroxidase-like activity. In the presence of UO2(2+), this activity can be efficiently restrained. The preliminary quenching mechanism and selectivity of UO2(2+) was also investigated and compared with other ions. This design strategy could be useful in understanding the binding affinity of protein-stabilized AuNCs to UO2(2+) and consequently prompt the recycling of UO2(2+) from seawater.


Auditory temporal processing: responses to sinusoidally amplitude-modulated tones in the inferior colliculus.
Time-varying envelopes are a common feature of acoustic communication signals like human speech and induce a variety of percepts in human listeners. We studied the responses of 109 single neurons in the inferior colliculus (IC) of the anesthetized Mongolian gerbil to contralaterally presented sinusoidally amplitude-modulated (SAM) tones with a wide range of parameters. Modulation transfer functions (MTFs) based on average spike rate (rMTFs) showed regions of enhancement and suppression, where spike rates increased or decreased respectively as stimulus modulation depth increased. Specifically, almost all IC rMTFs could be described by some combination of a primary and a secondary region of enhancement and an intervening region of suppression, with these regions present to varying degrees in individual rMTFs. rMTF characteristics of most neurons were dependent on sound pressure level (SPL). rMTFs in most neurons with "onset" or "onset-sustained" peri-stimulus time histograms (PSTHs) in response to brief pure tones showed only a peaked primary region of enhancement. The region of suppression tended to occur in neurons with "sustained" or "pauser" PSTHs, and usually emerged at higher SPLs. The secondary region of enhancement was only found in eight neurons. The lowest modulation frequency at which the spike rate reached a clear peak ("best modulation frequency" or BMF) was measured. All but two mean BMFs lay between 0 and 100 Hz. Fifty percent of the 49 neurons tested over at least a 20-dB range of SPLs showed a BMF variation larger than 66% of their mean BMF. MTFs based on vector strength (tMTFs) showed a variety of patterns; although mostly similar to those reported from the cochlear nucleus, tMTFs of IC neurons showed higher maximum values, smaller dynamic range with depth, and a lower high-frequency limit for significant phase locking. Systematic and large increases in phase-lead commonly occurred as SPL increased. rMTFs measured at multiple carrier frequencies (F(c)s) showed that the suppressive region was not the result of sideband inhibition. There was no systematic relationship between BMF and F(c) of stimulation in the cells studied, even at low carrier frequencies. The results suggest various possible mechanisms that could create IC MTFs, and strongly support the idea that inhibitory inputs shape the rMTF by sharpening regions of enhancement and creating a suppressive region. The paucity of BMFs above 100 Hz argues against simple rate-coding schemes for pitch. Finally, any labeled line or topographic representation of modulation frequency is unlikely to be independent of SPL.


Pathophysiologic Mechanisms of Tobacco Smoke Producing Atherosclerosis.
Despite the convincing epidemiologic association between smoking and vascular disease, the pathophysiologic mechanisms by which smoking initiates and contributes to the progression of atherosclerosis remain incompletely understood. A precise dose-dependent correlation has never been demonstrated, suggesting that the biological relationship is complex and influenced by individual genetic and possibly environmental factors. Although endothelial dysfunction and intimal damage appear to be central to atherogenesis, how tobacco products cause this effect has not been established. The purpose of this review is to describe the current state of knowledge of the main pathophysiologic pathways of how tobacco smoking abets atherosclerosis. Constituents of Tobacco Smoke: Tobacco combustion produces a mixture of organic substances. derived from burning organic materials. The predominant gaseous phase constituents include carbon monoxide, acetaldehyde, formaldehyde, acrolein, and other carbonyls, as well as nicotine and tobacco-specific nitrosamines. Potential Pathophysiologic Mechanisms: Smoking-induced changes in coronary vasomotor tone, platelet activation, and endothelial integrity are major components of both the development of atherosclerosis and its clinical presentation. Smoking may initiate and accelerate the progression of atherosclerosis by injuring the vascular intima. Other potential mechanisms include intimal damage and endothelial dysfunction, oxidative stress and injury, thrombosis, lipid abnormalities, and inflammation. Smoking tobacco products contributes measurably to the incidence of acute vascular events and chronic disease. The causative compound, the exact mechanism of injury, and whether the atherogenic effect is modifiable are not known.