Thrombosed external hemorrhoids: outcome after conservative or surgical management.
Few data exist on the actual recurrence rates of thrombosed external hemorrhoids. We wished to determine the incidence of recurrence, intervals to recurrence, and factors predicting recurrence of thrombosed external hemorrhoids after conservative or surgical management. Two hundred and thirty-one consecutive patients with thrombosed external hemorrhoids treated from 1990 to 2002 were identified. Recurrence was defined as complete resolution of the index lesion with subsequent return of a thrombosed external hemorrhoid and did not include patients with chronic symptoms. Data were gathered retrospectively. Multiple potential risk factors were reviewed. The index thrombosed external hemorrhoid was managed conservatively in 51.5 percent of cases and surgically in 48.5 percent. There were no differences between groups in gender, age, or race, and 44.5 percent of all patients had a prior history of thrombosed external hemorrhoid. A prior history was less common in the conservative group than in the surgical group (38.1 percent vs. 51.3 percent; P < 0.05). The frequency of pain or bleeding as the primary complaint was higher in the surgical group ( P < 0.001 and P < 0.002). In addition, the surgical group was more likely to report all three symptoms of pain, bleeding, and a lump ( P < 0.005). Mean follow-up was 7.6 months, with the range extending to 7 years. Time to symptom resolution averaged 24 days in the conservative group vs. 3.9 days in the surgical group ( P < 0.0001). The overall incidence to recurrence was 15.6 percent-80.6 percent in the conservative group vs. 19.4 percent in the surgical group. The rate of recurrence in the conservative group was 25.4 percent (4/29; 14 percent were excised) whereas only 6.3 percent of the surgical patients had recurrence ( P < 0.0001). Mean time to recurrence was 7.1 months in the conservative group vs. 25 months in the surgical group ( P < 0.0001). Survival analysis for time to recurrence of thrombosed external hemorrhoid indicated that time to recurrence was significantly longer for the surgical group ( P < 0.0001). Logistic regression analysis of multiple factors (including diverticular disease, constipation, straining, benign prostatic hypertrophy, diarrhea, skin tags, history of travel, anoreceptive sex, anal fissures, internal hemorrhoids, and obesity) was performed to determine the outcome of each group. None of these variables were significant predictors of recurrence. Patients whose initial presentation was pain or bleeding with or without a lump were more like to be treated surgically. Surgically treated patients had a lower frequency of recurrence and a longer time interval to recurrence than conservatively treated patients. None of the variables analyzed were significant predictors of a particular treatment, except for a prior history of thrombosed external hemorrhoids, which may represent patient choice. Although most patients treated conservatively will experience resolution of their symptoms, excision of thrombosed external hemorrhoids results in more rapid symptom resolution, lower incidence of recurrence, and longer remission intervals.


How accurate are orthopaedic surgeons in visually estimating lower limb alignment?
This study aimed to determine the accuracy and reliability of visual estimation of limb alignment and knee flexion by orthopaedic surgeons when compared to recordings done by computed navigation. Orthopaedic surgeons attending a national conference were asked to place a lower limb synthetic bone model in 6 positions of the knee in the coronal and sagittal planes. These were simultaneously quantified and recorded by a computer navigation system. In the sagittal plane, 44%, 54% and 60% of the surgeons deviated by more than 5 degrees when positioning the knee in 0 degrees flexion, 10 degrees flexion and 90 degrees flexion respectively. In the coronal plane, 15%, 12% and 8% of the surgeons deviated by more than 5 degrees when positioning the knee in 0 degrees varus/valgus, 5 degrees varus and 5 degrees valgus respectively. Only 25% of the surgeons could position the knee both within 3 degrees of neutral varus/valgus and within 5 degrees of neutral flexion. Accuracy of visual estimation was not different when surgeons were compared based on time since residency, experience with TKA and experience with computer-assisted TKA. Visual estimation of knee alignment in both the sagittal and coronal plane is prone to error and may lead to inaccurate limb alignment during procedures such as TKA.


The β-ketoacyl-ACP synthase from Mycobacterium tuberculosis as potential drug targets.
The continuous preventive measures and control of tuberculosis are often hampered by re-emergence of multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis. A novel drug approach is desperately needed to combat the global threat posed by MDR strains. In spite of current advancement in biological techniques viz. microarray and proteomics data for tuberculosis, no such potent drug has been developed in the past decades yet. Therefore, mycolic acid is an essential constituent which is involved in the formation of cell wall of Mycobacterium species. The biosynthesis of mycolic acid is involved in two fatty acid synthase systems, the multifunctional polypeptide fatty acid synthase I (FASI) which performs de novo fatty acid synthesis and dissociate FASII system. FASII system consists of monofunctional enzymes and acyl carrier protein (ACP), elongating FASI products to long chain mycolic acid precursor. In this review, the β-ketoacyl-ACP synthases (fadH, kasA and kasB) are distinct and play a vital role in mycolic acid synthesis, cell wall synthesis, biofilm formation and also pathogenesis. On the basis of substantial observation we suggest that these enzymes may be used as promising and attractive targets for novel anti-TB drugs designing and discovery.


Preliminary results on the association with feeding and recovery length in equine colic patients after laparotomy.
Colic is a serious disease for horses and the nutritional management of postoperative colic patients is an extremely important field. The aim of this retrospective study was to analyse the different factors, especially related to nutritional management, that may be associated with recovery length during hospitalization after a surgical intervention for colic, using a multivariate model. Data were collected from the records of horses presented to two hospitals and undergoing surgery for colic. The length (days) of recovery was the outcome of interest and was taken into account as a reference parameter (short, medium, long). The parameters collected (patient details, preoperative clinical and laboratory examinations, postoperative parameters and post-surgery nutritional parameters) were subjected to multivariate analysis (MCA and PCoA). A ranking class dataset was used to calculate Kendall's tau correlation of the length of recovery with respect to other parameters. Descriptive statistic to identify differences in the recovery length among groups (Kruskal-Wallis and Dunn's Multiple Comparison Test) was also performed. p value was set at < 0.05. Groups were not different in preoperative clinical parameters (BCS, PCV, total protein), postoperative parameters (time to 1st defecation, time to the end of IV fluid therapy and time to first water drinking, anaesthesia) and patient details (age). The comparison among groups revealed differences on the post-surgical nutritional parameters. Horses with short recovery consumed higher % of DM as forages in the 24 hr compared with the horses that have a long recovery and reach the minimum DM intake in a shorter period. Both Kendall and MCA analysis confirmed that the time to first feeding had a positive association with the length of recovery. Only 37 horses undergoing colic surgery were included in the study. From a clinical standpoint, this study has shown which nutritional parameters are associated with short recovery.


[Target-oriented infusion therapy in patients during myocardial revascularization].
The paper analyzes goal-oriented infusion therapy used during myocardial revascularization on the working heart. Forty-seven patients with coronary heart disease were examined. Group 1 (control) (n = 20) received standard infusion therapy (a combination of colloids and crystalloids (1:1) at a rate of 6-7 ml/kg/h, by being oriented to indices, such as heart rate, blood pressure, central venous pressure, and diuresis rate. In group 2, an anesthetist was oriented to central hemodynamic parameters during infusion therapy. In addition, the patients of this group underwent the 45 degrees passive leg raising test. In this group, a volume load was done at the beginning of an operation until the maximum possible SV resulted from increased preload (global end-diastolic volume index). The goal of infusion therapy throughout the operation was to maintain these values of the latter index. Goal-oriented infusion therapy, the purpose of which was to determine and maintain the individual optimal values of preload, was found to minimize hemodynamic disorders at surgery and to reduce the frequency of use of cardiotonic agents and the duration of artificial ventilation.


Omega 3 fatty acids increase the chemo-sensitivity of B-CLL-derived cell lines EHEB and MEC-2 and of B-PLL-derived cell line JVM-2 to anti-cancer drugs doxorubicin, vincristine and fludarabine.
B-Cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. Clinical treatment of CLL is often limited due to drug resistance and severe therapy-induced toxicities. We hypothesized that the omega 3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), would increase the sensitivity of malignant B-lymphocytes to anti-cancer drugs doxorubicin, vincristine and/or fludarabine in vitro and that increased sensitivity is achieved by alterations in cell-cycle progression leading to growth inhibition and/or enhanced cell death. We further postulate that enhanced sensitivity is dependent on the formation of lipid peroxides and to the generation of reactive oxygen species (ROS). In the present study, B-CLL-derived leukemic cell lines EHEB and MEC-2 and the B-Prolymphocytic leukemic-derived (PLL) cell line JVM-2 were tested for in vitro sensitivity against doxorubicin, vincristine or fludarabine in the presence or absence of vehicle, arachidonic acid (omega 6), EPA or DHA. Cell cycle analysis and Annexin-V assays were performed to determine cell cycle progression and % apoptotic cells, respectively. Assays for malondialdehyde, a measure of lipid peroxidation, and DCF fluorescence assays, a measure of intracellular ROS, were performed to determine if enhanced sensitivity of cells to the drugs by n-3 was dependent on the formation of ROS. Our results indicated that: 1) EPA and DHA differentially sensitized B-leukemic cell lines EHEB, JVM-2 and MEC-2 to doxorubicin, vincristine and fludarabine in vitro; 2) n-3 alone and with drug treatment increased cell death and induced G2/M arrest in a cell-type specific manner; 3) lipid peroxidation increased in the presence of n-3; 4) there was higher lipid peroxidation in MEC-2 cells in presence of DHA and doxorubicin than with either alone; 5) n-3 increased generation of ROS in MEC-2, and 6) the addition of vitamin-E abrogated the increase in ROS generation and chemo-sensitivity of MEC-2 to doxorubicin by DHA. N-3's are promising chemo-sensitizing agents for the treatment of CLL. Selective enhancement of chemo-sensitivity of EHEB, JVM-2 and MEC-2 to drugs by n-3 that is not dependent on increased lipid peroxidation and ROS generation indicates alternative mechanisms by which n-3 enhances chemo-sensitivity.


Ultrastructural alterations in skeletal muscle of pigs with selenium-vitamin E deficiency.
Light and electron microscopic studies were made of lesions which developed in skeletal muscles of 24 of 38 young growing pigs fed a semisynthetic diet deficient in selenium and vitamin E for 13 to 59 days. The major alterations in injured fibers progressed from hyaline degeneration, with subsequent macrophagic invasion and phagocytosis of disrupted sarcoplasm, to muscle fiber regeneration by myoblastic proliferation, fusion, and differentiation into fibers with mature myofibrils. The earliest electron microscopic alterations were myofibrillar lysis and disruption, with thick filaments persisting longest. Disruption of mitochondria, sarcoplasmic reticulum, and plasma membranes occurred in fibers with myofibrillar alterations. The basal lamina of the sarcolemma remained after destruction of the enclosed sarcoplasm and served as a scaffold for subsequent regeneration. Stages of regeneration included myoblastic proliferation, fusion into cords and myotubes, and, finally, fibrillogenesis to restore contractile material. The sequence of structural alterations in skeletal muscles of these affected pigs was discussed in terms of present theories of the biochemical role of these nutrients in maintaining cellular integrity.


Hospitalist management of vaso-occlusive pain crisis in patients with sickle cell disease using a pathway of care.
Patients with sickle cell disease (SCD) suffer from intermittent vaso-occlusive pain crises (VOCs). These crises lead to frequent hospitalizations, significant morbidity, and increased mortality risk. Care pathways can enhance efficiency and quality of care. Our study sought to evaluate the development and implementation of a care pathway for patients with SCD experiencing VOCs. The University of North Carolina (UNC) Comprehensive Sickle Cell Program provides all levels of care for a large population of patients with sickle cell anemia. All patients admitted to UNC Hospitals with SCD VOCs from January 2009 through June 2011 were evaluated. During this time period, we also assessed sequential prospective cohorts during progressive phases of developing and implementing a quality improvement and pathway of care program for this patient population in our study. The developed pathway entailed geographic localization for VOC patients, a single group of faculty physicians caring for these patients, and early use of patient-controlled analgesia (PCA) to achieve pain control. Physicians from the UNC Hospital Medicine Program were responsible for the initiatives. Cohorts were compared to a baseline historical control. Outcomes of interest included patient length of stay (LOS) in the hospital, 30-day readmission rate, need for transfusion, incidence of acute chest syndrome, use of naloxone, and use of PCA. Compared with an historical baseline cohort, the development and implementation of a VOC care pathway for patients with SCD led to reduction in average hospital LOS by 1.44 days (P < 0.05) and an increase in use of PCAs (P < 0.05). Patient readmission rates, number of transfusions, incidence of acute chest syndrome, and use of naloxone did not significantly change. Hospitalist-led management of patients with SCD VOCs using a care pathway that emphasizes early, aggressive PCA-based pain control is associated with reduced hospital LOS. The LOS reduction seen in our study is clinically meaningful. Notably, other measures of patient outcomes and quality of care metrics did not change significantly, and some trended towards improvement.


Vertebral body pneumatocyst in the cervical spine and review of the literature.
A pneumatocyst in the cervical spine is extremely rare and to our knowledge only a few reports have been published in the English literature. Although the etiology and natural course of vertebral body pneumatocyst is unclear, nitrogen gas accumulation is claimed. A 65-year-old-man was admitted to the emergency department with neck pain and numbness and incapacity in his both hands and fingers. The radiological images revealed a vertebral located pneumatocyst in the C4 cervical vertebra. In this report, we present a case of cervical pneumatocyst located in the C4 vertebral body. The clinical and radiological features and natural course of the pneumatocyst were evaluated.


Single-scatter vector-wave scattering from surfaces with infinite slopes using the Kirchhoff approximation.
This paper presents a new formulation of the 3D Kirchhoff approximation that allows calculation of the scattering of vector waves from 2D rough surfaces containing structures with infinite slopes. This type of surface has applications, for example, in remote sensing and in testing or imaging of printed circuits. Some preliminary calculations for rectangular-shaped grooves in a plane are presented for the 2D surface method and are compared with the equivalent 1D surface calculations for the Kirchhoff and integral equation methods. Good agreement is found between the methods.


Chest CT Imaging Signature of Coronavirus Disease 2019 Infection: In Pursuit of the Scientific Evidence.
Chest CT may be used for the diagnosis of coronavirus disease 2019 (COVID-19), but clear scientific evidence is lacking. Therefore, we systematically reviewed and meta-analyzed the chest CT imaging signature of COVID-19. What is the chest CT imaging signature of COVID-19 infection? A systematic literature search was performed for original studies on chest CT imaging findings in patients with COVID-19. Methodologic quality of studies was evaluated. Pooled prevalence of chest CT imaging findings were calculated with the use of a random effects model in case of between-study heterogeneity (predefined as I2 ≥50); otherwise, a fixed effects model was used. Twenty-eight studies were included. The median number of patients with COVID-19 per study was 124 (range, 50-476), comprising a total of 3,466 patients. Median prevalence of symptomatic patients was 99% (range, >76.3%-100%). Twenty-seven of the studies (96%) had a retrospective design. Methodologic quality concerns were present with either risk of or actual referral bias (13 studies), patient spectrum bias (eight studies), disease progression bias (26 studies), observer variability bias (27 studies), and test review bias (14 studies). Pooled prevalence was 10.6% for normal chest CT imaging findings. Pooled prevalences were 90.0% for posterior predilection, 81.0% for ground-glass opacity, 75.8% for bilateral abnormalities, 73.1% for left lower lobe involvement, 72.9% for vascular thickening, and 72.2% for right lower lobe involvement. Pooled prevalences were 5.2% for pleural effusion, 5.1% for lymphadenopathy, 4.1% for airway secretions/tree-in-bud sign, 3.6% for central lesion distribution, 2.7% for pericardial effusion, and 0.7% for cavitation/cystic changes. Pooled prevalences of other CT imaging findings ranged between 10.5% and 63.2%. Studies on chest CT imaging findings in COVID-19 suffer from methodologic quality concerns. More high-quality research is necessary to establish diagnostic CT criteria for COVID-19. Based on the available evidence that requires cautious interpretation, several chest CT imaging findings appear to be suggestive of COVID-19, but normal chest CT imaging findings do not exclude COVID-19, not even in symptomatic patients.


The Impact of Injury on Health-Related Quality of Life in College Athletes.
Health-related quality of life (HRQOL) is a broad term for the impact of injury or illness on physical, psychological, and social health dimensions. Injury has been associated with decreased HRQOL in athletes. However, the influence of injury history, participation status, time since last injury, and injury severity on HRQOL remains unclear. To compare HRQOL in collegiate athletes based on injury history, participation status, time since last injury, and injury severity and to examine relationships between HRQOL outcomes. Cross-sectional. 3 National Collegiate Athletic Association (NCAA) institutions. 467 collegiate athletes (199 males, 268 females; 19.5 ± 1.3 y, 173.9 ± 10.5 cm, 71.9 ± 13.6 kg) were recruited from NCAA Division I (n = 299) and Division III (n = 168) institutions. Athletes were included regardless of participation status, which created a diverse sample of current and past injury histories. During a single session, participants completed an injury history form, the Disablement in the Physically Active Scale (DPA), and the Fear-Avoidance Beliefs Questionnaire (FABQ). Dependent variables included DPA-Physical Summary Component (DPA-PSC), DPA-Mental Summary Component (DPA-MSC), and FABQ Scores. HRQOL differences were detected between groups based on injury history, participation status, and time since last injury. No differences were detected for injury severity. A moderate correlation was identified between the DPA-PSC and FABQ (rs = 0.503, P < .001) and a weak relationship was identified between the DPA-MSC and FABQ (rs = 0.266, P < .001). Injury negatively influenced HRQOL in athletes with a current injury. While those individuals participating injured reported better HRQOL than the athletes sidelined due to injury, deficits were still present and should be monitored to ensure a complete recovery. Identifying the patient's perception of impairment will help facilitate evidencebased treatment and rehabilitation strategies that target the physical and psychosocial aspects of health.


Assessing environmental impacts of treated wastewater through monitoring of fecal indicator bacteria and salinity in irrigated soils.
To assess the potential for treated wastewater irrigation to impact levels of fecal indicator bacteria (FIB) and salinity in irrigated soils, levels of Escherichia coli, Enterococcus, and environmental covariates were measured in a treated wastewater holding pond (irrigation source water), water leaving the irrigation system, and in irrigated soils over 2 years in a municipal parkland in Arizona. Higher E. coli levels were measured in the pond in winter (56 CFU 100 mL(-1)) than in summer (17 CFU 100 mL(-1)); however, in the irrigation system, levels of FIB decreased from summer (26 CFU 100 mL(-1)) to winter (4 CFU 100 mL(-1)), possibly related to low winter water use and corresponding death of residual bacteria within the system. For over 2 years, no increase in FIB was found in irrigated soils, though highest E. coli levels (700 CFU g(-1) soil) were measured in deeper (20-25 cm) soils during summer. Measurements of water inputs vs. potential evapotranspiration indicate that irrigation levels may have been sufficient to generate bacterial percolation to deeper soil layers during summer. No overall increase in soil salinity resulting from treated wastewater irrigation was detected, but distinct seasonal peaks as high as 4 ds m(-1) occurred during both summers. The peaks significantly declined in winter when surface ET abated and more favorable water balances could be maintained. Monitoring of seasonal shifts in irrigation water quality and/or factors correlated with increases and decreases in FIB will aid in identification of any public health or environmental risks that could arise from the use of treated wastewater for irrigation.


Electrode measurement of oxygen tension with 1-ms time resolution.
A continuous flow device utilizing a Clark oxygen electrode was constructed; this device had a dead time and resolution of 1 ms. Mixing was tested by observing the neurtralization of acid with base, and at the maximal flow rate, the mixing was 94% complete within 1 ms and better than 98% complete within 2 ms after initial mixing. Observation o of the oxygenation of hemoglobin gave data which agreed with previous data obtained by a stopped-flow optical experiment. The respiration of phosphorylating submitochondrial particles was measured utilizing this device. The burst of respiration in submitochondrial particles was triphasic, with a very rapid burst lasting some 60 ms, followed by a longer burst of respiration lasting more than 4 s.


Lung particulate burdens of subjects from the Cincinnati, Ohio urban area.
Because of the relatively small data base existing for lung particulate burdens of subjects with no overt pneumoconioses, the total exogenous lung particulate concentrations of 91 subjects from the Cincinnati, Ohio urban area were determined using an automated scanning electron microscope-energy dispersive x-ray analysis-image analysis system. Four of these subjects were foundry workers and had the highest exogenous particle concentrations seen in the 91 lungs, ranging from 1860 to 2990 x 10(6) particles per gram of dry lung (ppg). The average exogenous particle concentration for the remaining 87 subjects was 476 +/- 380 x 10(6) ppg with a range of 71 to 1860 x 10(6) ppg. The median size of the exogenous particles in the 87 lungs was narrow, ranging from 0.37 to 1.02 microns. The geometric mean particle size over all 87 lungs was 0.60 microns with a geometric standard deviation (sigma g) of 2.35. The total exogenous particle levels were elevated for the male subjects compared to females (p=0.015), and were positively associated with age (p=0.021). However, no correlation was seen between total particle concentration and race or smoking history.


Plasma membrane of Entamoeba histolytica.
Axenically propagated Entamoeba histolytica (HK9:NIH strain) were employed as starting material for the isoation of plasma membrane by a novel procedure. In the absence of known enzymatic markers, the externally disposed polypeptides of intact amoebae were iodinated and the incorporated label used to monitor membrane separation and recovery. 12 major plasma membrane polypeptides (12 x 10(3)-200 x 10(3) mol wt) were labeled and separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Each of these was a glycoprotein. Preincubation of amoebae with concanavalin A stabilized the plasma membranes as large sheets, facilitating its separation by low-speed centrifugation. Dissociation of the lectin with alpha-methyl mannoside, followed by additional homogenization led to vesiculation and further purification. The isolated plasma membrane was recovered in high yield (28%) and enriched 30-fold in terms of incorporated iodide. All iodinated surface glycoproteins of the intact organism were present in the plasma membrane fraction. A Ca++-dependent ATPase was enriched in the plasma membrane to a similar extent, but over one-half of the total activity was associated with internal, unlabeled membranes, suggesting a dual localization of this activity. The isolated plasma membrane was enriched in cholesterol and had a cholesterol:molar ratio of 0.87. It also contained larger amounts of an unusual phospholipid--ceramide aminoethyl phosphonate--a phospholipase-resistant species.


Effects of hand hygiene campaigns on incidence of laboratory-confirmed influenza and absenteeism in schoolchildren, Cairo, Egypt.
To evaluate the effectiveness of an intensive hand hygiene campaign on reducing absenteeism caused by influenza-like illness (ILI), diarrhea, conjunctivitis, and laboratory-confirmed influenza, we conducted a randomized control trial in 60 elementary schools in Cairo, Egypt. Children in the intervention schools were required to wash hands twice each day, and health messages were provided through entertainment activities. Data were collected on student absenteeism and reasons for illness. School nurses collected nasal swabs from students with ILI, which were tested by using a qualitative diagnostic test for influenza A and B. Compared with results for the control group, in the intervention group, overall absences caused by ILI, diarrhea, conjunctivitis, and laboratory-confirmed influenza were reduced by 40%, 30%, 67%, and 50%, respectively (p<0.0001 for each illness). An intensive hand hygiene campaign was effective in reducing absenteeism caused by these illnesses.


Angle-closure glaucoma: impact, etiology, diagnosis, and treatment.
Recent studies underscore the importance of angle-closure glaucoma (ACG) as a cause of world blindness. A major contribution in assessing the true impact of this disease has been an article estimating the number of persons with occludable angles, angle closure, and blindness from ACG in China as 28.2 million, 9.1 million, and 1.7 million, respectively. Although these numbers are based on data from Singapore and Mongolia, which may be applied to China only with caution, they emphasize the blinding potential of ACG, which is three times as likely to be associated with blindness as open-angle glaucoma (OAG). Recent reports in the Chinese literature on ACG prevalence suffer from definitional problems that would appear to lead to systematic overestimates of ACG prevalence and underestimates of OAG prevalence. Nonetheless, data from studies by Chinese investigators further emphasize the strong association between ACG and blindness, with fully 16% of subjects with ACG blind in one report-a far higher proportion than for OAG in China and elsewhere. The importance of topiramate as a cause of secondary angle closure has recently been understood, in part, because of a series of 19 such cases reported by investigators at the Food and Drug Administration. Angle closure in this setting appears to be caused by uveal effusion and anterior rotation of the ciliary body with resultant closure of the angle. The condition is not always responsive to laser iridectomy, and elimination of the causative agent appears to be critical. Ultrasonic biomicroscopy is a potential new diagnostic modality for ACG, allowing the measurement of novel parameters, such as the angle opening distance (AOD) at 500 microm (AOD 500). The efficacy of such parameters in improving screening for ACG can only be established by prospective studies of potentially at-risk eyes. A number of novel treatments for AC and angle closure have recently been proposed, including cataract extraction, paracentesis, and argon laser iridoplasty. As with proposed new diagnostic modalities, the efficacy of these treatments remains to be demonstrated with prospective studies, ideally organized in a controlled, randomized fashion.


[Invasive pulmonary aspergillosis in AIDS.].
Aspergillosis is a fungal infection rarely observed in Cuba during the first years of the AIDS epidemic. However, the increase in aspergillosis cases diagnosed by autopsy in recent years, led us to study the epidemiological, clinical, radiological and anatomopathological characteristics of this disease among the Cuban AIDS patients. A total of 307 autopsies were reviewed, seven of them had invasive pulmonary aspergillosis (2.2%). The disease was predominant in men and in the white race. Neutropenia and drugs use were the risk factor more frequently observed. Clinical manifestations were those unspecific and common to other opportunistic infection of the respiratory system. The more common radiological picture were bilateral nodular infiltrates and cavitary lesions in the upper lobes (two cases). The anatomopathological diagnosis was based on the morphological characteristics of the agent and in the angioinvasive features of the pulmonary lesions. We suggest that aspergillosis should be considered in the differential diagnosis of opportunistic respiratory events of AIDS patients in advanced stages.


Specialized expression of simple O-glycans along the rat kidney nephron.
Glycosyltransferases can exhibit tissue-specific expression. By histochemistry glycosyltransferases and their products can be localized to specific cell types in organs of complex cellular composition. We have applied the lectin Amaranthin, having a nominal specificity for Galbeta1,3GalNAcR and Neu5Ac2,3Galbeta1, 3GalNAcalpha-R, and a monoclonal antibody raised against Galbeta1, 3GalNAcalphaR to examine the distribution of these simple O-glycans in adult rat kidney. The monoclonal antibody stained ascending thin limbs of Henle, distal convoluted tubules, and collecting ducts of cortex and outer medulla. Remarkably, the ascending thick limb of Henle, located between ascending thin limb and distal convoluted tubules, was unreactive. However, Amaranthin staining was detectable in ascending thick limbs of Henle, in addition to the structures positive with the monoclonal antibody. In kidney extracts, two bands of approximately 160 kDa and >210 kDa were reactive with both Amaranthin and the monoclonal antibody. One band at approximately 200 kDa, and a smear at approximately 100 kDa, were reactive only with Amaranthin. Our data show that in rat kidney simple O-linked glycans are expressed in a highly specialized manner along the renal tubule and can be detected only on a few glycoproteins. This may reflect a cell-type-specific expression of the corresponding glycosyltransferases.


Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells.
Myeloid (CD11c+) dendritic cells (DC) are present in cerebrospinal fluid (CSF), as well as in the meninges and choroid plexus. Functional studies of these DC are hindered or impossible. To obviate this problem, we investigated the effects of CSF supernatants from patients with non-inflammatory neurological diseases (NIND), multiple sclerosis (MS), bacterial meningitis (BM) and Lyme meningoencephalitis (LM) on immature monocyte-derived DC (moDC) from healthy donors. CSF supernatants caused maturation of moDC (MS > LM > NIND > BM), as reflected by a decrease in CD1a, and an increase in HLA-DR, CD80 and CD86 expression. The maturation effect of MS CSF and LM CSF could be blocked by anti-TNF-alpha MoAb or recombinant human IL-10. moDC cultured with BM CSF either remained immature or turned into CD14+ macrophage-like cells and were relatively inefficient at inducing T cell responses in vitro. In contrast, moDC cultured with LM CSF induced strong Th1 responses. Both BM CSF and LM CSF contained IFN-gamma, a cytokine that augments IL-12 production by moDC and hence should confer an ability to induce a Th1 response. However, BM CSF also contained high levels of IL-10, which could antagonize the effects of IFN-gamma on moDC. moDC cultured with MS CSF induced a higher production of IFN-gamma from T cells compared to moDC cultured with NIND CSF or BM CSF. In summary, soluble factors present in the CSF may influence the phenotype and functions of meningeal, choroid plexus and CSF DC which, in turn, may have an impact on the character of intrathecal T cell responses.


[The ecological debate from the hospital workers' standpoint].
This study seeks to ascertain what hospital workers think about the ecologic debate, looking for opinions that may elicit a discussion about the development of responsible actions to be taken by this group in the context of hospital work. The theoretical benchmark used for this discussion is based on the Reflexive Modernization and the Risk Society concept proposed by contemporary sociologists. This involved qualitative research using case study strategy and it was carried out with hospital workers at a public institution. The data were collected using document analysis, field observation and individual and group interviews. The study revealed that hospital workers take a somewhat distant view in terms of the environmental issue, which is reflexively affected by the current ecological debate. This concept has the influence of specific factors in the context of hospital work. In conclusion, the importance of educational actions together with the workers was identified, in order to establish more responsible actions with respect to environmental preservation.


Effect of black tea on enteral feeding tolerance in ICU patients.
Tea consumption has been known mostly as a well-drink after water in the world. Tea drink can affect balance of fluids and renal function. In addition, it can cause loss of many viruses in the stomach and can increase or decrease gastrointestinal movements. This research was done to determine the effect of tea on increasing enteral feeding tolerance in ICU patients in Alzahra Hospital. In this clinical trial study, 45 patients were enrolled in two groups, tea consumption group and the standard method of nutrition as control group. Tea gavage was performed two times in the morning; 100 cc tea used for the study group and the same volume of water was used for the control group. Residual volume was measured before gavage. Data collected for one week. Information sheet had two pages; the first page described how to complete the form and the method of tea gavage and the second page was for data collection. Data were analyzed by t-student test, chi-square, and analysis of variance. In two groups, 92% of patients tolerated liquid gavage. Their difference by chi-square test was not significant. Average urine volume after black tea gavage was 783.3 L in the study group and 802.2 L in the control group. ANOVA test showed no significant difference. Although the difference was not statistically significant between the two groups, but in study group consumption of tea was acceptable by patients.


Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro.
Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC50 = 1.28 μM, IC90 = 2.31 μM, and IC99 = 4.39 μM in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor.


The seasonal incidence of helminth parasites of cattle in the eastern Transvaal Lowveld.
Two helminth-free tracer calves were exposed to natural helminth infestation of a farm in the eastern Transvaal Lowveld for one month. On a nearby farm calves grazed with the herd for at least 3 months before slaughter so that the cumulative worm burden could be determined. The gastro-intestinal parasites increased markedly after rain. The major species and order or prevalence were: Cooperia pectinata, Cooperia punctata, Haemonchus placei and Oesophagostomum radiatum; minor species were Bunostomum phlebotomum, Trichostrongylus falculatus, Nematodirus helvetianus, Trichuris spp., Parafilaria bovicola and Paramphistomum spp. The highest worm burdens of Cooperia spp. on the first farm were between December and March and with the exception of O. radiatum, which had a peak in January, the other species reached peak worm burdens on the other farm in March.


Age-Related Effect of Uric Acid on Contrast-Induced Acute Kidney Injury of Patients Undergoing Coronary Angiography.
The association between uric acid (UA) and contrast-induced acute kidney injury (CI-AKI) following coronary angiography (CAG) has been established. However, whether the association would vary with age remained undetermined. We performed the retrospective analysis based on the Cardio-renal Improvement II study, (ClinicalTrials.gov NCT05050877), which enrolled consecutive patients undergoing coronary angiography in 5 teaching hospitals in China from 2007 to 2020. The primary outcome was CI-AKI defined as the rise of serum creatinine (SCr) ≥ 0.5 mg/dL or 25% compared with the baseline value within 48 hours following CAG. The effect of age on the association between uric acid and CI-AKI was assessed by the logistic regression model. A total of 36,550 patients (mean age 63.08±5.6-year-old, 41.7% men) were included in the study. After adjusting for the confounders, the risk of CI-AKI between each quartile of uric acid was insignificant in the young group. In patients of the middle group, lower UA was associated with a lower risk of CI-AKI while higher UA was associated with a higher risk (Q1 OR: 0.853, 95% CI: 0.734-0.993; Q4 OR: 1.797, 95% CI: 1.547-2.09). In patients of the elder group, lower and higher UA were both associated with a higher risk of CI-AKI (Q1 OR: 1.247, 95% CI: 1.003-1.553; Q4 OR: 1.688, 95% CI: 1.344-2.124). The restricted cubic spline indicated a non-linear association between UA and CI-AKI in middle and elder age groups but a linear association in the young age group. The association between uric acid and CI-AKI vary in patients of different age. Patients with elder age should maintain a middle level of uric acid while patients with middle age should consider a lower level of uric acid to reduce the risk of CI-AKI. The level of UA was an insignificant risk factor for CI-AKI in young patients.


The information content of panoramic images II: view-based navigation in nonrectangular experimental arenas.
Two recent studies testing navigation of rats in swimming pools have posed problems for any account of the use of purely geometric properties of space in navigation (M. Graham, M. A. Good, A. McGregor, & J. M. Pearce, 2006; J. M. Pearce, M. A. Good, P. M. Jones, & A. McGregor, 2004). The authors simulated 1 experiment from each study in a virtual reality environment to test whether experimental results could be explained by view-based navigation. The authors recorded a reference image at the target location and then determined global panoramic image differences between this image and images taken at regularly spaced locations throughout the arena. A formal model, in which an agent attempts to minimize image differences between the reference image and current views, generated trajectories that could be compared with the search performance of rats. For both experiments, this model mimics many aspects of rat behavior. View-based navigation provides a sufficient and parsimonious explanation for a range of navigational behaviors of rats under these experimental conditions.


Nursing students' experiences of delivering dementia friends sessions to peers.
Nursing students and registered nurses often feel underprepared for their roles in dementia care. Extracurricular activities offer nursing students additional opportunities for professional development. A student-academic partnership initiative was developed in which nursing students delivered dementia friends sessions to their peers before formal taught content. To explore dementia champion nursing students' experiences, identify factors that affect collaborative working and make recommendations for future student-academic partnership projects. In individual and dual interviews, three students were asked about their experiences of participating in the initiative. Interviews were recorded, transcribed and analysed using a thematic analysis framework. Four themes were identified: commitment to working with people who have dementia, difficulties in taking on extracurricular responsibilities, personal development, and relationships and collaboration. Students were motivated by the need to provide high-quality dementia care. They identified benefits of collaborative working including development of time management, team working, leadership, communication and presentation skills. Future projects should take into account student workloads and offer rewards that are congruent with nursing students' values.


The evidence for tamoxifen and chemotherapy as treatment for metastatic melanoma.
Tamoxifen, an oestrogen antagonist routinely used in the treatment of breast cancer, has been used in clinical trials for patients with melanoma since the late 1970s. Following initial promise as a single agent for the treatment of metastatic melanoma, tamoxifen was first combined with chemotherapy in this setting in 1984. Since then, numerous phase II studies have combined tamoxifen with different chemotherapeutic agents, with some suggesting that tamoxifen significantly improves the efficacy of cisplatin-containing regimens. Overall response rates range from 8 to 60%. Several randomised trials also have been completed, with response rates of 12-30%. One such study showed statistically significant improvements in response rate and survival when tamoxifen was added to dacarbazine; however, other studies have not observed these benefits with the addition of tamoxifen to cisplatin-containing regimens. At present, the author's opinion is that the strength of evidence does not support the use of tamoxifen in combination with cisplatin-containing chemotherapy for the treatment of metastatic melanoma. Controversy remains as to whether the strength of evidence from the randomised trials outweighs the combined evidence from numerous nonrandomised trials. Resolution of this controversy may depend on the results of the North Central Cancer Therapy Group and/or a common agreement as to relative strength of evidence from clinical trials of different designs.


Pause, Persist, Pivot: Key Decisions Health Professions Education Researchers Must Make About Conducting Studies During Extreme Events.
When extreme events occur, some research becomes a clear priority, but what becomes of all other research? Does it stop indefinitely, or can it be paused with plans to resume, persist with modifications, or pivot to address new priorities? Facing this dilemma and witnessing it among their fellow health professions education researchers, the authors recognized a need for guidance. This Invited Commentary presents a framework, organized as key questions related to the research stage and process, to assist health professions education researchers in making decisions about how to proceed with research that was planned or in progress when an extreme event occurred. Although at the time of this writing, the COVID-19 pandemic was the extreme event at hand, the authors intentionally created questions and discussed considerations that can be helpful for thinking through decisions in a variety of disruptions in health professions education research-many of which require similar difficult decisions and creative solutions to carry important research forward and maintain high quality.


Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3.
The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is critical for embryo implantation. Disturbance of this balance may lead to tumour metastasis. To understand the roles of MMP-26 and TIMP-4 in physiological and pathological invasion, the expression of these proteins in normal human cytotrophoblast cells and in a malignant choriocarcinoma cell line, JEG-3, was investigated. MMP-26 and TIMP-4 proteins were detected in the cytoplasm of these cells. The expression levels of MMP-26 mRNA and protein in JEG-3 cells were significantly higher than those in the cytotrophoblasts; conversely, the expression levels of TIMP-4 mRNA and protein were much lower in JEG-3 cells than those in cytotrophoblasts (P < 0.01). Enzyme inhibition studies demonstrated that TIMP-4 was a potent inhibitor of MMP-26 with an IC50 value of 0.4 nmol/l. This study confirms that MMP-26 is an epithelial enzyme and suggests that MMP-26 and TIMP-4 may play a role in tissue-remodelling processes associated with placentation and tumour progression, and that a higher MMP-26 to TIMP-4 ratio may promote cancer invasion.


Dietary medium chain fatty acid supplementation leads to reduced VLDL lipolysis and uptake rates in comparison to linoleic acid supplementation.
Dietary medium chain fatty acids (MCFA) and linoleic acid follow different metabolic routes, and linoleic acid activates PPAR receptors. Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention. Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a randomized double blind cross-over trial, 12 male subjects (age 51±7 years; BMI 28.5±0.8 kg/m2), were divided into 2 groups according to waist-hip ratio. They were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid for three weeks, with a wash-out period of six weeks in between. Lipoprotein subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers. Lipoprotein and tracer data were analyzed using computational modeling. Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention. In addition, LDL subclass concentrations were higher in lower body obese individuals. Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation. These differences were not due to elevated VLDL production, but rather to lower lipolysis and uptake rates.


Hong Kong Children's School Readiness in Times of COVID-19: The Contributions of Parent Perceived Social Support, Parent Competency, and Time Spent With Children.
School readiness is an important but challenging issue of child development, especially during COVID-19 when most of the traditional offline activities that could promote school readiness (e.g., on-site visit) have been canceled. There is a gap between the knowledge needed to promote children's school readiness in times of pandemic and the limited understanding of this topic so far. This gap could be particularly concerning in the social contexts where examinations are stressed and educational competition is high (e.g., Hong Kong). In this study, we examined how well children were ready for primary school, the extent to which parent perceived social support was related to children's school readiness, and whether parent competence and their time spent with children would moderate the said link. A cross-sectional design survey with total population sampling (supplemented with convenience sampling) was conducted. Massive e-mails were sent to all kindergartens in Hong Kong inviting them to join the study by distributing the survey link to the parents of their K3 students. A total of 643 Hong Kong parents whose children were about to transition to primary school (87.1% mother) participated, answering measures specifically designed for this study online about how well they thought their children were ready for school, their competence to help with children's school transition, and how much time they spent with children. Data were analyzed with PROCESS macro (model 3) in SPSS. The results found that most parents considered that their children were not fully ready for school, especially in terms of academic skills, self-management, and mental preparation. Furthermore, moderation analyses showed that after controlling for a number of demographic variables, parent perceived social support was positively related to better school readiness in children and this link was jointly moderated by parent competence and time spent with children. Specifically, children were rated most ready when parent perceived stronger social support, felt more competent, and spent more time with children. By contrast, the link between perceived social support and children's school readiness was insignificant for parent who felt more competent but spent less time with children. Implications of how to enhance children's school readiness are discussed.


Contralateral fracture of the proximal femur. Implications for planning trials.
In three consecutive years 462 patients over the age of 60 years presented at Waikato Hospital, Hamilton, New Zealand, with a fracture of the proximal femur. Within two years, 11 (2.4%) returned with a fracture of the contralateral femur. If the effectiveness of any form of treatment aiming at reducing the incidence of contralateral fracture were subjected to a trial, a sample size of 5000, randomly distributed equally between treatment and placebo groups, would be needed for the trial to have a power of 80% to detect a reduction.


The effect of the Ebbinghaus illusion on grasping behaviour of children.
Within the context of the Ebbinghaus illusion, adults regularly misjudge the physical size of a centre disc, yet scale their hand aperture according to its actual size. Separate visual pathways for perception and action are assumed to account for this finding. The dorsal visual stream is said to elaborate on egocentric (visuomotor), while the ventral stream is involved in allocentric transformations (object recognition). This study examines the ontogenetic development of this dissociation between perception and action in 35 children between the ages of 5 and 12 years. We report four major results. First, when children judged object size without grasping the disc, their judgements were deceived by the illusion to the same extent as adults. However, when asked to estimate size and then to grasp the disc, young children's (5-7 years) perceptual judgements became unreliable, while adults were still reliably deceived by the illusion in 80% of their trials. Second, the younger the children, the more their aperture was affected by the illusional surround. Discs of the same size were grasped with a smaller aperture when surrounded by a small annulus, although they were perceived as being larger. Third, young children used the largest safety margin during grasping. Fourth, the reliance on visual feedback decreased with increasing age, which was documented by shorter movement times and earlier maximum hand opening during grasping in the older children (feedforward control). Our results indicate that grasping behaviour in children is subject to an interaction between ventral and dorsal processes. Both pathways seem not to be functionally segregated in early and middle childhood. The data are inconclusive about whether young children predominantly use a specific visual stream for either a perceptual or motor task. However, our data demonstrate that children were relying on both visual processing streams during perceptual as well as visuomotor tasks. We found that children used egocentric cues to make perceptual judgements, while their grasping gestures were not exclusively shaped by viewer-centred but also by object-centred information.


Frequency of restoration replacement in posterior teeth for U.S. Navy and Marine Corps personnel.
There are no recent data that describe the replacement rates of resin composite and dental amalgam restorations placed by US Navy dentists. Information is needed to provide the best possible care for our military personnel which would minimize the probability of dental emergencies, especially for those who are deployed. The purpose of this study was to determine if the frequency of posterior restoration replacement in military personnel differed based on the type of restorative material utilized. Data contained in dental records in an observational study (retrospective cohort) were evaluated to identify resin composite and dental amalgam restorations placed by navy dentists in posterior teeth. The status of all erupted, unerupted, missing, and replaced teeth was documented. The type and condition of all existing restorations were recorded for each posterior tooth. Investigators reviewed 2921 dental records, and of those, 247 patients met the criteria for inclusion in the study. A total of 1050 restorations (485 resin composite and 565 amalgam) were evaluated. A Cox proportional hazards model was adjusted for number of tooth surfaces restored, caries risk, and filled posterior surfaces at initial exam. The overall rate of replacement for all restorations in the sample was 5.7% during the average 2.8-year follow-up. No significant elevation of risk for restoration replacement existed when comparing resin composite and amalgam. Both the number of restored surfaces and caries risk status were independent risk factors for replacement. When restoring multisurface cavity preparations, providers placed amalgams by an approximate 2:1 ratio over resin composites for this study population. The results for this study show that no difference existed in the rate of replacement for amalgam vs resin composite. When restorations increased from just a single occlusal surface to additional surfaces, the rate of replacement was elevated and statistically significant for both materials. A higher caries risk status was also significant in elevating replacement rates for both materials.


CT for Treatment Selection in Acute Ischemic Stroke: A Code Stroke Primer.
CT is the primary imaging modality used for selecting appropriate treatment in patients with acute stroke. Awareness of the typical findings, pearls, and pitfalls of CT image interpretation is therefore critical for radiologists, stroke neurologists, and emergency department providers to make accurate and timely decisions regarding both (a) immediate treatment with intravenous tissue plasminogen activator up to 4.5 hours after a stroke at primary stroke centers and (b) transfer of patients with large-vessel occlusion (LVO) at CT angiography to comprehensive stroke centers for endovascular thrombectomy (EVT) up to 24 hours after a stroke. Since the DAWN and DEFUSE 3 trials demonstrated the efficacy of EVT up to 24 hours after last seen well, CT angiography has become the operational standard for rapid accurate identification of intracranial LVO. A systematic approach to CT angiographic image interpretation is necessary and useful for rapid triage, and understanding common stroke syndromes can help speed vessel evaluation. Moreover, when diffusion-weighted MRI is unavailable, multiphase CT angiography of collateral vessels and source-image assessment or perfusion CT can be used to help estimate core infarct volume. Both have the potential to allow distinction of patients likely to benefit from EVT from those unlikely to benefit. This article reviews CT-based workup of ischemic stroke for making tPA and EVT treatment decisions and focuses on practical skills, interpretation challenges, mimics, and pitfalls.©RSNA, 2019.


Repurposing itraconazole as a treatment for advanced prostate cancer: a noncomparative randomized phase II trial in men with metastatic castration-resistant prostate cancer.
The antifungal drug itraconazole inhibits angiogenesis and Hedgehog signaling and delays tumor growth in murine prostate cancer xenograft models. We conducted a noncomparative, randomized, phase II study evaluating the antitumor efficacy of two doses of oral itraconazole in men with metastatic prostate cancer. We randomly assigned 46 men with chemotherapy-naïve metastatic castration-resistant prostate cancer (CRPC) to receive low-dose (200 mg/day) or high-dose (600 mg/day) itraconazole until disease progression or unacceptable toxicity. The primary endpoint was the prostate-specific antigen (PSA) progression-free survival (PPFS) rate at 24 weeks; a 45% success rate in either arm was prespecified as constituting clinical significance. Secondary endpoints included the progression-free survival (PFS) rate and PSA response rate (Prostate Cancer Working Group criteria). Exploratory outcomes included circulating tumor cell (CTC) enumeration, serum androgen measurements, as well as pharmacokinetic and pharmacodynamic analyses. The high-dose arm enrolled to completion (n = 29), but the low-dose arm closed early (n = 17) because of a prespecified futility rule. The PPFS rates at 24 weeks were 11.8% in the low-dose arm and 48.0% in the high-dose arm. The median PFS times were 11.9 weeks and 35.9 weeks, respectively. PSA response rates were 0% and 14.3%, respectively. In addition, itraconazole had favorable effects on CTC counts, and it suppressed Hedgehog signaling in skin biopsy samples. Itraconazole did not reduce serum testosterone or dehydroepiandrostenedione sulfate levels. Common toxicities included fatigue, nausea, anorexia, rash, and a syndrome of hypokalemia, hypertension, and edema. High-dose itraconazole (600 mg/day) has modest antitumor activity in men with metastatic CRPC that is not mediated by testosterone suppression.


Ultrasound findings in acute viral hepatitis.
Serological markers for the virus remain mainstay of diagnosis of acute viral hepatitis. However, it is not available in all part of our country. The aim of this study is to find out the sonological findings of the hepatobiliary system that may aid to clinch the diagnosis of acute viral hepatitis. One hundred seventy seven consecutive patients with clinical diagnosis of acute viral hepatitis from June 2004 to June 2006 attending liver clinic were enrolled in this study. After exclusion of 32 patients 145 patients with definitive diagnosis by serological confirmation were studied. Hepatitis E (85%) was most common followed by B (10%) and A (5%). Gall bladder finding was more common than hepato-splenomegaly. Collapsed gall bladder with increased wall thickness and pericholecystic oedema was present in more than 50% of the patient. In HAV hepatitis it was present in all patients while in HEV hepatitis it was present in 84% patients. Gall bladder findings in ultrasound are present in over 80% of enterically transmitted hepatitis virus. Thus, it can be used to diagnose acute hepatitis when serological tests are not available.


Predictive parameters of mitoxantrone effectiveness in the treatment of multiple sclerosis.
In a number of controlled trials it was established that mitoxantrone has a beneficial effect on disease progression in multiple sclerosis (MS) patients with a worsening disease course. The aim of this study was to investigate the use of mitoxantrone in clinical practice, and especially to describe predictive parameters of its effectiveness under these conditions. In a retrospective, open-label mitoxantrone study we analysed 94 MS patients (49% relapsing remitting MS (RRMS), 41% secondary progressive MS and 10% primary progressive MS) who received monthly 20 mg i.v. mitoxantrone and 1 g i.v. methylprednisolone for six months, and selected as a criterion of effectiveness the percentage of patients with an Expanded Disability Status Scale (EDSS) improvement of at least one point (confirmed after one year) after stopping the treatment. A multivariate analysis was undertaken to assess the predictive value of five parameters on mitoxantrone effectiveness: (1) total number of relapses since disease onset and before treatment, (2) number of relapses within the past 24 months before treatment, (3) number of relapses in separate areas within the past 24 months before treatment, (4) active MRI scans (including Gd-enhanced lesions), and (5) clinical course of MS. During the observation period from 1 January 1997 to 30 May 2000 more than 44% of the patients improved by one point or more on the EDSS (confirmed after one year), 39% remained stable and 17% deteriorated. In patients with a RRMS course three or more relapses within the past 24 months preceding treatment, and at least one Gd-enhancing lesion resulted in a strong relative benefit (i.e., relative risk) of mitoxantrone effectiveness. In contrast, total number of relapses since disease onset had no impact on disease evolution and disability progression. Multivariate analysis revealed the number of relapses in separate areas within the past 24 months before treatment as the strongest predictive parameter (P < 0.001). Mitoxantrone is effective in improving and stabilizing patients with a worsening MS course in routine clinical practice. Several strong predictive parameters of mitoxantrone effectiveness were investigated among which the number of relapses in separate areas within the past 24 months before treatment was found to be the strongest parameter to predict clinical improvement.


Testing the egocentric mirror-rotation hypothesis.
Although observers know about the law of reflection, their intuitive understanding of spatial locations in mirrors is often erroneous. Hecht et al. (2005) proposed a two-stage mirror-rotation hypothesis to explain these misconceptions. The hypothesis involves an egocentric bias to the effect that observers behave as if the mirror surface were rotated by about 2 degrees to be more orthogonal than is the case. We test four variants of the hypothesis, which differ depending on whether the virtual world, the mirror, or both are taken to be rotated. We devised an experimental setup that allowed us to distinguish between these variants. Our results confirm that the virtual world--and only the virtual world--is being rotated. Observers had to perform a localization task, using a mirror that was either fronto-parallel or rotated opposite the direction of the predicted effect. We were thus able to compensate for the effect. The positions of objects in mirrors were perceived in accordance with the erroneous conception that the virtual world behind the mirror is slightly rotated and that the reconstruction is based on the non-rotated fronto-parallel mirror. A covert rotation of the mirror by about 2 degrees against the predicted effect was able to compensate for the placement error.


Giving off mixed signals--distinct functions of alpha5beta1 and alphavbeta3 integrins in regulating cell behaviour.
The formation, maturation, and dissolution of focal adhesions are basic prerequisites of cell migration and rely on the recruitment, signalling, and endocytosis of integrins. In many instances, extracellular matrix molecules are recognised by a number of integrins, and it is the sequential involvement of different integrins that allows establishment of cell polarity and migration towards a matrix stimulus. In this review, we consider both the similarities and differences between two key fibronectin receptors, alpha(v)beta(3) and alpha(5)beta(1) integrin. By considering the GTPase and kinase signalling and trafficking of two such closely-related receptors, we begin to understand how cell migration is coordinated.


The use of the seminar to teach group process and group leadership with registered nurse students at the baccalaureate level.
Group process and group leadership "are areas in which definite skills can and must be learned; we are not all intuitively capable of working effectively with groups" (Sampson & Marthas, 1977, p. 18). A knowledge of effective group process and leadership ability in working with groups are essential for RN baccalaureate graduates who will be working with groups in a variety of settings in professional nursing practice. Through the use of the seminar as a teaching method, students learn the principles of group process and group leadership, function as a member of a group, and have the opportunity to practice leadership skills through leading seminar discussions. All of these experiences are vital components of baccalaureate nursing education for RN students.


Catechin or quercetin guests in an intrinsically microporous polyamine (PIM-EA-TB) host: accumulation, reactivity, and release.
Microporous polymer materials based on molecularly "stiff" structures provide intrinsic microporosity, typical micropore sizes of 0.5 nm to 1.5 nm, and the ability to bind guest species. The polyamine PIM-EA-TB contains abundant tertiary amine sites to interact via hydrogen bonding to guest species in micropores. Here, quercetin and catechin are demonstrated to bind and accumulate into PIM-EA-TB. Voltammetric data suggest apparent Langmuirian binding constants for catechin of 550 (±50) × 103 M-1 in acidic solution at pH 2 (PIM-EA-TB is protonated) and 130 (±13) × 103 M-1 in neutral solution at pH 6 (PIM-EA-TB is not protonated). The binding capacity is typically 1 : 1 (guest : host polymer repeat unit), but higher loadings are readily achieved by host/guest co-deposition from tetrahydrofuran solution. In the rigid polymer environment, bound ortho-quinol guest species exhibit 2-electron 2-proton redox transformation to the corresponding quinones, but only in a thin mono-layer film close to the electrode surface. Release of guest molecules occurs depending on the level of loading and on the type of guest either spontaneously or with electrochemical stimuli.


Endotracheal intubation at birth for preventing morbidity and mortality in vigorous, meconium-stained infants born at term.
On the basis of evidence from non-randomised studies, it has been recommended that all babies born through thick meconium should have their tracheas intubated so that suctioning of their airways can be performed. The aim is to reduce the incidence and severity of meconium aspiration syndrome. However, for term babies who are vigorous at birth endotracheal intubation may be both difficult and unnecessary. To determine if endotracheal intubation and suction of the airways at birth in vigorous term meconium-stained babies is more beneficial than routine resuscitation including aspiration of the oro-pharynx. The search was made from Oxford Database of Perinatal Trials, the Neonatal Trials Registry of the Cochrane Neonatal Collaborative Review Group and information obtained from knowledgeable practising neonatologists. Randomised trials which compared a policy of routine vs no (or selective) use of endotracheal intubation and aspiration in the immediate management of vigorous term meconium-stained babies at birth. Data regarding clinical outcomes including mortality, meconium aspiration syndrome, other respiratory conditions, pneumothorax, need for oxygen supplementation, stridor, convulsions and hypoxic-ischaemic encephalopathy were abstracted and analysed using Revman 3.1.1. Four randomised controlled trials of endotracheal intubation at birth in vigorous term meconium-stained babies were identified. Meta-analysis of these trials does not support routine use of endotracheal intubation at birth in vigorous meconium-stained babies to reduce mortality, meconium aspiration syndrome, other respiratory symptoms or disorders, pneumothorax, oxygen need, stridor, HIE and convulsions. Routine endotracheal intubation at birth in vigorous term meconium-stained babies has not been shown to be superior to routine resuscitation including oro-pharyngeal suction. This procedure cannot be recommended for vigorous infants until more research is available.


Interferon alfa-associated anterior ischemic optic neuropathy.
To report a possible association between interferon alfa therapy and anterior ischemic optic neuropathy (AION). Database study and review of the literature. Thirty-six case reports from spontaneous reporting systems and the literature. Case reports from a review of the literature were combined with spontaneous reports from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, and the Food and Drug Administration looking for reports on interferon therapy associated with optic neuropathy. Data from the spontaneous reports include the type of interferon, age, gender, adverse drug reaction (ADR), dosage, duration of therapy until onset of ADR, concomitant drugs, systemic disease, and dechallenge and rechallenge data. Thirty-six case reports of AION are described in association with interferon alfa therapy. The average age of subjects was 54.5 years; 26 were male and 10 were female. The median duration of therapy to onset of AION was 4.5 months, with 50% of subjects having some form of permanent vision loss. Anterior ischemic optic neuropathy was bilateral in 67% of subjects. There are 3 positive rechallenge case reports. Interferon alfa's association with AION can be classified as "possible" using the World Health Organization classification system. If optic neuropathy is suspected, rapid cessation of interferon therapy may portend a better prognosis because multiple case reports indicate visual defects may be permanent if this possible ADR remains unrecognized.


Melatonin-mediated CcARP1 alters F-actin dynamics by phosphorylation of CcADF9 to balance root growth and salt tolerance in pigeon pea.
As a multifunctional hormone-like molecule, melatonin exhibits a pleiotropic role in plant salt stress tolerance. While actin cytoskeleton is essential to plant tolerance to salt stress, it is unclear if and how actin cytoskeleton participates in the melatonin-mediated alleviation of plant salt stress. Here, we report that melatonin alleviates salt stress damage in pigeon pea by activating a kinase-like protein, which interacts with an actin-depolymerizing factor. Cajanus cajan Actin-Depolymerizing Factor 9 (CcADF9) has the function of severing actin filaments and is highly expressed under salt stress. The CcADF9 overexpression lines (CcADF9-OE) showed a reduction of transgenic root length and an increased sensitivity to salt stress. By using CcADF9 as a bait to screen an Y2H library, we identified actin depolymerizing factor-related phosphokinase 1 (ARP1), a novel protein kinase that interacts with CcADF9. CcARP1, induced by melatonin, promotes salt resistance of pigeon pea through phosphorylating CcADF9, inhibiting its severing activity. The CcARP1 overexpression lines (CcARP1-OE) displayed an increased transgenic root length and resistance to salt stress, whereas CcARP1 RNA interference lines (CcARP1-RNAi) presented the opposite phenotype. Altogether, our findings reveal that melatonin-induced CcARP1 maintains F-actin dynamics balance by phosphorylating CcADF9, thereby promoting root growth and enhancing salt tolerance.


Antiproliferative activity of brown Cuban propolis extract on human breast cancer cells.
Brown Cuban propolis (BCP) is the major type of propolis in Cuba; its chemical composition is exclusive and the principal component is nemorosone. In this study we investigated the antiproliferative activity of the ethanol extract of BCP on human breast cancer cell lines. The MTT assay showed a significant antiproliferative activity (P<0.005) of BCP on MCF-7 (estrogen receptor positive ER+) rather than MDA-MB 23 1 (ER-). This effect was concentration- (1-25 microg/mL) and time- (24-48 h) dependent, but it is only partially attributable to apoptosis. Indeed, our data showed that BCP administration to MCF-7 caused a significant (P>0.01) inhibition of cell growth in the G1 phase of cell cycle, which was mechanism dose- and time-dependent. 17-beta Estradiol (10 nM) administration to MCF-7 caused a significant (P<0.001), but not total reduction of BCP antiproliferative activity at concentrations of 1, 5 and 10 microg/mL, but not at the highest concentration (25 microg/mL). The coadministration of ICI 182,780 (100 nM), an antagonist of ER, on MCF-7 totally reduced the effect of BCP at 24 h, and showed a significant (P<0.001) reduction of BCP antiproliferative activity at 48 h. Thus it was hypothesized that BCP possesses an estrogen-like activity. It is to be noted, however, that BCP application to MDA-MB 23 1 at 48 h also induced increased cell mortality. Thus, it cannot be ruled out that BCP could not only interact with the ER, but also have an ER-independent activity.


Decreased AIRE expression and global thymic hypofunction in Down syndrome.
The Down syndrome (DS) immune phenotype is characterized by thymus hypotrophy, higher propensity to organ-specific autoimmune disorders, and higher susceptibility to infections, among other features. Considering that AIRE (autoimmune regulator) is located on 21q22.3, we analyzed protein and gene expression in surgically removed thymuses from 14 DS patients with congenital heart defects, who were compared with 42 age-matched controls with heart anomaly as an isolated malformation. Immunohistochemistry revealed 70.48 ± 49.59 AIRE-positive cells/mm(2) in DS versus 154.70 ± 61.16 AIRE-positive cells/mm(2) in controls (p < 0.0001), and quantitative PCR as well as DNA microarray data confirmed those results. The number of FOXP3-positive cells/mm(2) was equivalent in both groups. Thymus transcriptome analysis showed 407 genes significantly hypoexpressed in DS, most of which were related, according to network transcriptional analysis (FunNet), to cell division and to immunity. Immune response-related genes included those involved in 1) Ag processing and presentation (HLA-DQB1, HLA-DRB3, CD1A, CD1B, CD1C, ERAP) and 2) thymic T cell differentiation (IL2RG, RAG2, CD3D, CD3E, PRDX2, CDK6) and selection (SH2D1A, CD74). It is noteworthy that relevant AIRE-partner genes, such as TOP2A, LAMNB1, and NUP93, were found hypoexpressed in DNA microarrays and quantitative real-time PCR analyses. These findings on global thymic hypofunction in DS revealed molecular mechanisms underlying DS immune phenotype and strongly suggest that DS immune abnormalities are present since early development, rather than being a consequence of precocious aging, as widely hypothesized. Thus, DS should be considered as a non-monogenic primary immunodeficiency.


Seeking the competitive advantage: it's more than cost reduction.
Most organizations focus considerable time and energy on reducing operating costs as a way to attain marketplace advantage. This strategy was not inappropriate in the past. To be competitive in the future, however, focus must be placed on other issues, not just cost reduction. The near future will be dominated by service industries, knowledge management, and virtual partnerships, with production optimization and flexibility, innovation, and strong partnerships defining those organizations that attain competitive advantage. Competitive advantage will reside in clarifying the vision and strategic plan, reviewing and redesigning work processes to optimize resources and value-added work, and creating change-ready environments and empowered workforces.


Ideal combination of dementia screening tests.
Although many neuropsychological tests have been developed to evaluate higher brain dysfunction, conducting several tests in daily medical care is very difficult for both the patient and the examiner. We herein reviewed the correlation between the results of 11 neuropsychological tests in order to create a new compact and easily administered combination of screening tests to detect dementia. We performed 11 neuropsychological tests in 1,674 outpatients suspected of having cognitive dysfunction and 46 normal control subjects. The 11 tests included the following examinations: the mini mental state examination (MMSE) and Hasegawa dementia rating scale-revised (HDS-R) for the total intelligence function, the frontal assessment battery (FAB) and Montreal cognitive assessment (MoCA) for the frontal lobe function, the neuropsychiatric inventory (NPI) and Abe's behavioral and psychological symptoms of dementia score (ABS) for emotional changes, the geriatric depression scale (GDS) for depressive conditions, the vitality index (VI) and apathy score (AS) for reduced motivation and the clinical dementia rating (CDR) and Alzheimer's disease cooperative study-activities of daily living (ADCS-ADL) scale for ADL's. In order to determine the most compact test series, we compared all test features, correlations between the scores and the time required to complete each test. Correlations were found between tests of the cognitive function, tests of the cognitive function vs NPI, tests of the cognitive function vs ADL, NPI vs ABS, NPI vs GDS, GDS vs AS, VI vs AS and CDR vs ADCS-ADL. The duration of testing was shorter for the FAB than for the MoCA and for the ABS than for the NPI. A combination of six tests (MMSE or HDS-R, FAB, ABS, GDS, AS and ADCS-ADL) was found to be useful for screening dementia and reducing the test burden on the patient in daily medical practice.


Identifying barriers to Papanicolaou smear screening in Korean women: Korean National Health and Nutrition Examination Survey 2005.
This study was conducted to provide a nationwide analysis on barriers to cervical cancer screening in Korea. Data used for this study was obtained in a survey called Korean National Health and Nutrition Examination Survey (KNHANES) 2005, which collected data from 2,590 Korean women aged older than 21 years who had not had a hysterectomy and were eligible for Papanicolaou (Pap) smears. Multivariate analysis was adopted to control each demographic factor and unhealthy behavior variable. Demographic factors included age, education, income, job and region; health-related behavior factors were defined as current smoking, obesity, hormone replacement therapy and disability. The study found that cervical cancer screening rate was significantly positively associated with income (odds ratio [OR], 1.002; 95% confidence interval [CI], 1.001 to 1.002), with education (OR, 1.324; 95% CI, 1.030 to 1.703), with job (OR, 1.420; 95% CI, 1.030 to 1.957), and with hormone replacement therapy (OR, 3.732; 95% CI, 2.354 to 5.916). Meanwhile, the age (OR, 0.977; 95% CI, 0.968 to 0.985), disability (OR, 0.358; 95% CI, 0.143 to 0.894) and smoking (OR, 0.447; 95% CI, 0.280 to 0.715) were significantly negatively associated with one's chances to take cervical cytology. In order to increase the rates of Korean women taking Pap test, cervical cancer screening programs will have to pay special attention to the elderly, low-income group, smokers, and the disabled.


Oral salmonella challenge and subsequent uptake by the peripheral lymph nodes in calves.
Previous attempts to infect peripheral lymph nodes (PLNs) with Salmonella via oral inoculation have been inconsistent. Therefore, we performed a series of experiments to determine whether multiple exposures to an oral challenge would result in Salmonella-positive PLN in cattle. In each of three experiments, calves were inoculated with Salmonella Montevideo. In the first experiment, calves were challenged with either no Salmonella (control), a single oral dose (∼10(10); PCON), or 10 consecutive doses in water (∼10(3); WAT). The positive control treatment resulted in an increase (P < 0.05) in the percentage of Salmonella-positive PLNs, compared with the WAT-treated and control animals. Experiments 2 and 3 were designed to additionally determine if the stress associated with feed and water deprivation influences the systemic spread of Salmonella from the gastrointestinal tract to PLNs. Following 14 days of oral inoculation (average 7.1 × 10(4) CFU/day) in experiment 1, Salmonella was recovered from one subiliac and one superficial cervical lymph node of calves that were deprived of feed and water (72 h). No treatment differences (P > 0.05) were observed between control and deprived calves. Based on the poor recovery of Salmonella from the PLNs in WAT-challenged calves in experiments 1 and 2, a higher challenge dose (average 1.2 × 10(7) CFU) was used in experiment 3. The increased dose resulted in the recovery of the challenge strain of Salmonella from the PLNs (70.8 and 75.0% of control and deprived calves, respectively). However, no treatment differences (P > 0.05) were observed between control and deprived calves. Results of this research demonstrated that a substantial oral challenge is required to produce Salmonella-positive PLNs. However, as the challenge periods examined herein were considerably shorter compared with the normal time spent by cattle in feedlots, increased exposure time to lower doses may produce the same effect observed in experiment 3.


Cyclic nucleotide regulation of the contractile proteins in mammalian cardiac muscle.
The contractile system of rat cardiac muscle that has been made hyperpermeable by soaking the tissue in EGTA (McClellan and Winegrad. 1978. J. Gen. Physiol. 72:737-764) can be probed directly with Ca buffer from the bathing solution without significant interference from either sarcoplasmic reticulum or mitochondria on the Ca concentration. Changes in Ca-activated force are due therefore to changes in the properties of the contractile system itself and not to regulation of Ca concentration. The addition of cAMP, cGMP, and GTP, guanylyl imidodiphosphate (GMP-PNP), or epinephrine to the bath does not alter maximum Ca-activated force, but when these drugs are added with 1% nonionic detergent to the bath, contractility increases by as much as 180%. An inhibitor of phosphodiesterase must be present for the inotropic effect of cAMP but not cGMP, GTP, GMP-PNP, or epinephrine. The inotropic response to cAMP is independent of the Ca sensitivity of the contractile system, but guanine nucleotides enhance contractility only when Ca sensitivity is not high. The inotropic effect of epinephrine is inhibited to a large extent by cGMP but not by GMP-PNP. These data can be explained by a model in which contractility is enhanced by a cAMP-regulated phosphorylation that can be controlled through the beta-receptor adenylate cyclase complex in the sarcolemma. The regulation involves two reactions, one a phosphorylation and a second that occurs in the presence of detergent. Phosphorylation of neither the myosin light chain nor the inhibitory subunit of troponin appears to be involved in this mechanism for regulating contractility.


Effects of dietary lysine/protein ratio and fat levels on growth performance and meat quality of finishing pigs.
This study aimed to evaluate the effects of dietary lysine/protein ratio and fat levels on the growth, carcass characteristics and meat quality of finishing pigs fed feed made from food waste, including noodles and chocolate. Four dietary treatments, 2 levels of lysine/protein ratio (0.035 and 0.046) and 2 levels of fat (3.3% and 6.0%), were adapted to a 2 × 2 factorial arrangement. Each diet for the finishing pigs contained the same levels of adequate crude protein (16%) and lysine (0.58-0.75%), and similar levels of high total digestible nutrients (90.2-92.6%). In total, 32 LWD pigs with an average body weight of 57.2 kg were assigned to 4 dietary groups. The pigs were slaughtered at about 115 kg. Growth performance was not influenced by the dietary treatments. Carcass characteristics were slightly influenced by the dietary fat level. As the dietary lysine/protein ratio decreased, the marbling score of Longissimus dorsi muscle increased and the intramuscular fat (IMF) increased from 6.82% to 9.46%. Marbling score was not significantly influenced by the dietary fat level. These results indicate that IMF increased without adverse effects on growth, carcass characteristics and meat quality, when pigs were fed a diet with low lysine/protein ratio.


The effect of antiplatelet autoantibodies on megakaryocytopoiesis.
Immune thrombocytopenic purpura (ITP) is a disorder manifested by isolated thrombocytopenia. In vivo infusion studies in the 1950s and 1960s provided evidence that the thrombocytopenia was due to autoantibody-induced platelet destruction. However, there is mounting evidence that platelet production in this disorder may also be suppressed by antibodies. Early morphologic studies showed megakaryocytic damage in ITP, and these results have been confirmed by ultrastructural studies. Autologous platelet turnover studies in the 1980s showed that most ITP patients have either normal or reduced platelet turnover rather than increased turnover, as would be expected if platelet destruction were the only pathogenetic mechanism. More recently, in vitro culture studies of both adult and pediatric ITP have shown that some ITP plasmas suppress both megakaryocytopoiesis and thrombopoiesis. In view of these findings, both platelet destruction and suppression of platelet production seem likely to be involved in the pathogenesis of ITP.


Inhibition of stimulated interleukin-2 production in whole blood: a practical measure of cyclosporine effect.
Prediction of cyclosporine (CSA) efficacy and toxicity in individual patients is difficult. There is no practical, biologically relevant, pharmacodynamic measure of CSA effect. A major effect of CSA is to decrease interleukin-2 (IL-2) production; however, measurement of this effect in isolated lymphocytes as a marker of response to CSA has been problematic. CSA inhibition of phytohemagglutinin-P (PHA)-stimulated IL-2 production, measured by ELISA, was studied ex vivo in whole blood drawn before, and after subjects received 4 mg/kg oral CSA. Four hours after CSA was administered, the mean (+/- SD) CSA concentration was 702 +/- 196 microg/L and PHA-stimulated IL-2 production decreased by 68.7% +/- 17.2% (P <0.0001; n = 17). Twenty-four hours after CSA was administered, concentrations were low (64 +/- 24 microg/L), with no inhibition of IL-2 production. A rapid, concentration-dependent response occurred. Maximum CSA concentrations (944 +/- 187 microg/L) and maximum inhibition of IL-2 production (86.9% +/- 13.7%) occurred 90 min after subjects received CSA. In vitro, 32.5-1200 microg/L CSA also inhibited PHA-stimulated IL-2 production in whole blood in a dose-dependent fashion with a similar IC(50) (approximately 300-400 microg/L) ex vivo and in vitro. In the search for a pharmacodynamic marker to better guide immunosuppressive therapy, the relationship between this simple, biologically relevant measure of CSA effect and clinical outcome should be determined.


Electrochemical determination of L-phenylalanine at polyaniline modified carbon electrode based on β-cyclodextrin incorporated carbon nanotube composite material and imprinted sol-gel film.
A sensitive and selective electrochemical sensor based on a polyaniline modified carbon electrode for the determination of L-phenylalanine has been proposed by utilizing β-cyclodextrin (β-CD) incorporated multi-walled carbon nanotube (MWNT) and imprinted sol-gel film. The electrochemical behavior of the sensor towards L-phenylalanine was investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and amperometric i-t curve. The surface morphologies of layer-by-layer assembly electrodes were displayed by scanning electron microscope (SEM). The response mechanism of the imprinted sensor for L-phenylalanine was based on the inclusion interaction of β-CD and molecular recognition capacity of the imprinted film for L-phenylalanine. A linear calibration plot was obtained covering the concentration range from 5.0 × 10(-7) to 1.0 × 10(-4) mol L(-1) with a detection limit of 1.0 × 10(-9) mol L(-1). With excellent sensitivity, selectivity, stability, reproducibility and recovery, the electrochemical imprinted sensor was used to detect L-phenylalanine in blood plasma samples successfully.


Fluoroscopy Is Essential in Retrograde Intrarenal Surgery.
This study aimed to investigate the necessity of using fluoroscopy in retrograde intrarenal surgery (RIRS). Material and Methods. A total of 612 patients who underwent RIRS for kidney stones were evaluated and divided into two groups. Group 1 routinely underwent the operation with fluoroscopy due to opaque stones (n: 504). In group 2, the procedure was performed without fluoroscopy because of nonopaque stones (n: 108). Both groups were assessed for stone size, location, and number. Success and complication rates were compared between the two groups. This study was designed with the thought of not using fluoroscopy in RIRS patients with nonopaque stones and having the same stone-free rates in opaque stones. In the statistical analysis, there was no difference between the groups with and without scope for stone side, size, localization, and number; likewise, the complication rates developed in the comparison of both groups, stone-free rates, and hospital stay were the same. Discussion. Advances in the calibration of instruments, the development of optical systems, and improvements in imaging system resolution have gradually reduced the need for fluoroscopy in RIRS. This study provides further evidence that fluoroscopy is unnecessary in RIRS procedures, thereby eliminating unnecessary radiation exposure.


The impact of distinct triple-negative breast cancer subtypes on misdiagnosis and diagnostic delay.
Triple-negative breast cancer (TNBC) includes mostly aggressive types of breast cancer with poor prognosis. Due to its growth pattern, misinterpretation in clinical imaging is more frequent than in non-TNBC. As the group of TNBC contains heterogeneous types of tumors, marker expression-based subtypes have recently been established. We analyzed clinical features and false-negative imaging findings that could potentially lead to diagnostic delay within the subtypes. An exploratory analysis compared the imaging features across the a priori defined subtypes and related these findings to molecular subtype, disease stage, potential diagnostic delay, and patient outcome. TNBC cases were categorized into basal-like (BL; 38.6%), mesenchymal-like (ML; 19.9%), luminal androgen receptor (LAR; 28.3%), and immunomodulatory (IM; 13.3%) subtype. In almost every third patient, malignant classification was missed in at least one imaging method. Misclassification in mammogram was more frequent in ML, while benign ultrasound features were reported more often in the BL subtype. Diagnostic delay due to misclassification in imaging led to tumor growth and/or upgrading of the tumor stage in 8.9% of BL tumors, which had the lowest overall survivals. Despite misclassification rate was higher in the ML subtype it showed better outcomes. Misdiagnosis of axillary lymph node metastasis was higher in LAR; however, this subtype showed a higher percentage of affected axillary lymph nodes. TNBC subtypes have different clinical features, benign appearances, and diagnostic delay, which can lead to tumor stage upgrade. Future clinical studies on TNBC outcomes might consider the confounder of clinical delay in the subtypes.


Search for the rare decay K(L)-->pi(0)e(+)e(-).
The KTeV/E799 experiment at Fermilab has searched for the rare kaon decay K(L)-->pi(0)e(+)e(-). This mode is expected to have a significant CP violating component. The measurement of its branching ratio could support the standard model or could indicate the existence of new physics. This Letter reports new results from the 1999-2000 data set. One event is observed with an expected background at 0.99+/-0.35 events. We set a limit on the branching ratio of 3.5x10(-10) at the 90% confidence level. Combining with the previous result based on the data set taken in 1997 yields the final KTeV result: BR(K(L)-->pi(0)e(+)e(-))<2.8x10(-10) at 90% C.L.


A homozygous founder variant in PDE2A causes paroxysmal dyskinesia with intellectual disability.
Intellectual developmental disorder with paroxysmal dyskinesia or seizures (IDDPADS, OMIM#619150) is an ultra-rare childhood-onset autosomal recessive movement disorder manifesting paroxysmal dyskinesia, global developmental delay, impaired cognition, progressive psychomotor deterioration and/or drug-refractory seizures. We investigated three consanguineous Pakistani families with six affected individuals presenting overlapping phenotypes partially consistent with the reported characteristics of IDDPADS. Whole exome sequencing identified a novel missense variant in Phosphodiesterase 2A (PDE2A): NM_002599.4: c.1514T > C p.(Phe505Ser) that segregated with the disease status of individuals in these families. Retrospectively, we performed haplotype analysis that revealed a 3.16 Mb shared haplotype at 11q13.4 among three families suggesting a founder effect in this region. Moreover, we also observed abnormal mitochondrial morphology in patient fibroblasts compared to controls. Belonging to diverse age groups (13 years-60 years), patients presented paroxysmal dyskinesia, developmental delay, cognitive abnormalities, speech impairment, and drug-refractory seizures with variable onset of disease (as early as 3 months of age to 7 years). Together with the previous reports, we observed that intellectual disability, progressive psychomotor deterioration, and drug-refractory seizures are consistent outcomes of the disease. However, permanent choreodystonia showed variability. We also noticed that the later onset of paroxysmal dyskinesia manifests severe attacks in terms of duration. Being the first report from Pakistan, we add to the clinical and mutation spectrum of PDE2A-related recessive disease raising the total number of patients from six to 12 and variants from five to six. Together, with our findings, the role of PDE2A is strengthened in critical physio-neurological processes.