Is the left hemisphere androcentric? Evidence of the learned categorical perception of gender.
Effects of language learning on categorical perception have been detected in multiple domains. We extended the methods of these studies to gender and pitted the predictions of androcentrism theory and the spatial agency bias against each other. Androcentrism is the tendency to take men as the default gender and is socialized through language learning. The spatial agency bias is a tendency to imagine men before women in the left-right axis in the direction of one's written language. We examined how gender-ambiguous faces were categorized as female or male when presented in the left visual fields (LVFs) and right visual fields (RVFs) to 42 native speakers of English. When stimuli were presented in the RVF rather than the LVF, participants (1) applied a lower threshold to categorize stimuli as male and (2) categorized clearly male faces as male more quickly. Both findings support androcentrism theory suggesting that the left hemisphere, which is specialized for language, processes face stimuli as male-by-default more readily than the right hemisphere. Neither finding evidences an effect of writing direction predicted by the spatial agency bias on the categorization of gender-ambiguous faces.


Social Cognition in Schizophrenia, Unaffected Relatives and Ultra- High Risk for Psychosis: What Do We Currently Know?
Schizophrenia patients show impairments in social cognition (SC), which is a set of cognitive processes that underlie social interactions. The research about SC in schizophrenia has identified four main domains: Theory of mind (ToM), social perception, attributional style and emotional processing. The present review aims to summarize the most recent and consistent findings about SC in patients with schizophrenia, unaffected relatives and ultra-high risk for psychosis individuals (UHR), as well as its association with clinical variables and functional outcome. A systematic PsycINFO and Pubmed/Medline databases search was conducted. ToM impairments have been observed in schizophrenia patients, unaffected relatives and UHR. Emotional processing disturbance has been consistently reported in schizophrenia patients and UHR. ToM and emotional processing have been correlated with symptomatology and functional outcome. However, inconsistencies have been found across studies that assess ToM and emotional processing as predictors of psychosis. Social perception and attributional style are affected in schizophrenia, but the research in at- risk populations is scarce, and their relationship with symptoms or functional outcome is not clear. All domains of SC are impaired in schizophrenia. Non affected relatives and UHR also display deficits of SC. More research must be conducted to assess the reliability of SC domains as endophenotypes or predictors of conversion to psychosis in at-risk populations.


Potential benefits of routine cystoscopy and vaginoscopy prior to reconstructive surgery in patients with an anorectal malformation.
First, to assess the number of patients with anorectal malformations (ARM) in whom additional urological and/or gynecological anomalies were identified through routine screening with cysto- or vaginoscopy prior to reconstructive surgery. Second, to assess potential procedure-related complications. Retrospective mono-center cohort study, including all ARM patients born between January 2019 and December 2022. Routine screening consisted of cystoscopy for male patients, with the addition of vaginoscopy for female patients. Chi-square was used to compare the screening percentages over time. In total, 38 patients were included, of whom 27 (71.1%) underwent cystoscopy ± vaginoscopy, without the occurrence of complications. Nine of 13 females (69.2%) underwent cysto- and vaginoscopy and 18 of 25 males (72.0%) underwent a cystoscopy. The percentage of patients that underwent these procedures improved over the 2 time periods (50.0% in 2019-2020 vs 90.0% in 2021-2022, p = 0.011). In 15 of 27 patients (55.6%) that underwent cystoscopy ± vaginoscopy, additional anomalies were found that were not identified through physical examination or US-kidney. In 56% of the patients that underwent cysto- ± vaginoscopy, additional anomalies were identified that were not with imaging studies or physical examination. This study emphasizes the potential benefit of routine cysto- and vaginoscopy in the diagnostic work-up of children with ARM. III.


Oral aspirin challenges in patients with a history of intolerance to single non-steroidal anti-inflammatory drugs.
Summary Background In the clinical practice patients with a history of acute urticaria induced by a single non-steroidal anti-inflammatory drug (NSAID) and seeking for safe alternative drugs generally undergo tolerance tests with alternative NSAIDs that have little or no cyclooxygenase-1 (COX-1) enzyme inhibitory activity. This practice does not allow for the detection of single NSAID reactors and may lead to unnecessary avoidance of many potentially useful NSAIDs. Evaluate aspirin challenge as a means to distinguish single from multiple NSAID intolerance in patients with a clinical history of acute urticaria induced by a single NSAID. Methods One hundred and seventeen otherwise normal subjects with a history of acute urticaria following the ingestion of a single NSAID (pyrazolones (n=58), nimesulide (n=17), propionic acid derivatives (n=13), aryl acetic acid derivatives (n=14), acetaminophen (n=9), piroxicam (n=5), and indometacin (n=1)) underwent single-blind placebo-controlled oral challenges with aspirin. Aspirin-intolerant subjects underwent further tolerance tests drugs exerting little or no inhibitory activity on COX-1 enzyme (including paracetamol, nimesulide, rofecoxib, tramadol, and floctafenine). Results Aspirin induced urticaria in 28/117 (24%) patients. Five out of 28 (18%) aspirin reactors did not tolerate alternative NSAID on subsequent oral challenges. Conclusion In subjects with a history of urticaria induced by a single NSAID (other than aspirin) the diagnostic workup should start with an aspirin challenge in order to detect single/multiple NSAID reactors.


[Pathogenesis of mural thrombi in idiopathic cardiomyopathy].
Thirty-two hearts from patients with idiopathic cardiomyopathy were examined postmortem. A comparative morphological study of the human hearts and of hearts from cardiomyopathic hamsters, rabbits and baboons indicates that severe cardiac dilatation with intracavitary stasis and abnormal turbulent blood flow are the most important factors in the pathogenesis of mural thrombi in idiopathic cardiomyopathy.


One-Tube-Only Standardized Site-Directed Mutagenesis: An Alternative Approach to Generate Amino Acid Substitution Collections.
Site-directed mutagenesis (SDM) is a powerful tool to create defined collections of protein variants for experimental and clinical purposes, but effectiveness is compromised when a large number of mutations is required. We present here a one-tube-only standardized SDM approach that generates comprehensive collections of amino acid substitution variants, including scanning- and single site-multiple mutations. The approach combines unified mutagenic primer design with the mixing of multiple distinct primer pairs and/or plasmid templates to increase the yield of a single inverse-PCR mutagenesis reaction. Also, a user-friendly program for automatic design of standardized primers for Ala-scanning mutagenesis is made available. Experimental results were compared with a modeling approach together with stochastic simulation data. For single site-multiple mutagenesis purposes and for simultaneous mutagenesis in different plasmid backgrounds, combination of primer sets and/or plasmid templates in a single reaction tube yielded the distinct mutations in a stochastic fashion. For scanning mutagenesis, we found that a combination of overlapping primer sets in a single PCR reaction allowed the yield of different individual mutations, although this yield did not necessarily follow a stochastic trend. Double mutants were generated when the overlap of primer pairs was below 60%. Our results illustrate that one-tube-only SDM effectively reduces the number of reactions required in large-scale mutagenesis strategies, facilitating the generation of comprehensive collections of protein variants suitable for functional analysis.


Sodium Content in Pre-Packaged Foods in China: A Food Label Analysis.
Sodium intake from pre-packaged foods is increasing in China and is well above the WHO recommendation of 5 g per day. The purpose of this study is to analyze the sodium content of pre-packaged foods collected by the National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention (NINH, China CDC) in 20 provinces of China from 2017 to 2022. The proportion of pre-packaged foods that meet or exceed the low-sodium, medium-sodium, and high-sodium classifications were analyzed. The proportion of pre-packaged foods that meet and do not meet the WHO global sodium benchmarks and the difference in sodium content between these foods was also calculated. High-sodium foods include sauces, dips, and dressings (3896 mg/100 g), convenience foods (1578 mg/100 g), processed fish products (1470 mg/100 g), processed meat products (1323 mg/100 g), processed poultry products (1240 mg/100 g), snack foods (750 mg/100 g), processed egg products (741 mg/100 g), and fine dried noodles (602 mg/100 g). A large number of pre-packaged foods currently collected in China have a sodium content above sodium benchmarks. This study provided data to support the assessment of sodium intake from pre-packaged foods in the Chinese population and the implementation of comprehensive salt reduction strategies.


The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes.
Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes. For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV. RSV was provided via oral gavage once daily during the in vivo experiments. RSV treatment of primary cultured brown preadipocytes promoted mitochondrial activity, along with over-expression of estrogen receptor α (ER-α). In OLETF rats, both HFD and RSV treatment increased the weight of BAT and the differentiation of BAT. However, only RSV increased the mitochondrial activity and ER-α expression of BAT in the HFD-fed group. Finally, RSV improved the insulin sensitivity of OLETF rats by increasing the mitochondrial activity of BAT, despite having no effects on white adipocytes and muscles in either diet group. RSV could improve insulin resistance, which might be associated with mitochondrial activity of brown adipocyte. Further studies evaluating the activity of RSV for both the differentiation and mitochondrial activity of BAT could be helpful in investigating the effects of RSV on metabolic parameters.


Bare Below the Elbows: A comparative study of a tertiary and district general hospital.
A 'Bare Below the Elbows' (BBTE) dress code policy has been introduced by the majority of NHS trusts in the UK. The aim of this Irish study was to evaluate the impact of an educational intervention on perception of medical attire. The study was carried out in two centres: a tertiary referral centre (Beaumont Hospital) and a district hospital (MRH, Portlaoise). Two questionnaires, incorporating photographic evaluation of appropriate attire for consultants and junior doctors, were completed pre and post BBTE education. One hundred and five patients participated. Analysis pre BBTE education indicated patients considered formal attire and white coats most appropriate for consultants and junior doctors respectively. Post-intervention analysis revealed a significant reduction in the popularity of both (p <0.001), with scrubs and smart casual attire gaining significant support in both cohorts (p <0.001). Our findings demonstrated that patient opinion on medical attire is malleable. The support of such a policy may be achieved if patients are informed that the aim is to reduce the spread of healthcare-associated infections.


APOE epsilon4 is associated with impaired verbal learning in patients with MS.
To investigate the effect of APOE epsilon4 on different cognitive domains in a population of Greek patients with multiple sclerosis (MS). A total of 125 patients with MS and 43 controls were included in this study and underwent neuropsychological assessment with Rao's Brief Repeatable Battery. All patients with MS were genotyped for APOE. The effect of APOE epsilon4 on different cognitive domains was investigated. Fifty-one percent of patients with MS were cognitively impaired. E4 carriers had a sixfold increase in the relative risk of impairment in verbal learning vs noncarriers (OR 6.28, 95% CI 1.74 to 22.69). This effect was domain-specific and was not observed in other cognitive domains assessed by the battery. We found an association of APOE epsilon4 with impaired verbal learning in patients with multiple sclerosis.


Female reproductive factors, exogenous hormone use, and pancreatic cancer risk: the Japan Public Health Center-based prospective study.
An association between female reproductive factors, exogenous hormone use, and pancreatic cancer risk has long been suggested in laboratory settings, but epidemiological findings remain mixed and inconclusive. Studies carried out on Asian populations are also limited. In this study, 45 617 women aged 40-69 years were followed for an average of 18.4 years in the Japan Public Health Center-based prospective cohort and 211 pancreatic cases were identified as of 31 December 2011. We applied multivariate-adjusted Cox proportional hazards regression models using age as a time-scale to assess the association between female reproductive factors (menstrual status, menarche age, menopause age, number of births, age at first birth, total years of fertility, history of breastfeeding) and exogenous hormone use with the incidence of pancreatic cancer through hazard ratios and confidence intervals. No significant associations were found between our examined female reproductive factors and pancreatic cancer incidence. The use of exogenous hormones was found to be associated with an increased risk of pancreatic cancer in a multivariate-adjusted model (hazard ratio: 1.47; 95%; confidence interval: 1.00-2.14) in the Japanese female population. Our results suggest that exogenous hormones may play a role in the formation of pancreatic cancer, and further prospective studies are warranted for clarification.


The Use of Surrogate and Patient-Relevant Endpoints in Outcomes-Based Market Access Agreements : Current Debate.
The high cost of novel treatments is the major driver of negative or restricted reimbursement decisions by healthcare payers in many countries. Costly drugs can be subject to Market Access Agreements (MAAs), which are financial (Commercial Agreements [CAs]) or outcomes-based (Payment for Performance Agreements [P4Ps] or Coverage with Evidence Development agreements [CEDs]). Outcomes in outcomes-based MAAs are assessed through changes in surrogate endpoints (SEPs) or patient-relevant endpoints (PEPs). In May 2015, we reviewed published and grey literature on MAAs between manufacturers and large, institutionalised payers from all geographical areas, and classified the schemes into CAs, P4Ps and CEDs, as well as by therapeutic area and country. Outcomes-based MAAs were further categorized by the endpoint used. Overall, we identified 143 MAAs, 56 (39.2 %) of which were pure CAs, 53 (37.1 %) were CEDs, and 34 (23.8 %) were P4Ps. Among the CEDs, 49 were PEP CEDs and four were SEP CEDs; of the 34 P4Ps, 29 were SEP P4Ps for 30 drugs, and five were PEP P4Ps for at least six drugs; and among 87 outcomes-based MAAs (CEDs + P4Ps), PEP CEDs were the most common (56.3 %), followed by SEP P4Ps (34.1 %). The high proportion of SEPs used in P4Ps contrasts with the high proportion of PEPs used in CEDs. CEDs employ PEPs and it appears that they are used to reduce uncertainty about a drug's clinical outcomes and/or real-life use, and thus allow payers to align a product's value with price. We argue that P4Ps do not reduce uncertainty about real-life effectiveness and can only constitute an outcome guarantee for payers if they are based on PEPs or validated SEPs.


STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.
STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein expressed early in cardiac development that acts as an acute stress sensor for pathological remodeling. However the role of STARS in cardiac development and function is incompletely understood. Here, we investigated the role of STARS in heart development and function in the zebrafish model and in vitro. Expression of zebrafish STARS (zSTARS) first occurs in the somites by the 16 somite stage [17 hours post fertilization (hpf)]. zSTARS is expressed in both chambers of the heart by 48 hpf, and also in the developing brain, jaw structures and pectoral fins. Morpholino-induced knockdown of zSTARS alters atrial and ventricular dimensions and decreases ventricular fractional shortening (measured by high-speed video microscopy), with pericardial edema and decreased or absent circulation [abnormal cardiac phenotypes in 126/164 (77%) of morpholino-injected embryos vs. 0/152 (0%) of control morpholino embryos]. Co-injection of zsrf (serum response factor) mRNA rescues the cardiac phenotype of zSTARS knockdown, resulting in improved fractional shortening and ventricular end-diastolic dimensions. Ectopic over-expression of STARS in vitro activates the STARS proximal promoter, which contains a conserved SRF site. Chromatin immunoprecipitation demonstrates that SRF binds to this site in vivo and the SRF inhibitor CCG-1423 completely blocks STARS proximal reporter activity in H9c2 cells. This study demonstrates for the first time that STARS deficiency severely disrupts cardiac development and function in vivo and revealed a novel STARS-SRF feed-forward autoregulatory loop that could play an essential role in STARS regulation and cardiac function.


Unusual forms of malaria transmission. A report of 2 cases.
Malaria is uncommonly acquired without mosquito transmission. Two patients presenting with malaria illustrate this rare phenomenon. The first was a 1-month-old child who had received an exchange blood transfusion for severe haemolytic anaemia due to ABO blood incompatibility. The second was a doctor who had taken blood from the first patient. The occurrence of both transfusion malaria and accidental malaria from the same blood transfusion must be very uncommon.


Impact of the COVID-19 Pandemic on a Physician Group's WhatsApp Chat: Qualitative Content Analysis.
Social media has emerged as an effective means of information sharing and community building among health professionals. The utility of these platforms is likely heightened during times of health system crises and global uncertainty. Studies have demonstrated that physicians' social media platforms serve to bridge the gap of information between on-the-ground experiences of health care workers and emerging knowledge. The primary aim of this study was to characterize the use of a physician WhatsApp (WhatsApp LLC) group chat during the early months of the COVID-19 pandemic. Through the lens of the social network theory, we performed a qualitative content analysis of the posts of a women physician WhatsApp group located in the United Arab Emirates between February 1, 2020, and May 31, 2020, that is, during the initial surge of COVID-19 cases. There were 6101 posts during the study period, which reflected a 2.6-fold increase in platform use when compared with platform use in the year prior. A total of 8 themes and 9 subthemes were described. The top 3 uses of the platform were requests for information (posts: 2818/6101, 46.2%), member support and promotion (posts: 988/6101, 16.2%), and information sharing (posts: 896/6101, 14.7%). A substantial proportion of posts were related to COVID-19 (2653/6101, 43.5%), with the most popular theme being requests for logistical (nonmedical) information. Among posts containing COVID-19-related medical information, it was notable that two-thirds (571/868, 65.8%) of these posts were from public mass media or unverified sources. Health crises can potentiate the use of social media platforms among physicians. This reflects physicians' tendency to turn to these platforms for information sharing and community building purposes. However, important questions remain regarding the accuracy and credibility of the information shared. Our findings suggest that the training of physicians in social media practices and information dissemination may be needed.


[NRAMP1 gene polymorphisms in individuals with leprosy reactions attended at two reference centers in Recife, northeastern Brazil].
To investigate susceptibility to leprosy reactions, three polymorphisms of the natural resistance-associated macrophage protein (NRAMP1) gene were determined in 201 individuals who were attended at two reference centers in Recife, between 2007 and 2008. Of these, 100 were paucibacillary and 101 were multibacillary. The 274C/T, D543N and 1729+55del4 polymorphisms of the NRAMP1 gene were determined using the technique of restriction fragment polymorphism on DNA extracted from peripheral blood. Allelic and genotypic frequencies were estimated by direct counting. The predominant genotypes were: CC (51.8%) for 274C/T; GG (86.6%) for D543N; and +-TGTG (59.9%) for 1729+55del4. The mutant genotype 274 TT predominated in negativity of the reverse reaction (p = 0.03) and in positivity of erythema nodosum leprosum (p = 0.04). Our results suggest that 274 C/T polymorphism of the NRAMP1 gene may aid in determining the susceptibility to type II reactions among leprosy patients.


Treatment Outcome of Traumatic Subclavian Artery Injuries.
Traumatic subclavian artery injuries are associated with high morbidity and mortality. Thoracic cage and clavicle provide a well protection of the underlying subclavian vessels and nerves and also cause a very limited operation space during open surgery. The endovascular modality is less invasive and alternative to conventional open surgical reconstruction. The purpose of this study was to analyze the different therapeutic effects on limb salvage. A retrospective review of patients who presented with blunt or penetrating injuries to the subclavian arteries between March 2012 and March 2021. Endovascular and open repairs were both effective for traumatic subclavian artery injury. There was no statistical difference in the limb salvage, mortality, procedure-related complication, reintervention rate and in-hospital medical complications. Intraoperative blood loss, red blood cell transfusion requirement and length of hospital stay were significantly lower in the endovascular intervention group. Endovascular treatment represents an attractive alternative to the traditional surgical approach for the treatment of traumatic injuries in the subclavian.


Label-free electrochemical impedance biosensor to detect human interleukin-8 in serum with sub-pg/ml sensitivity.
Biosensors with high sensitivity and short time-to-result that are capable of detecting biomarkers in body fluids such as serum are an important prerequisite for early diagnostics in modern healthcare provision. Here, we report the development of an electrochemical impedance-based sensor for the detection in serum of human interleukin-8 (IL-8), a pro-angiogenic chemokine implicated in a wide range of inflammatory diseases. The sensor employs a small and robust synthetic non-antibody capture protein based on a cystatin scaffold that displays high affinity for human IL-8 with a KD of 35 ± 10 nM and excellent ligand specificity. The change in the phase of the electrochemical impedance from the serum baseline, ∆θ(ƒ), measured at 0.1 Hz, was used as the measure for quantifying IL-8 concentration in the fluid. Optimal sensor signal was observed after 15 min incubation, and the sensor exhibited a linear response versus logarithm of IL-8 concentration from 900 fg/ml to 900 ng/ml. A detection limit of around 90 fg/ml, which is significantly lower than the basal clinical levels of 5-10 pg/ml, was observed. Our results are significant for the development of point-of-care and early diagnostics where high sensitivity and short time-to-results are essential.


Role of postoperative computed tomography in patients with severe liver injury.
The role of postoperative computed tomography (CT) in asymptomatic patients with severe liver injury has not been investigated. The aim of the present study was to investigate the nature and incidence of significant liver-related abnormalities detected by postoperative CT in asymptomatic patients with severe liver injury. This was a prospective study of survivors with severe liver injury (grades III-V) who were treated surgically. The patients underwent CT to evaluate the liver after operation, irrespective of symptoms. During the study interval there were 181 patients with severe liver injury, of whom 49 fulfilled the criteria for inclusion. The overall incidence of liver-related complications detected by CT was 49 per cent (necrotic areas in the liver in seven patients, seven bilomas, four abscesses, three perihepatic collections and three false aneurysms). In the subgroup of 17 asymptomatic patients CT revealed four abnormalities: two large bilomas, one false aneurysm and one fluid collection. Two of these patients required therapeutic intervention and the other two remained under observation. In view of the incidence of asymptomatic significant liver abnormalities following operative management of severe liver injury, it is recommended that these patients undergo routine postoperative CT.


Clinical implementation of an online adaptive plan-of-the-day protocol for nonrigid motion management in locally advanced cervical cancer IMRT.
To evaluate the clinical implementation of an online adaptive plan-of-the-day protocol for nonrigid target motion management in locally advanced cervical cancer intensity modulated radiation therapy (IMRT). Each of the 64 patients had four markers implanted in the vaginal fornix to verify the position of the cervix during treatment. Full and empty bladder computed tomography (CT) scans were acquired prior to treatment to build a bladder volume-dependent cervix-uterus motion model for establishment of the plan library. In the first phase of clinical implementation, the library consisted of one IMRT plan based on a single model-predicted internal target volume (mpITV), covering the target for the whole pretreatment observed bladder volume range, and a 3D conformal radiation therapy (3DCRT) motion-robust backup plan based on the same mpITV. The planning target volume (PTV) combined the ITV and nodal clinical target volume (CTV), expanded with a 1-cm margin. In the second phase, for patients showing >2.5-cm bladder-induced cervix-uterus motion during planning, two IMRT plans were constructed, based on mpITVs for empty-to-half-full and half-full-to-full bladder. In both phases, a daily cone beam CT (CBCT) scan was acquired to first position the patient based on bony anatomy and nodal targets and then select the appropriate plan. Daily post-treatment CBCT was used to verify plan selection. Twenty-four and 40 patients were included in the first and second phase, respectively. In the second phase, 11 patients had two IMRT plans. Overall, an IMRT plan was used in 82.4% of fractions. The main reasons for selecting the motion-robust backup plan were uterus outside the PTV (27.5%) and markers outside their margin (21.3%). In patients with two IMRT plans, the half-full-to-full bladder plan was selected on average in 45% of the first 12 fractions, which was reduced to 35% in the last treatment fractions. The implemented online adaptive plan-of-the-day protocol for locally advanced cervical cancer enables (almost) daily tissue-sparing IMRT.


Preparation of budesonide/gamma-cyclodextrin complexes in supercritical fluids with a novel SEDS method.
The aim was to investigate if solid drug/cyclodextrin complexes could be produced in a single-step process with a solution enhanced dispersion by supercritical fluids (SEDS) method. Budesonide and gamma-cyclodextrin (CD) solutions (50% or 99.5% ethanol) were pumped from the same (conventional method) or separate (modified method) containers together with supercritical carbon dioxide through a coaxial nozzle into a particle formation chamber. The pressure was maintained at 100, 150 or 200 bar with a temperature of 40, 60 or 80 degrees C. SEDS-processed powders were characterised with HPLC, DSC and XRPD for budesonide content, complexation and crystallinity. The budesonide dissolution rate was determined in 1% gamma-CD aqueous solution. Solid, white budesonide/gamma-CD complex particles were formed using the conventional and modified SEDS processes. The complexation efficiency was dependent on the processing conditions. For example, with the conventional method (100 bar, 60 degrees C) the yield of the powder was 65+/-12% with 0.14+/-0.02 mg budesonide/mg powder, corresponding to 1:2 drug:CD molar ratio. The dissolution rate of this complexed budesonide (93+/-2% after 15 min) was markedly higher compared to unprocessed micronised budesonide (41+/-10%) and SEDS-processed budesonide without CD (61+/-3%). As a conclusion, SEDS is a novel method to produce solid drug/CD complexes in a single-step process.


Clonal analysis by chromosome 11 microsatellite-PCR of microdissected parathyroid tumors from MEN 1 patients.
Loss of heterozygosity (LOH) at chromosome 11q13 loci has been described in the majority of larger parathyroid tumors from patients affected by Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome. Since classical histology of the whole parathyroid gland does not permit a clear morpho-genetic correlation, the clonal composition of abnormal parathyroid tissue was analyzed in DNA obtained from single nodules and non-nodular areas within MEN 1 parathyroid lesions. Microdissected sections were analyzed by chromosome 11q13 microsatellite-PCR for LOH and by patterns of X-inactivation. We detected LOH for chromosome 11q13 loci in at least one microdissected area for each familial MEN 1 patient, but not in the single sporadic case. X-inactivation pattern of two "clonal" tumors exhibited a polyclonal cell composition of these microdissected samples, indicating the existence of a genetic heterogeneity in MEN 1 parathyroid microareas exhibiting a "clonal" pattern for allelic losses.


Dual Somatostatin Receptor/FDG PET/CT Imaging in Metastatic Neuroendocrine Tumours: Proposal for a Novel Grading Scheme with Prognostic Significance.
Background: PET scans using FDG and somatostatin receptor imaging agents have both been used to study neuroendocrine tumours. Most reports have documented the sensitivity and specificity of each radiopharmaceutical independently, and even suggested the superiority of one over the other for different grades of disease. Aim: The aim of this work was to develop a grading scheme that describes the joint results of both the FDG and somatostatin receptor imaging PET scans in staging subjects with neuroendocrine tumours in a single combined parameter. The grading scheme that has been developed is referred to as the NETPET grade. Methods: This is a retrospective study which assessed subjects who had both FDG and somatostatin receptor PET imaging at our institution within 31 days of each other. The NETPET grade was assigned by experienced nuclear medicine physicians and compared with other clinical data such as WHO grade and overall survival. Results: In the period 2011-2015 we were able to recruit 62 subjects with histologically proven metastatic neuroendocrine tumour for review. The NETPET grade incorporating both the FDG and somatostatin receptor imaging results was significantly correlated with overall survival by univariate analysis (p=0.0018), whereas in this cohort the WHO grade at the time of diagnosis did not correlate with survival. Conclusions: The NETPET grade has promise as a prognostic imaging biomarker in neuroendocrine tumours. It permits the capturing of the complexity of dual radiotracer imaging in a single parameter which describes the subjects' disease and is readily amenable to use in patient management and further research.


Sequence charge decoration dictates coil-globule transition in intrinsically disordered proteins.
We present an analytical theory to compute conformations of heteropolymers-applicable to describe disordered proteins-as a function of temperature and charge sequence. The theory describes coil-globule transition for a given protein sequence when temperature is varied and has been benchmarked against the all-atom Monte Carlo simulation (using CAMPARI) of intrinsically disordered proteins (IDPs). In addition, the model quantitatively shows how subtle alterations of charge placement in the primary sequence-while maintaining the same charge composition-can lead to significant changes in conformation, even as drastic as a coil (swelled above a purely random coil) to globule (collapsed below a random coil) and vice versa. The theory provides insights on how to control (enhance or suppress) these changes by tuning the temperature (or solution condition) and charge decoration. As an application, we predict the distribution of conformations (at room temperature) of all naturally occurring IDPs in the DisProt database and notice significant size variation even among IDPs with a similar composition of positive and negative charges. Based on this, we provide a new diagram-of-states delineating the sequence-conformation relation for proteins in the DisProt database. Next, we study the effect of post-translational modification, e.g., phosphorylation, on IDP conformations. Modifications as little as two-site phosphorylation can significantly alter the size of an IDP with everything else being constant (temperature, salt concentration, etc.). However, not all possible modification sites have the same effect on protein conformations; there are certain "hot spots" that can cause maximal change in conformation. The location of these "hot spots" in the parent sequence can readily be identified by using a sequence charge decoration metric originally introduced by Sawle and Ghosh. The ability of our model to predict conformations (both expanded and collapsed states) of IDPs at a high-throughput level can provide valuable insights into the different mechanisms by which phosphorylation/charge mutation controls IDP function.


Infection control hazards and near misses reported by nursing students.
Hazard and near-miss reporting has been integrated into the curriculum for postbaccalaureate bachelor of science in nursing/master of science in nursing degree students at our institution through a Web-based reporting system since 2006. The system is used during their 25-week clinical rotations of 2 days per week in community, medical-surgical, obstetrics, pediatrics, and psychiatric settings. The purpose of this article is to describe the frequency and types of hazard and near-miss comments about infection control issues over 3 years of data collection. For each clinical rotation, students were required to complete 2 entries per week into a structured electronic hazard and near-miss reporting system. Three years worth of comments associated with these reports (2006-2009) were extracted and analyzed by 3 independent reviewers (κ statistic = 0.85). Seven categories of infection control problems were identified. Five hundred nursing students submitted 3492 comments related to hazards and near misses. Of these, 886 responses (25.4%) were related to infection control practices. The most common category was nonadherence to isolation precautions (27.6%), followed by contamination of the environment or equipment (18.5%), breaks in aseptic technique (17.2%), hand hygiene (15.9%) or gloving failures (11.5%), and occupational risks (8.2%). Infection control hazards and near misses were commonly reported across clinical settings by nursing students. Awareness of such problems among clinicians is necessary before work flow process changes can be made, but clinical change require systems-level change. To be effective and sustainable, reporting methods must be easy to use and available in real time.


Targeted toxins in brain tumor therapy.
Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of the molecule in all clinically used toxins is modified from bacterial or plant toxins, fused to an antibody or carrier ligand. Targeted toxins are very effective against cancer cells resistant to radiation and chemotherapy. They are far more potent than any known chemotherapy drug. Targeted toxins have shown an acceptable profile of toxicity and safety in early clinical studies and have demonstrated evidence of a tumor response. Currently, clinical trials with some targeted toxins are complete and the final results are pending. This review summarizes the characteristics of targeted toxins and the key findings of the important clinical studies with targeted toxins in malignant brain tumor patients. Obstacles to successful treatment of malignant brain tumors include poor penetration into tumor masses, the immune response to the toxin component and cancer heterogeneity. Strategies to overcome these limitations are being pursued in the current generation of targeted toxins.


Regulation and characterization of the dadRAX locus for D-amino acid catabolism in Pseudomonas aeruginosa PAO1.
D-amino acids are essential components for bacterial peptidoglycan, and these natural compounds are also involved in cell wall remodeling and biofilm disassembling. In Pseudomonas aeruginosa, the dadAX operon, encoding the D-amino acid dehydrogenase DadA and the amino acid racemase DadX, is essential for D- and L-Ala catabolism, and its expression requires a transcriptional regulator, DadR. In this study, purified recombinant DadA alone was sufficient to demonstrate the proposed enzymatic activity with very broad substrate specificity; it utilizes all D-amino acids tested as substrates except D-Glu and D-Gln. DadA also showed comparable k(cat) and K(m) values on D-Ala and several D-amino acids. dadRAX knockout mutants were constructed and subjected to analysis of their growth phenotypes on amino acids. The results revealed that utilization of L-Ala, L-Trp, D-Ala, and a specific set of D-amino acids as sole nitrogen sources was abolished in the dadA mutant and/or severely hampered in the dadR mutant while growth yield on D-amino acids was surprisingly improved in the dadX mutant. The dadA promoter was induced by several L-amino acids, most strongly by Ala, and only by D-Ala among all tested D-amino acids. Enhanced growth of the dadX mutant on D-amino acids is consistent with the finding that the dadA promoter was constitutively induced in the dadX mutant, where exogenous D-Ala but not L-Ala reduced the expression. Binding of DadR to the dadA regulatory region was demonstrated by electromobility shift assays, and the presence of L-Ala but not D-Ala increased affinity by 3-fold. The presence of multiple DadR-DNA complexes in the dadA regulatory region was demonstrated in vitro, and the formation of these nucleoprotein complexes exerted a complicated impact on promoter activation in vivo. In summary, the results from this study clearly demonstrate DadA to be the enzyme solely responsible for the proposed D-amino acid dehydrogenase activity of broad substrate specificity and the physiological functions of DadRAX in catabolism of several D-amino acids and support L-Ala as the signal molecule for induction of the dadAX genes through DadR binding to several putative operator sites.


[Stereotactic brain biopsy in the diagnosis of focal brain lesions in AIDS].
Focal brain lesions are frequent complications among HIV/AIDS patients. Between January 1999 and May 2007, 83 procedures of stereotactic brain biopsies in HIV/AIDS patients with focal cerebral lesions were carried out. The inclusion criteria were lack of response to current diagnostic and therapeutic guidelines for brain lesions. All the samples underwent microscopic evaluation during surgery to assert valid material and delayed histopathological and microbiological examination. Forty one patient images demonstrated multiple brain lesions. Sixty two cases had supratentorial localization, 4 lesions were located beneath the tentorium and 17 showed both settings. Fifty one lesions presented peripheral enhancement after contrast computed tomography (CT) or magnetic resonance imaging (MRI). A 100% of useful samples recovery was achieved. Progressive multifocal leucoencephalopathy (PML) was the most frequent diagnosis (29%), followed by primary central nervous system lymphoma (PCNSL) (23%), and toxoplasmosis (15.7%). Statistically significant association was observed between histopathological diagnosis and lesion location and between those and peripheral ring enhancement images. The positive diagnostic rate of the invasive procedure was 90.3%. The morbidity/mortality rate was 2.4% in this series. In conclusion, the stereotactic brain biopsy ordered early during the patient's evolution showed a good performance in order to achieve a prompt and accurate diagnosis and to guide the therapeutic scheme in these AIDS patients with focal brain lesions.


Evaluating laboratory usage in the intensive care unit: patient and institutional characteristics that influence frequency of blood sampling.
To develop a predictive equation to estimate the frequency of blood drawing for intensive care unit (ICU) laboratory tests and to evaluate variations in ICU blood sampling practices after adjusting for patient and institutional factors. Prospective, inception, cohort study. Forty-two ICUs in 40 hospitals, including 20 teaching and 17 nonteaching ICUs. A consecutive sample of 17,440 ICU admissions, in which 14,043 blood samples were drawn for laboratory testing on ICU days 2 to 7. None. Patient demographic, physiologic, and treatment data were obtained on ICU day 1; the type and number of blood samples for laboratory testing were recorded on ICU days 1 to 7. In the 42 ICUs, a mean of 16.2 blood samples were drawn for tests on ICU days 2 to 7, but varied between 23 samples in the teaching ICUs and 9.9 samples in nonteaching ICUs. Using only ICU day 1 patient data, we predicted the subsequent number of samples drawn on ICU day 2 (R2 = .26 across individual patients) and on ICU days 2 to 7 (R2 = .26 across individual patients). The most important determinants of the number of blood samples drawn on ICU days 2 to 7 were the ICU day 1 Acute Physiology Score and admission diagnosis. After controlling for patient variables, hospital teaching status, number of beds, and location in the East and South were significantly (p < .05) associated with increased blood sampling on ICU day 2 and on ICU days 2 to 7. More frequent use of an arterial cannula and mechanical ventilation were also associated with increased blood sampling on subsequent days. The ability to adjust for patient and institutional variables and to predict the number of blood samples drawn for laboratory tests can allow ICUs to compare their practices with those of other units. When integrated into a continuous quality improvement process, this information can be used to identify and focus on opportunities for improving blood conservation and reducing excessive diagnostic testing.


A large degree of functional diversity exists among helper T cells specific for the same antigenic site of influenza hemagglutinin.
The site-1 determinant of the hemagglutinin molecule of influenza virus (A/PR/8/34) is one of several immunodominant sites in the BALB/c Th cell response to Ha. A synthetic peptide comprising this T cell site (HA110-120), a panel of analogs containing single substitutions in this determinant, and homologs truncated at the amino- or carboxyl-terminal were used to examine the fine specificities of 15 T cells specific for site-1 in the context of I-Ed. The results indicate that every residue within the minimal determinant plays a role in the T cell recognition process, as single substitutions at any of these positions affected the ability of the peptide to stimulate at least some site 1-specific T cells. For the majority of the residues examined, substitutions had dissimilar effects on distinct T cells, indicating that the substituted residues were affecting recognition in a receptor-specific manner. Each of the 15 T cells examined had a distinct fine specificity pattern, suggesting that the BALB/c T cell repertoire for this site is likely to exceed 100 distinct clonotypes.


Peroxisome Proliferator Activated Receptor gamma (PPARγ) Agonist Rosiglitazone Ameliorate Airway Inflammation by Inhibiting Toll-Like Receptor 2 (TLR2)/Nod-Like Receptor with Pyrin Domain Containing 3 (NLRP3) Inflammatory Corpuscle Activation in Asthmatic Mice.
BACKGROUND The purpose of this study was to explore the function and mechanism of peroxisome proliferator activated receptor agonist (PPARγ) in the toll-like receptor 2 (TLR2)/nod-like receptor with pyrin domain containing 3 (NLRP3) inflammatory corpuscle pathway of asthmatic mice. MATERIAL AND METHODS Eighteen female mice (C57) were randomly divided into 4 groups: the control group, the asthma model group challenged by ovalbumin (OVA), the rosiglitazone group, and the PPARγ agonist rosiglitazone treatment group. The infiltration of peribronchial inflammatory cells as well as the proliferation and mucus secretion of bronchial epithelial goblet cells were observed by hematoxylin and eosin and periodic acid-Schiff staining. Western blots were employed to detect the expression levels of TLR2, PPARγ, nuclear factor-kappa B (NF-kappaB), NLRP3, and ASC [apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain [CARD]). RESULTS The number of inflammatory cells and eosinophils, and the levels of OVAs IgE, interleukin-4 (IL-4), and IL-13 were significantly higher in the C57 asthma group compared to the C57 control group and the treatment group (P<0.05). The infiltration of peribronchiolar inflammatory cells, wall thickening, goblet cell hyperplasia, and mucus secretion in the treatment group were all significantly decreased compared to those in the asthma group. PPARg expression in the treatment group was significantly higher compared to the asthma group and the control group (P<0.05). The protein expression levels of TLR2, NF-kappaB, NLRP3, and ASC were significantly lower compared to the asthma group but were higher compared to the control group (P<0.05). CONCLUSIONS PPARγ rosiglitazone ameliorates airway inflammation by inhibiting NF-kappaB expression in asthmatic mice, and further inhibits the activation of TLR2/NLRP3 inflammatory corpuscles.


Azide quenching of singlet oxygen in suspensions of microenvironments of neutral and surface charged liposomes and micelles.
The azide anion is often used as a physical quencher of singlet oxygen, the important active intermediate in photosensitized oxidation. An observed effect of azide on the rate of a reaction is considered an indication to the involvement of singlet oxygen. In most biological photosensitizations, the light-absorbing sensitizer is located in a membrane or in an intracellular organelle, whereas azide is water soluble. The quenching it causes relies on a physical encounter with singlet oxygen during the latter's short lifetime. This can happen either if azide penetrates into the membrane's lipid phase or if singlet oxygen is intercepted when diffusing in the aqueous phase. We demonstrate in this article the difference, in liposomes' suspension, between the effect of azide when using a water-soluble and membrane-bound chemical targets of singlet oxygen, whereas this difference does not exist when micelles are used. We explain the difference on the population of sensitizer and target in the liposome vs micelle. We also show the effect that exists on azide quenching of singlet oxygen by electrically charged lipids in liposomes. This is a result of the accumulation or dilution of azide in the debye layer near the membranes' surface, due to the surface Gouy-Chapman potential.


Diagnosis of urologic malignancies in patients with asymptomatic dipstick hematuria: prospective study with 13 years' follow-up.
To appraise the outcomes, determine the natural history, and instigate a rationale plan for follow-up of patients with asymptomatic dipstick hematuria. A total of 292 consecutive patients with asymptomatic dipstick hematuria referred between January 1992 and December 1994 were investigated and prospectively followed up. The initial investigations included urinalysis, urine culture and sensitivity, cytology, intravenous urography, with or without ultrasonography, and cystoscopy. Baseline data and follow-up events, particularly the development of urologic malignancy, were recorded for a 13-year period. Sixteen patients (5.4%) were found to have urologic malignancies on initial evaluation. Of these, 11 died. During a follow-up of 13 years, 21 patients (7%) were lost to follow-up and 42 died of various unrelated causes (other than urologic malignancies). Of the remaining 213 patients, 180 (84.5%) subsequently had negative urinalysis. None with negative urinalysis developed a urologic malignancy during follow-up. The presence of dipstick hematuria persisted in 33 patients. Of these 33 patients, 10 had nephrologic causes, 8 had urinary tract infection, and 15 underwent repeat investigation with no pathologic cause identified. One patient, discharged with negative findings after full initial investigations, presented 2 years later with frank hematuria and was found to have a new bladder tumor. Patients presenting with asymptomatic dipstick hematuria who have undergone thorough initial negative investigations can be discharged from tertiary urologic care services. Nephrologic referral is recommended if dipstick hematuria and proteinuria persist. The repetition of the urologic investigations is unwarranted, unless patients present with symptoms or develop frank hematuria.


Recent advancements in nanoelectrodes and nanopipettes used in combined scanning electrochemical microscopy techniques.
In recent years, major developments in scanning electrochemical microscopy (SECM) have significantly broadened the application range of this electroanalytical technique from high-resolution electrochemical imaging via nanoscale probes to large scale mapping using arrays of microelectrodes. A major driving force in advancing the SECM methodology is based on developing more sophisticated probes beyond conventional micro-disc electrodes usually based on noble metals or carbon microwires. This critical review focuses on the design and development of advanced electrochemical probes particularly enabling combinations of SECM with other analytical measurement techniques to provide information beyond exclusively measuring electrochemical sample properties. Consequently, this critical review will focus on recent progress and new developments towards multifunctional imaging.


Diverse effects of taurine on vascular response and inflammation in GSH depletion model in rabbits.
A reduction in GSH and an increase in free radicals are observed in inflammatory diseases, indicating oxidative stress. Taurine protects cells from the cytotoxic effects of inflammation. There have been limited studies to date evaluating the effect of taurine in oxidative stress-induced vascular dysfunction and its role in vascular inflammatory diseases. Therefore, we aimed to investigate the effect of taurine on the regulation of vascular tonus and vascular inflammatory markers in rabbit aortae and carotid arteries in oxidative stress-induced by GSH depletion. Rabbits were treated subcutaneously with buthionine sulfoximine (BSO), GSH-depleting compound and/or taurine. Cumulative concentration-response curves for acetylcholine (ACh), phenylephrine and 5-hydroxytriptamine (5-HT) were constructed with or without Nω-nitro-L-arginine (LNA) in the carotid artery and aorta rings. Immunohistochemical staining was performed for TNF-α and IL-1β. BSO increased ACh-induced NO-dependent relaxations, phenylephrine-induced contractions in the carotid artery and 5-HT induced-contractions in both the carotid artery and the aorta. BSO decreased EDHF dependent relaxations only in the aorta. ACh-induced NO-dependent relaxations and augmented contractions were normalized by taurine. BSO increased TNF-α expressions in both carotid arteries and aortas, which were reversed by taurine. The BSO-induced increase in IL-1β was reversed by taurine only in aortae. Treatment with BSO resulted in vascular reactivity changes and increased immunostaining of TNF-α in mainly carotid arteries in this model of oxidative stress. The effect of taurine on BSO-induced vascular reactivity changes varied depending on the vessel. The inhibition of the increase in TNF-α expression by taurine in both carotid arteries and aortae supports the proposal that taurine has a beneficial effect in the treatment of inflammatory diseases such as atherosclerosis.


Happiness in the neonatal intensive care unit: merits of ethnographic fieldwork.
Research has focused on the destructive effects of distress on professionals who work in ethically complex wards such as neonatal intensive units (NICUs). This article examines the accounts of health professionals, including nurses, pediatricians and assistant nurses, of their work at a NICU in Iceland. The aim is to understand how health professionals, who work under stressful conditions in an ethically sensitive ward, can counteract the negative sides of work too such a degree that they experience happiness. The collection of data was based on the ethnographic fieldwork, and the methods used were participant observation and semi-structured interviews. The professionals evaluated their wellbeing in line with conventional definitions of happiness. Working with children and opportunities to help others, engage in social relations and experience professional pride contributed to their happiness at work. Nonetheless, they did not dismiss the difficult experiences, and when confronted with these the professionals negotiated their meanings and the goals and priorities of work. In contrast to the findings of much quantitative and survey-based research, the professionals attributed constructive meanings to stress and argued that the positive experiences at work buffered the negative ones. Research on happiness would benefit from multifaceted methodological and theoretical perspectives. Thanks to its openness to the unforeseen, controversial, contradictory, and ambiguous aspects of human life, ethnography can contribute to happiness research and research on job satisfaction.


Neutron-induced electronic failures around a high-energy linear accelerator.
After a new in-vault CT-on-rails system repeatedly malfunctioned following use of a high-energy radiotherapy beam, we investigated the presence and impact of neutron radiation on this electronic system, as well as neutron shielding options. We first determined the CT scanner's failure rate as a function of the number of 18 MV monitor units (MUs) delivered. We then re-examined the failure rate with both 2.7-cm-thick and 7.6-cm-thick borated polyethylene (BPE) covering the linac head for neutron shielding. To further examine shielding options, as well as to explore which neutrons were relevant to the scanner failure, Monte Carlo simulations were used to calculate the neutron fluence and spectrum in the bore of the CT scanner. Simulations included BPE covering the CT scanner itself as well as covering the linac head. We found that the CT scanner had a 57% chance of failure after the delivery of 200 MUs. While the addition of neutron shielding to the accelerator head reduced this risk of failure, the benefit was minimal and even 7.6 cm of BPE was still associated with a 29% chance of failure after the delivery of 200 MU. This shielding benefit was achieved regardless of whether the linac head or CT scanner was shielded. Additionally, it was determined that fast neutrons were primarily responsible for the electronic failures. As illustrated by the CT-on-rails system in the current study, physicists should be aware that electronic systems may be highly sensitive to neutron radiation. Medical physicists should therefore monitor electronic systems that have not been evaluated for potential neutron sensitivity. This is particularly relevant as electronics are increasingly common in the therapy vault and newer electronic systems may exhibit increased sensitivity.


Expression of PTHrP and PTHR (PTH/PTHrP-r) mRNAs and polypeptides in bovine ovary and stimulation of bovine blastocyst development in vitro following PTHrP treatment during oocyte maturation.
Parathyroid hormone related protein (PTHrP) and its receptor have well-established roles in the development and regulation of many tissues, including bone and mammary gland. The objectives of this study were: (1) to characterize the distribution of mRNAs encoding parathyroid hormone (PTH)-related protein (PTHrP) and receptor (PTHR) in bovine ovary; (2) to characterize the distribution of PTHrP and PTHR polypeptides in bovine ovary; (3) to examine the influences of PTHrP (1-141) treatment during bovine oocyte maturation in vitro on blastocyst development. mRNAs encoding PTHrP and PTHR were detected by in situ hybridization methods in oocytes, and granulosa cells in all follicles from primordial to large antral. PTHrP and PTHR polypeptides displayed distinct distribution patterns with PTHrP polypeptides primarily confined to oocytes from primordial to large antral follicles. PTHrP polypeptides were detectable but at a reduced level in ovarian stroma and in granulosa and thecal layers. PTHR polypeptides were detected in oocytes of all follicular stages but were predominantly found in ovarian stroma, granulosa and theca follicular layers. Supplementation of serum-free cSOFMaa oocyte maturation medium with PTHrP (1-141) resulted in a concentration-dependent increase in development to the blastocyst stage in vitro. The results suggest that granulosa cells may be a primary site of PTHrP production and release. Oocytes from all follicular stages stained strongly for PTHrP polypeptides and PTHrP enhanced development to the blastocyst stage in vitro.


Urate and p-aminohippurate transport in rat renal basolateral vesicles.
We examined the transport of urate in basolateral membrane vesicles from the rat kidney and determined the relationship between the transport of urate and p-aminohippurate (PAH). Urate was not converted to allantoin, and the uptake of urate represented transport into an osmotically active intravesicular space. The 10-s uptake of 53 microM [14C]urate in basolateral vesicles was inhibited 39 +/- 6, 49 +/- 10, and 35 +/- 3% by (in mM) external 2.4 probenecid, 2.4 DIDS, and 1.4 unlabeled urate, respectively. The 10-s uptake of 353 microM [14C]urate was trans-stimulated 82 +/- 8% by preloading basolateral vesicles with 1.5 mM unlabeled urate. The uptake of urate was stimulated by an outwardly directed gradient for Cl- (Cl-in = 25 mM, Cl-out = 5 mM). This effect was not consequent to a more electropositive intravesicular space, as monitored by the voltage-sensitive sodium-L-malate cotransport system. The Cl- gradient-stimulated component of urate uptake in basolateral vesicles was not cis-inhibited by 4.8 mM PAH, whereas Cl gradient-stimulated urate uptake in brush border vesicles was cis-inhibited 43 +/- 5% by PAH. In the absence of Cl-, 4.8 mM PAH did not cis-inhibit, and 5.4 mM PAH or 6.4 mM lactate did not trans-stimulate the uptake of urate in basolateral vesicles, contrasting with results obtained with brush border vesicles. The uptake of urate in basolateral vesicles was not stimulated by external Na+ relative to K+, Li+, or Cs+. In contrast, PAH uptake in basolateral vesicles was stimulated 87 +/- 9% by external Na+.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of perceptual motor training on gross-motor skill and self-concept of young children.
Preschool teachers from four different day care centers assessed four-and five-year-old children for deficits in gross-motor skill and self-concept. Forty subjects were randomly assigned to experimental and control groups. The experimental group participated in a 30 minute per day, 5 day per week perceptual-motor training program for 10 weeks, while the control group received no specialized intervention other than their regular classroom activities. Two posttests were administered: Cratty's Six-Category Gross-Motor Test and Goodenough's House, Tree, Person Projective Test. The experimental group performed better on the gross-motor test, but the results were not statistically significant. Analysis of the projective test supported the hypothesis that a perceptual-motor program may improve the self-concept of young children. Specialized intervention with perceptual-motor activities improved self-concept and these results were discussed in relation to recognizing the need for early screening and remediation of perceptual-motor dificits exhibited by preschool children.


Identification of microRNAs and their mRNA targets during soybean nodule development: functional analysis of the role of miR393j-3p in soybean nodulation.
Plant microRNAs (miRNAs) play important regulatory roles in a number of developmental processes. The present work investigated the roles of miRNAs during nodule development in the crop legume soybean (Glycine max). Fifteen soybean small RNA libraries were sequenced from different stages of nodule development, including young nodules, mature nodules and senescent nodules. In order to identify the regulatory targets of the miRNAs, five parallel analysis of RNA ends (PARE) libraries were also sequenced from the same stages of nodule development. Sequencing identified 284 miRNAs, including 178 novel soybean miRNAs. Analysis of miRNA abundance identified 139 miRNAs whose expression was significantly regulated during nodule development, including 12 miRNAs whose expression changed > 10-fold. Analysis of the PARE libraries identified 533 miRNA targets, including three nodulation-related genes and eight nodule-specific genes. miR393j-3p was selected for detailed analysis as its expression was significantly regulated during nodule formation, and it targeted a nodulin gene, Early Nodulin 93 (ENOD93). Strong, ectopic expression of miR393j-3p, as well as RNAi silencing of ENOD93 expression, significantly reduced nodule formation. The data indicate that miR393j-3p regulation of ENOD93 mRNA abundance is a key control point for soybean nodule formation.


[A Case of Mucinous Adenocarcinoma of the Descending Colon with Extramural Progression].
A 63-year-old man was admitted to our hospital with a cough. Based on imaging studies, the patient was diagnosed with locally advanced descending colon cancer with extensive infiltration into peripheral organs by extramural progression. There was no distant metastasis. Therefore, he received left hemicolectomy with splenectomy, partial gastrectomy, and partial diaphragm resection. Histopathological examination showed a mucinous adenocarcinoma, pT4b, pN1, cM0, fStage III A. We report a rare case of extramural progression colon cancer with invasion of various organs and review 12 previous case reports.


Kinetic insights into the reactivity of the intermediates generated from hydrogen peroxide and diiron(III) complex with tris(picolyl)amine (TPA).
Two intermediates (2 and 3) are formed consecutively in the reaction of a diiron(III) complex [Fe(III)(2)(μ-O)(OH)(H(2)O)(TPA)(2)](ClO(4))(3) (TPA = tris(2-pyridylmethyl)amine, tris(picolyl)amine) with H(2)O(2) in CH(3)CN at -40 °C. Low-temperature stopped-flow studies showed that both species are kinetically competent in oxidation of phosphines and phenols. The first intermediate (2) reacts with substrates very rapidly (second-order rate constants reach 10(5)-10(6) M(-1) s(-1) for substituted triarylphosphines and 10(3)-10(5) M(-1) s(-1) for substituted phenols), in keeping with a diiron(IV)-oxo formulation. The second intermediate (3), a mixed-valent Fe(III)Fe(IV) species, is more stable than 2, and reacts with substrates more slowly (second-order rate constants range from 150 to 550 M(-1) s(-1) for triaryl phosphine oxidation, and from 18 to 790 M(-1) s(-1) for phenol oxidation). Reaction rates increase with increasing electron donating abilities of substituents, indicating that both 2 and 3 act as electrophilic oxidants.


A case report with COVID-19 during perioperative period of lobectomy.
Currently, COVID-19 has made a significant impact on many countries in the world. However, there have been no reported cases of pulmonary lobectomy with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) infection. We are the first to report such a case. We report a 63-year-old Wuhan male patient with smoking history of 40 cigarettes per day for 40 years. He sought medical consultation for right lower lung nodules found by CT scan. The patient's postoperative pathological diagnosis was squamous cell carcinoma of the right lower lung. On the fourth day after the operation, the real-time reverse transcription polymerase chain reaction test showed a positive result. After the operation, we routinely give symptomatic treatments such as anti-infection, nebulization and oxygen inhalation. We also change antibiotics several times depending on the patient's condition. The patient's condition continued to deteriorate. On the fifth day after surgery, the patient died despite medical treatment. We are the first to report the diagnosis and treatment process of patients with COVID-19 during perioperative period of lobectomy. It provides a case for the postoperative management of such patients.


Graft pathology at the time of harvest: impact on long-term survival.
This study aims to present the graft pathology at the time of harvest and its impact on long-term survival. The remnants of the bypass grafts from 66 consecutive patients with coronary artery disease receiving a coronary artery bypass grafting were investigated pathologically, and pertinent predictive risk factors and survival were analyzed. Medial degenerative changes with or without intimal proliferation were present in 36.8%, 37.8% and 35.6% of left internal mammary artery (IMA), radial artery and saphenous vein grafts. There were 2 (3.0%) hospital deaths and 9 (14.1%) late deaths. Multinomial logistic regression revealed left IMA pathological changes, dyslipidemia, history of percutaneous transluminal coronary angioplasty/stent deployment and Y-graft were significant predictive risk factors negatively influencing the patients' long-term survival. Kaplan-Meier survival analysis revealed that the long-term survival of patients with left IMA pathological changes were significantly reduced compared with those without (74.1% vs. 91.4%, P=0.002); whereas no differences were noted in long-term survivals between patients with and without pathological changes of the radial arterial or saphenous vein grafts. Pathological changes may be seen in the bypass graft at the time of harvest. The subtle ultrastructural modifications and the expressions of vascular tone regulators might be responsible for late graft patency. The pathological changes of the left IMA at the time of harvest rather than those of the radial artery or saphenous vein graft affect significantly longterm survival. Non-traumatic maneuver of left IMA harvest, well-controlled dyslipidemia and avoidance of using composite grafts can be helpful in maintaining the architecture of the grafts.


Dispelling the chronic Lyme disease myth.
Lyme disease is a tick-borne illness endemic to Minnesota that can have potentially severe complications. As the incidence of Lyme disease continues to increase, it is important for physicians in Minnesota to become familiar with its clinical aspects, including the concept of "chronic Lyme disease." Chronic Lyme disease is a misnomer that is often applied to patients with nonspecific presentations who may or may not have a history of infection with Borrelia burgdorferi, the agent that causes Lyme disease. When a patient does present with persistent nonspecific symptoms attributed to chronic Lyme disease, clinicians should ascertain the presence of objective manifestations, obtain laboratory results, and get a history of tick exposure. If active infection with B. burgdorferi is unlikely, they should avoid prescribing empiric antibiotic therapy and instead thoroughly evaluate the patient for other possible causes of the complaints and recommend appropriate care.


An electron microscopic study of the location of peptidoglycan in group A and C streptococcal cell walls.
The morphological appearance of deproteinized Group A and C streptococcal walls after treatment by different procedures extracting teichoic acids and polysaccharides (formamide, hydrochloric acid, nitrous acid, trichloroacetic acid, sulphuric acid, sodium hydroxide and sodium deoxycholate) was compared with the content of teichoic acids and polysaccharides remaining in the treated walls. All procedures extracted teichoic acids almost completely, but polysaccharides were extracted to various degrees. The ultrastructural appearance of walls after these extractions still exhibited the triple-layered wall profile; only a reduction of thickness of the wall and of electron density of the layers occurred. There was no direct correlation between the reduction of rhamnose content and thickness of walls. The ultrastructural localization of peptidoglycan in the streptococcal walls was explored by means of the indirect immunoferritin technique using anti-peptidoglycan antibodies isolated from anti-Group A-variant antisera. Ferritin particles were bound predominantly to filamentous structures which protruded from both surfaces of peptidoglycan fragments and isolated walls. Peptidoglycan was also detected on the filamentous protrusions of whole cocci. These results contradict models of the streptococcal wall in which peptidoglycan forms the innermost layer and support a mosaic structure in which peptidoglycan forms a network of the peptidoglycan-polysaccharide complex.


Replication of the broad host range plasmid RSF1010: requirement for three plasmid-encoded proteins.
Cloning of specific regions of plasmid RSF1010, in conjunction with in vitro replication studies, has revealed three novel genes: repA, repB, and repC. They are clustered in one region of the plasmid, separated from the origin of replication by regions that are not essential for plasmid viability in an Escherichia coli host. In vivo, a 2.1-kilobase segment of the plasmid, bearing the replication origin, can establish itself as an autonomous replicon if the DNA region carrying the three rep genes is present in the same cell on an independent plasmid. In vitro, RSF1010 DNA is efficiently replicated by an ammonium sulfate fraction from the E. coli extract, provided the extracts are prepared from cells that can supply the required rep gene products. Using cells containing the cloned rep gene region as a source of elevated levels of the rep proteins, we have partially purified these proteins in functional form. When added to an enzyme fraction derived from plasmid-free cells, they specifically promote the replication of plasmid DNA bearing the RSF1010 origin.


[Mineral analysis and study of asbestos pathology].
Several tools are available for the evaluation of the exposure to asbestos, particularly occupational questionnaire and mineralogical analysis of biological samples. These analysis allow quantification of the level of retention of asbestos fibres in the respiratory tract. Two groups of analysis may be used: quantification of asbestos bodies in sputum, bronchoalveolar lavage fluid or lung tissue samples using light microscopy; quantification and identification of asbestos fibres in bronchoalveolar lavage fluid or lung tissue using analytical electron microscopy. Profiles of lung retention of asbestos bodies or asbestos fibres have been described in various asbestos-related disorders, and reference values are available in control populations mainly for asbestos bodies using light microscopy. Mineralogical analysis of biological samples is not required for compensation of occupational asbestos-related diseases. However, this type of analysis may prove to be useful to the chest physician when looking for the etiology of some nonspecific respiratory diseases (interstitial pulmonary fibrosis, lung cancer), particularly when the occupational questionnaire is not contributive. As they are quite easier and less expensive, analysis using light microscopy will be performed first.


Professional development needs of nurse educators. An Australian case study.
Because there is a global shortage of nurse educators, highly productive and committed nurse educators are needed to supply a rapidly expanding and changing health landscape. To support the aforementioned effort professional development needs of nurse educators must be systematically identified. This study explores practical issues around professional development needs of nurse educators. One hundred and thirty eight Australian nurse educators based in Queensland answered an online survey around professional development needs. Results indicate that 83% (n = 115) of the respondents were enthusiastic about nurse education yet only 45% (n = 62) were confident in their skills and less than 10% (n = 13) saw themselves as expert nurse educators. The most desired areas of future development in teaching were information technology skills, assessment and technical knowledge. There seems to be a shared need for developing global online and offline support resources and communities of practice to support nurse educators in their teaching and research endeavours.


Ecdysteroid coordinates optic lobe neurogenesis via a nitric oxide signaling pathway.
Proliferation of neural precursors in the optic lobe of Manduca sexta is controlled by circulating steroids and by local production of nitric oxide (NO). Diaphorase staining, anti-NO synthase (NOS) immunocytochemistry and the NO-indicator, DAF-2, show that cells throughout the optic anlage contain NOS and produce NO. Signaling via NO inhibits proliferation in the anlage. When exposed to low levels of ecdysteroid, NO production is stimulated and proliferation ceases. When steroid levels are increased, NO production begins to decrease within 15 minutes independent of RNA or protein synthesis and cells rapidly resume proliferation. Resumption of proliferation is not due simply to the removal of NO repression though, but also requires an ecdysteroid stimulatory pathway. The consequence of these opposing pathways is a sharpening of the responsiveness to the steroid, thereby facilitating a tight coordination between development of the different elements of the adult visual system.


Mortality trends and disparities among racial/ethnic and sex subgroups in New York City, 1990 to 2000.
New York City census data for 1990 and 2000 for all-cause and disease-specific mortality adjusted by age were examined by race/ethnicity. Primary cause of death was coded as HIV/AIDS, cardiovascular disease, coronary heart disease, acute myocardial infarction, stroke, diabetes, or cancer. For White, Black, Hispanic and Asian groups, relative mortality ratios (RMR) were derived for 2000 relative to 1990. Ratios of RMR's for minority groups were derived relative to Whites. From 1990 to 2000, HIV, cancer, CVD, CHD, AMI, and stroke-related mortality decreased. Decreases in HIV-related mortality were notably less for minority males. Diabetes mortality rates rose dramatically, with Hispanic and Asian males having notably greater increases than White males. Increases in mortality among Asians exceeded those of other groups, and appear to correspond with increased immigration/acculturation. Mortality shifts among different diseases and racial groups should alert public health officials to consider immigration patterns in designing, implementing, and evaluating interventions to prevent disease-related mortality, with a goal to eliminate disparities.


Epilepsy, intelligence, and psychiatric disorders in patients with cerebellar hypoplasia.
The cerebellum is involved in motor and cognitive functions and behavior. Its role in controlling epileptic seizures has been demonstrated in the literature. Genetic factors can enhance epilepsy susceptibility when the cerebellum is damaged. We examined the occurrence and features of epilepsy, intelligence, and psychiatric disorders in 28 patients with cerebellar hypoplasia. We compared patients with (10; 35.7%) and without (18; 64.3%) epilepsy. The statistical evaluation showed a significant prevalence of familial antecedents for seizures in patients with epilepsy (P < .01); cerebral associated lesions and type of cerebellar hypoplasia did not influence the occurrence of epilepsy, which was partial in 80% of cases. Profound mental retardation prevailed in patients with epilepsy (P < .05). Both mental retardation (75%) and pervasive developmental disorders (17.8%) prevailed in our cases with respect to the general population (P < .000). Cerebellar hypoplasia in our sample seems to be an important risk factor for the occurrence of epilepsy, mental retardation, and psychiatric disorders.


Assessment of the effect of UV and chlorination in the transformation of fragrances in aqueous samples.
The removal and transformation of 15 common fragrance allergens and two polycyclic musks in water samples were studied using UV irradiation and chlorination treatments. The monitoring of the reaction was carried out by a HS-SPME method coupled to GC-MS analysis. Different behaviours were observed depending on the compound and the treatment applied. Elimination experiments showed that all target compounds were affected by at least one of the two treatments. A total of 15 UV transformation products were detected and chemical structures were proposed for five of them. In the chlorination experiments, only galaxolide and benzyl cinnamate transformation products were observed.


Compression stockings for the initial treatment of varicose veins in patients without venous ulceration.
Compression hosiery or stockings are often the first line of treatment for varicose veins in people without either healed or active venous ulceration. Evidence is required to determine whether the use of compression stockings can effectively manage and treat varicose veins in the early stages. This is an update of a review first published in 2011. To assess the effectiveness of compression stockings for the only and initial treatment of varicose veins in patients without healed or active venous ulceration. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched August 2013) and CENTRAL (2013, Issue 5). Randomised controlled trials (RCTs) were included if they involved participants diagnosed with primary trunk varicose veins without healed or active venous ulceration (Clinical, Etiology, Anatomy, Pathophysiology (CEAP) classification C2 to C4). Included trials assessed compression stockings versus no treatment, compression versus placebo stockings, or compression stockings plus drug intervention versus drug intervention alone. Trials comparing different lengths and pressures of stockings were also included. Trials involving other types of treatment for varicose veins (either as a comparator to stockings or as an initial non-randomised treatment), including sclerotherapy and surgery, were excluded. Two authors assessed the trials for inclusion and quality (SS and LR). SS extracted the data, which were checked by LR. Attempts were made to contact trial authors where missing or unclear data were present. Seven studies involving 356 participants with varicose veins without healed or active venous ulceration were included. Different levels of pressure were exerted by the stockings in the studies, ranging from 10 to 50 mmHg. One study assessed compression hosiery versus no compression hosiery. The other six compared different types or pressures of stockings. The methodological quality of all included trials was unclear, mainly because of inadequate reporting.The symptoms subjectively improved with the wearing of stockings across trials that assessed this outcome, but these assessments were not made by comparing one randomised arm of a trial with a control arm and are therefore subject to bias.Meta-analyses were not undertaken due to inadequate reporting and actual or suspected high levels of heterogeneity. There is insufficient, high quality evidence to determine whether or not compression stockings are effective as the sole and initial treatment of varicose veins in people without healed or active venous ulceration, or whether any type of stocking is superior to any other type. Future research should consist of a large RCT of participants with trunk varices either wearing or not wearing compression stockings to assess the efficacy of this intervention. If compression stockings are found to be beneficial, further studies assessing which length and pressure is the most efficacious could then take place.


Self-assembling molecular wires of halogen-bridged platinum complexes in organic media. Mesoscopic supramolecular assemblies consisting of a mixed valent Pt(II)/Pt(IV) complex and anionic amphiphiles.
A novel class of supramolecular assemblies in organic media consisting of a molecular wire of a halogen-bridged platinum complex [Pt(en)2][PtCl2(en)2]4+ (en = 1,2-diaminoethane) and anionic amphiphiles is developed. When double-chained phosphates or sulfonates are employed, the resultant [Pt(en)2][PtCl2(en)2](4+)-lipid complexes displayed intervalence charge transfer (CT) absorption bands in the crystalline state. They are soluble in organic solvents because of the amphiphilic superstructure, in which the solvophobic one-dimensional platinum complex is surrounded by solvophilic alkyl chains. CT absorption bands of halogen-bridged linear complexes are maintained in organic media, with varied colors that depend on the chemical structure of constituent amphiphiles. Monoalkylated phosphates failed to form colored, halogen-bridged ternary complexes probably because of their coordination to the axial position of PtII(en)2. Formation of mesoscopic supramolecular assemblies in organic media was confirmed for the [Pt(en)2][PtCl2(en)2] complexes by electron microscopy. Interestingly, a supramolecular complex consisting of dihexadecyl sulfosuccinate and [Pt(en)2][PtCl2(en)2]4+ displayed clear, indigo solutions that are distinct from the yellow color observed for those of [Pt(en)2][PtCl2(en)2]/dialkyl phosphate complexes. The indigo color of the former complex disappeared upon heating the solution to 60 degrees C, whereas it reappeared reversibly by cooling the solution to room temperature. In electron microscopy, rodlike nanostructures with a minimum width of 18 nm and lengths of 700-1700 nm were observed after cooling, though not at elevated temperatures. Apparently, the lipid-[Pt(en)2][PtCl2(en)2]4+ complex undergoes reversible dissociation and reassembly processes in chloroform, and it becomes better dispersed after the reassembling process. The present finding opens a general route to solution chemistry of low-dimensional inorganic complexes and enables rational design and control of self-assembling inorganic molecular wires.


Defective cAMP generation underlies the sensitivity of CNS neurons to neurofibromatosis-1 heterozygosity.
Individuals with the neurofibromatosis type 1 (NF1) inherited cancer syndrome exhibit neuronal dysfunction that predominantly affects the CNS. In this report, we demonstrate a unique vulnerability of CNS neurons, but not peripheral nervous system (PNS) neurons, to reduced Nf1 gene expression. Unlike dorsal root ganglion neurons, Nf1 heterozygous (Nf1+/-) hippocampal and retinal ganglion cell (RGC) neurons have decreased growth cone areas and neurite lengths, and increased apoptosis compared to their wild-type counterparts. These abnormal Nf1+/- CNS neuronal phenotypes do not reflect Ras pathway hyperactivation, but rather result from impaired neurofibromin-mediated cAMP generation. In this regard, elevating cAMP levels with forskolin or rolipram treatment, but not MEK (MAP kinase kinase) or PI3-K (phosphatidylinositol 3-kinase) inhibition, reverses these abnormalities to wild-type levels in vitro. In addition, Nf1+/- CNS, but not PNS, neurons exhibit increased apoptosis in response to excitotoxic or oxidative stress in vitro. Since children with NF1-associated optic gliomas often develop visual loss and Nf1 genetically engineered mice with optic glioma exhibit RGC neuronal apoptosis in vivo, we further demonstrate that RGC apoptosis resulting from optic glioma in Nf1 genetically engineered mice is attenuated by rolipram treatment in vivo. Similar to optic glioma-induced RGC apoptosis, the increased RGC neuronal death in Nf1+/- mice after optic nerve crush injury is also attenuated by rolipram treatment in vivo. Together, these findings establish a distinctive role for neurofibromin in CNS neurons with respect to vulnerability to injury, define a CNS-specific neurofibromin intracellular signaling pathway responsible for neuronal survival, and lay the foundation for future neuroprotective glioma treatment approaches.


Giga-pixel fluorescent imaging over an ultra-large field-of-view using a flatbed scanner.
We demonstrate a new fluorescent imaging technique that can screen for fluorescent micro-objects over an ultra-wide field-of-view (FOV) of ~532 cm(2), i.e., 19 cm × 28 cm, reaching a space-bandwidth product of more than 2 billion. For achieving such a large FOV, we modified the hardware and software of a commercially available flatbed scanner, and added a custom-designed absorbing fluorescent filter, a two-dimensional array of external light sources for computer-controlled and high-angle fluorescent excitation. We also re-programmed the driver of the scanner to take full control of the scanner hardware and achieve the highest possible exposure time, gain and sensitivity for detection of fluorescent micro-objects through the gradient index self-focusing lens array that is positioned in front of the scanner sensor chip. For example, this large FOV of our imaging platform allows us to screen more than 2.2 mL of undiluted whole blood for detection of fluorescent micro-objects within <5 minutes. This high-throughput fluorescent imaging platform could be useful for rare cell research and cytometry applications by enabling rapid screening of large volumes of optically dense media. Our results constitute the first time that a flatbed scanner has been converted to a fluorescent imaging system, achieving a record large FOV.


Establishment of a sensitive UPLC-MS/MS method to quantify safinamide in rat plasma.
A fast, simple, and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established for the quantification of safinamide in rat plasma. Plasma samples were treated with acetonitrile for protein precipitation, and diazepam was used as an internal standard (IS). The analytes were separated on an Acquity UPLC C18 (2.1 mm × 50 mm, 1.7 μm) chromatographic column with gradient elution using a mobile phase (0.1% formic acid-acetonitrile). Then, the eluates were detected by electrospray ionization (ESI) in positive ion mode. The analytes were quantified by multiple reaction monitoring (MRM) using the transition m/z 303.3→215.0 of safinamide and m/z 285.0→154.0 of IS. Safinamide had good linearity in the concentration range of 1.0-2000 ng/mL, and the lower limit of quantitation (LLOQ) was 1.0 ng/mL. The intra- and inter-day precision and accuracy of safinamide were less than 7.63%, while the average recovery rate was 92.98%-100.29%. The method was validated to be stable and had low noise, short chromatographic run time, wide linear range, small sample volumes, low sample injection volumes, and high sensitivity. Therefore, it can be used in pharmacokinetics and preclinical and clinical studies.


[Brachymetacarpia in disorders of the rate of physical growth].
On the basis of studying roentgenograms of 1007 wrists in 769 persons the author presents the incidence of the metacarpal syndrome in the population and in some disturbances of the rate of physical development. A metacarpal index determined by roentgenogram as the ratio of the IV and the II metacarpal bones multiplied by 100 is suggested. The value ocal and is often encountered in gonad dysgenesia. Estrogen therapy failed to eliminate this ratio disturbance in the metacarpus. Girls with an accelerated physical development had a tendency to increase of the metacarpal index. As a rule this index was within the normal limits in Klinefelter's syndrome.


Cognitive processing in relation to psychological distress in women with breast cancer: a theoretical approach.
To evaluable a cognitive procession model developed by Creamer and colleagues, this study examined the longitudinal relationship between intrusion and psychological distress, via avoidance, in women with breast cancer. Participants included 189 patients who were newly diagnosed with breast cancer. The longitudinal association between intrusion, avoidance and psychological distress and the mediating role of avoidance between intrusion and psychological distress were examined. Intrusion was measured at inclusion (T1), avoidance at 3 months post-inclusion (T2) and psychological distress at 12 months post-inclusion (T3). Results suggested that avoidance at T2 did not mediate the relationship between intrusions at T1 and psychological distress at T3. The results did not provide support for Creamer's model in an early-stage breast cancer population, which suggests that early-stage breast cancer patient's process trauma differently from late-stage cancer patients. Therefore, it might be suggested that early-stage and late-stage cancer patients require different types of support and treatment for the distress experienced.


Recurrence of Cushing's disease after long-term remission due to pituitary apoplexy.
We encountered a case with long-term remission of Cushing's disease due to pituitary apoplexy. The apoplexy of pituitary adenoma secreting adrenocorticotropin hormone was diagnosed by successive and timely magnetic resonance imaging when the symptoms of the patient were not yet severe and anterior pituitary dysfunction was only a transient reduction of growth hormone secretion. Seven years after the first episode of pituitary apoplexy, hypercorticism recurred, and pituitary magnetic resonance imaging showed a regrowth of the pituitary adenoma. A spontaneous remission of Cushing's disease without significant visual, neurologic or hormonal defects seems to be a much more common phenomenon than has been previously suggested. Cases with relapse after spontaneous remission of Cushing's disease are rare and the duration of remission in previous reports was within 5 years. We observed such a patient with a 7 year-remission caused by pituitary apoplexy. We consider that a careful long-term follow-up is required for patients with Cushing's disease whose remission was due to pituitary apoplexy.


First record of Colpodidium caudatum (Ciliophora, Colpodidiidae) in Europe.
The present study documents the discovery of the first European population of Colpodidium caudatum (Ciliophora, Colpodidiidae) in a water drain in a school playground in Manzanares (Ciudad Real, Spain). This species has been documented on every continent except Antarctica and Europe, until now. The ciliate was isolated from wet run-off soil collected from the water drain and was grown in semi-permanent cultures in the laboratory. The infraciliature of the ciliate was revealed using silver carbonate impregnation and cell measurements were taken from living and silver-impregnated specimens. A comparative analysis of published data from various populations of C. caudatum across the globe showed high intraspecific morphological variability in this species. To differentiate between species within the Colpodidium genus, a dichotomous key is presented. This investigation shows that C. caudatum is a ciliate that is found all over the world and is particularly associated with terrestrial habitats that are periodically flooded.


Action-concept usage by nonretarded and retarded children on structured tasks with praise for performance.
In equivalence-formation tasks, retarded children have been ovserved to use fewer action concepts than expected on the basis of their MA. When tasks were structured and praise for performance was introduced, mildly retarded children performed like nonretarded children in most respects, except for total number of responses. Moderately retarded children of the same MA showed improved performance but still performed more poorly than either of the other two groups. The implications of these findings were discussed.


Quantifying lipofuscin in retinal pigment epithelium in vivo by visible-light optical coherence tomography-based multimodal imaging.
Lipofuscin in the retinal pigment epithelium (RPE) is the major source of fundus autofluorescence (FAF). A technical challenge to accurately quantify the FAF intensities, thus the lipofuscin concentration, is to compensate the light attenuation of RPE melanin. We developed the VIS-OCT-FAF technology to accomplish optical coherence tomography (OCT) and FAF simultaneously with a single broadband visible light source. We demonstrated that light attenuation by RPE melanin can be assessed and corrected using the depth-resolved OCT signals. FAF images from albino and pigmented rats showed that without compensation, FAF signals from pigmented rats are lower than that from albinos. After compensation, however, FAF signals from pigmented rats are higher. This finding is supported by measurements of lipofuscin fluorophore A2E in the RPE using liquid chromatography/mass spectrometry (LC/MS) showing that compensated FAF intensities correlate linearly with A2E contents. The present work represents an important step toward accurately assessing RPE lipofuscin concentrations by FAF.


Intestinal lipid handling: evidence and implication of insulin signaling abnormalities in human obese subjects.
Animal models have evidenced the role of intestinal triglyceride-rich lipoprotein overproduction in dyslipidemia. However, few studies have confronted this issue in humans and disclosed the intrinsic mechanisms. This work aimed to establish whether intestinal insulin resistance modifies lipid and lipoprotein homeostasis in the intestine of obese subjects. Duodenal specimens obtained from 20 obese subjects undergoing bariatric surgery were paired for age, sex, and body mass index with or without insulin resistance, as defined by the homeostasis model assessment of insulin resistance. Insulin signaling, biomarkers of inflammation and oxidative stress, and lipoprotein assembly were assessed. The intestine of insulin-resistant subjects showed defects in insulin signaling as demonstrated by reduced protein kinase B phosphorylation and increased p38 mitogen-activated protein kinase phosphorylation, likely as the result of high oxidative stress (evidenced by malondialdehyde and conjugated dienes) and inflammation (highlighted by nuclear factor-κB, tumor necrosis factor-α, interleukin-6, intercellular adhesion molecule-1, and cyclooxygenase-2). Enhanced de novo lipogenesis rate and apolipoprotein B-48 biogenesis along with exaggerated triglyceride-rich lipoprotein production were observed, concomitantly with the high expression levels of liver and intestinal fatty acid-binding proteins and microsomal transfer protein. The presence of an aberrant intracellular cholesterol transport/metabolism was also suggested by the reduced expression of ATP-binding cassette A1 transporter and proprotein convertase subtilisin/kexin type 9. According to the present data, the small intestine may be classified as an insulin-sensitive tissue. Dysregulation of intestinal insulin signaling, possibly triggered by oxidative stress and inflammation, was associated with exaggerated lipogenesis and lipoprotein synthesis, which may represent a key mechanism for atherogenic dyslipidemia in patients with metabolic syndrome.


Systemic granulomatous reaction secondary to treatment of bladder cancer with bacillus calmette-guerin.
Intravesical instillation of Bacillus Calmette-Guérin is the elective treatment for transitional cell and in situ bladder carcinoma. Severe complications occur very seldom, but must be known and promptly recognized. We describe the case of a 48-year-old man, treated with chemo-immunotherapy ten years before for a follicular lymphoma, who developed a systemic granulomatous reaction after his twelfth intravescical BCG instillation for bladder cancer.