Higher proportions of peripheral CD19+CD5+ B cells predict the effect of corticosteroid in patients with late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.
The cause of late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains obscure. In clinical practice, some LOHC patients respond to immunosuppression. The aim of this study was to determine the immune pathogenesis of LOHC post allo-HSCT. With the diagnosis of LOHC, patients were given initial treatment consisting of fluid hydration, alkalization and forced diuresis, and empirical anti-viral therapy for 10 - 14 days or until a week after the virus became negative. The nonresponders were applied corticosteroid. Seven to ten days later, patients' response was evaluated. Along with treatment, CD19(+) B lymphocyte subsets were measured at various study points. From October 2009 to March 2010, we found 28 cases of LOHC occurred in 25 patients who underwent allo-HSCT in our hospital. Except that three cases were not treated according to the protocol, the other 25 cases were divided into three groups: anti-virus responders (Group A, n = 6), corticosteroid responders (Group B1, n = 16), corticosteroid and anti-virus nonresponders (Group C, n = 3) according to their clinical response. Percentages of CD19(+)CD5(+) B lymphocytes were not significantly different among three groups at onset of LOCH. However, in Group B1 after the first anti-virus phase, percentages of CD19(+)CD5(+) lymphocytes significantly increased comparing with those at onset (P = 0.022), and then significantly decreased at PR (P = 0.003) and CR (P = 0.002) with corticosteroid treatment. But significant change was not observed in Groups A and C. The immune etiology seems to be involved in the development of LOHC and the proportion of CD19(+)CD5(+) lymphocytes may serve as a cellular biomarker to predict the response to corticosteroid in LOHC.


Detection rates of trichomonas vaginalis, in different age groups, using real-time polymerase chain reaction.
The study aimed to compare the overall detection rate of Trichomonas vaginalis to Chlamydia trachomatis and Neiserria gonorrhea and report detection rates by age groups. Real-time polymerase chain reaction was used to detect the presence of T. vaginalis, C. trachomatis, and N. gonorrhea in cervical samples obtained from patients during gynecological examinations. A total of 78,428, 119,451, and 117,494 samples from women age 12 to 75 years were retrospectively analyzed for the presence of T. vaginalis, C. trachomatis, and N. gonorrhea, respectively. T. vaginalis and C. trachomatis detection rates in Florida, New Jersey, and Texas were calculated in different age groups. The overall detection rate was 4.3% for T. vaginalis, 3.8% for C. trachomatis, and 0.6% for N. gonorrhea. The overall detection rate of T. vaginalis in Florida was 4.7% (n = 22,504), in New Jersey was 3.6% (n = 22,249), and in Texas was 4.5% (n = 33,675). Calculation of infection rates with T. vaginalis revealed differences between selected age groups with the highest detection rates in all 3 states found in age group 46 to 55 years (6.2%), which was higher than the overall detection rates in other age groups (p < .05 for all states). For C. trachomatis, the highest detection rate was found in age group 12 to 25 years (7.3%). The overall infection rates of T. vaginalis were higher compared with those of C. trachomatis and N. gonorrhea. Detection rates of T. vaginalis were found to be highest among women age 46 to 55 years and may be due to T. vaginalis infiltrating the subepithelial glands and being detected only during hormone-induced or antibiotic-induced changes in the vaginal flora.


Overview of findings from a 2-year study of claimants who had sustained a mild or moderate injury in a road traffic crash: prospective study.
Studies have shown that in people injured in a road traffic crash, persistent symptoms are common and can lead to significant ongoing personal impact. Hence, elucidating factors associated with the human costs are key to reducing the socio-economic burden of road traffic injuries. Therefore, in this study we aimed to track the experience and key outcomes of persons who had sustained mild/moderate injuries as they returned to health (and work, where relevant) following a road traffic crash. It is an inception study cohort of adults who had sustained mild to moderate injuries (that is, except serious injuries) in motor vehicle crashes in New South Wales, Australia, who were recruited and interviewed at baseline (within 3 months of the crash) and at 6, 12 and 24 months post-injury. We found that minor injuries had major impacts on pain ratings, physical and mental well-being, health-related quality of life and return to work and pre-injury participation during the 24 months post-injury phase. Further, for mild to moderately severe injuries, biopsychosocial factors appear to be prognostic indicators of recovery (not the location or type of injury). Examples of key biopsychosocial factors are: age; preinjury health; quality of life; reactions to injury (catastrophising, and pain); social support and the third party insurance compensation system. This study highlights the considerable impact of apparently "minor" road traffic crash injuries at a population level and suggests targeted approaches to the tertiary prevention of long-term morbidity and disability. Study findings have also reiterated the importance of looking beyond the injury to the 'whole person'.


Continuous-flow cell saver reduces cognitive decline in elderly patients after coronary bypass surgery.
Cerebral microembolization during cardiopulmonary bypass may lead to cognitive decline after cardiac surgery. Transfusion of the unprocessed shed blood (major source of lipid microparticulates) into the patient during cardiopulmonary bypass is common practice to reduce blood loss and blood transfusion. Processing of shed blood with cell saver before transfusion may limit cerebral microembolization and reduce cognitive decline after surgery. A total of 226 elderly patients were randomly allocated to either cell saver or control groups. Anesthesia and surgical management were standardized. Epiaortic scanning of the proximal thoracic aorta was performed in all patients. Transcranial Doppler was used to measure cerebral embolic rates. Standardized neuropsychological testing was conducted 1 week before and 6 weeks after surgery. The raw scores for each test were converted to Z scores, and then a combined Z score of 10 main variables was calculated for both study groups. The primary analysis was based on dichotomous composite cognitive outcome with a 1-SD rule. Cognitive dysfunction was present in 6% (95% confidence interval, 1.3% to 10.7%) of patients in the cell saver group and 15% (95% confidence interval, 8% to 22%) of patients in the control group 6 weeks after surgery (P=0.038). The severity of aortic atheroma and cerebral embolic count were similar between the 2 groups. The present report demonstrates that processing of shed blood with cell saver results in clinically significant reduction in postoperative cognitive dysfunction after cardiac surgery. These findings emphasize the clinical importance of lipid embolization in contributing to postoperative cognitive decline in patients exposed to cardiopulmonary bypass.


Control of capsular polysaccharide chain length by UDP-sugar substrate concentrations in Streptococcus pneumoniae.
Regulation of chain length is essential to the proper functioning of prokaryotic and eukaryotic polysaccharides. Modulation of polymer size by substrate concentration is an attractive but unexplored control mechanism that has been suggested for many polysaccharides. The Streptococcus pneumoniae capsular polysaccharide is essential for virulence, and regulation of its size is critical for survival in different host environments. Synthesis of the type 3 capsule [-4)-beta-d-Glc-(1-3)-beta-d-GlcUA-(1-] from UDP-glucose (UDP-Glc) and UDP-glucuronic acid (UDP-GlcUA) is catalysed by the type 3 synthase, a processive beta-glycosyltransferase, and requires a UDP-Glc dehydrogenase for conversion of UDP-Glc to UDP-GlcUA. Strains containing mutant UDP-Glc dehydrogenases exhibited reduced levels of UDP-GlcUA, along with reductions in total capsule amount and polymer chain length. In both the parent and mutant strains, UDP-Glc levels far exceeded UDP-GlcUA levels, which were very low to undetectable in the absence of blocking synthase activity. The in vivo observations were consistent with in vitro conditions that effect chain termination and ejection of the polysaccharide from the synthase when one substrate is limiting. These data are the first to demonstrate modulation of polysaccharide chain length by substrate concentration and to enable a model for the underlying mechanism. Further, they may have implications for the control of chain length in both prokaryotic and eukaryotic polymers synthesized by similar mechanisms.


New Cerebral Microbleeds After Catheter-Based Structural Heart Interventions: An Exploratory Analysis.
Background Cerebral microbleeds (CMBs) are increasingly recognized as "covert" brain lesions indicating increased risk of future neurological events. However, data on CMBs in patients undergoing catheter-based structural heart interventions are scarce. Therefore, we assessed occurrence and predictors of new CMBs in patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Methods and Results We conducted an exploratory analysis using data derived from 2 prospective, observational studies. Eligible patients underwent cerebral magnetic resonance imaging (3 Tesla) examinations and cognitive tests (using the Montreal Cognitive Assessment) before and after catheter-based left atrial appendage closure and percutaneous mitral valve repair. Forty-seven patients (53% men; median age, 77 years) were included. New CMBs occurred in 17 of 47 patients (36%) following catheter-based structural heart interventions. Occurrences of new CMBs did not differ significantly between patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair (7/25 versus 10/22; P=0.348). In univariable analysis, longer procedure time was significantly associated with new CMBs. Adjustment for heparin attenuated this association (adjusted odds ratio [per 30 minutes]: 1.77 [95% CI, 0.92-3.83]; P=0.090). Conclusions New CMBs occur in approximately one-third of patients after catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Our data suggest that longer duration of the procedure may be a risk factor for new CMBs. Future studies in larger populations are needed to further investigate their clinical relevance. Clinical Trial Registration German Clinical Trials Register: DRKS00010300 (https://drks.de/search/en/trial/DRKS00010300); ClinicalTrials.gov : NCT03104556 (https://clinicaltrials.gov/ct2/show/NCT03104556?term=NCT03104556&draw=2&rank=1).


Detection of point mutation for human growth hormone in patients with anti-pituitary antibody positive type 1 diabetes mellitus.
We investigated genetic mutations in the coding region of the human growth hormone (hGH) gene in anti-pituitary antibody (APA)-positive patients with type 1 diabetes mellitus (n = 6) or autoimmune thyroid diseases (n = 10) and in APA-negative, healthy controls (n = 10). A point mutation in the hGH gene was discovered in two patients with type 1 diabetes mellitus. No mutations were found in the hGH gene in control subjects, patients with autoimmune thyroid diseases (Hashimoto's thyroiditits, Graves' disease) or in the remaining four patients with type 1 diabetes mellitus. The mutation was located in the coding region for the second amino acid in the N-terminal region of hGH. This point mutation was identified in codon 2 in exon 2 of the hGH gene. We successfully developed an allele-specific amplification method for detecting this mutation using the polymerase chain reaction.


Minor Physical Anomalies in Bipolar Disorder-A Meta-Analysis.
Introduction: Minor physical anomalies (MPAs) may reflect basic neurobiological features underlying bipolar disorders (BPD), as they are sensitive physical indicators of morphogenetic failure of the brain. Despite several researches about the presence of MPAs in BPD, the results are still controversial. Objectives: The aim of the present meta-analysis was to assess the standardized weighted mean effect sizes of MPAs in BPD and to examine if MPAs may be found predominantly in the head and/or facial regions in BPD patients compared to controls (HC). Methods: Four studies, involving 155 patients with BPD, and 187 HC, were involved in the analysis after searching the literature. For the investigation of MPAs in the peripheral (MPA-P) and in the head and facial regions (MPA-CF), two studies involving 121 BPD patients, and 133 HC passed the inclusion criteria. Results: The number of the MPAs in the BPD group was significantly higher compared to HC. Another important finding of the present study is that BPD patients' MPA-P scores do not significantly differ from those of the HC. In contrast, BPD patients' MPA-CF scores were found to be significantly higher compared to HC subjects. It is important to note that there was a low number of eligible publications included, which caused higher heterogeneity. Conclusions: Low quality of evidence suggests that MPAs are more common in patients with BPD than in HC and the higher rate of MPAs is found predominantly in the head and facial regions.


An acetate-buffered balanced crystalloid versus 0.9% saline in patients with end-stage renal disease undergoing cadaveric renal transplantation: a prospective randomized controlled trial.
Recent studies have shown a decline in glomerular filtration rate and increased renal vasoconstriction after administration of normal saline when compared with IV solutions with less chloride. In this study, we investigated the impact of normal saline versus a chloride-reduced, acetate-buffered crystalloid on the incidence of hyperkalemia during cadaveric renal transplantation. The incidence of metabolic acidosis and kidney function were secondary aims. In this prospective randomized controlled trial, 150 patients received normal saline or an acetate-buffered balanced crystalloid during and after cadaveric renal transplantation. Venous blood gases were obtained at the start of anesthesia and every 30 minutes until discharge from the postoperative surveillance unit. Serum creatinine and 24-hour urine output were obtained on postoperative days 1, 3, and 7. Patients received a similar amount of fluid (median: 2625mL [interquartile range: 2000 to 3100] vs 2500 mL [2000 to 3050], P = 0.83). Hyperkalemia, defined as serum potassium >5.9 mmol/L, occurred in 13 patients (17%) in the saline and 15 (21%) in the balanced group (P = 0.56; difference between proportions -0.037 [-16.5% to 8.9%]). Minimum base excess was lower in the saline group compared with the balanced regimen (-4.5 mmol/L [-6 to -2.4] vs -2.6 mmol/L [-4 to -1], P < 0.001) and maximum chloride was significantly higher in the saline group (109 mmol/L [107 to 111] vs 107 mmol/L [105 to 109], P < 0.001). No difference in creatinine or urine output was seen postoperatively. Significantly more patients needed catecholamines in the saline group (30% vs 15%, P = 0.03). The incidence of hyperkalemia differed by less than 17% between groups. Use of balanced crystalloid resulted in less hyperchloremia and metabolic acidosis. Significantly more patients in the saline group required administration of catecholamines for circulatory support.


Elaboration and Evaluation of Contents about Hearing Health Inserted in Cybertutor.
Introduction Cybertutor (electronic tutor) is a type of information and communication technology to disseminate knowledge about hearing, aiming at the prevention of hearing alterations and, when needed, early treatment, in addition to social inclusion of the hearing impaired. However, it is important to evaluate the level of language used in the content and the subjective perception of the target public regarding improvements of the tool. Objective To improve content about hearing health inserted in a cybertutor and to evaluate the level of legibility and the quality of the content and material made available. Method For the construction of the content, text and audiovisual resources were used, based on scientific publications, and were evaluated objectively with Flesch Reading Ease test and subjectively with a questionnaire created by the authors and answered by 10 ninth-year pupils. Results Two modules on hearing health were created, "Hearing Health" and "Intervention and Rehabilitation," which received Flesch scores of 50.8 and 51.4%, respectively, making it necessary to have a sixth- to ninth-year education to understand the material. The students' evaluation in reference to language and material showed that 55.5% considered the contents excellent; 38.2% classified the contents as satisfactory; 6.3% considered them reasonable; and 0% classified them as unsatisfactory. Conclusion The contents inserted in the cybertutor about hearing health presented a language level considered easy for the age group of the target population, in addition to receiving good subjective evaluation from the pupils, facilitating access to the information.


Clinical and radiographic study of activated carbon workers.
Activated carbon is made in Sri Lanka by passing steam through charcoal made from coconut shells. The carbon does not contain free silica. Sixty six men who had worked in a factory making activated carbon for an average of 7.2 years had no more respiratory symptoms than a control group, and none showed radiological evidence of pneumoconiosis. There was no evidence that people exposed to charcoal and pure carbon for up to 11 years are at risk of developing pneumoconiosis.


The role of neurokinin B in pre-eclampsia.
Pre-eclampsia, a life-threatening disease unique to pregnancy, has been called a disease of theories. To date, there has been no widely accepted predictive test or therapeutic intervention to prevent or delay pre-eclampsia. The discovery of a new placental hormone, neurokinin B, may finally help to answer some of the past mysteries.


A long-range RNA-RNA interaction between the 5' and 3' ends of the HCV genome.
The RNA genome of the hepatitis C virus (HCV) contains multiple conserved structural cis domains that direct protein synthesis, replication, and infectivity. The untranslatable regions (UTRs) play essential roles in the HCV cycle. Uncapped viral RNAs are translated via an internal ribosome entry site (IRES) located at the 5' UTR, which acts as a scaffold for recruiting multiple protein factors. Replication of the viral genome is initiated at the 3' UTR. Bioinformatics methods have identified other structural RNA elements thought to be involved in the HCV cycle. The 5BSL3.2 motif, which is embedded in a cruciform structure at the 3' end of the NS5B coding sequence, contributes to the three-dimensional folding of the entire 3' end of the genome. It is essential in the initiation of replication. This paper reports the identification of a novel, strand-specific, long-range RNA-RNA interaction between the 5' and 3' ends of the genome, which involves 5BSL3.2 and IRES motifs. Mutants harboring substitutions in the apical loop of domain IIId or in the internal loop of 5BSL3.2 disrupt the complex, indicating these regions are essential in initiating the kissing interaction. No complex was formed when the UTRs of the related foot and mouth disease virus were used in binding assays, suggesting this interaction is specific for HCV sequences. The present data firmly suggest the existence of a higher-order structure that may mediate a protein-independent circularization of the HCV genome. The 5'-3' end bridge may have a role in viral translation modulation and in the switch from protein synthesis to RNA replication.


Chondroblastoma patella presenting as a pathological fracture.
A 24-year-old male presented with an inability to walk after a trivial fall. He had pain and mild swelling anterior to the right knee for the past one year. X-ray showed a transverse fracture of patella with a lytic lesion occupying most of the two halves of the patella. Fine needle aspiration cytology (FNAC) of the lytic lesion revealed a few osteoclastic giant cells and occasional osteoblasts against a hemorrhagic background. Patellectomy was performed. Histology revealed trabecular bone admixed with proliferating chondroid tissue at places admixed with myxoid and fibrous tissue with focal areas of calcification suggestive of chondroblastoma. Focal areas showed osteoclastic giant cells with areas of hemorrhage. The purpose is to present a rare tumor occurring at an unusual site which presented as pathological fracture.


Longitudinal myocardial contribution to peak systolic flow and stroke volume in the neonatal heart.
Systolic longitudinal myocardial function is important for cardiac ejection. Data describing hemodynamic determinants and the time course of myocardial longitudinal contraction as measured by tissue Doppler are lacking. Ten newborn pigs were used for invasive hemodynamic investigation. Tissue Doppler assessment of the lateral part of the mitral valve annulus during systole was performed during pharmacological modulation of inotropy, cardiac pacing, and modulations of loading conditions. The strongest association was found between peak systolic velocity (S') and peak systolic flow (PSF) and end-systolic pressure (ESP), respectively (β = 0.09 cm/mL, p < 0.001 and β = -0.07 cm/mL, p = 0.003). Displacement (D) was mostly influenced by stroke volume (SV) (β = 0.05 cm/mL, p < 0.001). Ejection time, SV, ESP, maximum first derivative of pressure (dP/dtmax), and PSF were all associated with S' and D under different states of hemodynamic modulation; however, the ratio between PSF and S', SV, and D were stable during hemodynamic modulations. Normalized cross correlations indicate that S' and D follow the same trajectory as flow and SV, respectively. In conclusion, this study provides validity of accounting systolic D in the long axis as the longitudinal contribution to SV and peak systolic tissue velocity as the longitudinal contribution to PSF.


Patterning chromatin: form and function for H2A.Z variant nucleosomes.
Although many histone variants are specific to higher eukaryotes, the H2A variant H2A.Z has been conserved during eukaryotic evolution. Genetic studies have demonstrated roles for H2A.Z in antagonizing gene-silencing, chromosome stability and gene activation. Biochemical work has identified a conserved chromatin-remodeling complex responsible for H2A.Z deposition. Recent studies have shown that two H2A.Z nucleosomes flank a nucleosome-free region containing the transcription initiation site in promoters of both active and inactive genes in Saccharomyces cerevisiae. This chromatin pattern is generated through the action of a DNA deposition signal and a specific pattern of histone tail acetylation.


Beyond peripheral arteries in Buerger's disease: angiographic considerations in thromboangiitis obliterans.
Thromboangiitis obliterans is an inflammatory peripheral vascular disease that is strongly associated with smoking. It predominantly affects distal small- and medium-sized blood vessels of both the upper and lower extremities. We present histological evidence of this disease process affecting the internal mammary arteries. This can be of paramount clinical significance for patients with Buerger's disease who present with obstructive coronary artery disease and require coronary artery bypass grafting surgery (CABG). Internal mammary arteries involved with thromboangiitis obliterans cannot be utilized as arterial conduits during CABG and other alternatives have to be used. Therefore, we recommend preoperative angiography of both internal mammary arteries in patients with Buerger's disease requiring CABG to prevent extensive intraoperative dissection of diseased internal mammary arteries.


CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets.
With the advent of OMICs technologies, both individual research groups and consortia have spear-headed the characterization of human samples of multiple pathophysiologic origins, resulting in thousands of archived genomes and transcriptomes. Although a variety of web tools are now available to extract information from OMICs data, their utility has been limited by the capacity of nonbioinformatician researchers to exploit the information. To address this problem, we have developed CANCERTOOL, a web-based interface that aims to overcome the major limitations of public transcriptomics dataset analysis for highly prevalent types of cancer (breast, prostate, lung, and colorectal). CANCERTOOL provides rapid and comprehensive visualization of gene expression data for the gene(s) of interest in well-annotated cancer datasets. This visualization is accompanied by generation of reports customized to the interest of the researcher (e.g., editable figures, detailed statistical analyses, and access to raw data for reanalysis). It also carries out gene-to-gene correlations in multiple datasets at the same time or using preset patient groups. Finally, this new tool solves the time-consuming task of performing functional enrichment analysis with gene sets of interest using up to 11 different databases at the same time. Collectively, CANCERTOOL represents a simple and freely accessible interface to interrogate well-annotated datasets and obtain publishable representations that can contribute to refinement and guidance of cancer-related investigations at all levels of hypotheses and design.Significance: In order to facilitate access of research groups without bioinformatics support to public transcriptomics data, we have developed a free online tool with an easy-to-use interface that allows researchers to obtain quality information in a readily publishable format. Cancer Res; 78(21); 6320-8. ©2018 AACR.


Intensive alternating chemotherapy regimen in small cell carcinoma of the lung.
Fifty-five patients with small cell carcinoma of the lung (SCCL) were treated with alternating courses of CAV (cyclophosphamide, doxorubicin, and vincristine) and VHM (etoposide, hexamethylmelamine, and methotrexate) at 21-day intervals. One regimen contained high-dose cyclophosphamide (2400 mg/m2 iv), while the second contained an increased dose of etoposide (250 mg/m2 iv on Days 1-3). Patients achieving a complete response (CR) received a minimum of six cycles of therapy or two cycles beyond the achievement of CR. These patients as well as those with partial response with disease limited to the lung then received radiotherapy to the lung primary (5100 rads in 300-rad fractions) as well as prophylactic cranial radiotherapy (3000 rads in 300-rad fractions). All therapy was subsequently stopped until relapse. There were no deaths during the aplastic periods induced by the intensive chemotherapy. CR was achieved in 57% of the patients and partial response was achieved in 38%. The actuarial median survival for the 27 patients with extensive disease was 13.5 months and for the 28 patients with limited disease was 13 months. Survival at this point appears comparable to less intensive regimens in which maintenance therapy was given. We conclude that prolonged intensive induction chemotherapy in SCCL is well-tolerated. Studies are needed to examine in a randomized trial the role of alternating combinations and maintenance therapy in SCCL.


Probing the coding logic of thermosensation using spinal cord calcium imaging.
The spinal cord dorsal horn is the first relay station of the neural network for processing somatosensory information. High-throughput optical recording methods facilitate the study of sensory coding in the cortex but have not been successfully applied to study spinal cord circuitry until recently. Here, we review the development of an in vivo two-photon spinal calcium imaging preparation and biological findings from the first systematic characterization of the spinal response to cutaneous thermal stimuli, focusing on the difference between the coding of heat and cold, and the contribution of different peripheral inputs to thermosensory response in the spinal cord. Here we also report that knockout of TRPV1 channel impairs sensation of warmth, and somatostatin- and calbindin2-expressing neurons in the spinal dorsal horn preferentially respond to heat. Future work combining this technology with genetic tools and animal models of chronic pain will further elucidate the role of each neuronal type in the spinal thermosensory coding and their plasticity under pathological condition.


Comparison of ultrasonography and transhepatic cholangiography in the evaluation of obstructive jaundice.
The diagnostic value of ultrasonography and percutaneous cholangiography was compared in 114 consecutive patients with obstructive jaundice. The final diagnosis was obtained by surgery or autopsy. Transhepatic cholangiography diagnosed obstruction and its level in all patients, whereas ultrasonography failed to find obstruction in 3 patients and was unable to determine the level in 11 patients. The cause of obstruction was correctly assessed in 106 patients by transhepatic cholangiography and in 74 by ultrasonography. In 15 patients with obstruction caused by common duct calculi ultrasonography only diagnosed the five, and in 9 patients malignant obstruction was diagnosed as calculi. Ultrasonography is a reliable tool for diagnosis of obstructive jaundice and in most cases for localisation of the level of the obstruction. However, diagnosis of the cause of obstruction and of its precise topography requires direct cholangiography.


Invasive carcinoma of the vulva. Changing trends in surgical management.
Four hundred fifteen patients who had invasive carcinoma of the vulva were treated with primary surgery from July 1, 1955, through June 30, 1989. Three hundred seventy-six (90%) of the patients had squamous carcinoma. Two hundred fourteen patients (52%) had radical vulvectomy with inguinofemoral lymphadenectomy. Twenty-four patients (6%) underwent radical vulvectomy with pelvic exenteration for advanced disease, and 55 patients (13%) had nonradical operations. The remaining 122 patients (29%) underwent radical vulvectomy, inguinofemoral lymphadenectomy, and pelvic lymphadenectomy. The primary morbidity was associated with lymphedema (8.6%) and groin wound breakdown (54%). No intraoperative deaths occurred among the 415 patients treated surgically, but there were 17 deaths (4%) within 28 days of operation. The absolute 5-year survival rate was 85% in patients with negative inguinofemoral lymph nodes and 39% when these lymph nodes were positive for metastatic carcinoma. The overall absolute 5-year survival rate was 67%.


Misoprostol induces gallbladder contraction during fasting, but does not influence postprandial emptying: an ultrasound study in healthy subjects.
The aim of this study was to evaluate the effect of the PGE1 analogue, Misoprostol, on gallbladder fasting volume and meal-stimulated emptying. Prostaglandins' effects on the gallbladder were studied principally regarding mucus production during lithogenesis. In the few in vitro and in vivo studies, contradictory results concerning their influence upon gallbladder motility were obtained. 13 healthy subjects, 8 females, 5 males, aged 23.4 years (ranges 22-25). Gallbladder volumes were assessed by ultrasound, after measuring the three diameters of the gallbladder in two perpendicular planes, using a conventional 2D equipment and a 3D equipment, after the 3D-reconstruction of the gallbladder. The volumes were calculated by means of the ellipsoid formula. Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were assessed during 90 minutes after a test meal (14 g fat, 425 kcal). Gallbladder emptying was evaluated in each subject on three different days: without prior Misoprostol administration, after 200 mg Misoprostol, and after 400 mg Misoprostol. Misoprostol was given orally as a single dose, 60 minutes before the meal. The two-tailed Student's t test for paired observations was used to compare the results. Misoprostol induced a significant decrease of the gallbladder fasting volume: from 12.8 +/- 4.4 (SD) ml (controls) to 9.1 +/- 3.6 ml (200 mg Misoprostol) and 5.4 +/- 2.6 ml (400 mg Misoprostol). Gallbladder meal-stimulated emptying was not influenced by Misoprostol. Our results indicated that, in healthy subjects, misoprostol induced a dose-dependent gallbladder emptying in the fasting state, but did not influence gallbladder postprandial emptying. Pre-prandial Misoprostol administration might be useful to treat gallbladder stasis in patients with chronic constipation, thus preventing gallstone formation.


An Efficient Iterative Learning Predictive Functional Control for Nonlinear Batch Processes.
Iterative learning model-predictive control (ILMPC) is very popular in controlling the batch process since it possesses not only the learning ability along batches but also the strong time-domain tracking properties. However, for a fast batch process with strong nonlinear dynamics, the application of the ILMPC is challenging due to the difficulty in balancing the computational efficiency and tracking accuracy. In this article, an efficient iterative learning predictive functional control (ILPFC) is proposed. The original nonlinear system is linearized along the reference trajectory to derive a 2-D tracking-error predictive model. The linearization error is compensated by utilizing the Lipschitz condition so that the objective function can be formulated with the upper bound of the actual tracking error. For enhancing control efficiency, predictive functional control (PFC) is applied in the time domain, which reduces the dimension of the decision variable in order to effectively cut down the computational burden. The stability and convergence of this ILPFC with terminal constraint are analyzed theoretically. Simulations on an unmanned ground vehicle and a typical fast batch reactor verify the effectiveness of the proposed control algorithm.


Daily life of women with alcoholic companions and the provided care.
The study aimed to know the daily life of women with alcoholic companions and the provided care. This is a comprehensive-interpretative, qualitative study, guided by the thematic Oral History method. Data collection occurred by semistructured interview. The empirical material was subjected to content analysis under the light of the King's Theory of Goal Attainment. Women are frustrated and frightened by the alcoholic companion's behavior and lifestyle, and still feel judged by society. Many abandon their life projects and self-care due to the overload caused by the companion's absence in the care of home and children. The family care they develop focuses on maintaining the family and protecting from further damage. The study revealed that these women are sick due to the companion's dependence and, even supporting a type of family care, they cannot control the effects of the alcohol in the family. This reinforces the need for health professionals' greater bond and involvement, establishing therapeutic projects in which women feel involved and, at the same time, supported.


Low-dose abdominopelvic computed tomography in patients with lymphoma: An image quality and radiation dose reduction study.
This study aimed to evaluate image quality, the detection rate of enlarged lymph nodes, and radiation dose exposure of ultralow-dose and low-dose abdominopelvic computed tomography (CT) in patients with lymphoma. Patients with lymphoma who underwent abdominopelvic CT using dual-source scanner were retrospectively recruited from a single center. CT images were obtained at 90 kVp dual-source mode reformatted in three data sets using the advanced modelled iterative reconstruction algorithm: 100% (standard-dose CT), 66.7% (low-dose CT), and 33.3% (ultralow-dose CT). Two radiologists analyzed subjective image quality and detection of abdominal enlarged lymph nodes on ultralow-dose, low-dose, and standard-dose CT blindly and independently. The results were compared with reference standards. Three readers (two radiologists and one hematologist) reviewed overall image quality and spleen size. In total, 128 consecutive CT scans (77 complete response, 44 partial response, 6 progressive disease, and 1 initial evaluation) from 86 patients (64 B-cell lymphoma, 14 T/NK-cell lymphoma, and 8 Hodgkin's lymphoma cases) were assessed. The enlarged lymph node-based detection rates for two readers were 97.0% (96/99) and 94.0% (93/99) on standard-dose CT, 97.0% (96/99) and 94.0% (93/99) on low-dose CT, and 94.0% (93/99) and 89.9% (89/99) on ultralow-dose CT. Overall image quality was 3.8 ± 0.5, 3.9 ± 0.5, and 4.1 ± 0.5 on ultralow-dose CT; 4.7 ± 0.4, 4.6 ± 0.5, and 4.8 ± 0.3 on low-dose CT; and 4.8 ± 0.4, 4.7 ± 0.4, and 4.9 ± 0.2 on standard-dose CT, according to two radiologists and one hematologist, respectively. Intraclass correlation coefficients of spleen size were 0.90 (95% confidence interval [CI], 0.87-0.93), 0.91 (95% CI, 0.88-0.93), and 0.91 (95% CI, 0.88-0.93) on ultralow-dose, low-dose, and standard-dose CT, respectively. Mean effective radiation doses of standard-dose, low-dose, and ultralow-dose CT were 5.7 ±1.8 mSv, 3.8 ± 1.2 mSv, and 1.9 ± 0.6 mSv, respectively. Our findings suggest that ultralow-dose and low-dose CT, even with radiation doses reduced by 66.7% and 33.3%, respectively, maintained adequate image quality. These imaging modalities may be employed for follow-up lymphoma evaluation in consideration of the long surveillance periods.


AcBr/DMSO Mediated Sulfenylation of Pyrrolo[2,1-a]isoquinolines.
We have developed a mild sulfenylation of pyrrolo[2,1-a]isoquinolines with acetyl bromide and dimethyl sulfoxide. A wide range of functionalized pyrrolo[2,1-a]isoquinolines could be prepared efficiently through the formation of a C-S bond with thiophenols (27 examples, 36-94% yields). The current strategy can also be utilized for functionalization of pyrrolo[1,2-a]quinolines and indole.


Surgical intervention and rehabilitation of chronic patellar tendinitis.
Patellar tendinitis is a common overuse injury that affects many basketball players. The key to successful management of patellar tendinitis is prevention and early intervention. In a small percentage of the athletic population, conservative management does not yield satisfactory results and surgery is necessary. Rehabilitation following surgery should consist of several stages, including: 1) range of motion, 2) strengthening, 3) flexibility, 4) sports-specific exercises, 5) cardiovascular conditioning, and 6) gradual return to play. Although there are many documented rehabilitation guidelines for conservative management of tendinitis, there are few for the surgical management of patellar tendinitis without complete rupture. More research is needed regarding postsurgical management.


Micronuclei assay in cytokinesis-blocked binucleated and conventional mononucleated methods in human peripheral lymphocytes.
Studies were performed to determine the genotoxic effect of cytochalasin-B (CYB) and to compare the efficacy of the cytokinesis-blocked binucleated cells (CB) for scoring micronuclei (MN) with the conventional mononuclear method, following treatment with mitomycin C and cyclophosphamide. The results show that 3-4 micrograms/ml of CYB induced maximum number of binucleated cells without any genotoxic effect and the frequency of MN in binucleated cells was higher than that in the mononucleated cells (P less than 0.05) but less than twofold. However, MN frequencies in binucleated cells were not equivalent to the frequencies of mononucleated cells, since MN in binucleated cells represent two nuclei. These results suggest that further study is required to consider CB method as a more reliable approach for scoring MN.


Audiology in Latin America: hearing impairment, resources and services.
Evidence is presented about the limitation of information available on prevalence/incidence of deafness and hearing impairment in the developing world; particularly in Latin America. Two questionnaires on audiological resources and services were mailed to Latin American and Caribbean countries in general and to Central American nations in particular. The information returned by Argentina, Chile, Colombia, Costa Rica, Cuba, Belize, El Salvador, Grenada, Guatemala, Honduras, Mexico, Nicaragua, Panama, Puerto Rico and Uruguay was analysed. Data was gathered about epidemiological studies on hearing impairment, about specific programmes, such as early identification of hearing impairment, national registers on deafness and programmes on hearing screening. Training programmes and availability of professionals in the field of hearing and deafness is also shown. Hearing services, hearing aids provision, hearing testing equipment, professional organization and legislation in audiology is also documented. It is our conclusion that hearing impairment is a low priority for health systems in the developing world, technology continues to be excessively costly and material and human resources are limited, and services are poor and restricted.


Neuronal-like cell differentiation of non-adherent bone marrow cell-derived mesenchymal stem cells.
Non-adherent bone marrow cell-derived mesenchymal stem cells from C57BL/6J mice were separated and cultured using the "pour-off" method. Non-adherent bone marrow cell-derived mesenchymal stem cells developed colony-forming unit-fibroblasts, and could be expanded by supplementation with epidermal growth factor. Immunocytochemistry showed that the non-adherent bone marrow cell-derived mesenchymal stem cells exposed to basic fibroblast growth factor/epidermal growth factor/nerve growth factor expressed the neuron specific markers, neurofilament-200 and NeuN, in vitro. Non-adherent bone marrow cell-derived mesenchymal stem cells from β-galactosidase transgenic mice were also transplanted into focal ischemic brain (right corpus striatum) of C57BL/6J mice. At 8 weeks, cells positive for LacZ and β-galactosidase staining were observed in the ischemic tissues, and cells co-labeled with both β-galactosidase and NeuN were seen by double immunohistochemical staining. These findings suggest that the non-adherent bone marrow cell-derived mesenchymal stem cells could differentiate into neuronal-like cells in vitro and in vivo.


Manipulation of sub-terahertz waves using digital coding metasurfaces based on liquid crystals.
This paper presents a novel sub-terahertz liquid crystal (LC) phase shifter based on digital coding metasurfaces. The proposed structure consists of metal gratings and resonant structures. They are both immersed in LC. The metal gratings function as reflective surfaces for electromagnetic waves and electrodes for controlling the LC layer. The proposed structure changes the state of the phase shifter by switching the voltage on every grating. It allows the deflection of LC molecules within a subregion of the metasurface structure. Four switchable coding states of the phase shifter are obtained experimentally. The phase of the reflected wave varies by 0°, 102°, 166°, and 233° at 120 GHz. Due to the presence of the transverse control electric field, modulation speed is approximately doubled compared to the free relaxation state. This work provides a novel idea for wavefront modulation of phase.


[Neuroendocrine carcinoma of the sphennoid sinuse: a case report].
Neuroendoerine carcinoma of paranasal sinuses are rare malignant tumors, neuroendocrine carcinomas cases with the lesions at different sites differ in the prognosis, The key to improving the survival rate of the disease is early accurate diagnosis and complete surgical removal of the lesions.


Cellular responses to modified Plasmodium falciparum MSP119 antigens in individuals previously exposed to natural malaria infection.
MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP1(19)), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP1(19) had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP1(19) would affect critical T-cell responses to epitopes in this antigen. The cellular responses to wild-type MSP1(19) and a panel of modified MSP1(19) antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-naïve and the second had been naturally exposed to Plasmodium falciparum infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults. Interestingly, stimulation indices (SI) for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP1(19). A protein with four amino acid substitutions (Glu27-->Tyr, Leu31-->Arg, Tyr34-->Ser and Glu43-->Leu) had the highest stimulation index (SI up to 360) and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins. This study suggests that specific MSP1(19) variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.


[Diagnosis and medical treatment of pulmonary arterial hypertension].
The idiopathic pulmonal arterial hypertension is characterized by a chronic proliferative conversion of the pulmonary arterial vessels leading to an increase of pulmonary vascular resistance and thus resulting in right heart failure and increase mortality rate. With growing advances in understanding of the underlying pathophysiological mechanisms and the development of modern medical treatment strategies, there is a significant improvement of the overall survival rate and quality-of life. In this review we will give an overview about the current knowledge of etiology, diagnosis and management of idiopathic pulmonal arterial hypertension.


Revised value of the eighth-order contribution to the electron g-2.
The contribution to the eighth-order anomalous magnetic moment (g-2) of the electron from a set of diagrams without closed lepton loops is recalculated using a new FORTRAN code generated by an automatic code generator. Comparing the contributions of individual diagrams of old and new calculations, we find an inconsistency in the old treatment of IR subtraction terms in two diagrams. Correcting this error leads to the revised value -1.9144(35)(alpha/pi)4 for the eighth-order term. This theoretical change induces the shift of the inverse of the fine structure constant by -6.411 80(73)x10(-7).


Telemetric measurement of body core temperature in exercising unconditioned Labrador retrievers.
This project evaluated the use of an ingestible temperature sensor to measure body core temperature (Tc) in exercising dogs. Twenty-five healthy, unconditioned Labrador retrievers participated in an outdoor 3.5-km run, completed in 20 min on a level, 400-m grass track. Core temperature was measured continuously with a telemetric monitoring system before, during, and after the run. Data were successfully collected with no missing data points during the exercise. Core temperature elevated in the dogs from 38.7 ± 0.3°C at pre-exercise to 40.4 ± 0.6°C post-exercise. While rectal temperatures are still the standard of measurement, telemetric core temperature monitors may offer an easier and more comfortable means of sampling core temperature with minimal human and mechanical interference with the exercising dog.


Association Between Beta-Blocker or Statin Drug Use and the Risk of Hemorrhage From Cerebral Cavernous Malformations.
We aimed to determine the association between beta-blocker or statin drug use and the future risk of symptomatic intracranial hemorrhage or persistent/progressive focal neurological deficit from cerebral cavernous malformations (CCM). The population-based Scottish Audit of Intracranial Vascular Malformations prospectively identified adults resident in Scotland first diagnosed with CCM during 1999 to 2003 or 2006 to 2010. We compared the association between beta-blocker or statin drug use after first presentation and the occurrence of new intracranial hemorrhage or persistent/progressive focal neurological deficit due to CCM for up to 15 years of prospective follow-up. We confirmed proportional hazards and used survival analysis with multivariable adjustment for age, intracranial hemorrhage at CCM presentation, and brain stem CCM location. Sixty-three (21%) of 300 adults used beta-blockers (27/63 [43%] used propranolol), and 73 (24%) used statin drugs over 3634 person-years of follow-up. At baseline, the only statistically significant imbalances in prespecified potential confounders were age by statin use and intracranial hemorrhage at presentation by beta-blocker use. Beta-blocker use was associated with a lower risk of new intracranial hemorrhage or persistent/progressive focal neurological deficit (adjusted hazard ratio, 0.09 [95% CI, 0.01-0.66]; P=0.018). Statin use was associated with a nonsignificant lower risk of intracranial hemorrhage or persistent/progressive focal neurological deficit (adjusted hazard ratio, 0.37 [95% CI, 0.01-1.07]; P=0.067). Beta-blocker, but not statin, use was associated with a lower risk of intracranial hemorrhage or persistent/progressive focal neurological deficit in patients with CCM.


Erythropoietin is involved in growth and angiogenesis in malignant tumours of female reproductive organs.
The accumulating evidence that erythropoietin and erythropoietin receptor are expressed in various non-haematopoietic organs suggests that erythropoietin signalling might be involved in the growth of tumours, but this possibility has never been examined. We found that mRNAs for erythropoietin and erythropoietin receptor are expressed in malignant tumours of female reproductive organs, where erythropoietin levels are higher than in normal tissues. Furthermore, tumour cells and capillary endothelium showed erythropoietin receptor immunoreactivity. To investigate the role of the erythropoietin/erythropoietin receptor pathway in these tumours, we injected mouse monoclonal antibody against erythropoietin or the soluble form of erythropoietin receptor into blocks of tumour specimens and cultured the blocks. After 12 h of injections, these blocks were examined and compared with control blocks injected with mouse monoclonal antibody, heat denatured soluble form of erythropoietin receptor, mouse serum or saline. Tumour cells and capillaries were markedly decreased in a dose-dependent manner after either injection. A marked increase of the cells containing fragmented DNA and the histopathological characteristics of these cells suggest that the decrease in tumour cells and capillary endothelial cells was due to apoptotic cell death. The co-existence of JAK2 and phosphorylated-JAK2, and STAT5 and phosphorylated STAT5, all of which are involved in the mitogenic signalling of erythropoietin, was found frequently in tumour cells and capillary endothelial cells in the untreated blocks. In contrast, most of the phosphorylated-JAK2- or phosphorylated-STAT5-positive cells had disappeared in the experimental blocks. Moreover, reduced tyrosine phosphorylation of STAT5 in the experimental blocks was confirmed by western blotting analysis. The results strongly indicate that erythropoietin signalling contributes to the growth and/or survival of both transformed cells and capillary endothelial cells in these tumours. Thus, deprivation of erythropoietin signalling may be a useful therapy for erythropoietin-producing malignant tumours.


Debris Cover Limits Subglacial Erosion and Promotes Till Accumulation.
Glaciers are commonly conceptualized as bodies composed of snow and ice. Yet, many glaciers contain a substantial amount of rock, especially those abutting steep mountains. Mountain slopes erode, depositing rocks on glaciers below. This loose rock (or debris) is buried in glaciers and melts out lower down creating a debris cover. Debris cover reduces ice melt, which changes the shape and movement of glaciers. Glacier movement, specifically basal sliding, efficiently sculpts landscapes. To date, we know little about the impacts of surface debris on conditions below glaciers. To help remedy this, we run numerical model simulations which show that debris-covered glaciers erode slower than glaciers unaffected by debris. Reduced melt under surface debris lowers sliding speeds and causes sediment to accumulate at the bed, potentially establishing conditions for surging. The influence of surface debris cover on the subglacial environment may hold substantial implications for alpine sediment storage and landscape evolution.


[The sexual " acting-in " between therapists and clients or the breakaway of words : on the subject of lost words and frantic bodies.].
The topic of sexual relationships between patients and therapists is taboo between the persons involved. This article deals with the sexual acting-in from a psycho-analytical point of view based on clinical hypotheses gathered from meetings with women involved in such acting in and from a theoretical reflexion. What seems evident for those women, is, behind an oedipal coloration, the basic question of the connexion with the need and therefore a difficulty with the symbolisation process: the relationship with the therapist becomes a hand to hand fighting without the possibility of an opening for the expression of the word which is one of the therapy's main objective. This article, while leaving open the question of the therapist's desire, deals with the avoidance, on both sides, of the transfer's elaboration which remains at the core of the sexual acting-in.


Intrauterine myelomeningocele repair: effect on short-term complications of prematurity.
To determine whether short-term complications of prematurity are affected by intrauterine myelomeningocele repair. Medical records of the first 100 infants undergoing intrauterine myelomeningocele repair (IUMR) at the Vanderbilt University Medical Center were reviewed. Infants born at <34 weeks' gestation were identified. Two controls were identified for each IUMR infant. Controls were matched for gestational age, sex, birth weight, antenatal steroids, and mode and month of delivery. Development of respiratory distress syndrome, intraventricular hemorrhage, and chronic lung disease and days on ventilator and length of hospital stay were recorded. The results are expressed as mean values and ranges. Comparison of data between groups was performed using the Mann-Whitney U test. Categorical data were compared using the chi-square test and Fisher's exact test. p </= 0.05 was considered statistically significant. One hundred infants underwent IUMR. Forty-four infants were born at <34 weeks of gestation. Complete data were available on 37 infants. Seventy-four matched controls were studied. Eleven infants from the IUMR group and 23 infants from the control group developed respiratory distress syndrome (29.7 vs. 31.1%; p = 0.8). Six infants from the IUMR group and 13 infants from the control group developed chronic lung disease (16.2 vs. 17.5%; p = 0.9). The length of stay was 28 (range 2-82) days for the IUMR group and 24 (range 1-99) days (p = 0.09) for the control group. There was also no significant difference between groups with regard to intraventricular hemorrhage and days on ventilators. There is no difference between short-term complications of prematurity following IUMR and those associated with prematurity resulting from other causes.


Theory inspired practice for end-of-life cancer care: an exploration of the McGill Model of Nursing.
Nursing theories provide inspiration for practice by describing how to meet needs, enhance wellness, and respond to clients as whole persons. This paper discusses the McGill Model of Nursing with reference to how its ideas can support nursing practice for patients with cancer during the end-of-life phase. We suggest this model provides for a relational approach that is congruent with the philosophy of palliative care. The goal of this paper is to stimulate reflection amongst oncology nurses and nursing leaders. By comparing the value base of our practice against extant nursing theory, we may discover new opportunities for teaching and learning about what it means to be an end-of-life care nurse.


Myeloid differentiation factor-88 (MyD88) is essential for control of primary in vivo Francisella tularensis LVS infection, but not for control of intra-macrophage bacterial replication.
The means by which Francisella tularensis, the causative agent of tularemia, are recognized by mammalian immune systems are poorly understood. Here we wished to explore the contribution of the MyD88/Toll-like receptor signaling pathway in initiating murine responses to F. tularensis Live Vaccine Strain (LVS). MyD88 knockout (KO) mice, but not TLR2-, TLR4- or TLR9-deficient mice, rapidly succumbed following in vivo bacterial infection via the intradermal route even with a very low dose of LVS (5 x 10(1)) that was 100,000-fold less than the LD(50) of normal wild-type (WT) mice. By day 5 after LVS infection, bacterial organ burdens were 5-6 logs higher in MyD88 knockout mice; further, unlike infected WT mice, levels of interferon-gamma in the sera of LVS-infected MyD88 KO were undetectable. An in vitro culture system was used to assess the ability of bone marrow macrophages derived from either KO or WT mice to support bacterial growth, or to control intracellular bacterial replication when co-cultured with immune lymphocytes. In this assay, bacterial replication was similar in macrophages derived from either WT or any of the TLR KO mice. Bacterial growth was controlled in co-cultures containing macrophages from MyD88 KO mice or TLR KO mice as well as in co-cultures containing immune WT splenic lymphocytes and WT macrophages. Further, MyD88-deficient LVS-immune splenocytes controlled intracellular growth comparably to those from normal mice. Thus MyD88 is essential for innate host resistance to LVS infection, but is not required for macrophage control of intracellular bacterial growth.


Local beam angle optimization with linear programming and gradient search.
The optimization of beam angles in IMRT planning is still an open problem, with literature focusing on heuristic strategies and exhaustive searches on discrete angle grids. We show how a beam angle set can be locally refined in a continuous manner using gradient-based optimization in the beam angle space. The gradient is derived using linear programming duality theory. Applying this local search to 100 random initial angle sets of a phantom pancreatic case demonstrates the method, and highlights the many-local-minima aspect of the BAO problem. Due to this function structure, we recommend a search strategy of a thorough global search followed by local refinement at promising beam angle sets. Extensions to nonlinear IMRT formulations are discussed.


Galaxitaenia toloi n. gen., n. sp. (Eucestoda: Pseudophyllidea) from Galaxias platei (Pisces: Osmeriformes, Galaxiidae), in the Patagonian region of Argentina.
Galaxitaenia n. gen. (Eucestoda: Pseudophyllidea) is proposed to accommodate Galaxitaenia toloi n. gen., n. sp. from Galaxias platei, a freshwater fish inhabiting Andean lakes in Argentine Patagonia. Galaxitaenia belongs to the Triaenophoridae because it possesses a marginal genital pore, a ventral uterine pore, and a follicular vitelline gland. The new genus can be distinguished from other triaenophorids by the following combination of characters: a scolex with a prominent rectangular apical disc without hooks, grooves, or indentations; neck present; segments wider than long to quadrangular; testes in 2 lateral fields, often connected anteriorly; cirrus unarmed; an ovary situated posteriorly; a vagina posterior to the cirrus sac; vitelline follicles medullary, in 2 ventral fields forming 2 wings interrupted medially; a uterus saccate to branched; and eggs without operculum. The types, distribution, and density of microtriches were analyzed on the surface of the tegument of scolex, neck, and immature segments. The presence of tumuli were observed on the apical disc of the scolex. Galaxitaenia toloi n. sp. is the first triaenophorid species recorded in a South American freshwater fish and the fourth helminth parasitizing the intestine of G. platei.


[Filtering capacity of Anodonta woodiana and its feeding selectivity on phytoplankton].
Lake eutrophication associated with algal bloom has become a major environmental challenge in China. Filter feeding organisms, e.g., silver carp, bighead carp, and zebra mussel, have been widely used to manipulate water environment through their top-down effects. The bivalve Anodonta woodiana is widely distributed across China, and has been used for bio-manipulation of some water bodies. In situ experiments were performed in a bay of Lake Dianchi and its surrounding ponds to study the filtering capacity and the filter feeding rate of Anodonta woodiana in these aguatic habitats, and to determine the controlling factors. The results showed that there was a relationship between filtration rate and total suspended substances measured in laboratory during August and September 2001 when the water temperature was 20 +/- 2 degrees C, which was expressed as y = 4 380.41 e(- 0.0184x) (R2 = 0.621, P < 0.05) based on at least squares analyses. The filtration rate was strongly related to the body weight by measuring in laboratory over 24 hours during August 2001 when the water temperature was 20 +/- 2 C. At least squares analyses gave the equation y = 2 904.16 + 12 076.24e(-0.0034x) (R2 = 0.9825, P = < 0.05). A slight variation of filtration rate was found over 24 hours, which could be explained by the bivalves' adaptation to the experimental circumstances rather than the daily change of its filtration feeding. In general, the filtration capacity of natural Anodonta woodiana population in the water bodies was very limited, as a result of its small population size. No significant selective feeding on algae was found by contrasting the relative abundance of algae in the habitats and the guts of Anodonta woodiana. The feeding selectivity on algae was neither correlated with the size of algae, nor with the initial abundance of algae in water column.


Lupus pernio: a clinico-radiological study of thirty-five cases.
Thirty-five patients with lupus pernio were observed in a series of 818 patients with clinical and histological evidence of sarcoidosis. This analysis provides the natural history of lupus pernio and its associated clinico-radiographic features. There was intrathoracic involvement in 74% of patients, upper respiratory tract disease in 54%, reticulo-endothelial involvement in 54%, bone cysts in 43% and ocular lesions in 37%. It predominated in West Indies-born women. Histological confirmation was easily obtained by nasal mucosal biopsy and this could be repeated serially to evaluate the response to various treatments. Nasal bone radiographs showed destruction of the nasal bones, porosis and alteration in bone texture. Peripheral bone cysts were evident in 50% of patients who were radiographed, and in about 50% of these patients, the cysts were found in both hands and feet.


Reducing Substance Use and HIV Health Disparities among Hispanic Youth in the U.S.A.: The Familias Unidas Program of Research.
Preventing/reducing substance use and HIV among Hispanic youth is essential to eliminating the health disparities that exist between Hispanics and other segments of the population. The objective of this article is to describe a program of research involving Familias Unidas, a Hispanic-specific, parent-centered intervention, aimed at reducing substance use and HIV health disparities among Hispanic youth. This article will focus on the theoretical foundation of the intervention, the empirical research supporting the theoretical model, the intervention model itself, the findings of the program of research, and the translation of this intervention into community practice.


Morphological keys in the differential diagnosis of bladder inverted papilloma. Study of two types, trabecular and glandular.
Inverted papilloma of the urinary bladder is an uncommon urothelial neoplasm that may be specially difficult to distinguish from urothelial carcinoma. Two patients with obstructive symptoms and hematuria have been studied. In the transurethral resection, accidentally, one showed a papillary lesion in the context of nodular hyperplasia of the prostate, where as the other showed a polypoid tumor of the urinary bladder Histologically, in both cases, a bladder inverted papilloma was demonstrated, originating from the surface transitional epithelium. Basal cells exhibited peripheral palisading pattern in the trabecular form. In the glandular type, Dogiel or umbrella cells into the gland-like structures, were recognized. Immunohistochemical stains for p53 and Ki-67 were negative. Umbrella cells were positive for cytokeratin 20. Two cases of bladder inverted papilloma with relevant morphological aspects are presented, which we consider useful for the differential diagnosis with urothelial carcinoma.


Selectin-independent adhesion during ovarian cancer metastasis.
Ovarian cancer (OvCa) progression mainly takes place by intraperitoneal spread. Adhesion of tumor cells to the mesothelial cells which form the inner surface of the peritoneum is a crucial step in this process. Cancer cells use in principle different molecules of the leukocyte adhesion cascade to facilitate adhesion. This cascade is initiated by selectin-ligand interactions followed by integrin - extracellular matrix protein interactions. Here we address the question whether all tumor cells predominantly employ selectin-dependent leukocyte-like adhesion cascade (SDAC) or whether they use integrin mediated adhesion for OvCa progression as well. A comparative transcriptomic analysis of the human OvCa cell lines OVCAR8 and SKOV3 was performed. Intraperitoneal xenograft model of OVCAR8 cells was used to determine whether there is a correlation between SDAC gene expression and the metastatic potential of the control cells and the cells overexpressing c-Fos. Transcriptomic analysis of OVCAR8 and SKOV3 samples was performed using microarrays. One-third of the protein-coding genes involved in SDAC exhibited lower expression levels in OVCAR8 than in SKOV3 cells. In contrast to SKOV3 cells, c-Fos overexpression in OVCAR8 cells did not significantly influence the expression of SDAC genes. Intraperitoneal xenograft model of OVCAR8 cells unexpectedly demonstrated that the aggressiveness of OVCAR8 tumors was not depended on the c-Fos expression level and was comparable to that of SKOV3 control tumors. Gene expression analysis of tumors suggests that SKOV3-derived tumor progression was mainly depended on SDAC. Progression of OVCAR8 tumors relied on other cell adhesion molecules that do not interact with selectins. High expression of c-Fos in ovarian cancer cells is not always associated with reduced metastatic potential. Low expression level of SDAC genes may not ensure low OvCa metastatic potential hence alternative adhesion mechanisms involving laminin-integrin interactions exist as well.


Biomarkers of collecting duct injury in Han-Wistar and Sprague-Dawley rats treated with N-phenylanthranilic Acid.
N-phenylanthranilic acid is a chloride channel blocker that causes renal papillary necrosis in rats. Studies were conducted in two strains of male rats to evaluate novel biomarkers of nephrotoxicity. Han-Wistar rats were given daily oral doses of 50, 350, or up to 700 mg/kg/day of NPAA, and Sprague-Dawley rats were given 50 or 400 mg/kg/day of NPAA. Rats were euthanized on days 8 and 15. The candidate kidney injury biomarkers renal papillary antigen-1 (RPA-1, for collecting duct injury), clusterin (for general kidney injury), α-glutathione-S-transferase (a proximal tubular marker), and µ-glutathione-S-transferase (a distal tubular marker) were measured in urine by enzyme immunoassay. Characteristic degeneration and necrosis of the collecting duct and renal papilla were observed in Han-Wistar rats at the high dose on day 8 and at the mid and high doses on day 15, and in Sprague-Dawley rats given the high dose on days 8 and 15. Increases in urinary RPA-1, and to a lesser extent urine clusterin, were generally associated with the presence of collecting duct injury and were more sensitive than BUN and serum creatinine. On the other hand, decreases in α-glutathione-S-transferase without proximal tubule lesions in both strains and decreases in µ-glutathione-S-transferase in Sprague-Dawley rats only were not associated with morphological proximal or distal tubule abnormalities, so both were of less utility. It was concluded that RPA-1 is a new biomarker with utility in the detection of collecting duct injury in papillary necrosis in male rats.


Properties of a U1/mRNA 5' splice site duplex containing pseudouridine as measured by thermodynamic and NMR methods.
Three RNA undecamers, 5'AUAC psi psi ACCUG (psi = pseudouridine), 5'AUACUUACCUG, and their complementary 11-mer 5'CAGGUAAGUAU, have been chemically synthesized by phosphite triester chemistry on a controlled-pore glass (CPG) support. The two duplexes formed with these molecules, 5'AUAC psi psi ACCUG/5'CAGGUAAGUAU and 5'AUACUUACCUG/5'CAGGUAAGUAU, represent the 5' end of human U1 snRNA paired to the mRNA consensus 5' splice site. In one undecamer, pseudouridines are incorporated at those positions corresponding to the native in vivo U1 snRNA, while the other (control) undecamer contains only uridine. Surprisingly, the NMR data show that the extra imino proton of the pseudouridines, which is found in the major groove and is presumably not hydrogen bonded, is clearly visible in the imino proton NMR spectrum at pH 6. This result suggests that the structure of the RNA restricts access of solvent to the major groove, slowing the exchange of the pseudouridine NH1 imino proton. A comparison of the thermodynamic properties of the two duplexes show that the free energy of duplex formation is unchanged by the substitution of pseudouridine for uridine.


The demand for human resources by the community: the implications of a community participation approach.
The author states that community participation needs to be designed at the national level and executed at the local level, which therefore places greater demands on the organizational efficiency and communication skills of national agencies. The ramifications of a community participation approach reach all aspects of national planning, including budget procedures and allocations of responsibility. Above all, the approach requires that authority, responsibility, and procedures be clearly spelled out and understood by all involved. Only when national strategies have been set for numbers of communities to be served, level of service, and degree of community involvement, can the specific implications for manpower needs, training, and national support services be discussed, evaluated, and quantified. Given a clear indication of national policy directions for community participation, sector planners can begin discussions with their regional offices, other agencies, and community leaders on how to implement it. This article reviews some of the major issues about human resources that need to be addressed in the planning process.


[Peculiarities of ferrorkinetis in adolescent girls with iron-deficiency anemia].
On the basis of follow up of 462 adolescent girls of 14-19 years old, in 110 of them iron-deficiency anemia was revealed. With the help of general blood analysis and biochemistry studies there was detected a disturbance of iron metabolism, declaring itself in decreasing iron serum indices, serum ferritin saturation factor and increase of general iron combined ability levels, latent combined ability and levels of serum erythropoietin.


Identification of the OsCML4 Gene in Rice Related to Salt Stress Using QTL Analysis.
Soil salinity is a major abiotic stress that causes disastrous losses in crop yields. To identify favorable alleles that enhance the salinity resistance of rice (Oryza sativa L.) crops, a set of 120 Cheongcheong Nagdong double haploid (CNDH) lines derived from a cross between the Indica variety Cheongcheong and the Japonica variety Nagdong were used. A total of 23 QTLs for 8 different traits related to salinity resistance on chromosomes 1-3 and 5-12 were identified at the seedling stage. A QTL related to the salt injury score (SIS), qSIS-3b, had an LOD score of six within the interval RM3525-RM15904 on chromosome 3, and a phenotypic variation of 31% was further examined for the candidate genes. Among all the CNDH populations, five resistant lines (CNDH 27, CNDH 34-1, CNDH 64, CNDH 78, and CNDH 112), five susceptible lines (CNDH 52-1, CNDH 67, CNDH 69, CNDH 109, and CNDH 110), and the parent lines Cheongcheong and Nagdong were selected for relative gene expression analysis. Among all the genes, two candidate genes were highly upregulated in resistant lines, including the auxin-responsive protein IAA13 (Os03g0742900) and the calmodulin-like protein 4 (Os03g0743500-1). The calmodulin-like protein 4 (Os03g0743500-1) showed a higher expression in all the resistant lines than in the susceptible lines and a high similarity with other species in sequence alignment and phylogenetic tree, and it also showed a protein-protein interaction with other important proteins. The genes identified in our study will provide new genetic resources for improving salt resistance in rice using molecular breeding strategies in the future.


Locomotion and motion sickness during horizontally and vertically reversed vision.
Locomotion and motion sickness during reversed vision were studied in ten normal subjects and a patient with bilateral labyrinthine loss. Whereas horizontal reversal produced moderate to severe gait disturbances as well as motion sickness in all normal subjects, vertical reversal failed to induce such symptoms. The patient, being free of motion sickness during both reversals, could not walk straight during horizontal reversal. The difference in the strength of sensory mismatch between both directions seemed to result from a difference in the role of vision for spatial orientation which is produced by the proprioceptive as well as otolithic inputs of gravity.


BACE1: Now We Can See You.
No in vivo imaging biomarker currently exists for BACE, a drug target for Alzheimer's disease (AD). A strategy aiming to find a novel brain-penetrant positron emission tomography (PET) radiotracer for BACE1 led to the discovery of a highly potent and selective aminothiazine inhibitor, PF-06684511. This scaffold has been now evaluated as BACE1 PET radiotracer ([18F]PF-06684511) after labeling with fluorine-18 (18F), allowing its evaluation in non-human primates (NHP) as the first a brain-penetrant PET radiotracer for imaging BACE1 in vivo.


Automated diagnosis of glaucoma using digital fundus images.
Glaucoma is a disease of the optic nerve caused by the increase in the intraocular pressure of the eye. Glaucoma mainly affects the optic disc by increasing the cup size. It can lead to the blindness if it is not detected and treated in proper time. The detection of glaucoma through Optical Coherence Tomography (OCT) and Heidelberg Retinal Tomography (HRT) is very expensive. This paper presents a novel method for glaucoma detection using digital fundus images. Digital image processing techniques, such as preprocessing, morphological operations and thresholding, are widely used for the automatic detection of optic disc, blood vessels and computation of the features. We have extracted features such as cup to disc (c/d) ratio, ratio of the distance between optic disc center and optic nerve head to diameter of the optic disc, and the ratio of blood vessels area in inferior-superior side to area of blood vessel in the nasal-temporal side. These features are validated by classifying the normal and glaucoma images using neural network classifier. The results presented in this paper indicate that the features are clinically significant in the detection of glaucoma. Our system is able to classify the glaucoma automatically with a sensitivity and specificity of 100% and 80% respectively.


Inverse Thermoelastic Analysis of a Cylindrical Tribo-Couple.
Within the framework of the one-dimensional model for a tribo-couple consisting of two elastic cylinders accounting for the frictional heat generation on the interface due to the roughness of the contacting dissimilar materials, a problem on the identification of the unknown temperature on one of the limiting surfaces of either inner or outer cylindrical layers is formulated and reduced to an inverse thermoelasticity problem via the use of the circumferential strain given on the other surface. To solve the latter problem, a semi-analytical algorithm is suggested, and its stability with respect to the small errors in the input data is analyzed. The efficiency of the proposed solution algorithm is validated numerically by comparing its results with the solution of a corresponding direct problem. The temperature and thermal stresses in the tribo-couple are analyzed.


Evaluation of the Minitek system for direct identification of anaerobic rods from positive blood cultures.
The direct inoculation of the Minitek anaerobe identification system (BBL Microbiology Systems, Cockeysville, Md.) from positive blood cultures was compared with subculture and Minitek results obtained using the manufacturer's recommended procedures. A total of 40 clinical anaerobic blood cultures were processed for rapid identification utilizing bacterial pellets obtained by centrifugation. Of these cultures, 30 yielded pure isolates of anaerobic rods that were used for comparison. In 87% of the pure cultures, identification from the direct inoculum method was identical to the routine procedure using Minitek biochemicals. When the additional test for lecithinase and lipase production was included, the identification agreement was 97%. Direct identification of anaerobic rods from blood cultures utilizing the Minitek system is reliable, easy to perform, and can provide a complete identification in 24 h from the time a blood culture showed growth.


Measuring and Reducing Off-Target Activities of Programmable Nucleases Including CRISPR-Cas9.
Programmable nucleases, which include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases (RGENs) repurposed from the type II clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system are now widely used for genome editing in higher eukaryotic cells and whole organisms, revolutionising almost every discipline in biological research, medicine, and biotechnology. All of these nucleases, however, induce off-target mutations at sites homologous in sequence with on-target sites, limiting their utility in many applications including gene or cell therapy. In this review, we compare methods for detecting nuclease off-target mutations. We also review methods for profiling genome-wide off-target effects and discuss how to reduce or avoid off-target mutations.


Fluorescence blinking statistics from CdSe core and core/shell nanorods.
We report fluorescence blinking statistics measured from single CdSe nanorods (NRs) of seven different sizes with aspect ratios ranging from 3 to 11. This study also included core/shell CdSe/ZnSe NRs and core NRs with two different surface ligands producing different degrees of surface passivation. We compare the findings for NRs to our measurements of blinking statistics from spherical CdSe core and CdSe/ZnS core/shell nanocrystals (NCs). We find that, for both NRs and spherical NCs, the off-time probability distributions are well described by a power law, while the on-time probability distributions are best described by a truncated power law, P(tau(on)) approximately tau(on)(-alpha)e((-tau)(on)/(tau)(c)). The measured crossover time, tau(c), is indistinguishable within experimental uncertainty for core and core/shell NRs, as well as for core NRs with different ligands, for the same core size, indicating that surface passivation does not affect the blinking statistics significantly. We find that, at fixed excitation intensity, 1/tau(c) increases approximately linearly with increasing NR aspect ratio; for a given sample, 1/tau(c) increases very gradually with increasing excitation intensity. Examining 1/tau(c)versus the single-particle photon absorption rate for all samples indicates that the change in NR absorption cross section with sample size can account for some but not all of the differences in crossover time. This suggests that the degree of quantum confinement may be partially responsible for the aspect ratio dependence of the crossover time.


Aggregatibacter actinomycetemcomitans as indicator for aggressive periodontitis by two analysing strategies.
To compare the subgingival microbiota of aggressive and chronic periodontitis (ChP) using single-site and pooled plaque samples. In 60 patients with aggressive or ChP, subgingival plaque was sampled from the four deepest pockets using two sterile paper points simultaneously. One paper point from each pocket was put in a separate transport vial, the second was pooled with the three other paper points of a respective patient. The content of each vial was analysed for Aggregatibacter actinomycetemcomitans, Tannerella forsythensis, Porphyromonas gingivalis, and Treponema denticola. Pooled plaque samples detected higher numbers for all tested pathogens than single-site samples. Detection frequencies were similar for both strategies. Using single-site samples, A. actinomycetemcomitans detection rate was statistically significantly a higher in aggressive than in ChP (p=0.01). A. actinomycetemcomitans was found in higher numbers, the other pathogens in lower numbers in aggressive than in ChP. Neither presence nor absence of one of the tested bacteria had sufficient positive or negative predictive value for aggressive periodontitis. A. actinomycetemcomitans was detected in higher numbers and frequency in aggressive than in ChP. Its detection may confirm the clinical diagnosis and influence therapy. As a diagnostic test, its sensitivity and predictive value was low.


Extraction of the Structural Properties of Skin Tissue via Diffuse Reflectance Spectroscopy: An Inverse Methodology.
For the laser treatment of vascular dermatosis, the blood vessel morphology and depth in skin tissue is essential to achieve personalized intelligent therapy. The morphology can be obtained from the laser speckle imaging, and vessel depth was extracted by an inverse methodology based on diffuse reflectance spectrum. With optimized spot size of 0.5 mm and known optical properties, the proposed method was experimentally validated via the spectral measurement of microcapillary with known size and depth embedded in an epoxy resin-based skin phantom. Results prove that vessel depth can be extracted with an average relative error of 5%, thereby providing the foundation for a personalized, precise, and intelligent laser treatment of vascular dermatosis.


Chronic traumatic encephalopathy: a neurodegenerative consequence of repetitive traumatic brain injury.
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that develops as a result of repetitive mild traumatic brain injury. Chronic traumatic encephalopathy is characterized by a unique pattern of accumulation of hyperphosphorylated tau in neurons and astrocytes. The tau abnormalities begin focally and perivascularly at the depths of the cerebral sulci, spread to the superficial layers of the adjacent cortex, and eventually become widespread throughout the medial temporal lobes, diencephalon, and brainstem. Abnormalities in 43 kDa TAR DNA-binding protein are also found in most cases of CTE. To date, CTE can only be diagnosed by postmortem neuropathological examination, although there are many ongoing research studies examining imaging techniques and biomarkers that might prove to have diagnostic utility. Currently, the incidence and prevalence of CTE are unknown, although great strides are being made to better understand the clinical symptoms and signs of CTE. Further research is critically needed to better identify the genetic and environmental risk factors for CTE as well as potential rehabilitation and therapeutic strategies.


In vivo T1 measurements of canine brain for deep tissue temperature measurements with MRI.
The possibility of deep tissue temperature imaging with a magnetic resonance (MR) imager was studied in 30 mongrel dogs. The coronary view of the brain of a dog anesthetized with muscle relaxant and pentobarbital and ventilated automatically with air was taken with a special head coil by a 0.1 Tesla MR imager, Asahi Mark-J, driven by a spin warp pulse sequence. T1s in the imaging of the right and left white matter, grey matter, thalamus and caudate nucleus were measured with rectal temperature in group I (10 dogs) for a control study every 30 min until 120 min without intervention, in group II (10 dogs) for hyperthermia with extracorporeal bypass method, before heating, at 41 and 42 degrees C, in group III (10 dogs) for hypothermia, before cooling, at 35 and 30 degrees C and after rewarming, respectively. In groups I, II and III, the T1s at all sites except the white matter at 42 degrees C did not change significantly at any rectal temperature. T1 prolongation in the white matter at 42 degrees C may be due to edema, probably because of biological reaction to hyperthermia. The present study suggests that deep tissue temperature imaging in vivo by T1s measured with the MR imager may be impossible in spite of obvious evidence of T1 dependance on temperature in theoretical, in vitro and ex vivo studies already achieved.


[Attempt to induce, in the rat, a hepatitis of cirrhotic origin, using amino steroids: holaphyllaminol or amino 3-beta hydroxy-20-beta pregnene-5].
Holaphyllaminol, or Amino-3 beta-Hydroxy-20-beta Pregnene-5, was administered by gastric tube to male Wistar rats at dose of 50, 100 and 200 mg/kg/24 hr respectively, during 10, 20, 40 and 80 days. This substance provokes hepatic lesions beginning at the periportal region, the characteristics of which are a cholestasis, a canalar proliferation and a fibrosis. The interest of these alterations lies in the fact that they present the same features as certain human chronic hepatitis; their progression, a function of the dose of the toxin and the duration of treatment, may make possible to realisation of a model of experimental chronic hepatitis.


Role of paleoclimatic and paleohydrological processes in lineage divergence in freshwater organisms: A snippet from lentic genus Pila.
The Indian subcontinent is extremely diverse in terms of its flora and fauna. However, only a handful of studies have aimed to understand the diversity of freshwater invertebrates using multiple lines of evidence in recent times. Here we aimed to estimate the cryptic diversity of two widespread freshwater snail species within the genus Pila (Röding, 1798) and uncover the processes behind lineage diversification in these species. We sequenced mitochondrial and nuclear markers from a comprehensive sampling of specimens from different river basins in India. We implemented an integrative taxonomy approach to delimit the lineages in these groups, employing phylogenetic, geometric morphometric and niche modelling-based methods. Then, we investigated the drivers of lineage divergence in these species using population genetic tools in conjunction with divergence time estimation. We found that both species consist of several genetically and ecologically distinct lineages. The genetic data showed that several of these lineages are restricted to a single or a few river basins. The divergence time estimation analyses indicated that the time frame of divergence within the species coincided with paleohydrological and paleoclimatic events in the Miocene. The diversification was primarily driven by allopatric isolation into different river basins. To conclude, the study sheds light on the complex interaction between the habitat preference of the species and the environment in shaping the diversification patterns in this group.


[Fertility after the surgical treatment of cryptorchism].
The authors carried out a study on the ejaculates of 85 men at the age of 16 to 38 years, who underwent surgical intervention for treatment of unilateral and bilateral cryptorchidism. The patients were divided into two basic groups: orchidopexy was made in 66 patients with cryptorchidism and unilateral orchidectomy was performed in 19 patients with atrophy of the cryptorchidic testis. Surgical treatment of cryptorchidism improved fertile capability in 15.30% of the patients. The high percentage of 84.70% of the infertile patients after surgical treatment of cryptorchidism raises the question for earlier surgical treatment of cryptorchidism up to 5 years of age. Orchidectomy is indicated in abdominal or highly retained in the inguinal canal testis with very short blood vessels. Orchidectomy is also indicated in patients with atrophic testes, in whom perspective for fertile capability lacks and presents high risk of malignization.


In Vitro Time Efficiency, Fit, and Wear of Conventionally- versus Digitally-Fabricated Occlusal Splints.
The purpose of the study was to compare conventional to digital workflows of occlusal splint production regarding time efficiency, overall fit, and wear. Fifteen Michigan splints were fabricated with a conventional and digital method. The duration for the dentist's and the dental technician's workload was recorded. Subsequently, the overall fit was examined with a four-level score (1-4). Paired t-tests were used to compare the time results for the conventional and digital workflows and the sign test to compare the overall fit. The mean time (16 min 58 s) for computerized optical impressions was longer than for conventional impressions (6 min 59 s; p = 0.0001). However, the dental technician needed significantly less mean time for the digital splint production (47 min 52 s) than for the conventional (163 min 32 s; p = 0.001). The overall fit of the digitally-fabricated splints was significantly better compared to the conventionally-fabricated splints (p = 0.002). There was no impact of the different materials used in the conventional and digital workflow on the wear (p = 0.26). The results suggest that the digital workflow for the production of occlusal splints is more time efficient and leads to a better fit than the conventional workflow.


Squamous cell carcinoma presenting as peri-implantitis: a case report.
Dental implants have proved to be a useful adjunct in the rehabilitation of oral cancer patients. We describe the case of a 62-year-old woman who presented with a white patch in the oral cavity, diagnosed to be a squamous cell carcinoma. She underwent extensive surgery including microvascular reconstruction, followed by implant rehabilitation. Unfortunately, she suffered from multiple episodes of peri-implantitis and later on went on to develop oral squamous cell carcinoma around two of the dental implants. Here, we highlight the importance of regular follow-up and maintaining a high index of suspicion in high-risk patients.


Clinical feasibility of miniaturized Lissajous scanning confocal laser endomicroscopy for indocyanine green-enhanced brain tumor diagnosis.
Intraoperative real-time confocal laser endomicroscopy (CLE) is an alternative modality for frozen tissue histology that enables visualization of the cytoarchitecture of living tissues with spatial resolution at the cellular level. We developed a new CLE with a "Lissajous scanning pattern" and conducted a study to identify its feasibility for fluorescence-guided brain tumor diagnosis. Conventional hematoxylin and eosin (H&E) histological images were compared with indocyanine green (ICG)-enhanced CLE images in two settings (1): experimental study with in vitro tumor cells and ex vivo glial tumors of mice, and (2) clinical evaluation with surgically resected human brain tumors. First, CLE images were obtained from cultured U87 and GL261 glioma cells. Then, U87 and GL261 tumor cells were implanted into the mouse brain, and H&E staining was compared with CLE images of normal and tumor tissues ex vivo. To determine the invasion of the normal brain, two types of patient-derived glioma cells (CSC2 and X01) were used for orthotopic intracranial tumor formation and compared using two methods (CLE vs. H&E staining). Second, in human brain tumors, tissue specimens from 69 patients were prospectively obtained after elective surgical resection and were also compared using two methods, namely, CLE and H&E staining. The comparison was performed by an experienced neuropathologist. When ICG was incubated in vitro, U87 and GL261 cell morphologies were well-defined in the CLE images and depended on dimethyl sulfoxide. Ex vivo examination of xenograft glioma tissues revealed dense and heterogeneous glioma cell cores and peritumoral necrosis using both methods. CLE images also detected invasive tumor cell clusters in the normal brain of the patient-derived glioma xenograft model, which corresponded to H&E staining. In human tissue specimens, CLE images effectively visualized the cytoarchitecture of the normal brain and tumors. In addition, pathognomonic microstructures according to tumor subtype were also clearly observed. Interestingly, in gliomas, the cellularity of the tumor and the density of streak-like patterns were significantly associated with tumor grade in the CLE images. Finally, panoramic view reconstruction was successfully conducted for visualizing a gross tissue morphology. In conclusion, the newly developed CLE with Lissajous laser scanning can be a helpful intraoperative device for the diagnosis, detection of tumor-free margins, and maximal safe resection of brain tumors.


Adiponectin stimulates proliferation and cytokine secretion in colonic epithelial cells.
Adiponectin is a recently described mediator secreted by adipose tissue. Here we report the growth promoting and pro-inflammatory actions of adiponectin on colonic epithelial cancer cells. Full-length and globular adiponectin produced an identical stimulation of HT-29 cell growth that was blocked by inhibition of adenylate cyclase and protein kinase A and partially inhibited by a pan-specific protein kinase C inhibitor, but was unaffected by specific inhibition of extracellular signal-related kinase (ERK) or p38 MAP kinase. Globular adiponectin but not full-length adiponectin significantly increased the secretion and mRNA levels of IL-8, GM-CSF and MCP-1. Globular adiponectin doubled IL-1beta-stimulated IL-8 and GM-CSF secretion. Adiponectin-stimulated cytokine secretion was blocked by pharmacological inhibitors of NF-kappaB, ERK and p38 MAP kinase. Globular adiponectin increased phosphorylation of both ERK and p38 MAP kinase and increased the nuclear translocation of active NF-kappaB. Adiponectin has pro-proliferative and pro-inflammatory actions on colonic epithelial cells; these appear to be differentially activated by the adiponectin isoforms. Adiponectin may have a role in the regulation of gastrointestinal mucosal function, inflammation and colon carcinogenesis.


Cytokine Profile in Children with Severe Multisystem Inflammatory Syndrome Related to the Coronavirus Disease 2019.
The multisystem inflammatory syndrome in children (MIS-C) is a novel and concerning entity related to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Although MIS-C has been the subject of intensive research efforts, its pathophysiology and optimal treatment remain elusive. We studied the clinical features, laboratory findings, and immunoinflammatory profiles of seven children prospectively admitted to a pediatric intensive care unit (PICU) during the first wave of the pandemic. All patients had immunoglobulin (Ig)-G against SARS-CoV-2, four of seven patients had both IgM and IgG, and in one of the 7 SARS-CoV-2 was detected in a respiratory sample. All patients received intravenous fluid boluses (median: 15 mL/kg) and norepinephrine. The most common form of respiratory support was supplemental oxygen via nasal cannula. None of the patients needed mechanical ventilation. The cardiovascular system was frequently involved. All patients had an elevated troponin-I (median: 107.3 ng/L). Four out of seven patients had coronary artery abnormalities, and two of seven had both abnormal electrocardiogram (EKG) findings and evidence of left ventricular dysfunction on echocardiogram. Ig levels and complement function were normal. Peripheral blood phenotyping with flow cytometry showed decreased T-cell numbers at the expense of CD8+ T-cells. Cytokine profiling showed a heterogeneous increase in interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-18, IL-2Ra, IL-10, and IL-1Ra that tended to normalize after treatment. Our study shows that children with MIS-C have elevated plasma levels of pro- and anti-inflammatory cytokines in the acute phase of the disease without other relevant immunologic disturbances. These findings suggest the presence of a mixed antagonist response syndrome (MARS) similar to that present in pediatric sepsis. Combining a meticulous differential diagnosis with cautiously coordinated immunomodulatory therapy and high-quality supportive care can help clinicians avoid causing iatrogenic harm in patients with MIS-C.


Elementary counting of cardinal and ordinal numbers by persons with mental retardation.
Cardinal and ordinal counting skills were assessed in 37 mentally retarded adult workers and 42 school children with mental retardation. The major results were the very poor performance of the younger children (essentially at chance beyond the numbers 1 and 2) and the overall marked inferiority in ordinal compared with cardinal counting.