Association Between Surgical Quality Metric Adherence and Overall Survival Among US Veterans With Early-Stage Non-Small Cell Lung Cancer.
Surgical resection remains the preferred treatment for functionally fit patients diagnosed with early-stage non-small cell lung cancer (NSCLC). Process-based intraoperative quality metrics (QMs) are important for optimizing long-term outcomes following curative-intent resection. To develop a practical surgical quality score for patients diagnosed with clinical stage I NSCLC who received definitive surgical treatment. This retrospective cohort study used a uniquely compiled data set of US veterans diagnosed with clinical stage I NSCLC who received definitive surgical treatment from October 2006 through September 2016. The data were analyzed from April 1 to September 1, 2022. Based on contemporary treatment guidelines, 5 surgical QMs were defined: timely surgery, minimally invasive approach, anatomic resection, adequate lymph node sampling, and negative surgical margin. The study developed a surgical quality score reflecting the association between these QMs and overall survival (OS), which was further validated in a cohort of patients using data from the National Cancer Database (NCDB). The study also examined the association between the surgical quality score and recurrence-free survival (RFS). Surgical treatment of early-stage NSCLC. Overall survival and RFS. The study included 9628 veterans who underwent surgical treatment between 2006 and 2016. The cohort consisted of 1446 patients who had a mean (SD) age of 67.6 (7.9) years and included 9278 males (96.4%) and 350 females (3.6%). Among the cohort, 5627 individuals (58.4%) identified as being smokers at the time of surgical treatment. The QMs were met as follows: timely surgery (6633 [68.9%]), minimally invasive approach (3986 [41.4%]), lobectomy (6843 [71.1%]) or segmentectomy (532 [5.5%]), adequate lymph node sampling (3278 [34.0%]), and negative surgical margin (9312 [96.7%]). The median (IQR) follow-up time was 6.2 (2.5-11.4) years. An integer-based score (termed the Veterans Affairs Lung Cancer Operative quality [VALCAN-O] score) from 0 (no QMs met) to 13 (all QMs met) was constructed, with higher scores reflecting progressively better risk-adjusted OS. The median (IQR) OS differed substantially between the score categories (score of 0-5 points, 2.6 [1.0-5.7] years of OS; 6-8 points, 4.3 [1.7-8.6] years; 9-11 points, 6.3 [2.6-11.4] years; and 12-13 points, 7.0 [3.0-12.5] years; P < .001). In addition, risk-adjusted RFS improved in a stepwise manner between the score categories (6-8 vs 0-5 points, multivariable-adjusted hazard ratio [aHR], 0.62; 95% CI, 0.48-0.79; P < .001; 12-13 vs 0-5 points, aHR, 0.39; 95% CI, 0.31-0.49; P < .001). In the validation cohort, which included 107 674 nonveteran patients, the score remained associated with OS. The findings of this study suggest that adherence to intraoperative QMs may be associated with improved OS and RFS. Efforts to improve adherence to surgical QMs may improve patient outcomes following curative-intent resection of early-stage lung cancer.


Shedding of tyrosine and serine/threonine ecto-protein kinases from human leukemic cells.
Ecto-protein kinases (ecto-PK), primarily of the serine/threonine kinase type, have been previously described on the surface of various normal, transformed, and tumor cells. We have found that in the presence of ATP and Mg2+, exogenously added substrates such as phosvitin and poly(Glu4-Tyr) are phosphorylated by intact K562 erythroleukemia, HL60 promyelocytic leukemia, and U937 histiocytic leukemia human cells. Phosphoamino acid analysis indicated that phosvitin, histone H2B, casein, and protamine are phosphorylated on serine and threonine residues, whereas poly(Glu4-Tyr) is phosphorylated on tyrosine. We also present evidence showing that the C9 complement protein, a key component of the membranolytic protein complex of the complement system, is exclusively phosphorylated by the K562 cells on serine residues. Phosphorylation of poly(Glu4-Tyr) is markedly enhanced by Mn2+, whereas C9 phosphorylation is rather inhibited by Mn2+. It is concluded that human leukemic cells express on their surface two types of ecto-PK, one phosphorylating serines and threonines and one specific to tyrosines. The ecto-PKs are spontaneously shed from fully viable cells into the medium in a temperature-dependent manner. Upon sedimentation of cell supernatants at 100,000g, the ecto-PKs are found sedimented with small membrane vesicles. Treatment of intact K562 cells or of released membrane vesicles with bacterial phospholipase C, but not with trypsin or pronase, releases the two types of ecto-PK from the cell or vesicle membrane, respectively. This is accompanied by a marked increase in the released phosphorylating activity. It is, therefore, suggested that these ecto-PKs are either covalently linked to phospholipids or strongly attached to lipid-anchored molecules in the cell surface membrane. Several endogenous proteins in the released membranes are phosphorylated by the ecto-PKs on serines and to a lesser extend on threonines. Two proteins (PTP79 and PTP54) are phosphorylated in a manganese-dependent manner on tyrosines.


Twelve Novel Mutations in the SLC26A3 Gene in 17 Sporadic Cases of Congenital Chloride Diarrhea.
We aimed to improve the knowledge of pathogenic mutations in sporadic cases of congenital chloride diarrhea (CCD) and emphasize the importance of functional studies to define the effect of novel mutations. All member 3 of solute carrier family 26 (SLC26A3) coding regions were sequenced in 17 sporadic patients with CCD. Moreover, the minigene system was used to analyze the effect of 2 novel splicing mutations. We defined the SLC26A3 genotype of all 17 patients with CCD and identified 12 novel mutations. Using the minigene system, we confirmed the in silico prediction of a complete disruption of splicing pattern caused by 2 of these novel mutations: the c.971+3_971+4delAA and c.735+4_c.735+7delAGTA. Moreover, several prediction tools and a structure-function prediction defined the pathogenic role of 6 novel missense mutations. We confirm the molecular heterogeneity of sporadic CCD adding 12 novel mutations to the list of known pathogenic mutations. Moreover, we underline the importance, for laboratories that offer molecular diagnosis and genetic counseling, to perform fast functional analysis of novel mutations.


CD3+ graft cell count influence on chronic GVHD in haploidentical allogeneic transplantation using post-transplant cyclophosphamide.
The effects of graft or donor characteristics in haploidentical hematopoietic cell transplantation (HCT) using post-transplant cyclophosphamide (PT-Cy) are largely unknown. In this multicenter retrospective study we analyzed the correlations between graft cell composition (CD34+, CD3+) and donor features on transplant outcomes in 234 patients who underwent HCT between 2010 and 2016. On multivariate analysis, the use of peripheral blood stem cells (PBSC) was associated with an increased incidence of grade 2-4 acute GVHD [HR 1.94, 95% confidence Interval (CI) = 1.01-3.98, p = 0.05]. An elevated CD3+ graft content was associated with an increased incidence of all-grade chronic GVHD [HR 1.36 (95% CI = 1.06-1.74), p = 0.01]. This effect was confirmed only for the PBSC graft group. A higher CD34+ graft content had a protective role on non-relapse mortality [HR 0.78 (95% CI = 0.62-0.96), p = 0.02] but this was confirmed only for the bone marrow (BM)-derived graft cohort. Donor characteristics did not influence any outcomes. GVHD prophylaxis should be modulated accordingly to CD3+ graft content, especially when a PBSC graft is used. These results need further validation in prospective trials.


Iatrogenic Cardiac Tamponade Secondary to Central Venous Catheter Placement: A Literature Review.
Cardiac tamponade is the fluid accumulation within the pericardial sac that compresses the heart and decreases cardiac output. More than 20% of the cases are surgical or non-surgical iatrogenic causes. Cardiac tamponade has been described as a rare complication of central venous catheter placement with an incidence in adults as low as less than 1% but with significantly high mortality of more than 60%. The purpose of this article is to review the incidence, clinical manifestations, pathophysiology, diagnosis, and management of cardiac tamponade after central venous catheter placement as well as different methods to prevent this fatal complication from occurring.


Alterations of consciousness in psychogenic nonepileptic seizures: emotion, emotion regulation and dissociation.
Impairment of consciousness and reduced self-control are key features of most psychogenic nonepileptic seizures (PNESs), although, compared with patients with epilepsy, those with PNESs demonstrate greater conscious awareness during their seizures. The neurobiological underpinnings of PNESs and of alterations of awareness associated with PNESs remain relatively unknown. We suggest that an understanding of conscious experiences and discrepancies between subjective impairment of consciousness and the lack of objectifiable neurobiological changes in PNESs may benefit from an examination of emotion processing, including understanding sensory, situational, and emotional triggers of PNESs; emotional and physiological changes during the attacks; and styles of emotional reactivity and regulatory capacity. We also suggest that in addition to the typical comparisons between patients with PNESs and those with epilepsy, studies of PNESs would benefit from the inclusion of comparison groups such as those with PTSD, dissociation, and other forms of psychopathology where dissociative and emotion regulatory mechanisms have been explored more fully. We conclude that current evidence and theory suggest that impairment of consciousness in PNESs is only "dissociative" in one subgroup of these seizures, when consciousness is suppressed as a collateral effect of the excessive inhibition of emotion processing. We propose that PNES behaviors and experiences of reduced control or awareness may also represent direct behavioral manifestation of overwhelming emotions, or that minor emotional fluctuations or relatively neutral stimuli may trigger PNESs through conditioning or other preconscious processes. Future studies exploring the neurobiological mechanisms underpinning PNESs are likely to be more fruitful if researchers bear in mind that it is unlikely that all PNESs result from the same processes in the brain.


Sexual behavior, contraceptive practice, and reproductive health among Liberian adolescents.
This paper reports on a survey that was aimed at obtaining information for use in designing programs to reduce the incidence of adolescent pregnancy in Liberia. The sample of 1,488 never-married adolescents aged 14-21 was divided into subgroups based on age, sex, student status, and (for non-students) level of education. Although 57-93 percent of respondents claimed to have received information on reproductive health, only 2-21 percent could identify the monthly fertile period. Thirty to 49 percent of females ages 14-17 years have sexual relations at least once a month; over 80 percent of female non-students ages 18-21 years are sexually active. Highest levels of current contraceptive use were reported for 18-21-year-old female students (51 percent). Never-use of contraception among sexually active respondents was 97 percent for 14-17-year-old non-student females with a low educational level. Insufficient information about family planning methods and inaccessibility were the main reasons cited for non-use. Half of females ages 14-21 years who are currently attending school have been pregnant, as have 67 percent of those not in school. These results indicate a substantial unmet need on the part of Liberian adolescents with respect to reproductive health knowledge, information, and access to contraceptive methods.


Temporal phase correction of multiple echo T2 magnetic resonance images.
Typically, magnetic resonance imaging (MRI) analysis is performed on magnitude data, and multiple echo T2 data consist of numerous images of the same slice taken with different echo spacing, giving voxel-wise temporal sampling of the noise as the signals decay according to T2 relaxation. Magnitude T2 decay data has Rician distributed noise which is characterized by a change in the noise distribution from Gaussian, through a transitional region, to Rayleigh as the signal to noise ratio decreases with increasing echo time. Non-Gaussian noise distributions may produce errors in the commonly applied non-negative least squares (NNLS) algorithm that is used to assess multiple echo decays for compartmentalized water environments through the creation of T2 distributions. Typically, Gaussian noise is sought by performing spatial-based phase correction on the MRI data however, these methods cannot capitalize on the temporal information available from multiple echo T2 acquisitions. Here we describe a temporal phase correction (TPC) algorithm that utilizes the temporal noise information available in multiple echo T2 acquisitions to put the relevant decay information in the Real portion of the decay data and leave only noise in the Imaginary portion. We apply this TPC algorithm to create real-valued multiple echo T2 data from human subjects measured at 1.5 T. We show that applying TPC causes changes in the T2 distribution estimates; notably the possible resolution of separate extracellular and intracellular water environments, and the disappearance of the commonly labeled cerebrospinal fluid peak, which might be an artefact observed in many previously published multiple echo T2 analyses.


Modeling administrative outcomes in fever and neutropenia: clinical variables significantly influence length of stay and hospital charges.
Administrative outcomes such as length of stay and charges are used to compare the quality of care across institutions and among individual providers. Clinical variables representing disease severity may explain some of the variability in these outcomes. To determine the extent to which readily available clinical data can explain the variability in length of stay and charges for children with cancer admitted to the hospital for fever and neutropenia, and to assess the appropriateness of using a time-efficient electronic case-finding strategy for the development of administrative outcome models. A retrospective cohort of 157 fever and neutropenia encounters in a single institution during 11 months in 1997 was identified using a largely automated case-finding strategy followed by independent, blinded review of the selected discharge summaries. Models of admission variables predicting log length of stay and log charges were developed using multiple linear regression. The "smearing" technique of Duan adjusted for logarithmic retransformation was used in calculating each subject's predicted length of stay and charges. R2 values were calculated. There were two secondary analyses. In one, the result of admission blood culture was entered as a potential covariate. In the second, to evaluate the appropriateness of basing models on automated case-finding without discharge summary review, the authors rederived the models using all of the encounters (n = 160) identified by the algorithm, which had included three false-positive cases. Mean length of stay was 6.45 days. Mean charges were $11,967. Absolute monocyte count at admission was a significant, independent negative predictor of length of stay and charges. Underlying cancer diagnosis also was significant. Charges were highest for acute myeloid leukemia, followed by central nervous system tumors, other solid tumors, and acute lymphoblastic leukemia and lymphomas. Length of stay was highest for acute myeloid leukemia, followed by central nervous system tumors, acute lymphoblastic leukemia and lymphomas, and other solid tumors. Absolute monocyte count and tumor type were the major components of the model, but admission temperature (for both administrative outcomes) and the presence of localized infection (for length of stay) also were significant predictors. R2 values were 35.3% (charges) and 38.5% (length of stay), with validation R2 values of 26.6% and 29.2%, respectively. Entering bacteremia as a covariate improved the models. Inclusion of the three false-positive cases generated models with only a modest loss of accuracy; it introduced over-and underreporting of some of the less significant predictors but did not disrupt the ability to identify the major predictors, absolute monocyte count and tumor type. The clinical variables that were significant in this study account, in validation R2 estimates, for more than 25% of the variability in administrative outcomes for encounters of fever and neutropenia. Adjusting length of stay and charges for these clinical variables would allow for a fairer comparison of institutions and individual providers. The electronic case-finding algorithm served as an efficient way to identify absolute monocyte count and tumor type as the major predictors and provided a conservative estimate of R2.


Casualty nurses' attitudes to attempted suicide.
This study explores the attitudes of casualty nurses to attempted suicide. The nurses' age and length of experience in casualty were the independent variables. A total of 142 nurses from 11 hospitals in Northern Ireland had questionnaires circulated to them, with a 66.9% response rate. There were significant differences on four of the variables in relation to nurses' ages, and on two of the variables in relation to the nurses' length of experience in casualty. The older and the more experienced nurses seem to have more positive attitudes than the younger or the less experienced nurses. However, further nursing research, in Northern Ireland, is needed to corroborate these findings. Other recommendations are made.


Clinical outcomes of patients with plasma cell leukemia in the era of novel therapies and hematopoietic stem cell transplantation strategies: a single-institution experience.
PCL carries a poor prognosis and the optimal management remains unknown. To evaluate the outcome of patients with PCL in the era of novel agents and innovative transplantation strategies, we conducted a review of patients with PCL who were treated at our institution from August 2003 to October 2009. Our primary endpoint was to determine overall survival, which was calculated from time of PCL diagnosis to death or last follow-up. Secondary endpoints included response rates and analyses regarding how the novel agents and presence of adverse cytogenetic analyses affected outcomes. We identified 25 patients with PCL (13 with primary PCL [pPCL], 12 with secondary PCL [sPCL]) from our institution. Eighteen patients received bortezomib-based regimens, 19 received high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HCT), and 6 underwent allogeneic HCT. The median overall survival for all patients was 23.6 months. Bortezomib-treated patients had a median survival of 28.4 months vs. 4.0 months for the non-bortezomib-treated group (P < .001). Our analysis suggests that patients with PCL who were treated with bortezomib and/or allogeneic HCT had improved outcomes.


Tripartite ATP-independent Periplasmic (TRAP) Transporters Use an Arginine-mediated Selectivity Filter for High Affinity Substrate Binding.
Tripartite ATP-independent periplasmic (TRAP) transporters are secondary transporters that have evolved an obligate dependence on a substrate-binding protein (SBP) to confer unidirectional transport. Different members of the DctP family of TRAP SBPs have binding sites that recognize a diverse range of organic acid ligands but appear to only share a common electrostatic interaction between a conserved arginine and a carboxylate group in the ligand. We investigated the significance of this interaction using the sialic acid-specific SBP, SiaP, from the Haemophilus influenzae virulence-related SiaPQM TRAP transporter. Using in vitro, in vivo, and structural methods applied to SiaP, we demonstrate that the coordination of the acidic ligand moiety of sialic acid by the conserved arginine (Arg-147) is essential for the function of the transporter as a high affinity scavenging system. However, at high substrate concentrations, the transporter can function in the absence of Arg-147 suggesting that this bi-molecular interaction is not involved in further stages of the transport cycle. As well as being required for high affinity binding, we also demonstrate that the Arg-147 is a strong selectivity filter for carboxylate-containing substrates in TRAP transporters by engineering the SBP to recognize a non-carboxylate-containing substrate, sialylamide, through water-mediated interactions. Together, these data provide biochemical and structural support that TRAP transporters function predominantly as high affinity transporters for carboxylate-containing substrates.


Deletion in the cardiac troponin I gene in a family from northern Sweden with hypertrophic cardiomyopathy.
The cardiac troponin I gene has been described to be associated with hypertrophic cardiomyopathy. Until now, mutations in this gene have been found only in the Japanese population. We now present the first non-Japanese family, from northern Sweden, with a mutation in the cardiac troponin I gene. Clinical diagnose was based on echocardiography, with a maximum left ventricular wall thickness of >13 mm, or major electrocardiographic abnormalities, excluding subjects with other known causes of cardiac hypertrophy. Mutation screening was performed with a single-strand conformation polymorphism analysis and identification of mutation by direct DNA sequencing. We have identified a 33-bp deletion in exon 8 encompassing the stop codon. Nine individuals in three generations were tested, and four were carriers of this deletion. The mother was genetically affected and died of heart failure aged 90. Echocardiography at 71 years of age revealed no hypertrophy, but the electrocardiogram showed signs of left ventricular hypertrophy. Her two sons, also genetically affected, had left ventricular hypertrophy, with maximum wall thickness of 15 and 16 mm, respectively. One daughter and four grandchildren were clinically unaffected, but one of them, a 27-year-old woman with maximum wall thickness of 8 mm and normal electrocardiogram, was found to be genetically affected. In conclusion, we describe a non-Japanese family in which hypertrophic cardiomyopathy is due to a genetic defect in the cardiac troponin I gene. This mutation is a deletion of 33 bp in the last exon, whereas the previously described mutations in this gene are single nucleotide changes and a single codon deletion. The deletion of the C-terminal part of the cardiac troponin I protein, seems in this particular family to be associated with a mild phenotypic expression of familial hypertrophic cardiomyopathy.


Molecular characterization and antibiotic susceptibility of Vibrio cholerae non-O1.
A collection of 64 clinical and environmental Vibrio cholerae non-O1 strains isolated in Asia and Peru were characterized by molecular methods and antibiotic susceptibility testing. All strains were resistant to at least 1 and 80% were resistant to two or more antibiotics. Several strains showed multiple antibiotic resistance (> or = three antibiotics). Plasmids most often of low molecular weight were found in 21/64 (33%) strains. The presence of plasmids did not correlate with antibiotic resistance or influence ribotype patterns. In colony hybridization studies 63/64 (98%) V. cholerae non-O1 strains were cholera toxin negative, whereas only strains recovered from patients were heat-stable enterotoxin positive. Forty-seven Bgl I ribotypes were observed. No correlation was shown between ribotype and toxin gene status. Ribotype similarity was compared by cluster analysis and two main groups of 13 and 34 ribotypes was found. Ribotyping is apparently a useful epidemiological tool in investigations of V. cholerae non-O1 infections.


Differential Uptake of Telehealth for Prenatal Care in a Large New York City Academic Obstetrical Practice during the COVID-19 Pandemic.
During the coronavirus disease 2019 (COVID-19) pandemic in New York City, telehealth was rapidly implemented for obstetric patients. Though telehealth for prenatal care is safe and effective, significant concerns exist regarding equity in access among low-income populations. We performed a retrospective cohort study evaluating utilization of telehealth for prenatal care in a large academic practice in New York City, comparing women with public and private insurance. We found that patients with public insurance were less likely to have at least one telehealth visit than women with private insurance (60.9 vs. 87.3%, p < 0.001). After stratifying by borough, this difference remained significant in Brooklyn, one of the boroughs hardest hit by the pandemic. As COVID-19 continues to spread around the country, obstetric providers must work to ensure that all patients, particularly those with public insurance, have equal access to telehealth. KEY POINTS: · Telehealth for prenatal care is frequently utilized during the COVID-19 pandemic.. · Significant concerns exist regarding equity in access among lower-income populations.. · Women with public insurance in New York City were less likely to access telehealth for prenatal care..


A Digital Game and School-Based Intervention for Students in Hong Kong: Quasi-Experimental Design.
In Hong Kong, with an increasing number of children experiencing mental health issues, there is a need to not only develop innovative interventions but also develop comprehensive prevention interventions so as to reduce their anxiety symptoms and enhance their emotional management and interpersonal relationships. The aim of this study was to determine the effectiveness of The Adventures of DoReMiFa, an integration model of the cognitive-behavioral approach and positive psychology by using digital game-based and school-based mental health enhancement intervention to magnify the social and emotional health and well-being of the school children in Hong Kong aged 9 to 11 years. A quasi-experimental design method was used to evaluate this digital game and school-based intervention. The Adventures of DoReMiFa was piloted in 4 primary schools where students were allocated to either an intervention or a control group. The participants were assessed at pre- and postintervention with a 6-month follow-up measuring their mental health knowledge, levels of anxiety symptoms, positive and negative thinking, perspective-taking, and self-esteem. A total of 459 primary school students from 4 primary schools participated in the study. The response rate on the questionnaires answered on the Web was up to 85.1% (391/459). Compared with the control group, the intervention group was found to have significant association with improved mental health knowledge at the time immediately after the intervention (beta=.46; P=.01) and in the 6-month postintervention period (beta=.66; P<.001); for perspective-taking, the intervention group had exhibited a significant improvement 6 months after the completion of the universal program (beta=1.50; P=.03). The intervention, however, was found not to be effective in reducing the rates of anxiety symptoms and negative thinking among the participating students. The Adventures of DoReMiFa, an integration of a digital game-based and school-based mental health enhancement intervention, was shown to be effective in elevating the knowledge of mental health and promoting perspective-taking in the primary school students of Hong Kong. Although there was insufficient evidence to support a reduction in symptoms of anxiety and negative automatic thoughts, the overall results were still encouraging in that a preventive effect was found, indicating that the program has the potential to enhance the mental well-being of schoolchildren. It also suggests that knowledge enhancement may not necessarily lead to behavior change, and more focused effort may be needed to achieve the translation. The implications and limitations of this study and suggestions for future research were also discussed.


Set Shifting and Inhibition Deficits as Potential Endophenotypes for Depression.
The etiology of Major Depressive Disorder (MDD) is poorly understood, and identifying endophenotypes, or intermediate processes implicated in pathophysiology, for MDD may inform treatment and identification/prevention efforts. Impaired set-shifting and inhibition are commonly observed in MDD; however, few studies have examined they are endophenotypes for MDD. Thus, the present study tested whether set-shifting and/or inhibition satisfy several endophenotype criteria: specifically, whether they were (1) impaired in current MDD, (2) impaired in remitted MDD, and (3) familial (i.e., correlated within sibling pairs). Set-shifting and inhibition were assessed using subtests from the Delis-Kaplan Executive Function System. Psychopathology was assessed using the Structured Clinical Interview for DSM-5. Results indicated set-shifting deficits were familial and present in both current MDD and in remitted MDD individuals who had no current disorders, suggesting they may be state-independent. Inhibition was familial, but was generally not impaired in current nor remitted MDD (although the remitted MDD group with no current disorders exhibited impairments on one of the two inhibition tasks). These findings indicate that impaired set-shifting is a promising endophenotype candidate for MDD. Findings are limited to young adults, and further research is needed to test generalizability to other populations, evaluate longitudinal relationships, and examine other endophenotype criteria.


Variation of somatic cell counts in colostrum and milk of first and second lactation cows during ten days after calving.
Samples of mammary gland secretions were collected during the first 10 post partum days from six 1st lactations and six 2nd lactation Holstein-Friesian cows. Mean (+/- SD) somatic cell counts in quarter foremilk samples were 447 (+/- 241). 10(3)/ml and 620 (+/- 246). 10(3)/ml in the 1st and 2nd lactation cows, respectively. The difference was significant (P < 0.05). The corresponding values for bucket milk samples were 355 (+/- 320). 10(3)/ml and 517 (+/- 242) 10(3)/ml, respectively. The difference was insignificant (P > 0.05). Mean foremilk somatic cell counts were significantly higher than mean bucket milk counts in both the 1st and the 2nd lactation cows (P < 0.05 and P < 0.01 respectively). A negative correlation between somatic cell counts in both foremilk and bucket milk samples and milk yield was evident in both groups of cows. Somatic cell counts decreased rapidly in bucket milk samples and were lower than 261.10(3)/ml and 192.10(3)/ml in the 1st and the 2nd lactation cows, respectively, on post partum day 10. Values higher than 300.10(3) cells/ml were not found in any of bucket milk samples collected on post partum day 5. Higher counts were found only in foremilk quarter samples collected from 2 glands of 1st lactation and 1 gland of a 2nd lactation cow. None of the mammary glands of any of the cows became infected during the investigation period. Somatic cell counts in non-infected 1st and 2nd lactation cows are apparently time-dependent and cannot be regarded as characteristic features of individual animals.


Risk factors for coronary calcification in older subjects. The Rotterdam Coronary Calcification Study.
We examined associations between cardiovascular risk factors and coronary calcification assessed by electron-beam tomography (EBT) in an unselected population of older subjects. The Rotterdam Coronary Calcification Study is a population-based study in subjects > =55 years. Participants underwent EBT scanning. Coronary calcification was quantified according to the Agatston score. Cardiovascular risk factors were assessed 7 years before and concurrently to scanning. We used the first 2013 participants for the present analyses. Risk factors assessed 7 years before scanning were strongly associated with calcium score. Associations with blood pressure and cholesterol attenuated when measured concurrently to scanning. Although the number of risk factors was strongly associated with a high calcium score in asymptomatic subjects, 29% of the men and 15% of the women without risk factors had a high calcium score. This population-based study in older subjects shows that cardiovascular risk factors are associated with coronary calcification. Associations were stronger for risk factors measured at earlier age. Almost 30% of the men and 15% of the women without risk factors had extensive coronary calcification.


Dental Caries Scenario Among 5, 12 and 15-Year-old Children in India- A Retrospective Analysis.
Dental caries is the most prevalent dental disease and children are one of the most affected groups. Thus, the present study was conducted to assess the average dental caries prevalence across different WHO index age groups (5, 12 & 15 years) for the past fifteen years. Literature search was performed electronically in various search engines like google scholar, PubMed, Copernicus, etc. using Dental caries and India as MeSH terms. Articles from the past 15 years reporting on dental caries prevalence and experience in India were searched and this online searching strategy collected and listed 781 articles. After evaluating their titles and abstracts, only 30 articles fulfilled the inclusion and exclusion criteria & were finally selected for complete review and data collection. Five articles which were hand searched were also included. Pooled estimates were calculated for different index age groups and different regions (Northern and Southern) separately with a confidence interval of 95% both for prevalence and experience of dental caries. The pooled prevalence of dental caries was found to be highest in 15 year olds followed by 5 and 12 years (62.02%, 48.11% & 43.34% respectively). Weighted mean was also found to be highest for 15 years, followed by 5 and 12 years (2.56±6.508, 2.49±7.78, 1.48±3.292 respectively). Pooled prevalence and weighted mean for the Northernern India region was found to be more in all the index age groups as compared to the Southernern India region. More than 40% of the children in India have shown dental caries in both primary and permanent teeth in the past 15 years. Also, Northernern region was found to be more affected by dental caries than Southern region. Since children are seen as the future of the nation, this data could be helpful in the planning of oral health care services by the concerned authorities in the community.


[E-RFC (T cells) and Ig-positive cells (B cells) in the peripheral blood of patients with lymphogranulomatosis and possible immunocorrection with levamisole].
Forty patients with Hodgkin's disease were examined for cell-mediated immunity. Analysis of peripheral blood showed a decrease in the relative and absolute E-RFU counts depending on the disease stages. The changes in B-cells bearing surface immunoglobulins were negligible. E-RFC (T-cells) prevailed in the spleen of patients with Hodgkin's disease. However, some of the patients had a high enough count of B-cells in the spleen and peripheral blood. Multiple modality treatment for Hodgkin's disease, radiation therapy in particular, aggravated disorders of cell-mediated immunity. Thirty-one patients received levamisole at the definite stages of multiple modality treatment with a purpose of correcting cell-mediated immunity disorders. Two schemes of levamisole intake were tried. The drug was given in a dose of 150 mg for 21 days, the total dose amounting to 3, 150 mg, or in a dose of 150 mg for 4 days with a 10-day interval, the total dose being 2, 100 mg. Only two patients noted side effects one of them had a "gas taste" in the mouth, whereas the other one skin itch and urticaria that did not require any treatment. Application of levamisole increased the relative and absolute E-RFU counts, absolute lymphocyte count. Patients on levamisole noted the improvement of the well-being.


Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects.
Segmentation defects of the vertebrae (SDV) are caused by aberrant somite formation during embryogenesis and result in irregular formation of the vertebrae and ribs. The Notch signal transduction pathway plays a critical role in somite formation and patterning in model vertebrates. In humans, mutations in several genes involved in the Notch pathway are associated with SDV, with both autosomal recessive (MESP2, DLL3, LFNG, HES7) and autosomal dominant (TBX6) inheritance. However, many individuals with SDV do not carry mutations in these genes. Using whole-exome capture and massive parallel sequencing, we identified compound heterozygous mutations in RIPPLY2 in two brothers with multiple regional SDV, with appropriate familial segregation. One novel mutation (c.A238T:p.Arg80*) introduces a premature stop codon. In transiently transfected C2C12 mouse myoblasts, the RIPPLY2 mutant protein demonstrated impaired transcriptional repression activity compared with wild-type RIPPLY2 despite similar levels of expression. The other mutation (c.240-4T>G), with minor allele frequency <0.002, lies in the highly conserved splice site consensus sequence 5' to the terminal exon. Ripply2 has a well-established role in somitogenesis and vertebral column formation, interacting at both gene and protein levels with SDV-associated Mesp2 and Tbx6. We conclude that compound heterozygous mutations in RIPPLY2 are associated with SDV, a new gene for this condition.


Computer user groups: a shared rural hospital experience.
For the small or rural hospital with a stand-alone system, a user group can be a way to obtain programming, education and training, assistance from the manufacturer, and greater influence in the marketplace--abilities which many larger hospitals have. Moreover, the use of such a group is a way for individual hospitals to maximize the use of and make computer operators more comfortable with their systems. The UB-82 programming project is an illustration of how a group of hospitals with limited resources can work together to achieve a common goal.


Evaluation of anti-inflammatory activity of methanolic extract of leaves of Bougainvillea spectabilis in experimental animal models.
Bougainvillea spectabilis (BS) (family Nyctaginaceae) is said to possess hypoglycemic and anti-inflammatory activities in experimental animals. We had set forward to examine the potential anti-inflammatory activities of BS in experimental models of inflammation. Fresh dried leaves from the flowering plant of BS were collected from the local area during the flowering season and air dried (215.00 g). Methanol was extracted, and the solvent was removed on a rotary evaporator under reduced pressure. The extract was freeze-dried (lyophilized) and the yield was 8 g. This was used as an emulsion prepared in propylene glycol and orally administered (20 and 50 mg/kg). Acute anti-inflammatory activity of BS was evaluated using carrageenan and dextran whereas chronic anti-inflammatory (immunoregulatory) activity was evaluated by Freund's adjuvant-induced arthritis model. BS (20 mg/kg and 50 mg/kg) had shown significant anti-inflammatory effects 20.6% and 67.6%, respectively, on carrageenan-induced acute inflammatory models. In dextran-induced edema, the effect was 30% and 66%, respectively. The standard drug indomethacin (87.3% and 91.5%, respectively) showed better inhibitory response in both models. In arthritic model 50 mg/kg of BS showed significant chronic anti-inflammatory effect (38.46%) in comparison to the standard drug dexamethasone (84.6%). Our data indicate that the methanol extract of BS (50 mg/kg) leaves has significant anti-inflammatory and immunoregulatory activity. Further studies involving isolation of active principles will help to pinpoint the mechanisms contributing to the observed activities of BS.


Pyogenic granuloma of the tongue early after allogeneic bone marrow transplantation for multiple myeloma.
Oral complications occur frequently after bone marrow transplantation (BMT). Some of them are caused by regimen-related toxicity of the preparative regimen, and others by infections. In addition, oral tissues are targets of graft-versus-host disease (GVHD). Oral granulomatous lesions are not a common complication after BMT, and are especially rare on the tongue. Such rare lesions reported in the literature, developed late after BMT with oral chronic GVHD. We present here a patient who developed pyogenic granuloma of the tongue early after allogeneic BMT done for multiple myeloma. Regimen-related mucositis, oral acute GVHD, the administration of cyclosporine A, and the preexisting macroglossia might be responsible for the formation of granuloma.


HITS: a short domestic violence screening tool for use in a family practice setting.
Domestic violence is an important problem that is often not recognized by physicians. We designed a short instrument for domestic violence screening that could be easily remembered and administered by family physicians. In phase one of the study, 160 adult female family practice office patients living with a partner for at least 12 months completed two questionnaires. One questionnaire was the verbal and physical aggression items of the Conflict Tactics Scale (CTS). The other was a new four-item questionnaire that asked respondents how often their partner physically Hurt, Insulted, Threatened with harm, and Screamed at them. These four items make the acronym HITS. In phase two, 99 women, who were self-identified victims of domestic violence, completed the HITS. For phase one, Cronbach's alpha was .80 for the HITS scale. The correlation of HITS and CTS scores was .85. For phase two, the mean HITS scores for office patients and abuse victims were 6.13 and 15.15, respectively. Optimal data analysis revealed that a cut score of 10.5 on the HITS reliably differentiated respondents in the two groups. Using this cut score, 91% of patients and 96% of abuse victims were accurately classified. The HITS scale showed good internal consistency and concurrent validity with the CTS verbal and physical aggression items. The HITS scale also showed good construct validity in its ability to differentiate family practice patients from abuse victims. The HITS scale is promising as a domestic violence screening mnemonic for family practice physicians and residents.


Measurement depth of laser-induced tissue fluorescence with application to laser angioplasty.
Laser-induced fluorescence spectroscopy can be used to discriminate between normal and atherosclerotic tissue and guide the delivery of high-power laser energy for laser angioplasty. The depth of tissue from which fluorescence is measured should closely match the depth of laser ablation and, from a practical standpoint, should be neither too small nor too large. This paper investigates the depth of the fluorescence signal. A simple mathematical model is presented. An experimental procedure for determining this depth is described. The results agree well with the model. The implications of the findings to the development of a practical fluorescence-guided laser angioplasty system are discussed.


Enzyme-constrained models predict the dynamics of Saccharomyces cerevisiae growth in continuous, batch and fed-batch bioreactors.
Genome-scale, constraint-based models (GEM) and their derivatives are commonly used to model and gain insights into microbial metabolism. Often, however, their accuracy and predictive power are limited and enable only approximate designs. To improve their usefulness for strain and bioprocess design, we studied here their capacity to accurately predict metabolic changes in response to operational conditions in a bioreactor, as well as intracellular, active reactions. We used flux balance analysis (FBA) and dynamic FBA (dFBA) to predict growth dynamics of the model organism Saccharomyces cerevisiae under different industrially relevant conditions. We compared simulations with the latest developed GEM for this organism (Yeast8) and its enzyme-constrained version (ecYeast8) herein described with experimental data and found that ecYeast8 outperforms Yeast8 in all the simulations. EcYeast8 was able to predict well-known traits of yeast metabolism including the onset of the Crabtree effect, the order of substrate consumption during mixed carbon cultivation and production of a target metabolite. We showed how the combination of ecGEM and dFBA links reactor operation and genetic modifications to flux predictions, enabling the prediction of yields and productivities of different strains and (dynamic) production processes. Additionally, we present flux sampling as a tool to analyse flux predictions of ecGEM, of major importance for strain design applications. We showed that constraining protein availability substantially improves accuracy of the description of the metabolic state of the cell under dynamic conditions. This therefore enables more realistic and faithful designs of industrially relevant cell-based processes and, thus, the usefulness of such models.


Video-confidence: a qualitative exploration of videoconferencing for psychiatric emergencies.
In psychiatric emergencies in rural areas the availability of psychiatrists are limited. Therefore, tele-psychiatry, via real-time videoconferencing (VC), has been developed to provide advanced consultative services to areas that lack psychiatrists. However, there is limited research on the use of VC for psychiatric emergencies. The University Hospital of North Norway has been the first hospital in Norway to implement this type of service by developing a new on-call system for psychiatric emergency practice through which psychiatrists are accessible by telephone and VC 24 hours a day for consultations with patients and nurses at three regional psychiatric centres. This study explores patients', psychiatrists' and nurses' experiences of using VC for psychiatric emergencies, as well as how the technology influenced their confidence. In this study, we used a qualitative explorative research design. With a particular focus on users' experiences of VC, we conducted 29 semi-structured interviews with patients, psychiatrists and nurses who had participated in a VC consultation in at least one psychiatric emergency. Our findings show that access to the VC system increased the experience of confidence in challenging psychiatric emergencies in four ways: (1) by strengthening patient involvement during the psychiatric specialist's assessment, (2) by reducing uncertainty, (3) by sharing responsibility for decisions and (4) by functioning as a safety net even when VC was not used. This study has demonstrated that an emergency psychiatric service delivered by VC may improve the confidence of psychiatrists, nurses and patients in challenging psychiatric emergencies. VC can serve as an effective tool for ensuring decentralised high-quality psychiatric services for emergency care.


Transgastric submucosal excision of small- to medium-sized gastrointestinal stromal tumours by pure minimally invasive approach.
The aim of this study is to evaluate the results of a single and common approach for transgastric submucosal excision of small- to medium-sized gastrointestinal stromal tumours (GIST) having different locations in upper two-third of the stomach by pure minimally invasive approach. A retrospective study from February 2012 to January 2015 on 11 patients was conducted including both male and female. Their age ranged from 40 to 65 years. All were subjected to laparoscopic transgastric submucosal excision of GIST in upper two-third of the stomach with 1 cm margin having different locations in stomach. Excised tumours were subjected to histopathological study. These patients were followed for 12 months assessing operative time, post-operative complications, conversion rates, morbidity, hospital stay and recurrence rate. Duration of surgery was 150.6 ± 20.4 min. Mean hospital stay was 8 (range: 7-10) days. There were no post-operative complications. There were no conversions to open procedure. There were no recurrences. Morbidity was comparable to any other laparoscopic procedures. We conclude that a single and common approach of transgastric submucosal excision of small- to medium-sized stromal tumours with 1 cm margin having different locations in upper two-third of stomach, by pure minimally invasive approach, has a better outcome and brings a uniformity in laparoscopic management of GIST.


Differential protein expression and surface presentation generate high-frequency antigenic variation in Mycoplasma fermentans.
Mycoplasma fermentans, a wall-less prokaryote, is currently under investigation as a potential human pathogen. Recently, several surface lipoproteins have been shown to vary in expression between M. fermentans strains. Using specific antibodies to these lipoproteins, we investigated the extent and nature of antigenic variation within this species. Immunoscreening of type strain PG18 agar-grown colonies revealed marked heterogeneity in expression of distinct surface lipoproteins. Subsequent isolation and propagation of clonal isolates established isogenic lineages which displayed high-frequency (10(-2) to 10(-5) per generation) antigenic phase variation. [35S]cysteine-labeled protein profiles and Western immunoblots of phase-variant clones showed that several distinct integral membrane proteins undergo noncoordinate variation in expression. In addition to differential expression of epitope-bearing lipoproteins, differential accessibility of epitopes to antibodies was also documented as a mechanism generating surface phenotypic variation. Examination of one strain-variant antigen showed high-frequency phase variation to underlie previously observed antigenic differences between strains of this species. Thus, M. fermentans has a complex system capable of creating rapid changes in surface mosaics. This may profoundly affect mycoplasma-host interactions and may limit the methods by which populations of M. fermentans may be studied in vivo.


Prosodic and segmental aspects of nonword repetition in 4- to 6-year-old children who are deaf and hard of hearing compared to controls with normal hearing.
Children who are deaf or hard of hearing (DHH) are at an increased risk of speech and language deficits. Nonword repetition (NWR) is a potential predictor of problems with phonology, grammar and lexicon in DHH children. The aim of the present study was to examine repetition of prosodic features and segments in nonwords by DHH children compared to children with normal hearing (NH) and to relate NWR performance to measures of language ability and background variables. In this cross-sectional study, 14 Swedish-speaking children with mild-profound sensorineural hearing loss, aged 4-6 years, and 29 age-matched controls with NH and typical language development participated. The DHH children used cochlear implants (CI), hearing aids or a combination of both. The assessment materials included a prosodically controlled NWR task, as well as tests of phonological production, expressive grammar and receptive vocabulary. The DHH children performed below the children with NH on the repetition of tonal word accents, stress patterns, vowels and consonants, with consonants being hardest, and tonal word accents easiest, to repeat. NWR performance was also correlated with language ability, and to hearing level, in the DHH children. Both prosodic and segmental features of nonwords are problematic for Swedish-speaking DHH children compared to children with NH, but performance on tonal word accent repetition is comparably high. NWR may have potential as a clinically useful tool for identification of children who are in need of speech and language intervention.


Growth rate of corpus callosum in very premature infants.
It is desirable to develop a bedside method for assessing cerebral development in the very premature infant to monitor the effectiveness of interventions aimed at improving cerebral development. Our aim was to describe the growth trajectory of the corpus callosum (CC) on cranial sonography in very premature infants. We recruited 100 very-low-birth-weight infants admitted to a single regional level III neonatal intensive care unit from November 1998 to November 2000. Cranial sonography images of the CC were obtained for 64 (32 boys) infants (mean gestational age, 28 weeks; range, 23-33 weeks) in the first week of life and at term equivalency. The growth rate of the CC was compared in the 64 study infants to the expected growth rate of 0.20-0.27 mm/day from antenatal data and correlated with clinical outcome at 2 years of age by using Mental Development Index (MDI) and Psychomotor Development Index (PDI). The average growth rate of the CC was half of that expected from antenatal data. Mean growth rates were similar for all gestational ages (mean, 0.11 mm/day; range, 0.05-0.29; P = .4). The CC at term equivalency was longer for those in MDI class 2 (mean, 44.3 mm) compared with MDI class 3 (mean 40.2 mm; P = .003) as well as for PDI class 2 versus 3 (P = .017). Measurement of the length of the CC at cranial sonography is reproducible. Those with poorer neurodevelopmental outcomes have a shorter CC at term equivalency. The CC grows at a much lower rate postnatally than in utero among very premature infants.


In Situ Tracking of Partial Sodium Desolvation of Materials with Capacitive, Pseudocapacitive, and Battery-like Charge/Discharge Behavior in Aqueous Electrolytes.
Aqueous electrolytes can be used for electrical double-layer capacitors, pseudocapacitors, and intercalation-type batteries. These technologies may employ different electrode materials, most importantly high-surface-area nanoporous carbon, two-dimensional materials, and metal oxides. All of these materials also find more and more applications in electrochemical desalination devices. During the electrochemical operation of such electrode materials, charge storage and ion immobilization are accomplished by non-Faradaic ion electrosorption, Faradaic ion intercalation at specific crystallographic sites, or ion insertion between layers of two-dimensional materials. These processes may or may not be associated with a (partial) loss of the aqueous solvation shell around the ions. Our work showcases the electrochemical quartz crystal microbalance as an excellent tool for quantifying the change in effective solvation. We chose sodium as an important cation for energy storage materials (sodium-based aqueous electrolytes) and electrochemical desalination (saline media). Our data show that a major amount of water uptake occurs during ion electrosorption in nanoporous carbon, while battery-like ion insertion between layers of titanium disulfide is associated with an 80% loss of the initially present solvation molecules. Sodiation of MXene is accomplished by a loss of 90% of the number of solvent molecules, but nanoconfined water in-between the MXene layers may compensate for this large degree of desolvation. In the case of sodium manganese oxide, we were able to demonstrate the full loss of the solvation shell.


[Laser prostatectomy as alternative to transurethral prostate resection in benign prostatic hyperplasia].
Assessment of the results of laser prostatectomy, as a treatment for benign prostatic hyperplasia (BPH). Prospective case control study. University Hospital Utrecht, the Netherlands. Between February 1992 and May 1993, 54 men with their micturition complaints due to BPH were treated with laser prostatectomy (TULIP system). Results were assessed using the international prostatic symptom score (IPSS), the maximal flow and urodynamic tests. The results were compared retrospectively with results of transurethral resection of the prostate (TURP; n = 40): both groups were urodynamically identical. Of the 54 patients, 10 could not be evaluated 6 months after treatment (5 of them underwent TURP or a second laser prostatectomy). In 40 patients complete evaluation including urodynamics before and six months after treatment was possible. A significant decrease in the symptom score from 19.3 (SD: 7.6) to 6.3 (SD: 5.4) and increase of the maximal flow during pressure-flow studies from 9.6 to 15.8 ml per second were observed. The decrease of the voiding pressure at 6 months after TURP in comparison with laser prostatectomy was close to significance (p = 0.05); the other improvements after urodynamics were comparable. Laser prostatectomy is a promising new therapy for BPH.


[Morphology of the neovagina and sexual functioning of patients with Mayer-Rokitansky-Küster-Hauser syndrome who underwent modified Wharton vaginoplasty].
To evaluate the anatomical results of Wharton vaginoplasty performed with Friebe modification for the surgical correction of vaginal aplasia in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and to assess multidimensionally the sexual functioning of the women. 20 out of 36 patients with MRKH syndrome who underwent surgical creation of neovagina between October 1995 and September 2009 participated in the study In the group 1 women (55%) had the typical form, 3 women (15%) had the atypical form and 6 women (30%) had the MURCS type of the MRKH syndrome. The dimensions of the vagina (length and width) and the quality of vaginal epithelium (Schiller test) were evaluated. The sexual functioning of the patients was assessed with the Female Sexual Function Index (FSFI) questionnaire and scored in 6 domains (desire, arousal, lubrication, orgasm, satisfaction and pain). The patients underwent the surgery at the median age of 21.7 years (range 16.3-36.6) and were followed-up from 6 months to 11.3 years (median 7.9 years) after the surgery at the median age of 24.7 years (range 18.3-37.3). The vaginal length and width ranged from 4.5 to 12cm (median 6.3) and from 1.5 to 4cm (median 3), respectively. The total FSFI score and 6 domains scores (medians and ranges) obtained within the group of 18 patients (2 patients reported no sexual activity) were as follows: desire 3.6 (1.2-6), arousal 4.5 (2.4-6), lubrication 5.7 (1.2-6), orgasm 4.2 (1.2-6), satisfaction 5.6 (2.4-6), pain 4.8 (0-6), total score 28.2 (10.8-36). No correlation was found between the vaginal dimensions and the total FSFI scores but in 16 (80%) patients the value of the latter was higher than the cut-off value of 26.55, discriminating women with and without sexual dysfunction. The modified Wharton vaginoplasty enables women with MRKH syndrome to get a functional vagina of normal anatomy.


Muscle cell fate choice requires the T-box transcription factor midline in Drosophila.
Drosophila Midline (Mid) is an ortholog of vertebrate Tbx20, which plays roles in the developing heart, migrating cranial motor neurons, and endothelial cells. Mid functions in cell-fate specification and differentiation of tissues that include the ectoderm, cardioblasts, neuroblasts, and egg chambers; however, a role in the somatic musculature has not been described. We identified mid in genetic and molecular screens for factors contributing to somatic muscle morphogenesis. Mid is expressed in founder cells (FCs) for several muscle fibers, and functions cooperatively with the T-box protein H15 in lateral oblique muscle 1 and the segment border muscle. Mid is particularly important for the specification and development of the lateral transverse (LT) muscles LT3 and LT4, which arise by asymmetric division of a single muscle progenitor. Mid is expressed in this progenitor and its two sibling FCs, but is maintained only in the LT4 FC. Both muscles were frequently missing in mid mutant embryos, and LT4-associated expression of the transcription factor Krüppel (Kr) was lost. When present, LT4 adopted an LT3-like morphology. Coordinately, mid misexpression caused LT3 to adopt an LT4-like morphology and was associated with ectopic Kr expression. From these data, we concluded that mid functions first in the progenitor to direct development of LT3 and LT4, and later in the FCs to influence whichever of these differentiation profiles is selected. Mid is the first T-box factor shown to influence LT3 and LT4 muscle identity and, along with the T-box protein Optomotor-blind-related-gene 1 (Org-1), is representative of a new class of transcription factors in muscle specification.


Report card on access to rural health care in Canada.
Canadians living in rural communities continue to experience challenges in accessing rural health care. The Rural Road Map for Action (RRM) was developed in February 2017 and provides a guiding framework for a coordinated, pan-Canadian approach to physician rural work force planning and improved access to rural health care. The Rural Road Map Implementation Committee (RRMIC) was formed in February 2018 to support the implementation of the RRM. The RRMIC was co-sponsored by the College of Family Physicians of Canada and the Society of Rural Physicians of Canada and had a broad membership that deliberately crossed sectors supporting the RRM's social accountability vision. In April 2021, the \"Rural Road Map: Report Card on Access to HealthCare in Rural Canada\" was discussed at a Society of Rural Physicians of Canada national forum. Next steps included: focusing on equitable access to rural health care service delivery; enhancing rural physician resource planning including national medical licensure and the adoption of more effective strategies for rural physician recruitment and retention; improving access to rural specialty care; supporting the work of the National Consortium on Indigenous Medical Education; and developing metrics as useful tools to facilitate change in rural health care, social accountability in medical education and provisions for supporting the delivery of virtual health care. Collaborative partnerships and commitments from all key stakeholders will be critical to addressing national and regional health work force needs. No one sector alone can fix the inequitable health care realities of people living in rural communities in Canada.


Methodological background of the Amersham Amerlex free thyroxine RIA.
This contribution describes the essential rules underlying a valid estimation of FT4 and compares the way in which various methods deviate from ideal behaviour. The Amerlex FT4 RIA test has been validated by several approaches. A practical demonstration of the ability of various methods to correct for differences in T4-binding protein concentration has been made by independent studies in a UK hospital on euthyroid non-pregnant, euthyroid contraceptive and euthyroid pregnant women. The Amersham kit has been shown to correspond closely to theoretical expectations for FT4 values in these groups.


Dietary Intake, Biological Status, and Barriers towards Omega-3 Intake in Elite Level (Tier 4), Female Athletes: Pilot Study.
Omega-3 polyunsaturated fatty acids (n-3 PUFA) have unique properties which benefit athlete populations. The literature investigating NCAA collegiate, rugby sevens and German endurance athletes indicates suboptimal n-3 PUFA dietary intake and biological status. The aims of this study were: (i) to explore the dietary intakes and FA profiles of elite level, team-based, female athletes and (ii) to understand perceived barriers towards achieving n-3 dietary guidelines. A total of 35 athletes (24.8 ± 4.5 years) completed both a questionnaire and a finger prick test. All the participants reported consuming fish and seafood over the previous six months however only nine athletes consumed ≥ 2 servings of fish per week. Four participants reported using an n-3 supplement. The mean omega-3 index (O3I; including supplementers) was below target levels of >8% (5.19 ± 0.86%). O3I was significantly higher (p < 0.001) in those consuming ≥ 2 servings of fish per week and/or supplements (5.91 ± 0.81%) compared with those who did not (4.82 ± 0.63%). The main barriers reported by those not consuming two servings of fish per week were sensory (n = 11; 42%), cooking skills (n = 10; 38%) and knowledge of n-3 benefits (n = 7; 27%). The current study shows that elite level female athletes present with suboptimal n-3 dietary intake and O3I due to their food preferences, cooking skills and n-3 knowledge.


Sophorolipid Candidates Demonstrate Cytotoxic Efficacy against 2D and 3D Breast Cancer Models.
Sophorolipids are biosurfactants derived from the nonpathogenic yeasts such as Starmerella bombicola with potential efficacy in anticancer applications. Simple and cost-effective synthesis of these drugs makes them a promising alternative to traditional chemotherapeutics, pending their success in preliminary drug-screening. Drug-screening typically utilizes 2D cell monolayers due to their simplicity and ease of high-throughput assessment. However, 2D assays fail to capture the complexity and 3D context of the tumor microenvironment and have consequently been implicated in the high percentage of drugs investigated in vitro that later fail in clinical trials. Herein, we screened two sophorolipid candidates and a clinically-used chemotherapeutic, doxorubicin, on in vitro breast cancer models ranging from 2D monolayers to 3D spheroids, employing optical coherence tomography to confirm these morphologies. We calculated corresponding IC50 values for these drugs and found one of the sophorolipids to have comparable toxicities to the chemotherapeutic control. Our findings show increased drug resistance associated with model dimensionality, such that all drugs tested showed that 3D spheroids exhibited higher IC50 values than their 2D counterparts. These findings demonstrate promising preliminary data to support the use of sophorolipids as a more affordable alternative to traditional clinical interventions and demonstrate the importance of 3D tumor models in assessing drug response.


Ultrasound in the meat industry: general applications and decontamination efficiency.
This review summarizes the findings of research focused on ultrasound as a "green", nonchemical technology in the meat industry to improve meat quality and safety. An overview of the importance of the decontamination in meat processing and microbial inactivation using ultrasound combined with some other applications is provided along with results of high power ultrasound studies which have been applied and adapted in the meat industry. The research results revealed that ultrasound by itself or in combination with other processing and/or preservation methods has a potential for improving the general quality, marination and tenderness of meat, preventing microbial growth and recontamination in meat and meat products as well as for the determination of defects in carcasses and cleaning process equipment. This review will provide an interpretation of ultrasound applications, an up-to-date summary of published articles, and an overview of the microbial inactivation in meat and poultry and their products by ultrasound. Since there is a need for not only a pathogen-free product but also a quality product; this review also can be accepted as a report on the results of research in the field of meat quality improvements with ultrasound applications.


Metaproteomics and ultrastructure characterization of Komagataeibacter spp. involved in high-acid spirit vinegar production.
Acetic acid bacteria (AAB) are widespread microorganisms in nature, extensively used in food industry to transform alcohols and sugar alcohols into their corresponding organic acids. Specialized strains are used in the production of vinegar through the oxidative transformation of ethanol into acetic acid. The main AAB involved in the production of high-acid vinegars using the submerged fermentation method belong to the genus Komagataeibacter, characterized by their higher ADH stability and activity, and higher acetic acid resistance (15-20%), compared to other AAB. In this work, the bacteria involved in the production of high-acid spirit vinegar through a spontaneous acetic acid fermentation process was studied. The analysis using a culture-independent approach revealed a homogeneous bacterial population involved in the process, identified as Komagataeibacter spp. Differentially expressed proteins during acetic acid fermentation were investigated by using 2D-DIGE and mass spectrometry. Most of these proteins were functionally related to stress response, the TCA cycle and different metabolic processes. In addition, scanning and transmission electron microscopy and specific staining of polysaccharide SDS-PAGE gels confirmed that Komagataeibacter spp. lacked the characteristic polysaccharide layer surrounding the outer membrane that has been previously reported to have an important role in acetic acid resistance in the genus Acetobacter.


Beliefs among black and white adults about causes and prevention of cardiovascular disease: the Minnesota Heart Survey.
We assessed beliefs about the symptoms, causes, and prevention of cardiovascular disease in population-based surveys of black and white Twin Cities adults in 1985-86. Whites had a generally higher awareness of heart attack symptoms than did blacks; 72% of blacks and 85% of whites mentioned chest pain as a likely symptom. Sixty-five percent of blacks and 76% of whites correctly offered at least one of the three major, modifiable risk factors (smoking, hypertension, and high cholesterol in blood or diet) as likely causes of cardiovascular disease. However, less than 5% of respondents mentioned all three major risk factors. The most frequent response offered as a cause was stress/worry (54% of blacks, 51% of whites). Individuals with higher educational levels generally responded more correctly than those with less education. After accounting for differences in educational level, blacks demonstrated a higher awareness of hypertension as a risk factor, whereas whites were more knowledgeable about smoking and cholesterol. In light of the high percentage of adults still lacking awareness about cardiovascular risk, public education about prevention should continue. Such efforts are broadly desirable but may be most effectively targeted toward minorities and groups with less education, in whom awareness is low and risk of disease is high.


[Fistula--fistula disease].
Management of the fistula disease is complex and requires definition of the exact underlying pathological anatomy by inspection and fistulography. Surgical intervention is required treatment of cause. The incision of fistula is the basic surgical treatment.


Skin temperature rise induced by calcitonin gene-related peptide in gonadotropin-releasing hormone analogue-treated female rats and alleviation by Keishi-bukuryo-gan, a Japanese herbal medicine.
The effects of Keishi-bukuryo-gan on calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature were investigated in gonadotropin-releasing hormone (GnRH) analogue-treated female rats. Leupline (1.0 mg/kg) as the GnRH analogue was subcutaneously (s.c.) injected into female rats. After Keishi-bukuryo-gan (100-1,000 mg/kg, p.o.) or 17beta-estradiol (0.010 mg/kg, s.c.) was administered to GnRH analogue-treated rats for 14 days, CGRP-induced skin temperature elevation, concentration of plasma 17beta-estradiol and pituitary gonadotropin (luteinizing hormone; LH, and follicle stimulating hormone; FSH) were measured. In addition, effects of 17beta-estradiol and Keishi-bukuryo-gan on the proliferation of estrogen-dependent human breast cancer (MCF-7) cells were investigated under in vitro conditions. GnRH analogue significantly lowered the concentrations of plasma 17beta-estradiol and pituitary gonadotropins. Tissue weights of the ovaries and uterus were also decreased by the analogue. Under the condition of estrogen deficiency, intravenous (i.v.) injection of exogenous CGRP (10 microg/kg) elevated the skin temperature of the hind paws more significantly than it did in sham-treated control rats. Estrogen supplementation inhibited this elevation of skin temperature with restoration of both the lowered plasma estrogen level and the decreased uterine weight in GnRH analogue-treated rats. On the other hand, Keishi-bukuryo-gan inhibited the elevation of skin temperature in a dose-dependent manner without restoring the plasma estrogen level and uterine weight. In addition, in an in vitro study, MCF-7 cells proliferated in a dose-dependent manner by the addition of 17beta-estradiol (10(-13)-10(-8) M) to the medium. However, Keishi-bukuryo-gan (10(-6)-10(-4) mg/ml) did not activate the MCF-7 cell proliferation. These results suggest that Keishi-bukuryo-gan, which does not exhibit estrogen activity, may be useful for the treatment of hot flashes in women who are undergoing medical ovariectomy with a GnRH analogue.


Metalloproteomic approach of mercury-binding proteins in liver and kidney tissues of Plagioscion squamosissimus (corvina) and Colossoma macropomum (tambaqui) from Amazon region: Possible identification of mercury contamination biomarkers.
Fish is an important source of protein, vitamins, and minerals. However, this food is also a major source of human exposure to toxic contaminants such as mercury. Thus, this paper aimed to evaluate mercury-binding proteins for possible application as biomarkers of mercury contamination in hepatic and renal tissues of Plagioscion squamosissimus (carnivorous fish) and Colossoma macropomum (omnivorous fish) from the Amazon region using metalloproteomic approach. The proteome of hepatic and renal tissues of fish species was separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), and the mercury concentrations in protein spots were determined by graphite furnace atomic absorption spectrometry (GFAAS). Finally, the protein spots associated to mercury were characterized by electrospray ionization mass spectrometry (ESI-MS/MS). The activity of antioxidant enzymes (SOD, CAT, GPx, and GST) and lipid peroxidation (LPO) were also determined. The results showed that the highest concentrations of mercury were found in the carnivorous species (P. squamosissimus) and that the accumulation pattern of this metal was higher in hepatic tissues than in renal tissues for both species. A tendency was observed for greater enzymatic activity in the hepatic and renal tissues of P. squamosissimus, the species with the highest concentration of mercury. Only GPx activity in the kidney and GST in the liver were lower for the P. squamosissimus species, and this finding can be explained by the interaction of mercury with these enzymes. The data obtained by ESI-MS/MS allowed for the characterization of the protein spots associated to mercury, revealing proteins involved in energy metabolism, biomolecules transport, protein synthesis and degradation, cell differentiation, gene regulation, and the antioxidant system. The results obtained in the present study can contribute to understanding the physiological processes underlying mercury toxicity and have provided new perspectives on possible candidates for mercury contamination biomarkers in fish.


Randomized clinical trial of immunogenicity and safety of a recombinant H1N1/2009 pandemic influenza vaccine containing Advax™ polysaccharide adjuvant.
Timely vaccine supply is critical during influenza pandemics. A recombinant hemagglutinin (rHA)-based vaccine could overcome production hurdles of egg-based vaccines but has never previously been tested in a real-life pandemic setting. The primary aim was to determine the efficacy of a recombinant pandemic vaccine and whether its immunogenicity could be enhanced by a novel polysaccharide adjuvant (Advax™). 281 adults aged 18-70 years were recruited in a randomized, subject and observer blinded, parallel-group study of rHA H1N1/2009 vaccine with or without adjuvant. Immunizations were at 0 and 3 weeks with rHA 3, 11 or 45 μg. Serology and safety was followed for 6 months. At baseline, only 9.1% of subjects (95% CI: 6.0-13.2) had seroprotective H1N1/2009 titers. Seroconversion rates varied by rHA dose, presence of adjuvant, subject age and number of immunizations. Eighty percent (95% CI: 52-96) of 18-49 year olds who received rHA 45 μg with adjuvant were seroprotected at week 3, representing a 11.1-fold increase in antibody titers from baseline. Advax™ adjuvant increased seroprotection rates by 1.9 times after the first, and 2.5 times after the second, immunization when compared to rHA alone. Seroprotection was sustained at 26 weeks and the vaccine was well tolerated with no safety issues. The study confirmed the ability to design, manufacture, and release a recombinant vaccine within a short time from the start of an actual influenza pandemic. Advax™ adjuvant significantly enhanced rHA immunogenicity.


Cloning and expression of a gene encoding hsc73, the major hsp70-like protein in unstressed rat cells.
The isolation and complete DNA sequence of a rat genomic clone encoding hsc73, the major hsp70-like protein found in growing cells is described. Unlike the heat-inducible genes characterized so far, the hsc73 gene is interrupted by introns, and there are also numerous intronless hsc73 pseudogenes in the rat genome. We show that the levels of hsc73 mRNA are approximately 5-fold higher in rapidly growing tissue-culture cells than in cells whose growth has been arrested by serum starvation. The abundance of hsc73 mRNA is not significantly increased by heat shock of either fed or starved cells. The hsc73 promoter contains putative binding sites for transcription factor Sp1, two CCAAT boxes and, surprisingly, two matches to the consensus heat-shock regulatory element. When fused to the CAT gene and transfected into COS or HeLa cells, the promoter is constitutively active, showing only a small induction by heat shock. Deletion of some constitutive elements makes it more strongly heat-inducible. The gene thus appears to be subject to more than one form of regulation, mediated by different promoter elements that are intermingled.


Stylizing Ribbons: Computing Surface Contours With Temporally Coherent Orientations.
Line work is a core element for the stylization of computer animations used by recent shows. However, existing stylization techniques are limited to edge treatments based on brush strokes or textures applied solely on top of curves. In this work, we propose new stylization effects by offering artists direct control over the inside and outside of surface contours. To this end, we introduce a method that creates ribbons, geometry strips of possibly varying width, that extrude from each side of the surface contour with temporally coherent orientations. Our contributions include the generation of spatially and temporally consistent normal orientations along visible contours and a trimming routine that converts arrangements of offset curves into ribbons free of intersections. We demonstrate the expressiveness and versatility of stylized ribbons by applying various effects on both character and shadow edges from animation sequences.


[Antibiotic formation in plasmid and plasmid-free strains].
Antibiotic activity of three plasmid and three plasmid-free strains of Bacillus pumilus was studied. The antibiotic activity was found in one plasmid and two plasmid-free strains. It was supposed that both the chromosomic and extrachromosomic genes could participate in regulation of the antibiotic production in Bac. pumilus. It was shown that the antibiotics produced by Bac. pumilus had a very narrow spectrum and inhibited multiplication only of several grampositive bacteria.


Diagnostic utility of kidney biopsy in patients with sarcoidosis and acute kidney injury.
Sarcoidosis is an idiopathic multisystem disease characterized by noncaseating granulomatous inflammation. Renal biopsy is often performed to evaluate the patient with sarcoidosis and acute kidney injury (AKI). Diagnosis rests on the demonstration of noncaseating granulomas and exclusion of other causes of granulomatous inflammation. This paper reports a patient with pulmonary sarcoidosis and AKI whose renal function improved after prednisone therapy despite the absence of kidney biopsy findings characteristic of sarcoidosis. A 63-year-old Caucasian male with history of hypertension was treated for pulmonary sarcoidosis with a 6-month course of prednisone. His creatinine was 1.6 mg/dL during the course. Two months after finishing treatment, he presented with creatinine of 4 mg/dL. A kidney biopsy was performed, which showed nonspecific changes without evidence of granuloma or active interstitial inflammation. He was empirically started on prednisone for presumed renal sarcoidosis, even with a nondiagnostic kidney biopsy finding. Within a month of treatment, his serum creatinine improved to 2 mg/dL, though not to baseline. He continues to be stable on low-dose prednisone. With this case as a background, we aimed to determine the incidence of inconclusive kidney biopsies in patients with sarcoidosis presenting with AKI and to identify the various histological findings seen in this group of patients. In this retrospective study, all patients who had native renal biopsies read at The Ohio State University over the period of 6 years were identified. Those patients with a diagnosis of sarcoidosis, presenting with AKI, were included for further review. Out of 21 kidney biopsies done in patients with sarcoidosis over a period of 6 years, only four (19%) showed granulomatous interstitial nephritis (GIN). An equal number of patients (4 [19%]) had presence of membranous nephropathy. Nephrocalcinosis was seen in three patients (14%). Almost half of the biopsies had findings suggestive of diabetic nephropathy or other nonspecific changes not characteristic of renal sarcoidosis (48%). Renal sarcoidosis can be focal in nature and characteristic lesions can be missed in a small-needle core biopsy. Inconclusive renal biopsies with only nonspecific findings are frequent in patients with sarcoidosis and AKI. The presence of GIN on renal biopsy, although classic, is uncommon. Renal sarcoidosis remains a presumptive clinical diagnosis and empiric treatment with steroids may be initiated in cases with a strong clinical suspicion even in the absence of characteristic renal biopsy findings.


Weak polyelectrolyte brushes: re-entrant swelling and self-organization.
We have studied the combined influence of pH and ionic strength on the properties of brushes of a weak polyion, poly(acrylic acid), in conditions of grafting density close to the mushroom-brush crossover. By combining atomic force microscopy AFM and quartz crystal microbalance, we show that at low ionic strengths the conformational change of grafted polyions is non-monotonic with increasing pH due to the counterintuitive variation of the ionization degree. Thus, reentrant swelling of the polymer chains is observed with increasing pH. This effect is more important at low polymer grafting densities, when it is accompanied by in-plane heterogeneous distribution at intermediate pH values. In addition, we observed self-assembly on the polymer brush (formation of holes and islands) at pH values below pKa, due to the short-range attractive interaction between uncharged grafted chains. The sensitivity of the ionization of grafted chains to the physicochemical environment was also studied by measuring the interaction force between a silica tip and polymer brushes by atomic force microscopy. The dependence of the ionization of polyions on the presence of the tip points toward important charge regulation effects, in particular at pH values corresponding to partial ionization of the polyion.


A linkage group on pig chromosome 4 comprising the loci for blood group L, GBA, ATP1B1 and three microsatellites.
Restriction fragment length polymorphisms (RFLPs) were described for the porcine loci for beta-glucosidase (GBA) and the beta-polypeptide 1 of the Na+,K(+)-transporting ATPase (ATP1B1). Linkage analyses using a three-generation pedigree provided evidence for the assignment of ATP1B1, GBA and two microsatellite loci (S0001 and S0067) to a previously described linkage group comprising the loci for blood group L (EAL) and an anonymous microsatellite (S0097). The linear order of the six markers was determined with confidence by multipoint analyses and the length of the linkage group was estimated at 88cM. This linkage group was assigned to pig chromosome 4 on the basis of a previous physical localization of the ATP1B1 gene. In situ hybridization data for S0001 presented in this study were consistent with a localization on chromosome 4 and suggested a regional localization to 4p12-p13. The present study reveals conflicting data concerning the genetic localization of the K88 loci controlling the expression of the receptors for the E. coli pilus antigens. One group has reported data suggesting a loose linkage between K88 and EAL, now mapped to chromosome 4, whereas two other groups have found linkage between K88 and the transferrin locus (TF), mapped to chromosome 13 by in situ hybridization.


Percentage of Myeloid Dendritic Cells in Peripheral Venous Blood Is Negatively Related to Incidence of Graves' Orbitopathy.
The aim of the study was to evaluate the distribution of blood dendritic cells (DCs) in patients with Graves' orbitopathy (GO) and to assess the influence of methylprednisolone therapy on subsets of peripheral blood mononuclear cells (PBMCs). Peripheral blood DC subsets were analyzed by flow cytometry in patients with active GO (n = 17), inactive GO (n = 8), and Graves' disease (GD) without GO (n = 8) and controls (n = 15); additionally, in patients with active GO (n = 17), analyses were done at three time points, i.e., before methylprednisolone treatment and after 6 weeks and after 12 weeks of the treatment. Percentage of myeloid DCs (mDCs) in PBMC fraction was significantly lower in patients with both active and inactive GO, compared to patients with GD without GO and controls (p < 0.05). In addition, mDCs were also documented to be an independent factor negatively associated with GO, however without essential differences between active and inactive phases. On the other hand, we did not observe any changes in the percentage of DCs after methylprednisolone therapy (p > 0.05). In the present study, we have succeeded to firstly demonstrate-according to our knowledge-that blood mDCs are negatively related to GO incidence.


Fiber-optic sensors for monitoring patient physiological parameters: a review of applicable technologies and relevance to use during magnetic resonance imaging procedures.
The issues involved with recording vital functions in the magnetic resonance imaging (MRI) environment using fiber-optic sensors are considered in this paper. Basic physiological parameters, such as respiration and heart rate, are fundamental for predicting the risk of anxiety, panic, and claustrophobic episodes in patients undergoing MRI examinations. Electronic transducers are generally hazardous to the patient and are prone to erroneous operation in heavily electromagnetically penetrated MRI environments; however, nonmetallic fiber-optic sensors are inherently immune to electromagnetic effects and will be crucial for acquiring the above-mentioned physiological parameters. Forty-seven MRI-tested or potentially MRI-compatible sensors have appeared in the literature over the last 20 years. The author classifies these sensors into several categories and subcategories, depending on the sensing element placement, method of application, and measure and type. The author includes five in-house-designed fiber Bragg grating based sensors and shares experience in acquiring physiological measurements during MRI scans. This paper aims to systematize the knowledge of fiber-optic techniques for recording life functions and to indicate the current directions of development in this area.


Predicting long-term mortality after Fontan procedures: A risk score based on 6707 patients from 28 studies.
Reported long-term outcome measures vary greatly between studies in Fontan patients making comprehensive appraisal of mortality hazard challenging. We sought to create a clinical risk score to assist monitoring of Fontan patients in the outpatient setting. A systematic review was conducted to evaluate risk factors for long-term (beyond the first postoperative year) mortality in Fontan patients. Studies were eligible for inclusion if ≥90 patients were included or ≥20 long-term mortalities we reported. Risk factors for long-term mortality were determined. The pooled hazard ratios were used to create components of a clinical score for long-term mortality using meta-analysis techniques. Twenty-eight studies were included. The total number of patients was 6707 with an average follow-up of 8.23 ± 5.42 years. There were 1000 deaths. Thirty-five risk factors for late mortality were identified and classified into 9 categories and their relative hazards were used to derive the initial components of a weighted, practical and clinically based Fontan risk score (ranging from 0 to 100). The final score included 8 risk factors: anatomic risk factors, elevated preoperative pulmonary artery pressure, atriopulmonary Fontan, heart failure symptoms, arrhythmia, moderate/severe ventricular dysfunction or atrioventricular valve regurgitation, protein losing enteropathy, and end organ disease (cirrhosis or renal insufficiency). In patients with Fontan circulation, the influence of readily available risk factors can be quantified in an integer score to predict long-term mortality. Prospective validation and refinement of this risk score will be undertaken.


Histone deacetylase knockouts modify transcription, CAG instability and nuclear pathology in Huntington disease mice.
Somatic expansion of the Huntington's disease (HD) CAG repeat drives the rate of a pathogenic process ultimately resulting in neuronal cell death. Although mechanisms of toxicity are poorly delineated, transcriptional dysregulation is a likely contributor. To identify modifiers that act at the level of CAG expansion and/or downstream pathogenic processes, we tested the impact of genetic knockout, in HttQ111 mice, of Hdac2 or Hdac3 in medium-spiny striatal neurons that exhibit extensive CAG expansion and exquisite disease vulnerability. Both knockouts moderately attenuated CAG expansion, with Hdac2 knockout decreasing nuclear huntingtin pathology. Hdac2 knockout resulted in a substantial transcriptional response that included modification of transcriptional dysregulation elicited by the HttQ111 allele, likely via mechanisms unrelated to instability suppression. Our results identify novel modifiers of different aspects of HD pathogenesis in medium-spiny neurons and highlight a complex relationship between the expanded Htt allele and Hdac2 with implications for targeting transcriptional dysregulation in HD.


[Olfactory esthesioneuroblastoma. Review of seven cases].
Esthesioneuroblastomas are fairly rare malignant tumors: only 20 cases have been reported in Spanish records. It is locally aggressive and produces late recurrences. There is no such thing as a universally accepted treatment model. We describe our experience with 7 cases seen in our hospital from 1980 to 1996. A or B stages can be treated with irradiation, surgery or a combination of both. C stages with the most aggressive tendencies may require the combined use of preoperative irradiation, surgery and chemotherapy. We analyzed the forms of presentation, diagnosis, differential diagnosis, treatment, prognosis, and survival. The 5-year survival rate was 75, 60 and 41% for stages A, B and C, respectively.


[Effect of verapamil on urinary calcium and oxalate excretion in renal stone formers].
The effect of the calcium antagonist verapamil on urinary calcium and oxalate excretion was examined and compared with that of trichlormethiazide to evaluate whether verapamil is useful in the prevention of calcium oxalate renal stones. Twenty-four-hour urine of 16 renal stone formers was measured at the outpatient clinic before and after administration of 120 mg/day verapamil for a mean duration of 2.7 months (range, 2 weeks to 6 months). The 24-hour urine was analyzed for creatinine, calcium, oxalic acid, magnesium and citric acid and the results compared with those in 20 renal stone formers who were administered trichlormethiazide. Verapamil was found to significantly reduce the urinary oxalate excretion of the 5 hyperoxaluric (> or = 50 mg/day) patients but no significant effect on urinary calcium, magnesium or citric acid was observed. Conversely, trichlormethiazide significantly decreased urinary calcium excretion in the hypercalciuric (> or = 250 mg/day) patients. Calcium oxalate risk index of hypercalciuric and hyperoxaluric patients was significantly reduced after the administration of verapamil. These findings suggest that verapamil is effective in reducing urinary oxalate excretion in the hyperoxaluric patients.


The effect of clenbuterol on body composition in spontaneously eating tumour-bearing mice.
The aim of this study was to investigate the effect of a selective beta 2-adrenoceptor agonist, clenbuterol, on body composition in tumour-bearing adult and growing mice. Therefore, adult female C57/BL6 mice (n = 20) were inoculated subcutaneously with a 3-methylcholanthrene-induced sarcoma and divided into two identical groups. One group received injections twice a day of clenbuterol corresponding to 1 mg/kg body weight, the other group received sham injections. Growing mice (n = 20) were similarly divided after tumour inoculation into one study group with clenbuterol injections and one control group. The growing animals were sacrificed on day 11 after commencement of treatment, the adult mice on day 16. Clenbuterol treatment had no statistically significant effect on accumulated food intake or body composition in the adult mice. However, food intake in these animals increased numerically compared to control animals after day 11 of the study. Tumour growth was also unaffected. The growing animals displayed an increased carcass dry weight with borderline significance (p = 0.06) and an increased quadriceps muscle fat free dry weight after clenbuterol treatment. Tumour growth was not affected. Food intake measured on a daily basis was significantly increased in the growing clenbuterol treated animals and accumulated food intake was increased with a trend towards statistical significance (p = 0.06). The results support the suggestion that treatment with a selective beta 2-adrenoceptor agonist does not improve body composition in tumour-bearing adult mice relying on spontaneous food intake while growing animals may benefit from such treatment.


Perceptual learning: a case for early selection.
Perceptual learning is any relatively permanent change of perception as a result of experience. Visual learning leads to sometimes dramatic and quite fast improvements of performance in perceptual tasks, such as hyperacuity discriminations. The improvement often is very specific for the exact task trained, for the precise stimulus orientation, the stimulus position in the visual field, and the eye used during training. This specificity indicates location of the underlying changes in the nervous system at least partly on the level of the primary visual cortex. The dependence of learning on error feedback and on attention, on the other hand, proves the importance of top-down influences from higher cortical centers. In summary, perceptual learning seems to rely at least partly on changes on a relatively early level of cortical information processing (early selection), such as the primary visual cortex under the influence of top-down influences (selection and shaping). An alternative explanation based on late selection is discussed.


[Transpenile venous occlusion in the treatment of erectile impotence].
In 15 of 18 patients, 2 of them with previous surgery, transpenile venoablation was performed for treatment of erectile dysfunction due to cavernous leakage. In 4 this was combined with retrograde venooclusion via the internal iliac vein. In 4 patients normal erectile status could be obtained. In 3 other patients erections became possible with use of intracavernous vasoactive agents. In two only mild amelioration, and in two others no change of erectile dysfunction were obtained. Follow-up studies are yet missing in 3 patients. Complications of the procedure were not observed.


Identification of synthetic host defense peptide mimics that exert dual antimicrobial and anti-inflammatory activities.
A group of synthetic antimicrobial oligomers, inspired by naturally occurring antimicrobial peptides, were analyzed for the ability to modulate innate immune responses to Toll-like receptor (TLR) ligands. These synthetic mimics of antimicrobial peptides (SMAMPs) specifically reduced cytokine production in response to Staphylococcus aureus and the S. aureus component lipoteichoic acid (LTA), a TLR2 agonist. Anti-inflammatory SMAMPs prevented the induction of tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-10 in response to S. aureus or LTA, but no other TLR2 ligands. We show that these SMAMPs bind specifically to LTA in vitro and prevent its interaction with TLR2. Importantly, the SMAMP greatly reduced the induction of TNF and IL-6 in vivo in mice acutely infected with S. aureus while simultaneously reducing bacterial loads dramatically (4 log(10)). Thus, these SMAMPs can eliminate the damage induced by pathogen-associated molecular patterns (PAMPs) while simultaneously eliminating infection in vivo. They are the first known SMAMPs to demonstrate anti-inflammatory and antibacterial activities in vivo.