t(10;12)(q24;q15): A new cytogenetic marker in hematological malignancies.
Cytogenetic studies have played a crucial role in the discovery of genes involved in several diseases. In the field of oncohematology, cytogenetics is still necessary for the classification and prognosis of many diseases. Here we report a new recurrent chromosome translocation, t(10;12)(q24;q15), in two patients with different hematological malignancies: myelodysplastic syndrome with excess blasts (MDS-EB), and myelofibrosis (MF) secondary to essential thrombocythemia (ET). The chromosome alteration was observed as a sole karyotype change in the patient with MDS-EB, both at the initial diagnosis and following progression to MDS-EB2. A putative HMGA2-KLLN rearrangement by RNA-sequencing was detected in this patient. The patient with ET, had a normal karyotype at diagnosis and the t(10;12)(q24;q15) translocation emerged as a sole cytogenetic alteration after transformation, and when MF was evident. We reviewed the literature to determine whether this chromosome abnormality had previously been described in other hematological patients and found two cases: an aggressive T-cell lymphoblastic lymphoma (T-LBL) and a case of transformed chronic myeloproliferative syndrome (CMS), in both of which t(10;12)(q24;q15) was also the only karyotype change. The clinical evolution of all four cases suggested that t(10;12)(q24;q15) is associated with a poor outcome in oncohematological patients.


Association study of VDR gene with rheumatoid arthritis in the French population.
Vitamin D is a potent regulator of calcium homeostasis and may have immunomodulatory effects. The influence of vitamin D on human autoimmune disease is controversial. The aim of this study was to investigate the role of vitamin D receptor gene (VDR) in rheumatoid arthritis (RA). Three polymorphisms for VDR gene FokI T>C (rs 10735810), BsmI A>G (rs 1544410) and TaqI C>T (rs 731236) were genotyped in 100 RA French nuclear families (set 1) and 100 additional French nuclear families for replication (set 2). The association analysis was performed using comparison of alleles frequencies (AFBAC), transmission disequilibrium test and genotype relative risk. Our results revealed a significant difference of F allele of FokI polymorphism between transmitted and nontransmitted frequencies (P=0.01) in set 1. Furthermore, the F/F genotype was more frequent in RA patients compared to controls (P=0.01) in set 1. The replication in set 2 showed similar patterns of transmission with a nonsignificant association. Association with FokI was found to be significant when the two sets were combined (P=0.006). These data suggest that the F allele and F/F VDR genotype are associated with RA. The mechanisms by which distinct receptor variants might confer disease susceptibility remain to be elucidated.


Orientation of bovine CTL responses towards PIM, an antibody-inducing surface molecule of Theileria parva, by DNA subunit immunization.
East Coast fever, an acute lymphoproliferative disease of cattle, is caused by the apicomplexan parasite Theileria parva. Protective immunity is mediated by CD8(+) cytotoxic T lymphocytes directed against schizont-infected cells. The polymorphic immunodominant molecule, although an antibody-inducing surface molecule of the schizont, has been hypothesized to play a role in protective immunity. In order to evaluate the immunogenicity of PIM for inducing CTL, cattle were immunized with PIM in isolation from other T. parva antigens, forcing the presentation of PIM-derived epitopes on the MHC class I molecules. Although parasite-specific cytotoxicity was induced in both vaccinated animals, their immune response was clearly different. One animal generated MHC-restricted parasite-specific CTL against PIM while the other calf exhibited a strong PIM-specific proliferative response but non-MHC-restricted parasite-specific cytotoxicity. Only calf 1 survived a lethal sporozoite challenge. This DNA immunization technique with an antigen in isolation of CTL-immunodominant antigens might open possibilities for directing CTL responses against predefined antigens, such as strain cross-reacting CTL antigens.


Not Every Low-Dose Is Low-Dose: Impact of Revising Low-Dose CT Protocol on Mean Effective Radiation Exposure.
Introduction: According to the American Urological Association imaging guidelines, patients presenting with renal colic should undergo low-dose (LD) rather than standard-dose (SD) noncontrast CT. The aim of the present study was to assess how often physicians ordered LD CT scans and to calculate mean effective radiation exposure (ERE) from CT scans from dose length products, and determine mean cumulative ERE over 1-year follow-up period. Methods: After obtaining ethics approval, a retrospective chart review was conducted for patients with renal colic presenting to the emergency department between August 1, 2015 and July 31, 2016 (Phase I) and between April 1, 2019 and October 1, 2019 (Phase II). All imaging studies performed within 1-year of initial presentation were cataloged. Results: In Phase I, 146 patients, with mean age of 51 years and mean body mass index (BMI) of 28.6 kg/m2, underwent 220 CT scans. In Phase II, 225 patients, with mean age of 55 years and mean BMI of 26.7 kg/m2, underwent 273 CT scans. Urologists were the only physicians ordering LD CT scans and they ordered significantly more LD than SD CT scans (71.3% vs 28.7%, p < 0.001). In Phase II, after revision of LD CT scan protocol in March 2019, the mean ERE per LD CT significantly decreased (6.5 vs 1.6 mSv, p < 0.001). In addition, there were significant differences in mean ERE from LD CT scans between two hospitals in the same health system (1.6 vs 7.8 mSv, p < 0.001). The mean cumulative ERE in Phase II over the 1-year period was 19.3 mSv, with 6.9% of patients exceeding 50 mSv. Conclusions: Although LD CT scans are being ordered, a small percentage of patients continue to exceed the 50 mSv annual threshold. It is important to keep track of mean ERE of LD CT scans and collaborate with medical physicists and the diagnostic imaging department to further refine LD CT scan protocols since not every low-dose is low-dose.


The effects of acute alcohol administration on the human brain: insights from neuroimaging.
Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'.


The impact of secondary cytoreductive surgery in platinum sensitive recurrent ovarian cancer treated with upfront neoadjuvant chemotherapy and interval debulking surgery.
The aims of the present study were to assess the oncological outcomes of platinum-sensitive recurrent ovarian cancer patients undergoing secondary cytoreduction (SCS) after treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) at diagnosis and to compare the performance of different selection models in these patients. Retrospective, observational, single-center cohort study including patients with platinum-sensitive recurrent epithelial ovarian cancer with abdominal/inguinal/cardiophrenic disease between November 2012 and November 2020. Patients were selected as surgical candidates with PET/CT-scan and with diagnostic laparoscopy. 272 patients were included in the study. Of these, 165 (60.7%) patients were treated with PDS at diagnosis and 107 (39.3%) with IDS. SCS was performed in 178 (65.4%) cases, with complete gross resection achieved in 155/178 (87.1%). No progression-free survival (PFS) difference was demonstrated when patients treated with PDS were compared with those treated with NACT+IDS at first diagnosis (median 21 versus 21 months; p = 0.684); no post-recurrence survival (PRS) difference was evident between the two groups (median 81 versus 77 months, respectively; p = 0.574). Current selection models to candidate patients to SCS adequately performed in patients treated with IDS at diagnosis, as well as in the PDS group, with combination of PET/CT-scan and laparoscopy being an accurate tool in prediction of no gross residual disease at SCS in this pre-selected population. Patients with platinum-sensitive recurrent epithelial ovarian cancer treated with NACT/IDS as primary treatment have similar post-recurrence survival outcomes of those treated with PDS. Current models to select patients for SCS can be safely applied to IDS patients.


Electric field effects on proteins - Novel perspectives on food and potential health implications.
Electric fields (EF) technologies have been establishing a solid position in emergent food processing and have seen as serious alternatives to traditional thermal processing. During the last decades, research has been devoted to elucidation of technological and safety issues but also fundamental aspects related with interaction of electric fields (EF) with important macromolecules, such as proteins. Proteins are building blocks for the development of functional networks that can encompass health benefits (i.e. nutritional and bioactive properties) but may be also linked with adverse effects such as neurodegenerative diseases (amyloid fibrils) and immunological responses. The biological function of a protein depends on its tridimensional structure/conformation, and latest research evidences that EF can promote disturbances on protein conformation, change their unfolding mechanisms, aggregation and interaction patterns. This review aims at bringing together these recent findings as well as providing novel perspectives about how EF can shape the behavior of proteins towards the development of innovative foods, aiming at consumers' health and wellbeing.


LncRNA XIST silencing protects against sepsis-induced acute liver injury via inhibition of BRD4 expression.
Sepsis is recognized as the acute systemic inflammatory response to severe infection. It is main cause of multiple organ system dysfunction and even organ failure. Long non-coding RNA X inactivate-specific transcript (XIST) is implicated in multiple inflammatory diseases. The aim of present work was to investigate the precise mechanism of XIST underlying sepsis-induced acute liver injury. Rats were underwent cecal ligation and puncture (CLP) to establish sepsis-induced the animal models of acute liver injury. Hematoxylin and eosin (H&E) staining was performed to observe pathological alterations. Corresponding commercial assay kits were employed to analyze the levels of inflammatory cytokines and oxidative stress. Western blot and reverse transcriptional quantitative PCR (RT-qPCR) were performed to determine the expression of proteins and target genes. Finally, TUNEL and CCK-8 assays were performed to test apoptosis rate and cell viability, respectively. In our study, XIST and BRD4 were highly expressed in serum of patients with sepsis-induced acute liver injury. XIST knockdown ameliorated sepsis-induced acute liver injury and inhibited inflammation, oxidative stress, and cell apoptosis in sepsis-induced acute liver injury rats. Interestingly, XIST knockdown downregulated the expression of BRD4, and BRD4 overexpression abolished the impacts of XIST knockdown on inflammation, oxidative stress, and apoptosis of that LPS-induced Kupffer cells. We conclude that lncRNA XIST silencing protects against sepsis-induced acute liver injury via inhibition of the BRD4 expression. Therefore, XIST may be a biomarker for sepsis diagnosis and treatment.


Glycine betaine transport in the obligate halophilic archaeon Methanohalophilus portucalensis.
Transport of the osmoprotectant glycine betaine was investigated using the glycine betaine-synthesizing microbe Methanohalophilus portucalensis (strain FDF1), since solute uptake for this class of obligate halophilic methanogenic Archaea has not been examined. Betaine uptake followed a Michaelis-Menten relationship, with an observed K(t) of 23 microM and a V(max) of 8 nmol per min per mg of protein. The transport system was highly specific for betaine: choline, proline, and dimethylglycine did not significantly compete for [(14)C]betaine uptake. The proton-conducting uncoupler 2, 4-dinitrophenol and the ATPase inhibitor N, N-dicyclohexylcarbodiimide both inhibited glycine betaine uptake. Growth of cells in the presence of 500 microM betaine resulted in faster cell growth due to the suppression of the de novo synthesis of the other compatible solutes, alpha-glutamate, beta-glutamine, and N(epsilon)-acetyl-beta-lysine. These investigations demonstrate that this model halophilic methanogen, M. portucalensis strain FDF1, possesses a high-affinity and highly specific betaine transport system that allows it to accumulate this osmoprotectant from the environment in lieu of synthesizing this or other osmoprotectants under high-salt growth conditions.


Trends and associations between maternal characteristics and infant birthweight among Indigenous and non-Indigenous people in Tasmania, Australia: a population-based study.
This study aimed to investigate the trends and associations of maternal characteristics and birthweight among Indigenous and non-Indigenous infants. This was a retrospective population-based study. Fourteen years (2005-2018) of birthweight and perinatal health data of live-born singletons and their mothers obtained from the Tasmanian Data Linkage Unit were used to assess the trends and associations between maternal characteristics and infant birthweight using regression modelling. Compared with non-Indigenous mothers (n = 76,750), Indigenous mothers (n = 3805) had a significantly higher prevalence of risk factors during the 14-year period. Although the prevalence of prepregnancy obesity and gestational diabetes mellitus (GDM) markedly increased in both groups, the rate of increase was higher (P < 0.001) for Indigenous than non-Indigenous mothers. Smoking, alcohol consumption and illegal drug use during pregnancy reduced over the years, and there was no significant difference in the rate of reduction between the groups. Large-for-gestational-age (LGA) births increased while small-for-gestational-age (SGA) births decreased in both groups over time. In addition, high birthweight (HBW) births decreased while low birthweight (LBW) births increased. The rates of increase in LGA and LBW births and the rates of decrease in SGA and HBW births were significantly higher in Indigenous mothers compared with non-Indigenous mothers (P < 0.001 for all). The association between Indigenous ethnicity and LBW and SGA births weakened after adjusting for other confounding maternal and perinatal variables. LBW and SGA were positively associated with Indigenous ethnicity, age <18 years, smoking, alcohol consumption and illegal drug use, pre-eclampsia, underweight prepregnancy body mass index and low socio-economic status. Women with higher parity, pre-existing diabetes and prepregnancy overweight or obesity were more likely to give birth to an infant with HBW or LGA. The prevalence of risk factors for abnormal birthweight is higher among Tasmanian Indigenous mothers, contributing to a gap in birthweight outcomes between Indigenous and non-Indigenous infants. The dramatic increase in prepregnancy obesity and GDM in both groups highlight the importance of screening and management of GDM during pregnancy. Comprehensive programmes co-designed and co-managed in consultation with Indigenous people are needed to support healthy lifestyle choices among Indigenous women to address the barriers to individuals adopting behaviour change and to help close the health outcomes-related gap between Indigenous and non-Indigenous mothers and infants.


Stimulatory effects of pituitary adenylate cyclase-activating polypeptide on inositol phosphates accumulation in avian cerebral cortex and hypothalamus.
This study has demonstrated that the short and long form of the pituitary adenylate cyclase-activating polypeptide (PACAP), i.e. PACAP(27) and PACAP(38), moderately but significantly, and in a concentration (0.5-5 microM)-dependent manner, stimulated inositol phosphates (IPs) accumulation in myo-[(3)H]inositol-prelabeled cerebral cortical and hypothalamal slices of chick and duck, and in slices of rat cerebral cortex; both peptides had no effect on IPs formation in rat hypothalamus. Vasoactive intestinal peptide (VIP; 0.5-5 microM) weakly enhanced IPs accumulation in chick hypothalamus, had no significant action in chick cerebral cortex (in fact there was a tendency to attenuate the IPs response in this tissue), and slightly, but significantly, inhibited the IPs accumulation in rat cerebral cortex. VIP showed no activity in rat hypothalamus. It is concluded that the stimulatory action of PACAP on phosphoinositide metabolism in avian cerebral cortex, similar to rat cerebral cortex, is mediated via phospholipase C-linked PAC(1) type receptors. In chick hypothalamus, however, there may be a component of VPAC type receptors stimulating IPs formation.


Moderating effects of uric acid and sex on cognition and psychiatric symptoms in asymmetric Parkinson's disease.
Non-motor symptoms are an important early feature of Parkinson's disease (PD), encompassing a variety of cognitive and psychiatric symptoms that seem to manifest differently depending on motor symptom asymmetry. Different factors, such as uric acid (UA) and sex, seem to influence cognitive and psychiatric expression in PD, however their interplay remains to be better understood. Participants taking part in the Parkinson's Progression Marker Initiative were studied based on the side of motor symptom asymmetry and sex. Three-way interaction modeling was used to examine the moderating effects of sex and UA on cognitive functions and psychiatric symptoms. Significant three-way interactions were highlighted at 1-year follow-up between motor symptom asymmetry, UA and sex for immediate and long-term memory in female patients exhibiting predominantly left-sided motor symptoms, and for processing speed and sleepiness in female patients exhibiting predominantly right-sided motor symptoms. No significant interactions were observed for male patients. Moreover, female patients exhibiting predominantly right-sided motor symptoms demonstrated lower serum UA concentrations and had overall better outcomes, while male patients with predominantly right-sided motor symptoms demonstrated particularly poor outcomes. These findings suggest that in the earliest stages of the disease, UA and sex moderate cognitive functions and psychiatric symptoms differently depending on motor asymmetry, holding important clinical implications for symptom management in patients.


Effects of GABA on presumed presynaptic Ca2+ entry in hippocampal slices.
Evoked field potentials and changes in [Ca2+]o were measured in the 'in vitro' hippocampal slice of the rat. When [Ca] in the perfusion medium was lowered to 0.2 mM synaptic transmission from Schaffer collateral/commissural fibers was blocked. Nevertheless, repetitive stimulation of afferent fibers still resulted in detectable decreases of [Ca2+]o. In contrast to findings in normal medium these decreases in [Ca2+]o could be larger in stratum radiatum than in stratum pyramidale, so mimicking the spatial distribution of activated afferent fibers. These findings suggest, that the loss of extracellular Ca2+ in low Ca2+ media is predominantly due to entry into presynaptic terminals. This permits to study effects of drugs on presynaptic endings. We found that iontophoretic application of GABA is capable to block this presumed presynaptic Ca2+ entry without affecting the electrical activity of the afferent fibers. This suggests, that presynaptic GABA receptors occur also in the Schaffer collateral/commissural fiber system.


Gender difference exists in sagittal curvature of the distal femoral condyle morphology for osteoarthritic population.
The aim of this study was to investigate gender-related differences in the sagittal curvature of the distal femoral condyle in the Korean osteoarthritic population METHODS: The sagittal curvatures of the distal femoral condyle of 1979 Korean patients (1680 female and 299 male) were evaluated using magnetic resonance imaging (MRI). MRI scans were obtained before total knee arthroplasty (TKA) in consecutive patients with end-stage osteoarthritis. The sagittal curvature of the distal medial and lateral femoral condyles was characterized with respect to the anterior, distal, and posterior circles. The diameter of each circle was measured. This study included 1873 varus and 106 valgus knees. The anterior, distal, and posterior diameters were significantly greater in the male patients than in the female patients (P < 0.05). In the male patients, the lateral diameter was significantly greater than the medial diameter in the anterior and posterior circles (P < 0.05). However, in the female patients, the lateral diameter was significantly greater only in the anterior circle. In both genders, the medial diameter was significantly greater than the lateral diameter of the distal circle (P < 0.05). For both the varus and valgus knees, the lateral diameter was greater than the medial diameter in the anterior circle. It has been concluded that the sagittal curvature of the femoral condyles in females is significantly different to their male counterparts. This study provides a reliable evaluation of the sagittal curvature of the femoral condyle in the Korean population. These gender-related differences in the sagittal curvature of the femoral condyle may require further investigation to determine surgical implications such as in TKA, and the existence of gender-related dimorphism in specific knee injuries and pathologies, such as ligament injuries and tibiofemoral problems. III.


Medical morbidity in binge eating disorder.
To explore the extent to which binge eating disorder (BED) is associated with medical morbidity. We reviewed all existing studies on the effects of BED on physical health. BED may be associated with medical morbidity independent of the effects of comorbid psychopathology or comorbid obesity. Additional research specifically designed to explore the effects of BED on physical health in both clinical and community samples is required before definitive conclusions can be drawn.


Cardiac malformations in trisomy-18: a study of 41 postmortem cases.
The cardiac malformations in 41 karyotyped and autopsy cases of trisomy-18 are presented in detail. The salient findings were a ventricular septal defect in all cases; tricuspid valve anomalies in 33 cases (80%); pulmonary valve anomalies in 30 (70%); aortic valve malformations in 28 (68%); mitral valve anomalies in 27 (66%); polyvalvular disease (that is, malformations of more than one valve) in 38 (93%); a subpulmonary infundibulum (conus) in 40 (98%); a bilateral conus with a short subaortic infundibulum in 1 case with double outlet right ventricle (this being the only documented case of bilateral infundibulum in trisomy-18); double outlet right ventricle in 4 cases (10%), three having a subpulmonary infundibulum only and all 4 having mitral atresia; tetralogy of Fallot in 6 cases (15%), 2 having pulmonary atresia; and a striking absence of transposition of the great arteries and inversion at any level (visceral or cardiac), findings that appear to be characteristic of all trisomies. These data suggest that excessive chromosomal material (as in trisomies) may result in situs solitus at all levels. The malformations of the atrioventricular and semilunar valves were characterized by redundant or thick myxomatous leaflets, long chordae tendineae and hypoplastic or absent papillary muscles. The ventricular septal defect was associated with anterosuperior conal septal malalignment in 25 cases (61%). On the basis of the characteristic valvular lesions, the type of ventricular septal defect and the absence of transposition or inversions, two-dimensional echocardiographic diagnosis of trisomy-18 in the fetus may become possible.


Monoclonal antibodies against human abnormal (des-gamma-carboxy)prothrombin specific for the calcium-free conformer of prothrombin.
A monoclonal antibody JO1 X 1 was prepared against human abnormal prothrombin using the hybridoma technique. The clone secreting this antibody was selected on the basis of the ability of this antibody to bind to abnormal prothrombin, but not to prothrombin, in the presence of calcium ions. The antibodies were purified by affinity chromatography in EDTA on columns of prothrombin-Sepharose. Bound antibodies were eluted with 15 mM CaCl2. The kinetics of dissociation of antibody from the antibody-prothrombin complex with the addition of calcium ions fit a first-order kinetic model. Increasing CaCl2 concentration increased the rate of antibody-prothrombin dissociation. Ca(II) and Mn(II) inhibited antibody-prothrombin interaction; half-maximal binding was observed at 0.9 and 4 mM, respectively. Mg(II) had little effect on antibody-antigen interaction. The JO1 X 1 antibody bound fragment 1, fragment (1-39), abnormal prothrombin, and prothrombin equivalently in the presence of EDTA, but did not bind to des(1-44)prothrombin in the presence of EDTA or prothrombin in the presence of CaCl2. These results indicate that the monoclonal antibody JO1 X 1 is conformation specific for the calcium-free conformer of prothrombin and directed against an antigenic determinant near the NH2 terminus of prothrombin expressed in the 1-39 region of the protein. This analysis provides confirmation of the presence of a metal-free conformer of prothrombin.


Nurses' and Doctors' Experiences of Transferring Adolescents or Young Adults With Long-Term Health Conditions From Pediatric to Adult Care: A Metasynthesis.
The transfer of adolescents and young adults (AYA) with long-term health conditions from pediatric to adult care is a multidisciplinary enterprise where nurses and doctors play an important role. This review aimed to identify and synthesize evidence from qualitative primary reports on how nurses and doctors experience the transfer of AYA aged 13 to 24 years with long-term health conditions to an adult hospital setting. We systematically searched seven electronic databases for reports published between January 2005 and November 2021 and reporting nurses' and doctors' experiences. We meta-summarized data from 13 reports derived from 11 studies published worldwide. Using qualitative content analysis, we metasynthesized nurses' and doctors' experiences into the theme "being boosters." Boosting AYA's transfer was characterized by supporting AYA's and their parents' changing roles, smoothening AYA's transition from pediatric to adult care, and handling AYA's encounters with a different care culture.


Ontogeny of the induction of tyrosine hydroxylase by reserpine in the superior cervical ganglion, nucleus locus coeruleus and adrenal gland.
The ontogeny of the induction of tyrosine hydroxylase by reserpine has been studied in the superior cervical ganglion, adrenal gland and nucleus locus coeruleus of the rat. The inductive response developed gradually over a period of days in all 3 areas. However, the onset of induction occurred at markedly different times in these regions, being present from day 2 of life, the earilest time tested, in the adrenal, day 6 in the locus coeruleus and day 24 in the ganglion. In the ganglion even extremely high, toxic doses of reserpine failed to induce the enzyme during the first 3 weeks of life. Decentralization studies indicated that the ganglion was functionally innervated at this time. Moreover, the onset of induction was not time-locked to a specific phase of the postnatal development of tyrosine hydroxylase activity in the areas examined. It is probable that the development of inducibility reflects maturation of mechanisms intrinsic to the adrenergic cell, and this timetable is different for cells in different areas.


Motion integration across differing image features.
To interpret the projected image of a moving object, the visual system must integrate motion signals across different image regions. Traditionally, researchers have examined this process by focusing on the integration of equally ambiguous motion signals. However, when the motions of complex, multi-featured images are measured through spatially limited receptive fields, the resulting motion measurements have varying degrees of ambiguity. In a series of experiments, we examine how human observers interpret images containing motion signals of differing degrees of ambiguity. Subjects judged the perceived coherence of images consisting of an ambiguously translating grating and an unambiguously translating random dot pattern. Perceived coherence of the dotted grating depended upon the degree of concurrence between the velocities of the grating terminators and dots. Depth relationships also played a critical role in the motion integration process. When terminators were suppressed with occlusion cues, coherence increased. When dots and gratings were presented at different depth planes, coherence decreased. We use these results to outline the conditions under which the visual system uses unambiguous motion signals to interpret object motion.


YOYO as a dye to track penetration of LK15 DNA complexes in spheroids: use and limits.
To elucidate the reasons underlying the poor penetration of non-viral vectors in tissues, relating transport properties to physico-chemical parameters of vectors may be crucial. These properties can be influenced by the presence of multiples labels that are used. Therefore utilizing a vector with minimum of labels preferably not more than one is important to studying penetration in tissues. The cell impermeant bisintercalating dye YOYO-1 was found suitable to both monitor the formation of complexes between DNA and an amphipathic peptide LK15 and, to track their penetration in HCT116 spheroids by confocal microscopy. The results revealed a limited decrease of fluorescence ascribed to the high affinity of YOYO-1 to bind DNA. The residual fluorescence of complexes can be exploited to monitor penetration into spheroids, after correction for YOYO-1 attenuation, and to revealing hyaluronidase-induced reduced binding. Hence high affinity dyes such as YOYO-1 with inefficiently quenched fluorescence may be important to establish a relation between novel medicines characteristics and penetration in tissues.


Early childhood suspected developmental delay in 63 low- and middle-income countries: Large within- and between-country inequalities documented using national health surveys.
2Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil. The Sustainable Development Goals call for inclusive, equitable and quality learning opportunities for all. This is especially important for children, to ensure they all develop to their full potential. We studied the prevalence and inequalities of suspected delay in child development in 63 low- and middle-income countries. We used the early child development module from national health surveys, which covers four developmental domains (physical, social-emotional, learning, literacy-numeracy) and provides a combined indicator (early child development index, ECDI) of whether children are on track. We calculated the age-adjusted prevalence of suspected delay at the country level and stratifying by wealth, urban/rural residence, sex of the child and maternal education. We also calculated measures of absolute and relative inequality. We studied 330 613 children from 63 countries. Prevalence of suspected delay for the ECDI ranged from 3% in Barbados to 67% in Chad. For all countries together, 25% of the children were suspected of developmental delay. At regional level, prevalence of delay ranged from 10% in Europe and Central Asia to 42% in West and Central Africa. The literacy-numeracy domain was by far the most challenging, with the highest proportions of delay. We observed very large inequalities, and most markedly for the literacy-numeracy domain. To date, our study presents the most comprehensive analysis of child development using an instrument especially developed for national health surveys. With a quarter of the children globally suspected of developmental delay, we face an immense challenge. The multifactorial aspect of early child development and the large gaps we found only add to the challenge of not leaving these children behind.


A group-specific sequencing approach to investigate the presence of atypical human leucocyte antigen alleles.
Accurate human leucocyte antigen (HLA) typing results are essential in determining the degree of compatibility between donor and recipient in both solid organ (SO) and hematopoietic stem cell (HSC) transplantation. Current HLA typing methodologies can generate ambiguous results which may need resolving. This group-specific sequencing approach allowed investigation into the presence of the low expressor HLA-A*24:02:01:02L allele and the rare HLA-A*02:64 allele in a SO transplant recipient and a HSC transplant recipient, respectively. Locus-specific amplification of HLA-A was performed. Exons 2 and 3 were sequenced in both directions followed by group-specific sequencing to resolve ambiguities. Hemizygous sequence data of intron 2 generated from the HLA-A*24 allele indicated the presence of the HLA-A*24:02:01:01 allele. HLA-A*02:64 was identified by sequencing the allele in isolation over exons 2 and 3 and allowed confirmation of this allele sequence with the IMGT/HLA database (Accession number AY297166). This approach is cost efficient and can be modified to sequence alleles at other HLA loci. It has also been adapted to characterize the novel HLA-DQB1*06:48 allele (Accession number HE647646) as well as the non-HLA gene, UGT2B17, making it a useful tool to augment existing typing methodologies.


High-cholesterol diet-induced lipoproteins stimulate lipoprotein lipase secretion in cultured rat alveolar macrophages.
We have previously shown that cultured rat alveolar macrophages synthesize and secrete lipoprotein lipase into the medium. The purpose of the present experiments is to examine whether cholesterol-enriched lipoproteins from cholesterol-fed animals have any effects on the lipoprotein lipase secretion and the lipid accumulation in macrophages. Macrophages incubated with the VLDL obtained from rats fed a normal diet secreted 2-fold higher amounts of lipoprotein lipase than those without lipoproteins. Intermediate-, low- and very-low-density lipoproteins from rats fed a high-cholesterol diet also enhanced the lipoprotein lipase secretion. Normal high- and low-density lipoproteins, and high-density lipoproteins from hypercholesterolemic animals did not cause any increase in the lipoprotein lipase secretion. The lipoproteins which stimulated the lipoprotein lipase secretion caused intracellular accumulation of both triacylglycerol and cholesterol. It is speculated that macrophages residing in the environment rich in lipoproteins, especially hypercholesterolemic lipoproteins, take them up and accumulate lipids intracellularly, and that this process links with the lipoprotein lipase secretion. The secreted lipoprotein lipase could facilitate, by degrading lipoproteins, the uptake of lipoprotein lipase-modified lipoproteins. Probably such a series of events is of importance in the foam cell formation of macrophages.


The Psychotherapy Research Project of the Menninger Foundation: an overview.
Studied processes and outcomes of psychoanalysis and psychoanalytic psychotherapy, both expressive and supportive. 42 Ss were followed via initial, termination, and follow-up studies over the entire natural course of treatment, with 100% follow-up 2-3 years posttermination. Some follow-ups extended over the 30-year life span of the study. Detailed case histories and life histories were obtained from all 42 Ss. Psychoanalyses achieved more limited outcomes than predicted; psychotherapies often achieved more than predicted. Supportive mechanisms infiltrated all therapies, psychoanalyses included, and accounted for more of the achieved outcomes (including structural changes) than anticipated. An expanded new categorization of supportive therapeutic mechanisms is proposed, along with an elaboration of expressive therapeutic mechanisms.


Decreased serum testosterone levels in long-term adult survivors with fatty liver after childhood stem cell transplantation.
Fatty liver and male gonadal dysfunction are potential late effects of therapy in adult survivors treated with stem cell transplantation (SCT) in childhood. Obesity and metabolic syndrome also are associated with low serum testosterone levels in the general population. However, the relationship between the degree of fatty liver and changes in serum testosterone levels in adult survivors has not been fully studied. We reviewed the clinical records of 34 male patients who received allogeneic SCT in childhood or adolescence. The median age at SCT was 10.0 years, and the median follow-up after SCT was 15.9 years. All but one patient showed no tendency toward overweight/obesity during the follow-up period. Fatty liver was diagnosed by ultrasound in 15 patients at 4 to 20 years after SCT. Patients who received cranial radiation therapy before SCT were more likely to develop fatty liver and insulin resistance. Moreover, fatty liver was statistically associated with decreased serum testosterone levels, whereas nonfatty liver was not (median, 527 ng/dL [range, 168-944 ng/dL] versus 302 ng/dL [165-698 ng/dL]; P < .0001). Changes in testosterone levels after SCT are affected not only by primary gonadal dysfunction but also by subsequent development or exacerbation of fatty liver.


Synergistic anti-inflammatory activity of apigenin and curcumin co-encapsulated in caseins assessed with lipopolysaccharide-stimulated RAW 264.7 macrophages.
Dietary polyphenols are potential anti-inflammatory agents, and their combinations with enhanced biological activities may lower toxicity and side effects. The objective of this work was to investigate the potential synergistic anti-inflammatory activities of apigenin and curcumin co-nanoencapsulated in sodium caseinate, with comparison to unencapsulated polyphenol combinations. Non-toxic concentrations of apigenin, curcumin, and their combinations in the free and co-encapsulated forms were studied in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Combinations of free polyphenols produced stronger inhibition of nitric oxide (NO) production, more significant at a higher proportion of curcumin, which was further enhanced after co-encapsulation. The enhanced reduction of NO was concomitant with the decreased expression of iNOS, the enhanced inhibition of pro-inflammatory cytokines of IL-6 and TNF-α, and the reduced production of intracellular reactive oxygen species. The potential multi-target effects and the enhanced solubility, proximity, and bioavailability of AP and CUR after co-encapsulation contributed to the synergistic activities. These results demonstrated that co-nanoencapsulation of apigenin and curcumin may enable the practical application utilizing the synergistic anti-inflammation effects to improve health.


Myeloid-derived suppressor cells deficient in cholesterol biosynthesis promote tumor immune evasion.
Cancer immunotherapy targeting myeloid-derived suppressor cells (MDSCs) is one of the most promising anticancer strategies. Metabolic reprogramming is vital for MDSC activation, however, the regulatory mechanisms of cholesterol metabolic reprogramming in MDSCs remains largely unexplored. Using the receptor-interacting protein kinase 3 (RIPK3)-deficient MDSC model, a previously established tumor-infiltrating MDSC-like model, we found that the cholesterol accumulation was significantly decreased in these cells. Moreover, the phosphorylated AKT-mTORC1 signaling was reduced, and downstream SREBP2-HMGCR-mediated cholesterol synthesis was blunted. Interestingly, cholesterol deficiency profoundly elevated the immunosuppressive activity of MDSCs. Mechanistically, cholesterol elimination induced nuclear accumulation of LXRβ, thereby promoting LXRβ-RXRα heterodimer binding of a novel composite element in the promoter of Arg1. Furthermore, itraconazole enhanced the immunosuppressive activity of MDSCs to boost tumor growth by suppressing the RIPK3-AKT-mTORC1 pathway and impeding cholesterol synthesis. Our findings demonstrate that RIPK3 deficiency leads to cholesterol abrogation in MDSCs, which facilitates tumor-infiltrating MDSC activation, and highlight the therapeutic potential of targeting cholesterol synthesis to overcome tumor immune evasion.


Breath alcohol analysis in the Accident and Emergency Department.
Breath alcohol analysis was undertaken in 1044 consecutive patients aged over 15 years attending the Accident and Emergency (A and E) Department of a rural district general hospital during a 50-day period. 16.5 per cent of all patients had the smell of alcohol on their breath, with 10.2 per cent of the patients recording a breath alcohol level equivalent to a blood level of 80 mg/100 ml or more. One-third of all patients attending between 9 pm and midnight, and almost two-thirds of patients attending between midnight and 3 am had positive breath tests. Positive breath tests were most likely in males, patients with head injuries, with overdoses, in victims of assault and in patients with a depressed conscious level, irrespective of cause. Clinical estimation of intoxication by alcohol may be accurate in the co-operative patient, but in the patient with a head injury or with a depressed conscious level from another cause, this is more difficult. Breath alcohol analysis is rapid, not-invasive, accurate and of clinical value in these and other high-risk patients attending hospital as emergencies.


Functional assessment of jailed side branches in coronary bifurcation lesions using fractional flow reserve.
This study was designed to assess the functional significance of side branches after stent implantation in main vessels using fractional flow reserve (FFR). Little is known about the functional significance of side branches after stent implantation in main vessels in coronary bifurcation lesions. Between May 2007 and January 2011, 230 side branches in 230 patients after stent implantation in main vessels were assessed by FFR and were consecutively enrolled. Median FFR at the side branch was 0.91 (interquartile range: 0.85 to 0.95). There was a negative correlation between the diameter stenosis (DS) by quantitative coronary angiography (QCA) and FFR of side branch (r=-0.21, p=0.002), but only 41 (17.8%) side branches were functionally significant after stent implantation in the main vessel. Among 67 side branches with >50% DS by QCA, 19 (28.4%) had FFR≤0.80, and among 163 side branches with ≤50% DS by QCA, 22 (13.5%) had FFR≤0.80 after stent implantation in main vessels. On the basis of receiver-operating characteristic curves, the optimal cutoff value of DS by QCA of the side branch was 54.9%, and the area under the curve was 0.64 (95% confidence interval [CI]: 0.58 to 0.71, p<0.001) with a 41.5% sensitivity, an 83.1% specificity, a 34.7% positive predictive value, an 86.3% negative predictive value, and a 75.7% accuracy. Multivariate binary logistic regression analysis identified DS by QCA (odds ratio [OR]: 1.04, 95% CI: 1.02 to 1.06, p=0.001) and reference vessel diameter (OR: 0.28, 95% CI: 0.10 to 0.77, p=0.014) before stent implantation as independent predictors of the side branches with FFR≤0.80 after stent implantation. Most side branch lesions do not have functional significance after stent implantation in the main vessel, and quantitative coronary angiography is unreliable in assessing the functional severity of these lesions.


Alkane production from biomass: chemo-, bio- and integrated catalytic approaches.
Linear, branched and cyclic alkanes are important intermediates and end products of the chemical industry and are nowadays mainly obtained from fossil resources. In search for alternatives, biomass feedstocks are often presented as a renewable carbon source for the production of fuels, chemicals and materials. However, providing a complete market for all these applications seems unrealistic due to both financial and logistic issues. Despite the very large scale of current alkane-based fuel applications, biomass definitely has the potential to offer a partial solution to the fuel business. For the smaller market of chemicals and materials, a transition to biomass as main carbon source is more realistic and even probably unavoidable in the long term. The appropriate use and further development of integrated chemo- and biotechnological (catalytic) process strategies will be crucial to successfully accomplish this petro-to-bio feedstock transition. Furthermore, a selection of the most promising technologies from the available chemo- and biocatalytic tool box is presented. New opportunities will certainly arise when multidisciplinary approaches are further explored in the future. In an attempt to select the most appropriate biomass sources for each specific alkane-based application, a diagram inspired by van Krevelen is applied, taking into account both the C-number and the relative functionality of the product molecules.


SB-restricted presentation of influenza and herpes simplex virus antigens to human T-lymphocyte clones.
The HLA-D region of the human major histocompatibility complex (MHC) has been shown to be homologous to the murine I region in terms of both structure and function. Both regions encode class II MHC molecules which restrict T-lymphocyte interactions with antigen-presenting cells. We have recently described the MHC restriction and antigen specificities of human T-lymphocyte clones directed at strain A influenza virus. The majority of T-lymphocyte clones recognized antigen in the context of cell surface interaction products encoded by HLA-D/DR genes. However, a few clones recognized antigen presented by cells histoincompatible for D/DR antigens. We report here that some of these clones recognized viral antigens in association with antigens encoded by genes identical with or closely linked to the recently described secondary B-cell (SB) locus of the MHC. This is the first report that SB-restricted antigen recognition may form an integral part of normal, human immune responses.


Chemically modified fullerene derivatives as photosensitizers in photodynamic therapy: a first-principles study.
The first-principles density functional theory (DFT) and its time-dependent approach (TD-DFT) are used to characterize the electronic structures and optical spectra properties of five chemically modified fullerenes. It is revealed that the metal fullerene derivatives possess not only stronger absorption bands in visible light regions than organically modified fullerene but also the large energy gaps (ΔE(S-T) > 0.98 eV) between the singlet ground state and the triplet state, which imply their significant aspect of potential candidates as a photosensitizer. We have found that a new metal-containing bisfullerene complexes (Pt(C(60) )(2) ), with the extended conjugated π-electrons, much degenerate orbitals and a uniform electrostatic potential surface, behave more pre-eminent photosensitizing properties than other examined fullerene derivatives.


Pancreatic secretory factor (PSF), a protein from Gila monster venom stimulating enzyme secretion from rat pancreatic acini.
Pancreatic secretory factor (PSF), a 17.5-kDa protein purified from the venom of Gila monster (Heloderma suspectum), stimulated amylase secretion from dispersed rat pancreatic acini more efficiently than CCK-8, bombesin, carbachol and secretin, and without increasing 45Ca2+ efflux and cyclic AMP levels. The secretory action was dependent on the presence of extracellular calcium and was additive to the secretion induced by agents acting via cyclic AMP or via Ca2+ efflux.


Effects of CFTR modulators on pharmacokinetics of tobramycin during acute pulmonary exacerbations in the pediatric cystic fibrosis population.
Individuals with cystic fibrosis (CF) require higher dosages of aminoglycosides due to an increased volume of distribution (Vd ) and clearance. Optimal dosing of aminoglycosides in the CF population is essential as repeated exposure to aminoglycosides during acute pulmonary exacerbations increases risk of nephrotoxicity and ototoxicity. To date, no studies have evaluated whether chronic cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy affects pharmacokinetics of aminoglycoside antibiotics in patients with CF. The objective of this study was to determine if the addition of a CFTR modulator affects elimination rate (Ke ) for intravenously administered tobramycin in the pediatric CF population. This retrospective study included patients aged 2 to 18 years with CF receiving chronic therapy with a CFTR modulator. Patients included had an admission both pre- and post-chronic CFTR modulator therapy during which they received therapy with IV tobramycin. Thirty-four patients were included in the study. The median time between pre- and post-modulator admissions was 16.5 (13.8) months. Duration of CFTR modulator therapy before post-modulator admission was a median of 8 (10.3) months. There was no significant difference in Ke (hr-1 ) between pre- and post-modulator therapy, 0.41 (0.21) pre and 0.39 (0.09) post (P = .5). Vd and peak concentration were similar between both groups. There was no difference in nephrotoxicity as defined by the pRIFLE criteria (P = .25). The pharmacokinetic parameters of intravenously administered tobramycin during admission for acute pulmonary exacerbation do not appear to change significantly after initiating chronic therapy with a CFTR modulator. Empiric dose adjustments for patients on CFTR modulators are not recommended.


Conducting research as a visiting scientist in a women's prison.
Incarcerated populations have disparities in health risks and illness conditions meriting study, but the history of prison research is marred by unethical conduct. Ethical participation strategies are discussed in the context of studies implemented by the author in a state prison system. This study used ethnographic approaches, observed adherence to federal and institutional review board regulations and corrections department directives, and maintained continuous communication with vested interests to provide entry and long-term access for studies on female prisoners and their civilian infants. A culture clash between the punitive restrictive environment that serves the custody-control-care mission of corrections systems and the open inquiry environment needed for conduct of health research exists. Federal regulations protect prisoners as human subjects but additional vigilance and communication by researchers are required. Gaining and maintaining access to prison inmates for nursing research are leadership challenges that can be met within the caring and collaborative paradigm of nursing.


Abdominal visceral and subcutaneous fat increase, insulin resistance and hyperlipidemia in testicular cancer patients treated with cisplatin-based chemotherapy.
Testicular cancer survivors treated with chemotherapy are at increased risk for metabolic syndrome (MetS) and cardiovascular disease (CVD). We explored acute effects of chemotherapy by assessing metabolic factors, abdominal fat volume, hepatic triglyceride content (HTC) and aortic wall stiffness. We studied 19 testicular cancer patients (age 20-54 years) before, at three and nine months after the start of chemotherapy. Blood serum was analyzed for lipids, glucose and insulin. Abdominal visceral and subcutaneous fat volume and aortic pulse wave velocity were assessed by magnetic resonance imaging (MRI) techniques; HTC was measured by proton MR spectroscopy. Three months after start of chemotherapy visceral abdominal fat volume had significantly increased from 202 ± 141 to 237 ± 153 ml (p = 0.009) whereas body mass index and subcutaneous fat volume significantly increased nine months after treatment from 24.4 ± 4.0 to 26.4 ± 4.1 kg/m(2) (p = 0.01) and from 556 ± 394 to 668 ± 460 ml (p = 0.002) respectively. Serum total cholesterol, low-density lipoprotein cholesterol and insulin also significantly increased three months after start of treatment from 4.88 ± 1.1 to 5.61 ± 1.50 mmol/l (p = 0.002), 3.31 ± 1.16 to 3.73 ± 1.41 mmol/l (p = 0.02) and 5.7 ± 4.4 to 9.6 ± 6.3 mU/ml (p = 0.03), respectively. Nine months after start of chemotherapy serum lipid and insulin concentrations had returned to baseline. HTC increased in seven of the 19 patients (36.8%) during follow-up. Aortic pulse wave velocity remained unchanged at the three time points measured. Cisplatin-based chemotherapy was associated with acute insulin resistance, dyslipidemia and an immediate increase in abdominal visceral adipose tissue and abdominal subcutaneous adipose tissue in testicular cancer patients. A large prospective cohort study with long follow-up is warranted to characterize the time course and relationship between acutely induced obesity and hypercholesterolemia and the development of metabolic syndrome and CVD years later in individual testicular cancer survivors.


The Relationships between Metabolic Disorders (Hypertension, Dyslipidemia, and Impaired Glucose Tolerance) and Computed Tomography-Based Indices of Hepatic Steatosis or Visceral Fat Accumulation in Middle-Aged Japanese Men.
Most studies on the relationships between metabolic disorders (hypertension, dyslipidemia, and impaired glucose tolerance) and hepatic steatosis (HS) or visceral fat accumulation (VFA) have been cross-sectional, and thus, these relationships remain unclear. We conducted a retrospective cohort study to clarify the relationships between components of metabolic disorders and HS/VFA. The participants were 615 middle-aged men who were free from serious liver disorders, diabetes, and HS/VFA and underwent multiple general health check-ups at our institution between 2009 and 2013. The data from the initial and final check-ups were used. HS and VFA were assessed by computed tomography. HS was defined as a liver to spleen attenuation ratio of ≤1.0. VFA was defined as a visceral fat cross-sectional area of ≥100 cm2 at the level of the navel. Metabolic disorders were defined using Japan's metabolic syndrome diagnostic criteria. The participants were divided into four groups based on the presence (+) or absence (-) of HS/VFA. The onset rates of each metabolic disorder were compared among the four groups. Among the participants, 521, 55, 24, and 15 were classified as HS(-)/VFA(-), HS(-)/VFA(+), HS(+)/VFA(-), and HS(+)/VFA(+), respectively, at the end of the study. Impaired glucose tolerance was more common among the participants that exhibited HS or VFA (p = 0.05). On the other hand, dyslipidemia was more common among the participants that displayed VFA (p = 0.01). It is likely that VFA is associated with impaired glucose tolerance and dyslipidemia, while HS might be associated with impaired glucose tolerance. Unfortunately, our study failed to detect associations between HS/VFA and metabolic disorders due to the low number of subjects that exhibited fat accumulation. Although our observational study had major limitations, we consider that it obtained some interesting results. HS and VFA might affect different metabolic disorders. Further large-scale longitudinal studies are needed to reveal the relationships between the components of metabolic disorders and HS/VFA.


Users' evaluation of Japan's cancer information services: process, outcomes, satisfaction and independence.
Cancer information service (CIS) programmes are becoming increasingly important because patients need to obtain appropriate information and take an active role in their treatment decisions. Programme evaluation is required to determine the level of satisfaction and quality of experiences of users. The purpose of this study is (1) to identify users' evaluation of CIS programmes by both satisfaction and outcomes that reflect the quality of experience and impact of using the CIS, (2) to examine the related factors of these evaluation outcomes and (3) to analyse the differences of those relations between patients and families. The self-reported questionnaire was answered by 447 patients and 216 families of patients who used Cancer Information Support Centres (CISCs) at 16 designated cancer hospitals from January 2016 to April 2016. We developed 12 evaluation items, including satisfaction, experience and the impact of using CISC. Respondents evaluated the CISC highly, especially in terms of overall satisfaction, followed by the counselling process. Immediate access to CISC was the strongest factor affecting outcomes. Patients who wanted to consult about 'disease or symptoms' or 'had no specific problem' tended to provide high scores for some outcomes, but those who wanted to consult about a 'financial problem' or 'discharge or care at home' provided negative scores. These trends were also observed in families but to a more limited extent. Users' evaluation of CISCs was sufficiently high in terms of overall satisfaction, showing reasonable scores in outcome levels. Immediate access was the strongest factor affecting outcomes and topics of consultation more directly affected evaluation by patients than by families. The distribution of the scores of the measures and related factors was reasonable. The 12-item measurement tool employed in this study seems to be useful for quality monitoring of the CIS.


Superoxide anion release from blood monocytes and alveolar macrophages in patients with diffuse lung fibrosis.
Superoxide anion release (O2-) after stimulation with phorbol myristate acetate was measured in alveolar macrophages (AM) obtained by bronchoalveolar lavage and in blood monocytes from 47 patients with diffuse interstitial lung disease: idiopathic pulmonary fibrosis (N = 15), hypersensitivity pneumonitis (N = 7), pneumoconiosis (N = 6) and sarcoidosis (N = 19). Differential cell counts demonstrated a lymphocyte predominance in patients with hypersensitivity pneumonitis (HP) and sarcoidosis while the other groups had neutrophil predominance. No correlation between O2- activity in alveolar macrophages (AM) or blood monocytes (BM) compared to lung function (VC and diffusing capacity) could be demonstrated. Smoking pneumoconiotics had significantly decreased BM O2- release (1.25 +/- 0.25 (SEM) nmol/min/10(6) cells) and significantly increased AM/BM O2- ratios (2.04 +/- 0.26) compared to smokers with idiopathic pulmonary fibrosis (IPF) who had the following mean values: BM O2- release = 2.58 +/- 0.25 and AM/BM O2- ratio = 0.86 +/- 0.23. When matched for sex and smoking, a significantly increased AM/BM O2- ratio was seen among patients with HP (2.19 +/- 0.98) in comparison with patients who had sarcoidosis (0.40 +/- 0.18). Patients with either HP or pneumoconiosis had generally elevated AM O2- release and reduced BM O2- release. These results suggest that environmentally related interstitial lung disorders (HP and pneumoconiosis) may be associated with elevated AM O2- release relative to BM O2- release in comparison to non-environmentally related disorders (IPF or sarcoidosis).


HI-TENS reduces moderate-to-severe pain associated with most wound care procedures: a pilot study.
This study systematically examined pain associated with wound care procedures (WCPs) and evaluated the effectiveness of high-intensity transcutaneous electrical nerve stimulation (HI-TENS) for reducing this pain in a two-phase design. Phase 1 (N = 57) examined patient, wound, and procedural factors, as well as analgesic intake, associated with WCPs. Pain during the WCPs was rated on a 0-10 numerical scale. Subjects reported a mean pain of 6.0 (standard deviation 3.04) during Phase 1, with 43 (75.4%) subjects experiencing moderate or severe pain (i.e., ≥4). Subjects who received opioid and/or nonopioid analgesia 1 hr before or during the WCPs (36.8%) reported significantly higher pain levels than those who had not received analgesia (p = .013). In Phase 2, 23 subjects with ≥4 pain during Phase 1 had HI-TENS applied to the area surrounding the wound during the WCPs. HI-TENS significantly reduced WCP pain by a mean of 2.0 (±2.31; effect size = 0.67; p = .001). This effect was significant for subjects with severe Phase 1 pain (i.e., ≥8; effect size = 1.00; p = .007) but not for subjects with moderate Phase 1 pain (i.e., 4-7; effect size = 0.40; p = .053). These findings demonstrate that pain during WCPs is a significant problem, that nurses appropriately administer analgesics but these are not sufficient, and that using HI-TENS may further reduce pain, particularly in patients experiencing severe WCP pain.


Predictors and prognostic impact of new left bundle branch block after surgical aortic valve replacement.
Left bundle branch block (LBBB) induces mechanical dyssynchrony that may lead to left ventricular systolic dysfunction. To evaluate the incidence, predictors and clinical impact of new LBBB in patients undergoing surgical aortic valve replacement (SAVR). After exclusion of patients with pre-existing LBBB, a previous pacemaker or a paced rhythm at hospital discharge, 547 consecutive patients undergoing SAVR were included. All-cause death, cardiovascular death and the combined outcome of all-cause death or a first heart failure event were assessed at 3months and 1year. Patients with and without new LBBB were compared. New LBBB occurred in 4.6% of patients after SAVR (compared with 16.4% of patients treated by transcatheter aortic valve implantation during the study period). Previous valve surgery and an immediate postoperative paced rhythm were independent predictors of new LBBB. At 1-year follow-up, there were no significant differences in all-cause death, cardiovascular death, or the combined outcome of all-cause death or a first heart failure event between patients with and without new LBBB. However, new LBBB was associated with a trend towards functional deterioration and more heart failure events at 1year. At 1-year follow-up, new LBBB did not have a significant impact on clinical outcome, but was associated with worse functional status and more heart failure events.


Experimental candidiasis in the hamster cheek pouch.
Sixty-four adult male BIO 87.20 hamsters were divided into four equal groups. Animals in three groups had 1 ml of a thick aqueous suspension of either Candida albicans (ATCC 10261), Candida albicans (UO1) or Candida tropicalis (3100, Puna Culture Collection) placed in each of their cheek pouches. The fourth group were controls. Four animals from each group were killed 1, 2, 4 and 6 weeks following treatment. Specimens were removed from all left-cheek pouches and processed routinely for light microscopy. All animals treated with strain UO1 and 35 per cent of animals treated with either 10261 or 3100 strains exhibited changes. At 1 week, the epithelium had localized areas of neutrophilic leukocyte infiltration and some small discrete micro-abscesses. At 2 weeks, most micro-abscesses were larger. At 4 weeks, most micro-abscesses involved the more superficial epithelial layers. At 6 weeks, there were only a few superficial micro-abscesses. At 4 and 6 weeks, there were areas of thickened, often parakeratinized, stratum corneum. The connective tissue adjacent to the inflamed epithelium was infiltrated by varying numbers and types of chronic inflammatory cell. Hyphal invasion of the epithelium was not found. Thus the hamster cheek pouch is a suitable site for the study of experimental candidiasis. The occurrence of both an acute and chronic inflammatory response does not support the suggestion that the pouch is an immunologically-privileged site.


Applications of comprehensive two-dimensional gas chromatography to the characterization of petrochemical and related samples.
This article discusses the application of comprehensive two-dimensional gas chromatography (GC x GC) to samples derived from petrochemicals. The use of GC x GC for characterization of petroleum and petroleum derivatives, through group type analysis, such as benzene, toluene, ethylbenzene, xylenes (BTEX), total aromatic hydrocarbons, polyaromatic hydrocarbons, and heteroatomic sulfur-, oxygen-, and nitrogen-containing compounds is presented. The capability of GC x GC to provide additional chemical-specific information regarding petroleum-processing steps, such as linear alkanes dehydrogenation, Fischer-Tropsch process, hydrogenation and oligomerization, is also described. In addition, GC x GC analyses of petrochemical biomarkers and environmental petrochemical-derived pollutants are reported. The role of comparison of samples through use of simple fingerprint approaches is highlighted.


Trends in Human Papillomavirus Vaccination in Commercially Insured Children in the United States.
The human papillomavirus (HPV) vaccine was recommended in 2006 for girls and in 2011 for boys. The Healthy People 2020 goal for 2-dose HPV vaccination coverage is 80% by age 15 for girls and boys. We used nationwide population-based data to describe trends in HPV vaccination in children. We conducted a cohort study nested within the MarketScan health care database between January 2003 and December 2017. Children were followed from the year they turned 9 until HPV vaccination, insurance disenrollment, or the end of the year when they turned 17, whichever came first. We estimated the cumulative incidence of at least 1- and 2-dose HPV vaccination, stratified by birth year, sex, and state. In secondary analyses, we evaluated the association between state-level vaccination policies and HPV vaccination coverage. This study included 7 837 480 children and 19.8 million person-years. The proportion of 15-year-old girls and boys with at least a 1-dose HPV vaccination increased from 38% and 5% in 2011 to 57% and 51% in 2017, respectively; the proportion with at least a 2-dose vaccination went from 30% and 2% in 2011 to 46% and 39% in 2017, respectively. By 2017, 2-dose HPV vaccination coverage varied from 80% in Washington, District of Columbia, among girls to 15% in Mississippi among boys and was positively correlated with legislation for HPV vaccine education and pediatrician availability. Despite the increasing trends in uptake, HPV vaccine coverage among commercially insured children in the United States remains behind target levels, with substantial disparities by state.


A 6-year Longitudinal Study of Self-harm and Suicidal Behaviors among Chinese Adolescents in Hong Kong.
To examine the trajectories of self-harm and suicidal behaviors among Chinese adolescents in Hong Kong and to investigate the related predictors, including gender, family nonintactness, economic disadvantage, positive youth development, and family functioning. We used quantitative data from a large sample of adolescent participants. Participants initially joined this study when they were in grade 7 (wave 1), and they were followed from grade 8 (wave 2) to grade 12 (wave 6). The participants consisted of 2023 grade 12 students from 28 secondary schools in Hong Kong. A multistage cluster random sampling method was adopted. Self-harm and suicidal behaviors. The trajectories of self-harm and suicidal behaviors in general declined from grade 7 to grade 12. Regarding the effect of gender, whereas adolescent girls showed a higher prevalence for self-harm and suicidal behaviors at baseline and other waves, adolescent boys showed a pronounced decline in self-harm rates. Adolescents from nonintact families were more likely to self-harm or engage in suicidal behaviors at wave 6. Economic disadvantage at wave 4 predicted higher suicidal behavior among adolescents but not self-harm at wave 6. Regarding positive youth development, several protective factors that include cognitive-behavioral competencies, prosocial attributes, general positive youth development qualities, and positive identity could help reduce self-harm and suicidal behaviors at different time points. Regarding the role of family functioning, more family conflicts predicted higher suicidality in adolescence (self-harm and suicidal behaviors), and family communication affected self-harming behaviors at wave 6. The trajectories of self-harm and suicidal behaviors decline from early to late adolescence among Chinese adolescents. Positive youth development and constructive family functioning are critical to help reduce suicidal behaviors. Regarding increased risk, more attention should be paid to adolescent girls and adolescents from nonintact and economic disadvantaged families.


Exposure of the vertebral bodies of the proximal lumbar segments. Some anatomic points.
The fascial structure of the left retroperitoneal region of the abdomen and its surgical anatomy are reviewed. The findings correlate with those of Tobin and Baumann. The muscular interval between the quadratus lumborum and the psoas muscle is elaborated upon as a useful route for entrance into the retroperitoneum. The occasional but significant occurrence of the artery of Haller is mentioned. The author's recommendation for exposure of the upper segments of the lumbar spin L1 through L3 is through a posterolateral abdominal incision with resection of the medial half of the twelfth rib (depending on the configuration of the twelfth rib) and oteotomy of the tip of the L1 transverse process as the routes of exposure of the proximal segments of the lumbar spine.


Descriptive account of the first use of the LeVe CPAP System, a new frugal CPAP System, in adult patients with COVID-19 Pneumonitis in Uganda.
Continuous positive airway pressure (CPAP) has been a key treatment modality for Coronavirus Disease 2019 (COVID-19) worldwide. Globally, the demand for CPAP outstripped the supply during the pandemic. The LeVe CPAP System was developed to provide respiratory support for treatment of COVID-19 and tailored for use in low- and middle-income country (LMIC) settings. Prior to formal trial approval, received in November 2021, these devices were used in extremis to support critically unwell adult patients requiring non-invasive ventilatory support. This is a retrospective descriptive review of adult patients with COVID-19 pneumonitis, who were treated with advanced respiratory support (CPAP and/or high-flow nasal oxygen, HFNO) at Mengo Hospital, Uganda. Patients were treated with the LeVe CPAP System, Elisa CPAP and/or AIRVO™ HFNO. Treatment was escalated per standard local protocols for respiratory failure, and CPAP was the maximum respiratory support available. Data were collected on patient characteristics, length of time of treatment, clinical outcome, and any adverse events. Overall 333 patients were identified as COVID-19 positive, 44 received CPAP ± HFNO of which 43 were included in the study. The median age was 58 years (range 28-91 years) and 58% were female. The median duration of advanced respiratory support was 7 days (range 1-18 days). Overall (all device) mortality was 49% and this was similar between those started on the LeVe CPAP System and those started non-LeVe CPAP System devices (50% vs 47%). The LeVe CPAP system was the most used CPAP device during the pandemic, bringing the hospital's number of available HFNO/CPAP devices from two to 14. They were a critical resource for providing respiratory support to the sickest group of patients when no alternative devices were available. The devices appear to be safe and well-tolerated with no serious adverse events recorded. This study is unable to assess the efficacy of the LeVe CPAP System; therefore, formal comparative studies are required to inform further use.


Efficacy of Melia azedarach L. extract on the malarial vector Anopheles stephensi Liston (Diptera: Culicidae).
Methanolic extracts of leaves and seeds from the chinaberry tree, Melia azedarach L. (Meliaceae) was tested against mature and immature mosquito vector Anopheles stephensi Liston (Diptera) under laboratory condition. The extract showed strong larvicidal, pupicidal, adulticidal, antiovipositional activity, repellency and biting deterency. The M. azedarach seed and leaf extracts were used to determine their effect on A. stephensi adults and their corresponding oviposition and consequent adult emergence in comparison with the control. The seed extracts showed high bioactivity at all doses, while the leaf extracts proved to be active, only in the higher dose. Results obtained from the laboratory experiment showed that the seed extracts suppressed the pupal and adult activity of A. stephensi even at low dose. In general, first and second instar larvae were more susceptible to both leaves and seed extracts. Clear dose-response relationships were established with the highest dose of 2% plant extract evoking 96% mortality. Entire development of A. stephensi was inhibited by M. azedarach treatment. Less expensive (less than 0.50 US dollars per 1 kg seed), naturally accruing bio-pesticide could be an alternative for chemical pesticides.


Hypoplasia of the lumbar vertebral body simulating spondylolisthesis.
Fifty cases of spondylosis and spondylolisthesis were reviewed. In 9 of the 20 cases interpreted as Grade I spondylolisthesis at L5-S1, the sagittal diameter of L5 was shortened, creating a false impression of vertebral slippage. Such cases are felt to represent spondylolysis with hypoplasia of the vertebral body rather than true spondylolisthesis.


An NIR-light-responsive surface molecularly imprinted polymer for photoregulated drug release in aqueous solution through porcine tissue.
The application of photoresponsive surface molecularly imprinted polymers based on azobenzene is limited by the UV light source required and their poor water solubility. Reducing the phototoxicity and solvent toxicity of the polymers therefore presents a challenge. In this work, an NIR-light-responsive surface molecularly imprinted polymer was fabricated by atom transfer radical polymerization using up-conversion nanoparticles as the core, a hydrophilic green-light-responsive azobenzene derivative as the functional monomer, and a drug as the template. The up-conversion nanoparticles core emitted green fluorescence in the range of 520-550 nm upon NIR irradiation (980 nm, 5 W cm-2), which was absorbed by the azobenzene containing molecularly imprinted polymers layer on the up-conversion nanoparticles surface. This caused the azobenzene chromophores to undergo trans→cis isomerization in phosphate buffered solution (pH = 7.4), thus resulting in NIR-light-induced drug release. The up-conversion fluorescence spectra were used to study the interaction mechanism between the azobenzene monomer and NIR light. Compared with structural analogues of the template (antifebrin and phenacetin), the NIR-light-responsive surface molecularly imprinted polymer showed excellent specificity of recognition for the template drug (paracetamol). The maximum adsorption capacity of the NIR-light-responsive surface molecularly imprinted polymer for loading of paracetamol was 16.80 μmol g-1. The NIR-light-responsive surface molecularly imprinted polymer was applied for NIR-light-induced paracetamol release in phosphate buffered solution (pH = 7.4) through porcine tissue. This work demonstrates the potential of drug delivery systems based on molecularly imprinted polymers for application in deep tissue delivery.


Identification of several forms of the glial fibrillary acidic protein, or alpha-albumin, by a specific monoclonal antibody.
A monoclonal antibody (mAb), termed UIA/NEU/I/G1 (G1), that reacted with the astroglial marker glial fibrillary acidic protein (GFAP), or alpha-albumin, is described. It was directed against a structural determinant of GFAP. The G1 mAb could be used for quantitative determination of GFAP in two-site radiometric assays and for histoimmunological demonstration of GFAP. The G1 mAb reacted with the GFAP from rat as well as from man. The presence of several different molecular weight forms of GFAP in aqueous and detergent extracts from human brain was shown with the G1 mAb. The possible meaning of these forms is discussed.


Changes in condylar position and morphology after mandibular reconstruction by vascularized fibular free flap with condyle preservation.
Changes in condylar position and morphology after mandibular reconstruction are important to aesthetic and functional rehabilitation. We evaluated changes in condylar position and morphology at different stages after mandibular reconstruction using vascularized fibular free flap with condyle preservation. A total of 23 patients who underwent mandibular reconstruction with fibular flap were included in this retrospective study. CT data of all patients were recorded before surgery (T0), 7 to 14 days after surgery (T1), and at least 6 months after surgery (T2). Five parameters describing the condylar position and 4 parameters describing the morphology were measured in sagittal and coronal views of CT images. The association between clinical characteristics and changes in condylar position and morphology was analyzed. A finite element model was established to investigate the stress distribution and to predict the spatial movement tendency of the condyle after reconstruction surgery. The condylar position changed over time after mandibular reconstruction. The ipsilateral condyles moved inferiorly after surgery (T0 to T1) and continually move anteriorly, inferiorly, and laterally during long-term follow-up (T1 to T2). Contrary changes were noted in the contralateral condyles with no statistical significance. No morphological changes were detected. The relationship between clinical characteristics and changes in condylar position and morphology was not statistically significant. A consistent result was observed in the finite element analysis. Condylar positions showed obvious changes over time after mandibular reconstruction with condylar preservation. Nevertheless, further studies should be conducted to evaluate the clinical function outcomes and condylar position. These findings can form the basis for the evaluation of short-term and long-term changes in condylar position and morphology among patients who have previously undergone mandibular reconstruction by FFF with condyle preservation.


Is hyperosmotic neurosecretion from motor nerve endings a calcium-dependent process?
Spontaneous liberation of neurotransmitter quanta is strongly affected by the osmotic pressure of the extracellular fluid. Elevation of the osmolarity by 20-30% increases the rate of release from motor nerve endings by more than one order of magnitude. In this respect the neuromuscular junction resembles some other secretory systems. The mechanism of this hyperosmotic neurosecretion is not yet understood; extracellular calcium ions are not directly responsible, since this effect can be produced in their absence. Recently, it has been suggested that the liberation of neurotransmitter is regulated by the intracellular concentration of free calcium ions. We have therefore examined the hypothesis that hyperosmotic neurosecretion originates from an increase in internal calcium concentration ([Ca]in). At the frog neuromuscular synapse however, it is impossible at present to estimate directly free [Ca]in; hence we used an indirect technique, which is based on two assumptions; first, the frequency of the miniature endplate potentials (m.e.p.p.s.) reflects free [Ca]in. Second, the movement of calcium ions across the presynaptic membrane is governed by the electrochemical gradient, and by the calcium conductance (g(Ca)). If hyperosmotic neurosecretion is caused by an increase in [Ca]in, then increasing g(Ca), under reversed electrochemical gradient for the calcium should cause a reduction in the effect of hyperosmotic stress on transmitter release. We report that hyperosmotic neurosecretion is dependent on [Ca]in.


Progression of the mycotoxin and nutrient concentration in wheat after inoculation withFusarium culmorum.
The aim of the study was to follow the mycotoxin formation and the changes in nutrient composition of wheat artificially inoculated withFusarium cuimorum. From anthesis until harvest, samples were taken once a week from the inoculated and control plots. The investigations were focused on the progression of the contamination of the wheat with deoxyni-valenol (DON) and zearalenone (ZON). Furthermore, the impact of the Fusarium inoculation on the quality parameters starch, crude protein, crude ash, viscosity, non starch polysaccharides (NSP) and thousand seed weight was examined. Deoxynivalenol was detected in higher concentrations and in earlier stages, while zearalenone was found later and in smaller amounts. Moreover, the infection withFusarium cuimorum had pronounced effects on some quality parameters.


Epstein-Barr virus LMP1 protein promotes proliferation and inhibits differentiation of epithelial cells via activation of YAP and TAZ.
Latent Epstein-Barr virus (EBV) infection promotes undifferentiated nasopharyngeal carcinomas (NPCs) in humans, but the mechanism(s) for this effect has been difficult to study because EBV cannot transform normal epithelial cells in vitro and the EBV genome is often lost when NPC cells are grown in culture. Here we show that the latent EBV protein, LMP1 (Latent membrane protein 1), induces cellular proliferation and inhibits spontaneous differentiation of telomerase-immortalized normal oral keratinocytes (NOKs) in growth factor-deficient conditions by increasing the activity of the Hippo pathway effectors, YAP (Yes-associated protein) and TAZ (Transcriptional coactivator with PDZ-binding motif). We demonstrate that LMP1 enhances YAP and TAZ activity in NOKs both by decreasing Hippo pathway-mediated serine phosphorylation of YAP and TAZ and increasing Src kinase-mediated Y357 phosphorylation of YAP. Furthermore, knockdown of YAP and TAZ is sufficient to reduce proliferation and promote differentiation in EBV-infected NOKs. We find that YAP and TAZ are also required for LMP1-induced epithelial-to-mesenchymal transition. Importantly, we demonstrate that ibrutinib (an FDA-approved BTK inhibitor that blocks YAP and TAZ activity through an off-target effect) restores spontaneous differentiation and inhibits proliferation of EBV-infected NOKs at clinically relevant doses. These results suggest that LMP1-induced YAP and TAZ activity contributes to the development of NPC.


Effects of conjugated linoleic acid isomers on monocyte, macrophage and foam cell phenotype in atherosclerosis.
Conjugated linoleic acid (CLA) is a generic term denoting a group of naturally occurring isomers of linoleic acid (18:2, n6) that differ in the position or geometry (i.e. cis or trans) of their double bonds. The predominant isomers in ruminant fats are cis-9,trans-11 CLA (c9,t11-CLA), and trans-10,cis-12 CLA (t10,c12-CLA). The biological activities of CLA have received considerable attention because of its protective effects in cancer, immune function, obesity and atherosclerosis. Importantly, dietary administration of a blend of the two most abundant isomers of CLA, has been shown to inhibit the progression and induce the regression of pre-established atherosclerosis in the ApoE⁻/⁻ murine model. Studies investigating the mechanisms involved in CLA induced protective effects are continually emerging with results from both in vitro and in vivo models yielding confounding and often inconsistent results depending on both the isomer of CLA and the species under investigation. The purpose of this review is to comprehensively discuss the effects of CLA on monocyte/macrophage function in atherosclerosis. This review also discusses the possible mechanisms through which CLA mediates its atheroprotective effects with a particular emphasis on the migratory capacity of the monocyte and the inflammatory and cholesterol homeostasis of the macrophage.


The antegrade dissection and re-entry technique as preparation of intravascular ultrasound guided re-wiring.
Although the antegrade dissection and re-entry technique (ADR) with Stingray system is one of the procedures for percutaneous coronary intervention (PCI) of chronic total occlusion (CTO), it has some risk of side-branch occlusion. This article reports a CTO case in the left circumflex artery successfully treated with combination use of ADR subintimal tracking and intravascular ultrasound (IVUS)-guided re-wiring without side-branch occlusion. Antegrade approach with single-wire and parallel-wire technique was failed. Retrograde approach through ipsilateral collateral was also failed. Therefore, the ADR was attempted and Stingray wire crossed through at the distal site of posterolateral (PL) branch. To avoid PL branch occlusion, IVUS-guided re-wiring to the true lumen was attempted. Finally, the CTO lesion was recanalized without any complication and 1 year follow-up angiography had good result. ADR as preparation of IVUS-guided re-wiring might be one of the useful procedures for those complex CTO cases.


Butyrate regulates the expression of inflammatory and chemotactic cytokines in human acute leukemic cells during apoptosis.
Butyrate is a histone deacetylase inhibitor implicated in many studies as a potential therapy for various forms of cancer. High concentrations of butyrate (>1.5mM) have been shown to activate apoptosis in several cancer cell lines including prostate, breast, and leukemia. Butyrate is also known to influence multiple signaling pathways that are mediators of cytokine production. The purpose of this study was to evaluate the impact of high concentrations of butyrate on the cancer microenvironment vis-à-vis apoptosis, cellular migration, and capacity to modulate cytokine expression in cancer cells. The results indicate that high concentrations of butyrate induced a 2-fold activation of caspase-3 and reduced cell viability by 60% in U937 leukemia cells. Within 24h, butyrate significantly decreased the levels of chemokines CCL2 and CCL5 in HL-60 and U937 cells, and decreased CCL5 in THP-1 leukemia cells. Differential effects were observed in treatments with valproic acid for CCL2 and CCL5 indicating butyrate-specificity. Many of the biological effects examined in this study are linked to activation of the AKT and MAPK signaling pathways; therefore, we investigated whether butyrate alters the levels of phosphorylated forms of these signaling proteins and how it correlated with the expression of chemokines. The results show that butyrate may partially regulate CCL5 production via p38 MAPK. The decrease in p-ERK1/2 and p-AKT levels correlated with the decrease in CCL2 production. These data suggest that while promoting apoptosis, butyrate has the potential to influence the cancer microenvironment by inducing differential expression of cytokines.


Redressing injustices: how women students enact agency in undergraduate medical education.
This study presents descriptions of epistemic injustice in the experiences of women medical students and provides accounts about how these students worked to redress these injustices. Epistemic injustice is both the immediate discrediting of an individual's knowledge based on their social identity and the act of persistently ignoring possibilities for other ways of knowing. Using critical narrative interviews and personal reflections over an eight-month period, 22 women students during their first year of medical school described instances when their knowledge and experience was discredited and ignored, then the ways they enacted agency to redress these injustices. Participants described three distinct ways they worked to redress injustices: reclaiming why they belong in medicine, speaking up and calling out the curriculum, and uplifting one another. This study has implications for recognizing medical students as whole individuals with lived histories and experiences and advocates for recognizing medical students' perspectives as valuable sources of knowledge.


A novel mutation tolerant padlock probe design for multiplexed detection of hypervariable RNA viruses.
The establishment of a robust detection platform for RNA viruses still remains a challenge in molecular diagnostics due to their high mutation rates. Newcastle disease virus (NDV) is one such RNA avian virus with a hypervariable genome and multiple genotypes. Classical approaches like virus isolation, serology, immunoassays and RT-PCR are cumbersome, and limited in terms of specificity and sensitivity. Padlock probes (PLPs) are known for allowing the detection of multiple nucleic acid targets with high specificity, and in combination with Rolling circle amplification (RCA) have permitted the development of versatile pathogen detection assays. In this work, we aimed to detect hypervariable viruses by developing a novel PLP design strategy capable of tolerating mutations while preserving high specificity by targeting several moderately conserved regions and using degenerate bases. For this, we designed nine padlock probes based on the alignment of 335 sequences covering both Class I and II NDV. Our PLP design showed high coverage and specificity for the detection of eight out of ten reported genotypes of Class II NDV field isolated strains, yielding a detection limit of less than ten copies of viral RNA. Further taking advantage of the multiplex capability of PLPs, we successfully extended the assay for the simultaneous detection of three poultry RNA viruses (NDV, IBV and AIV) and combined it with a paper based microfluidic enrichment read-out for digital quantification. In summary, our novel PLP design addresses the current issue of tolerating mutations of highly emerging virus strains with high sensitivity and specificity.


Renal transplantation.
This article provides an overview of the renal transplantation process from the evaluation phase through hospitalization and follow-up care. Nursing care of the postoperative transplant patient in the intensive care unit is detailed in this article, using nursing various diagnoses as a guideline.


Reducing drinking to cope among heavy episodic drinking college women: Secondary outcomes of a web-based combined alcohol use and sexual assault risk reduction intervention.
College students are at high risk for engaging in heavy episodic drinking and for experiencing sexual assault. Further, drinking to cope with anxiety motives are associated with sexual assault history and drinking, and thus should be examined when targeting both sexual assault and drinking in college populations. The current study examined the effectiveness of decreasing coping with anxiety drinking motives among underage heavy episodic drinking college women (n=264). Results indicate that a web-based combined alcohol use and sexual assault risk reduction intervention was effective at decreasing drinking to cope with anxiety motives among those with stronger drinking to cope with anxiety motives at baseline. However, the alcohol-only and sexual assault-only interventions were not. Decreases in drinking motives were associated with decreases in heavy episodic drinking. This suggests that alcohol interventions in college populations may not be effectively targeting drinking motives and this preliminary study provides evidence indicating that targeting alcohol and sexual assault together may decrease drinking to cope motives among a high risk population.


Phospholipase C from Clostridium novyi type A. I.
1. Phospholipase C (EC 184.108.40.206) from Clostridium novyi (oedematiens) type A was purified 2000-fold by (NH4)2SO4 precipitation, DEAE-Sephadex treatment in a batchwise system and Sephadex G-100 column chromatography. 2. The purified preparation had a specific activity of 95 mumol per min per mg protein toward phosphatidylcholine. This preparation was free from protease, lipase and oxygen-labile delta-hemolysin. 3. Phosphatidylcholine was hydrolyzed at the highest rate, while sphingomyelin and lysophosphatidylcholine were hydrolyzed at much lower rates. 4. Sodium deoxycholate and divalent cations such as Mg2+ and Ca2+ were extremely effective in stimulating phosphatidylcholine-hydrolyzing activity of this enzyme. 5. This enzyme hemolyzed horse red cells by hydrolyzing phosphatidylcholine, spingomyelin and phosphatidylethanolamine.


The Assessment of the Quality of Life in Patients with Rheumatoid Foot.
The negative effects of rheumatoid arthritis (RA) are multi-dimensional. Foot deformities lead to disability, pain, and impaired quality of life. Identifying the difficulties in functioning rheumatoid foot and assessing the quality of life in this aspect. The material included 50 patients of Rheumatology Policlinic of the Central Clinical Hospital of Interior Affairs in Warsaw and a matched control group of 50 individuals without RA. The degree of foot joint damage was assessed using the Manchester scale, lower limb movement and quality of life using the American Orthopedic Foot and Ankle Society Score and HAQ. The duration of symptoms was 16.0 ± 8.9 years. High activity of RA measured by the DAS was observed in 20% of patients, moderate in 26%, and low in 54%. The most common foot deformities were: hammer toes (82%), longitudinal flat feet (74%), and hyperkeratosis (56%). The least frequent were: stiff toe (38%) and overlapping fingers (28%). In the RA group, the outcomes of the FAOS questionnaire were statistically significantly worse than in the control group in all categories (p<0.001). The worst-rated domain was the sport and recreation subscale (median 55.0), the best daily activity (median 86.8). The strongest relationship was demonstrated between the FAOS and HAQ indices. Spearman's HAQ correlation coefficient with the ADL subscale was r=-0.85, p<0.001; with the QOL, sport/recreation and pain subscales moderate, it was r=-0.72; r= 0.71, p <0.001. Lower limb movement function and quality of life are worse in RA patients; pain accompanies climbing and descending stairs; running and jumping require effort.


Auditory identification of pelvic blood vessels during laparoscopically assisted vaginal hysterectomy. Use of the endoscopic Doppler probe.
The endoscopic Doppler probe allows instantaneous, audible detection of the uterine arteries and other large pelvic blood vessels by simple contact. In addition, the Doppler probe reduces the probability of ureteral injury since it allows the surgeon to clearly distinguish the uterine artery from the ureter. In our experience, the endoscopic Doppler system has effectively reduced the risk of bleeding and ureteral injury during difficult laparoscopic hysterectomies in which the recognition and safe dissection of the uterine arteries and ureters are difficult to achieve.


In vitro culture of intramolluscan stages of the avian schistosome Trichobilharzia ocellata.
Several different procedures for in vitro cultivation of intramolluscan stages of the avian schistosome Trichobilharzia ocellata were tried. A medium was found and culture conditions were established that not only supported in vitro transformation of miracidia into mother sporocysts, but also resulted in substantial subsequent growth; moreover, some degree of germinative development appeared to occur as well. Cerebral ganglia from uninfected adult snails of the intermediate host species, Lymnaea stagnalis, could produce factors promoting in vitro development of young mother sporocysts. Results are compared with data from the literature and it is concluded that greater success in in vitro culturing of young mother sporocysts of T. ocellata can be achieved than has hitherto been reported for other schistosome species. The same culture procedures were less successful when applied to other intramolluscan stages of T. ocellata, but can be used for in vitro maintenance of these stages. The procedures described here will be a useful tool in the study of schistosome-snail interactions in T. ocellata-L. stagnalis and possibly in other systems as well.


Analysis of 1242 cases with upper gastrointestinal system bleeding in Southeastern Turkey: a different etiologic spectrum.
There are few detailed reports on gastrointestinal system bleeding in Turkey. The aim of this study is to analyze the characteristics of the patients with upper gastrointestinal system bleeding who were hospitalized in our clinic. The patients who were hospitalized in Dicle University Hospital Department of Gastroenterology from March 1992 to June 2002 were analyzed retrospectively. During this period of time, 296 females (23.8%) and 946 males (76.2%), total 1242 patients were hospitalized for upper gastrointestinal system bleeding. Mean age was 47 for both sexes. Distribution of the cases was as follows: 31.6% duodenal ulcer (n: 393), 30.5% esophageal variceal bleeding (n: 379), 13.7% erosive gastritis (n: 171), 6.8% erosive duodenitis (n: 85), 4.9% gastric ulcer (n: 62), 2.8% carcinoma (n: 35), and 3.5% other causes. Peptic ulcer related bleeding was the most encountered reason (37.5%, n: 466). Four percent of the cases other than esophageal variceal bleeding underwent urgent surgical intervention. Eleven percent of the cases (n: 138) resulted in death of which 65.9% were esophageal variceal bleeding (n: 91). The most striking result is the very high rate of esophageal variceal bleeding. This finding is in concordance with the high prevalence of the viral hepatitis in the region.