Net energy of hemp hulls and processed hemp hull products fed to growing pigs and the comparison of net energy determined via indirect calorimetry and calculated from prediction equations.
An experiment was conducted to determine the NE of hemp hulls (HH), extruded HH (EHH), and a blended product of HH with pea (HHP) fed to growing pigs using indirect calorimetry (IC) and to determine effects of dietary fiber on heat production (HP) and fasting HP (FHP). Twenty-four growing barrows with an average initial BW of 22.9 ± 1.75 kg were individually housed in adjustable metabolism crates. Pigs were randomly allotted to 1 of 4 dietary treatments with 6 replicates per treatment. A corn-soybean meal basal diet was prepared. Three additional diets were formulated to contain a constant ratio of corn and soybean meal and each of the test ingredients. Pigs were fed experimental diets for 16 d including 10 d for adaptation and 6 d for total collection of feces and urine to determine DE and ME of experimental diets. Pigs were then moved into IC chambers to determine HP and FHP. The apparent total tract digestibility (ATTD) of DM was greater ( < 0.01) in the HHP diet than in the HH and EHH diets but less ( < 0.01) than in the basal diet. Similarly, the ATTD of GE in the basal diet was greater ( < 0.01) compared with the HH, EHH, and HHP diets. The DE, ME, and NE of the basal diet were greater ( < 0.01) than those of the HH, EHH, and HHP diets. No significant differences were observed for the HP (on average, 1,904 kcal/kg DM) and FHP (on average, 1,320 kcal/kg DM) among treatments. However, the retained energy of pigs fed the basal diet (1,763 kcal/kg DM) was greater ( < 0.05) than for those fed the HH (1,501 kcal/kg DM) and HHP (1,482 kcal/kg DM) diets. The NE:ME ratio tended to be greater ( ≤ 0.10) for the basal diet (0.85) than for the HH (0.82), EHH (0.82), and HHP (0.83) diets. The NE of HH, EHH, and HHP determined by the IC method were 2,375, 2,320, and 2,399 kcal/kg DM, respectively, whereas values calculated using published prediction equations were 2,308, 2,161, and 2,278 kcal/kg DM, respectively. However there was no difference between determined and predicted values. In conclusion, the NE of HH, EHH, and HHP determined using the IC method were 2,375, 2,320, and 2,399 kcal/kg DM, respectively, and these values were 2.9, 7.1, and 5.2% greater, respectively, than the predicted values, although no difference was observed between determined and predicted values. However, the HP values observed for the basal diet and the diets containing high dietary fiber in the form of HH, EHH, or HHP were similar.


1,25-Dihydroxycholecalciferol deficiency: the probable cause of hypocalcemia and metabolic bone disease in pseudohypoparathyroidism.
Pseudohypoparathyroidism (PsH) is a genetic disease characterized by hypocalcemia, hyperphosphatemia, and metabolic unresponsiveness to parathyroid hormone (PTH). The administration of PTH elicits neither a significant rise in serum calcium (calcemic response) nor a decrease in the renal tubule reabsorption of phosphorus (phosphaturic response). The diminished phosphaturic response is due to an inability of PTH to generate cyclic AMP in renal tubule cells. We investigated the question of whether hypocalcemia and deficient calcemic response to PTH are due to a similar cyclic AMP defect in bone or to an acquired vitamin D deficiency. Four patients were studied. The active form of vitamin D (1,25-dihydroxycholecalciferol) was measured in 3 and was low. Treatment with vitamin D2 restored the serum calcium and the calcemic response to PTH to normal without changing the impaired renal response. Bone biopsy was performed in 2 patients and showed morphologic evidence of increased osteoclastic activity and osteomalacia. The data indicate that the hypocalcemia and bone disease in PsH are due to active vitamin D deficiency, possibly resulting from the genetic renal lesion.


Excess mortality rates for estimating the non-fatal burden of stroke in Western Australia: a data linkage study.
Non-fatal stroke burden measured in Years Lived with Disability (YLD) requires valid estimates of stroke case fatality to allow modelling of disease duration. In the model, case fatality can be calculated from the absolute risk of mortality in cases in excess of that in the non-diseased. Our purpose was to estimate excess mortality rates in 28-day survivors of stroke in Western Australia and to evaluate differentials in survival by stroke type, age and time since the first stroke event. Excess mortality among prevalent (first-ever plus existing) survivors was estimated from linked hospital and mortality data. Changes in excess mortality over time were calculated over a 6-year period. Excess mortality increased with age for both males (21 per 1,000 in the 15- to 54-year to 109 per 1,000 in the > or =85-year age group) and females (16 and 122 per 1,000 for the 15- to 54-year and > or =85-year groups, respectively). Survival by stroke sub-types differed at ages <55 years but not >55 years. During the first year excess mortality was markedly higher, after which it was relatively constant for each age group. The assumption of constant rather than changing excess mortality in 28-day survivors of stroke had minimal effect on estimates of duration. Measures of excess mortality in prevalent survivors have not previously been available for estimating YLD for stroke. An analysis of all stroke types combined is not likely to substantially bias estimates of non-fatal stroke burden nor is an assumption of constant excess mortality for survivors.


The use of cannabinoids in chronic pain.
We present the case of a 56-year-old man who developed chronic pain following the excision of a facial cancer that was poorly controlled despite multiple analgesic medications. Following the starting of nabilone (a synthetic cannabinoid) his pain control was greatly improved and this had a huge impact on his quality of life. We also managed to significantly reduce his doses of opioid analgesia and ketamine. We review the current literature regarding the medicinal use of cannabinoids, with an emphasis on chronic pain, in an attempt to clarify their role and how to select patients who may benefit from this treatment.


Maternal healthcare seeking and determinants of adequate antenatal care and institutional childbirth among Indian tribes: A cross-sectional study from nine districts.
To report the utilisation of maternal healthcare services and factors associated with adequate antenatal care and institutional childbirths among mothers in the tribal communities from nine districts in India. Cross-sectional data were collected from 2636 tribal women who had a childbirth experience in the past 12 months. Socio-demographic, maternal healthcare services and health system-related details were collected. Multiple logistic regression analyses were done to identify factors associated with adequate antenatal care (receiving at least four antenatal care visits, the first visit being in the first trimester and receiving a minimum of 100 iron-folic acid tablets) and institutional childbirth (mother giving birth in a health facility). Only 23% of the mothers received adequate antenatal care. 82% were institutional childbirths. The logistic regression revealed that particularly vulnerable tribal groups (PVTGs), those lacking all-weather roads, and women of advanced age were at risk of inadequate antenatal care. Mother's education, health worker's home visits during pregnancy and reception of advice on antenatal care were significantly associated with the reception of adequate antenatal care. Having all-weather roads, and education of the mother and head of the household were positively associated with institutional childbirths, whereas PVTGs, children of birth order three or above, and working mothers were more likely to give childbirth at home. PVTGs are at risk of foregoing adequate antenatal care and are more likely to give childbirth at home. Having all-weather roads is a strong correlate of adequate maternal care. Outreach activities by the health workers are to be strengthened as they are positively and significantly associated with the reception of adequate antenatal care. Investing in education and other social determinants and addressing certain socio-cultural practices is important to improve maternal health.


The Lysine Methyltransferase G9a in Immune Cell Differentiation and Function.
G9a (KMT1C, EHMT2) is a lysine methyltransferase (KMT) whose primary function is to di-methylate lysine 9 of histone H3 (H3K9me2). G9a-dependent H3K9me2 is associated with gene silencing and acts primarily through the recruitment of H3K9me2-binding proteins that prevent transcriptional activation. Gene repression via G9a-dependent H3K9me2 is critically required in embryonic stem (ES) cells for the development of cellular lineages by repressing expression of pluripotency factors. In the immune system, lymphoid cells such as T cells and innate lymphoid cells (ILCs) can differentiate from a naïve state into one of several effector lineages that require both activating and repressive mechanisms to maintain the correct gene expression program. Furthermore, the long-term immunity to re-infection is mediated by memory T cells, which also require specific gene expression and repression to maintain a quiescent state. In this review, we examine the molecular machinery of G9a-dependent functions, address the role of G9a in lymphoid cell differentiation and function, and identify potential functions of T cells and ILCs that may be controlled by G9a. Together, this review will highlight the dynamic nature of G9a-dependent H3K9me2 in the immune system and shed light on the nature of repressive epigenetic modifications in cellular lineage choice.


Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1.
Myotonic dystrophy type 1 (DM1), the most common form of adult-onset muscular dystrophy, is caused by a CTG expansion resulting in significant transcriptomic dysregulation that leads to muscle weakness and wasting. While strength training is clinically beneficial in DM1, molecular effects had not been studied. To determine whether training rescued transcriptomic defects, RNA-Seq was performed on vastus lateralis samples from 9 male patients with DM1 before and after a 12-week strength-training program and 6 male controls who did not undergo training. Differential gene expression and alternative splicing analysis were correlated with the one-repetition maximum strength evaluation method (leg extension, leg press, hip abduction, and squat). While training program-induced improvements in splicing were similar among most individuals, rescued splicing events varied considerably between individuals. Gene expression improvements were highly varied between individuals, and the percentage of differentially expressed genes rescued after training were strongly correlated with strength improvements. Evaluating transcriptome changes individually revealed responses to the training not evident from grouped analysis, likely due to disease heterogeneity and individual exercise response differences. Our analyses indicate that transcriptomic changes are associated with clinical outcomes in patients with DM1 undergoing training and that these changes are often specific to the individual and should be analyzed accordingly.


Cloning, expression, and homology modeling of GroEL protein from Leptospira interrogans serovar autumnalis strain N2.
Leptospirosis is an infectious bacterial disease caused by Leptospira species. In this study, we cloned and sequenced the gene encoding the immunodominant protein GroEL from L. interrogans serovar Autumnalis strain N2, which was isolated from the urine of a patient during an outbreak of leptospirosis in Chennai, India. This groEL gene encodes a protein of 60 kDa with a high degree of homology (99% similarity) to those of other leptospiral serovars. Recombinant GroEL was overexpressed in Escherichia coli. Immunoblot analysis indicated that the sera from confirmed leptospirosis patients showed strong reactivity with the recombinant GroEL while no reactivity was observed with the sera from seronegative control patient. In addition, the 3D structure of GroEL was constructed using chaperonin complex cpn60 from Thermus thermophilus as template and validated. The results indicated a Z-score of -8.35, which is in good agreement with the expected value for a protein. The superposition of the Ca traces of cpn60 structure and predicted structure of leptospiral GroEL indicates good agreement of secondary structure elements with an RMSD value of 1.5 Å. Further study is necessary to evaluate GroEL for serological diagnosis of leptospirosis and for its potential as a vaccine component.


Cisplatin-DNA binding specificity of calf high-mobility group 1 protein.
We have identified a series of proteins with an affinity for cisplatin -damaged DNA using damaged DNA affinity chromatography. We have purified one of these proteins to homogeneity on the basis of a mobility shift assay detecting binding to cisplatin-damaged DNA. The protein was identified as high-mobility group 1 protein (HMG-1) by N-terminal protein sequence analysis. Analysis of a variety of DNA structures revealed that fully duplex DNAs were the best substrates for HMG-1 binding, while partial duplexes were less avidly bound. The decreased levels of binding are attributed to the length of the duplex region of the DNA substrates. A 3-fold increase in binding was observed when a cisplatin-damaged DNA substrate containing a single break in the phosphodiester backbone was joined by DNA ligase. The strict DNA size dependence of binding was also assessed, and a 10-fold increase in binding was observed when the length of the DNA duplex was increased from 44 to 180 base pairs (bp) at the same level of cisplatin damage. HMG-1 binding also was correlated with the degree of cisplatin-DNA damage, suggesting a higher affinity for DNA containing multiple cisplatin adducts. Nuclease degradation of the cisplatin-damaged DNA demonstrated that at the lowest levels of cisplatin damage all of the substrates contained at least one cisplatin adduct. The potential role of HMG-1 in the repair of cisplatin-DNA adducts is discussed.


Assembly, secretion, and vacuolar delivery of a hybrid immunoglobulin in plants.
Secretory immunoglobulin (Ig) A is a decameric Ig composed of four alpha-heavy chains, four light chains, a joining (J) chain, and a secretory component (SC). The heavy and light chains form two tetrameric Ig molecules that are joined by the J chain and associate with the SC. Expression of a secretory monoclonal antibody in tobacco (Nicotiana tabacum) has been described: this molecule (secretory IgA/G [SIgA/G]) was modified by having a hybrid heavy chain sequence consisting of IgG gamma-chain domains linked to constant region domains of an IgA alpha-chain. In tobacco, about 70% of the protein assembles to its final, decameric structure. We show here that SIgA/G assembly and secretion are slow, with only approximately 10% of the newly synthesized molecules being secreted after 24 h and the bulk probably remaining in the endoplasmic reticulum. In addition, a proportion of SIgA/G is delivered to the vacuole as at least partially assembled molecules by a process that is blocked by the membrane traffic inhibitor brefeldin A. Neither the SC nor the J chain are responsible for vacuolar delivery, because IgA/G tetramers have the same fate. The parent IgG tetrameric molecule, containing wild-type gamma-heavy chains, is instead secreted rapidly and efficiently. This strongly suggests that intracellular retention and vacuolar delivery of IgA/G is due to the alpha-domains present in the hybrid alpha/gamma-heavy chains and indicates that the plant secretory system may partially deliver to the vacuole recombinant proteins expected to be secreted.


Self-efficacy moderates but collective efficacy mediates between motivational climate and athletes' well-being.
The relationship between perceived motivational climate and athletes' well-being may depend on personal resource factors such as self-efficacy beliefs which are expected to shield individuals from negative outcomes when environmental factors may not suffice to secure positive outcomes. We explored the roles of self-efficacy and collective efficacy by investigating whether they operated either as moderators or as mediators within this relationship. Study 1 was carried out among 56 athletes (basketball, volleyball, or soccer players), with a two-week follow-up, whereas Study 2 was conducted among 113 soccer players, with three measurement points (baseline, two-month follow-up, and nine-month follow-up). Their satisfaction with sport skills and performance served as an index of well-being. The findings of Study 1 indicated that general self-efficacy moderated the relationship between task-oriented motivational climate and satisfaction. Task-oriented climate predicted satisfaction only among athletes with low self-efficacy. Study 2 showed that self-efficacy moderated the link between task-oriented motivational climate and satisfaction at nine-month follow-up. In contrast, collective efficacy at two-month follow-up mediated the relationship between perceived motivational climate at baseline and satisfaction at nine-month follow-up. Athletes are at risk for lower well-being if they perceive a negative task-involving climate and if they harbor either low general self-efficacy or low personal-barrier self-efficacy.


Reconfigurable Mechanochromic Patterns into Chameleon-Inspired Photonic Papers.
Photonic crystal (PC) patterns have shown wide applications in optical devices, information encryption, anticounterfeiting, etc. Unfortunately, it is still a great challenge to reconfigure the PC patterns once fabricated. Herein, a new strategy is presented to reconfigure self-recordable PC patterns by printing local patterns into the chameleon-inspired PC papers using the phase change material (PCM) as ink and then erasing the patterns in ethanol. Multicolor and high-resolution (25 and 75 μm for dot and lines, respectively) patterns can be efficiently and repeatedly reconfigured. In addition, the photonic patterns based on the PC paper and PCM combinations are gifted with mechanochromic characteristics and can show programmable and reversible color change under pressure. The high melting point of the ink, nonclosely packed structures of the PC paper, and the similar solubility parameter of PC paper, PCM, and ethanol are the keys for all these characteristics. This work offers a simple, flexible, efficient way to reconfigure PC patterns with mechanochromic properties and could open up exciting applications for novel hand-operation-based anticounterfeiting and optical devices.


Distribution of galanin messenger RNA-expressing cells in murine brain and their regulation by leptin in regions of the hypothalamus.
Galanin is widely distributed throughout the mammalian brain and has been implicated in the regulation of food intake, metabolism and reproduction-functions that are also thought to be under the control of leptin. To investigate the possible role of galanin in mediating the physiological effects of leptin in the mouse, we had three experimental objectives: first, to map the distribution of galanin messenger RNA-expressing cells in the brain of the mouse; second, to assess the effects of leptin on galanin gene expression in areas of the brain thought to be involved in the regulation of body weight and reproduction; and third, to determine whether galanin neurons in these regions express leptin receptor messenger RNA. We found the pattern of galanin messenger RNA expression in the mouse brain to be similar, but not identical, to that in the rat. Leptin treatment (2microg/g for six days) significantly reduced cellular levels of galanin messenger RNA in the hypothalamic periventricular nucleus of leptin-deficient obese (ob/ob) mice (P<0.01) by approximately 30%; however, leptin did not appear to influence the expression of galanin in the arcuate or dorsomedial nucleus of the hypothalamus. Galanin-producing neurons in the arcuate, dorsomedial and periventricular nuclei did not appear to express leptin receptor messenger RNA (P>0.05). These results demonstrate that galanin distribution patterns in the mouse brain are comparable to other species and, yet, possess unique features. In addition, galanin-expressing neurons in the hypothalamic periventricular nucleus are targets for regulation by leptin; however, the effect of leptin on galanin gene expression is likely to be mediated indirectly, perhaps through either proopiomelanocortin- or neuropeptide Y-expressing cells in the hypothalamus.


Expulsive choroidal haemorrhage: an experimental study.
The closure of 2 or more vortex veins in rabbits' eyes results in a persistent rise in intraocular pressure. In these circumstances a small opening into the anterior chamber at the corneoscleral limbus resulted in an iris prolapse, while a larger limbal wound was immediately followed by a massive choroidal expulsive haemorrhage. It appears from this experimental study that a definite and persistent rise in intraocular pressure could be a sign of impaired venous outflow and that the occurrence of an iris prolapse after small limbal opening into the anterior chamber should prompt us to examine the fundus of the eye and look for a choroidal complication. It is possible that the present set of experiments is relevant to the mechanism of expulsive haemorrhage in man.


Neural correlates of duplex perception: a whole-head magnetencephalography study.
Simultaneous experience of the same acoustic stimulus in two distinct phenomenological modes, e.g. as a speech-like and as a non-speech event, is referred to as duplex perception (DP). The most widely investigated DP paradigm splits each of the stop consonant-vowel (CV) syllables /ga/ and /da/ into an isolated formant transient (chirp) and the remaining sound structure (base). The present study recorded mismatch fields in response to a series of dichotically applied base and chirp components using whole-head magnetencephalography (MEG). Preattentive mismatch fields showed larger amplitudes in response to contralateral deviants. During attention to the fused percept /da/, the left ear deviants chirps elicited an enhanced and posteriorly shifted dipole field over the ipsilateral hemisphere. These data provide first neurophysiological evidence that the integration of acoustic stimulus elements into a coherent syllable representation constitutes a distinct stage of left-hemisphere speech sound encoding.


Physician health and wellness.
Physician health and wellness is a critical issue gaining national attention because of the high prevalence of physician burnout. Pediatricians and pediatric trainees experience burnout at levels equivalent to other medical specialties, highlighting a need for more effective efforts to promote health and well-being in the pediatric community. This report will provide an overview of physician burnout, an update on work in the field of preventive physician health and wellness, and a discussion of emerging initiatives that have potential to promote health at all levels of pediatric training. Pediatricians are uniquely positioned to lead this movement nationally, in part because of the emphasis placed on wellness in the Pediatric Milestone Project, a joint collaboration between the Accreditation Council for Graduate Medical Education and the American Board of Pediatrics. Updated core competencies calling for a balanced approach to health, including focus on nutrition, exercise, mindfulness, and effective stress management, signal a paradigm shift and send the message that it is time for pediatricians to cultivate a culture of wellness better aligned with their responsibilities as role models and congruent with advances in pediatric training. Rather than reviewing programs in place to address substance abuse and other serious conditions in distressed physicians, this article focuses on forward progress in the field, with an emphasis on the need for prevention and anticipation of predictable stressors related to burnout in medical training and practice. Examples of positive progress and several programs designed to promote physician health and wellness are reviewed. Areas where more research is needed are highlighted.


Regulation of calcium channels and exocytosis in mouse adrenal chromaffin cells by prostaglandin EP3 receptors.
Prostaglandin (PG) E(2) controls numerous physiological functions through a family of cognate G protein-coupled receptors (EP1-EP4). Targeting specific EP receptors might be therapeutically useful and reduce side effects associated with nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors that block prostanoid synthesis. Systemic immune challenge and inflammatory cytokines have been shown to increase expression of the synthetic enzymes for PGE(2) in the adrenal gland. Catecholamines and other hormones, released from adrenal chromaffin cells in response to Ca(2+) influx through voltage-gated Ca(2+) channels, play central roles in homeostatic function and the coordinated stress response. However, long-term elevation of circulating catecholamines contributes to the pathogenesis of hypertension and heart failure. Here, we investigated the EP receptor(s) and cellular mechanisms by which PGE(2) might modulate chromaffin cell function. PGE(2) did not alter resting intracellular [Ca(2+)] or the peak amplitude of nicotinic acetylcholine receptor currents, but it did inhibit Ca(V)2 voltage-gated Ca(2+) channel currents (I(Ca)). This inhibition was voltage-dependent and mediated by pertussis toxin-sensitive G proteins, consistent with a direct Gβγ subunit-mediated mechanism common to other G(i/o)-coupled receptors. mRNA for all four EP receptors was detected, but using selective pharmacological tools and EP receptor knockout mice, we demonstrated that EP3 receptors mediate the inhibition of I(Ca). Finally, changes in membrane capacitance showed that Ca(2+)-dependent exocytosis was reduced in parallel with I(Ca). To our knowledge, this is the first study of EP receptor signaling in mouse chromaffin cells and identifies a molecular mechanism for paracrine regulation of neuroendocrine function by PGE(2).


Glucocorticoid receptor activation is involved in producing abnormal phenotypes of single-prolonged stress rats: a putative post-traumatic stress disorder model.
Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experience, and presents with characteristic symptoms, such as intrusive memories, a state of hyperarousal, and avoidance, that endure for years. Single-prolonged stress (SPS) is one of the animal models proposed for PTSD. Rats exposed to SPS showed enhanced inhibition of the hypothalamo-pituitary-adrenal (HPA) axis, which has been reliably reproduced in patients with PTSD, and increased expression of glucocorticoid receptor (GR) in the hippocampus. In this study, we characterized further neuroendocrinologic, behavioral and electrophysiological alterations in SPS rats. Plasma corticosterone recovered from an initial increase within a week, and gross histological changes and neuronal cell death were not observed in the hippocampus of the SPS rats. Behavioral analyses revealed that the SPS rats presented enhanced acoustic startle and impaired spatial memory that paralleled the deficits in hippocampal long-term potentiation (LTP) and depression. Contextual fear memory was enhanced in the rats 1 week after SPS exposure, whereas LTP in the amygdala was blunted. Interestingly, blockade of GR activation by administering 17-beta-hydroxy-11-beta-/4-/[methyl]-[1-methylethyl]aminophenyl/-17-alpha-[prop-1-ynyl]estra-4-9-diene-3-one (RU40555), a GR antagonist, prior to SPS exposure prevented potentiation of fear conditioning and impairment of LTP in the CA1 region. Altogether, SPS caused a number of behavioral changes similar to those described in PTSD, which marks SPS as a putative PTSD model. The preventive effects of a GR antagonist suggested that GR activation might play a critical role in producing the altered behavior and neuronal function of SPS rats.


Reversibility of platelet thrombosis in vivo. Quantitative analysis in porcine carotid arteries.
Reversibility in vivo of acute platelet thrombosis in response to specific anticoagulants is analyzed with thrombi that develop in segments (1 cm) of porcine carotid arteries externally crushed with a hemostat. Most thrombi fill the lumens of the injured segments (ca. 1 cm x 3 mm, 1 x w) within 30 min and comprise masses of platelets interpenetrated with neutrophil-lined seepage channels of blood. Continuous quantitative assay of thrombus mass is provided by a gamma detector placed over the injured segments to collect counts from 111In-labeled platelets. Thrombi established 30 min after injury, otherwise stable for 6 h, clear during 30-60 min of continuous infusion of either hirudin, tick anticoagulant or activated porcine protein C, or intermittent activation of endogenous protein C with a latent thrombin reagent. Anticoagulant dose-dependence of thrombus clearance is established for hirudin between 0.01 and 1.0 mg/kg/min. Thrombi become progressively refractory to hirudin between 0.5 and 6 h after injury. Neither heparin no low-molecular-weight heparin in full (clinical) anticoagulant doses yield significant dethrombosis. It is concluded that, within time limits, controlled thrombin generation in platelet thrombi maintains platelet cohesion without catalyzing irreversible platelet aggregation or clotting of fibrinogen.


Cdx4 is required in the endoderm to localize the pancreas and limit beta-cell number.
Cdx transcription factors have crucial roles in anteroposterior patterning of the nervous system and mesoderm. Here we focus on the role of cdx4 in patterning the endoderm in zebrafish. We show that cdx4 has roles in determining pancreatic beta-cell number, directing midline convergence of beta-cells during early pancreatic islet formation, and specifying the anteroposterior location of foregut organs. Embryos deficient in cdx4 have a posteriorly shifted pancreas, liver and small intestine. The phenotype is more severe with knockdown of an additional Cdx factor, cdx1a. We show that cdx4 functions within the endoderm to localize the pancreas. Morpholino knockdown of cdx4 specifically in the endoderm recapitulates the posteriorly shifted pancreas observed in cdx4 mutants. Conversely, overexpression of cdx4 specifically in the endoderm is sufficient to shift the pancreas anteriorly. Together, these results suggest a model in which cdx4 confers posterior identity to the endoderm. Cdx4 might function to block pancreatic identity by preventing retinoic acid (RA) signal transduction in posterior endoderm. In support of this, we demonstrate that in cdx4-deficient embryos treated with RA, ectopic beta-cells are located well posterior to the normal pancreatic domain.


Global analysis of differential luminal epithelial gene expression at mouse implantation sites.
Although implantation types differ between species, the interaction between blastocyst trophectoderm and apical surface of the uterine epithelium is a common event during the implantation process. In this study, uterine luminal epithelium at implantation and inter-implantation sites was isolated by enzymatic digestion and used for microarray analysis. In a mouse microarray containing 12 345 unigenes, we found 136 genes upregulated more than twofold at the implantation site, while 223 genes were downregulated by at least twofold. Reverse transcription-PCR was used to verify the differential expression of seven upregulated and six downregulated genes chosen randomly from our microarray analysis, and the expression trends were similar. The differential expression patterns of eight upregulated genes were verified by in situ hybridization. Compared with the inter-implantation site on day 5 of pregnancy and the uterus on day 5 of pseudopregnancy, protease, serine, 12 neurotrypsin, endothelin-1, gamma-glutamyl hydrolase, Ras homolog gene family, member U, T-cell immunoglobulin, and mucin domain containing 2, proline-serine-threonine phosphatase-interacting protein 2, 3-monooxgenase/tryptophan 5-monooxgenase activation protein, gamma-polypeptide, and cysteine-rich protein 61 (Cyr61) were upregulated in the luminal epithelium at implantation site on day 5 of pregnancy. These genes may be related to embryo apposition and adhesion during embryo implantation. Cyr61, a gene upregulated at the implantation site, was chosen to examine its expression and regulation during the periimplantation period by in situ hybridization. Cyr61 mRNA was specifically localized in the luminal epithelium surrounding the implanting blastocyst at day 4 midnight and on day 5 of pregnancy, and in the activated uterus, but not expressed in inter-implantation sites and under delayed implantation, suggesting a role for Cyr61 in mediating embryonic-uterine dialog during embryo attachment. Our data could be a valuable source for future study on embryo implantation.


[Diagnosis of heart contusion in associated chest trauma].
The efficacy of different methods of heart contusion diagnosis in patients with concomitant chest trauma was studied. Criteria of heart contusion diagnosis by electrocardiography, integral body rheography, ultrasonic diagnosis, heart enzymes analysis were covered. Comparative analysis revealed that there was no modern method with 100% diagnostic value. Only complex use of these methods permits to make objective diagnosis of heart contusion. This approach allowed to decrease diagnostic mistakes rate in patients with concomitant chest trauma by 18%.


[Prenatal diagnosis of fetal cardiac defect].
The prevalence of congenital cardiac defects is 8 per 1000 neonates, and it's different if high or low risk populations are studied. The fetal ultrasonographic increase prenatal detection but varies from 7 to 90%. To know the prevalence of fetal cardiopathy and detection in high risk pregnancies. A observational study was made in pregnancies women with 16 old week of gestation. We received a total of 3500 high-risk pregnancies and were detected 112 cases with fetal cardiopathy (3.2%). The 30% of them had a risk factor of cardiopathy. The most frequent fetal cardiac defect detected were arrhythmia in 34 fetus, septal defects in 30, valvular defects in 17, hypoplasic or absence of cardiac cavities 16, tronco-conus defects 8, and other 7 included ectopia cordis 3, cardiac tumor 2, abnormal drainage of pulmonary veins 2. The diagnosis increased every year since started study. The prenatal diagnoses suspected in fetal echocardiography were confirmed in 80% of the cases in neonatal period. The detection rate of fetal cardiac defect was 3.2% in high-risk pregnancies, four times higher than general population prevalence of congenital heart disease. We found a 30% overall perinatal mortality in fetal cardiac defect. The most frequent fetal cardiac defects found in this screening were arrhythmias and septal ventricular defects in almost 50% of patients.


Student experience of hub and spoke model of placement allocation - An evaluative study.
An evaluative project was undertaken at the University of Wolverhampton centring on the Hub and Spoke model utilised for organisation of placement allocation across the BNurs programme for all fields of nursing. Student experience was of particular interest throughout the evaluation with the research team focusing on the views, feelings and experiences of student nurses in relation to the hub and spoke model applied for practice. A qualitative approach was adopted, initially using Survey Monkey to collect student views through a series of open questions, and further enhanced by focus groups. These were transcribed and together with the data from the surveys, data was categorized and themed. Themes were analysed and conclusions drawn. The hub and spoke method for placements was found to enhance student understanding of the whole patient journey which offered students a wide breadth of experience and development of transferable skills such as communication and adaptability. A sense of increased belonging was highlighted by students which encouraged the development of strong effective relationships positively affecting their learning. Some less positive aspects were apparent revolving around personality difficulties and organisational problems, in particular relating to spoke placements. The purpose of spoke placements was not always apparent and sometimes there was a lack of appropriate student placement experiences provided by spoke mentors. Overall the hub and spoke model for organising placement was found to be beneficial and enhanced the student's experience, satisfaction and learning, which in turn had a positive effect on practice.


Murine roseolovirus does not accelerate amyloid-β pathology and human roseoloviruses are not over-represented in Alzheimer disease brains.
The role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-β (Aβ) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen that is highly-related to the human roseoloviruses, providing an opportunity to perform well-controlled studies of the impact of roseolovirus on Aβ deposition. We utilized the 5XFAD mouse model to test whether MRV induces Aβ deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Aβ interaction with MRV, we performed electron microscopy. RNA-sequencing of a cohort of AD brains compared to control was used to investigate the association between human roseolovirus and AD. We found that 5XFAD mice were susceptible to MRV infection and developed neuroinflammation. Moreover, we demonstrated that Aβ interacts with viral particles in vitro and, subsequent to this interaction, can disrupt infection. Despite this, neither peripheral nor brain infection with MRV increased or accelerated Aβ plaque formation. Moreover, -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Our RNA-sequencing analysis of a cohort of AD brains compared to controls did not show an association between roseolovirus infection and AD. Although MRV does infect the brain and cause transient neuroinflammation, our data do not support a role for murine or human roseoloviruses in the development of Aβ plaque formation and AD.


Parasympathetic control of resting heart rate: relationship to aerobic power.
The degree of parasympathetic control of resting heart rate (PC) was assessed by measurement of variation in heart period (VHP) during cardiopulmonary synchronization of respiration. Respiratory period was arbitrarily preset and standardized at 7 heart beats (3 beats inspiration, 4 beats expiration). The mathematical and experimental evidence for this technique is elucidated. Twenty-one healthy subjects were examined for the relationship of aerobic power (VO2max) to (1) VHP and (2) respiratory sinus arrhythmia (RSA) waveform amplitude and phase. Intraindividual variability in VHP was low (test-retest r = 0.97-0.98). VHP in msec was a logarithmic function of VO2max (ml X kg FFW-1 X min-1) according to the equation: 1n VHP = 0.27 + 0.082 X VO2max where r = 0.92, P less than 0.001). VHP was more closely related to VO2max than was resting HR (r = -0.75). In addition, a higher VO2max was associated with a leftward shift of the HR: respiratory cycle sinusoidal curve. These results illustrate the close relationship between aerobic power and vagal tone in control of resting heart rate. Individuals with a higher aerobic power maintain lower resting heart rates mainly via an increase in parasympathetic tone (as opposed to a decreased sympathetic tone). Previous correlations between RSA characteristics and age may be accounted for by age-related decreases in VO2max.


Supramolecular Large Nanosheets Assembled at Air/Water Interfaces and in Solution from Amphiphilic Heptagon-Containing Nanographenes.
We report the synthesis of a new set of amphiphilic saddle-shaped heptagon-containing polycyclic aromatic hydrocarbons (PAHs) functionalized with tetraethylene glycol chains and their self-assembly into large two-dimensional (2D) polymers. An in-depth analysis of the self-assembly mechanism at the air/water interface has been carried out, and the proposed arrangement models are in good agreement with the molecular dynamics simulations. Quite remarkably, the number and disposition of the tetraethylene glycol chains significantly influence the disposition of the PAHs at the interface and conditionate their packing under pressure. For the three compounds studied, we observed three different behaviors in which the aromatic core is parallel, perpendicular, and tilted with respect to the water surface. We also show that these curved PAHs are able to self-assemble in solution into remarkably large sheets of up to 150 μm2. These results show the relationship, within a family of curved nanographenes, between the monomer configuration and their self-assembly capacity in air/water interfaces and organic-water mixtures.


[Plant hormones as bioregulators (author's transl)].
The discovery and general nature of phytohormones are described and the chemical nature and physiological modes of action presented of the five groups known at present: cytokinins, abscisins, gibberellins, auxins, and ethylene. These groups of substances interact in hormonal patterns that determine the measure of development of the different plant organs, also in relation to the environmental conditions. In their ability to control the growth and development of plants, both in the field and in in vitro culture, phytohormones form an interesting class of bioregulators.


PolyQ repeat expansions in ATXN2 associated with ALS are CAA interrupted repeats.
Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ) repeats of 27-33 in ATAXIN-2 (ATXN2), encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥ 34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs) rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1-3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT), while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC). Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2.


Visual Tracking Using Sparse Coding and Earth Mover's Distance.
An efficient iterative Earth Mover's Distance (iEMD) algorithm for visual tracking is proposed in this paper. The Earth Mover's Distance (EMD) is used as the similarity measure to search for the optimal template candidates in feature-spatial space in a video sequence. The local sparse representation is used as the appearance model for the iEMD tracker. The maximum-alignment-pooling method is used for constructing a sparse coding histogram which reduces the computational complexity of the EMD optimization. The template update algorithm based on the EMD is also presented. When the camera is mounted on a moving robot, e.g., a flying quadcopter, the camera could experience a sudden and rapid motion leading to large inter-frame movements. To ensure that the tracking algorithm converges, a gyro-aided extension of the iEMD tracker is presented, where synchronized gyroscope information is utilized to compensate for the rotation of the camera. The iEMD algorithm's performance is evaluated using eight publicly available videos from the CVPR 2013 dataset. The performance of the iEMD algorithm is compared with eight state-of-the-art tracking algorithms based on relative percentage overlap. Experimental results show that the iEMD algorithm performs robustly in the presence of illumination variation and deformation. The robustness of this algorithm for large inter-frame displacements is also illustrated.


Evaluation of fluorescence polarization method for binding study in carbohydrate-lectin interaction.
The fluorescence polarization (FP) technique was evaluated to determine molecular interaction between plant lectins and polysaccharides, yeast cells and glycopeptide after labeling the lectins with fluorescein isothiocyanate. Use of Lycoris radiata agglutinin allowed determination of the molecular interactions with large biomolecules containing mannose oligomers and polymers. Another example using a fluorescein-labeled glycopeptide also indicated that use of the FP method would allow easy observation of the molecular interactions on the quantitative base. The present technique is highly sensitive and facile because it does not require any washing procedures before measurement.


Histone H3 threonine 11 phosphorylation by Sch9 and CK2 regulates chronological lifespan by controlling the nutritional stress response.
Upon nutritional stress, the metabolic status of cells is changed by nutrient signaling pathways to ensure survival. Altered metabolism by nutrient signaling pathways has been suggested to influence cellular lifespan. However, it remains unclear how chromatin regulation is involved in this process. Here, we found that histone H3 threonine 11 phosphorylation (H3pT11) functions as a marker for nutritional stress and aging. Sch9 and CK2 kinases cooperatively regulate H3pT11 under stress conditions. Importantly, H3pT11 defective mutants prolonged chronological lifespan (CLS) by altering nutritional stress responses. Thus, the phosphorylation of H3T11 by Sch9 and CK2 links a nutritional stress response to chromatin in the regulation of CLS.


Human placental lactogen induces CYP2E1 expression via PI 3-kinase pathway in female human hepatocytes.
The state of pregnancy is known to alter hepatic drug metabolism. Hormones that rise during pregnancy are potentially responsible for the changes. Here we report the effects of prolactin (PRL), placental lactogen (PL), and growth hormone variant (GH-v) on expression of major hepatic cytochromes P450 expression and a potential molecular mechanism underlying CYP2E1 induction by PL. In female human hepatocytes, PRL and GH-v showed either no effect or small and variable effects on mRNA expression of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4, and 3A5. On the other hand, PL increased expression level of CYP2E1 mRNA with corresponding increases in CYP2E1 protein and activity levels. Results from hepatocytes and HepaRG cells indicate that PL does not affect the expression or activity of HNF1α, the known transcriptional activator of basal CYP2E1 expression. Furthermore, transient transfection studies and Western blot results showed that STAT signaling, the previously known mediator of PL actions in certain tissues, does not play a role in CYP2E1 induction by PL. A chemical inhibitor of PI3-kinase signaling significantly repressed the CYP2E1 induction by PL in human hepatocytes, suggesting involvement of PI3-kinase pathway in CYP2E1 regulation by PL. CYP2E1-humanized mice did not exhibit enhanced CYP2E1 expression during pregnancy, potentially because of interspecies differences in PL physiology. Taken together, these results indicate that PL induces CYP2E1 expression via PI3-kinase pathway in human hepatocytes.


A prospective study of diet and prostate cancer in Japanese men.
It has been hypothesized that some aspect of a traditional 'Asian' diet, that is low in animal products and high in soya, may be associated with a reduced risk of prostate cancer. This study aimed to examine the association between dietary intake and prostate cancer risk among 18,115 men in Hiroshima and Nagasaki, Japan, using prospective data from the Life Span Study. Subjects completed a food-frequency questionnaire at baseline (1963, 1965 and/or 1979) and were followed for incident prostate cancer until the end of 1996. During this time, 196 incident prostate cancer cases were identified after 252,602 person-years of observation. Poisson regression was used to calculate incidence rates for each dietary factor after adjustment for age, calendar period, city of residence, radiation dose and education level. Fish intake was significantly associated with an increased risk of prostate cancer; men who consumed fish more than four times per week had a 54 increased risk of developing prostate cancer compared with men who ate fish less than twice per week (RR = 1.54; 95% CI, 1.03-2.31). No other food items, including soya products, were significantly associated with prostate cancer risk. These data suggest that dietary factors may not be strong determinants of prostate cancer in these Japanese men, although the increased risk associated with a high consumption of fish warrants further study.


Somatotropic and thyroid hormones in the acute phase of subarachnoid haemorrhage.
Somatotropic and thyroid hormones are probably important for the recovery after acute brain injury. Still, the dynamics of these hormones after spontaneous subarachnoid haemorrhage (SAH) is not well described. The purpose of this study was to investigate the relation between somatotropic and thyroid hormones and clinical factors after SAH. Twenty patients with spontaneous SAH were included prospectively. Serum concentrations of TSH, fT4, T3, IGF-1 and GH were measured once a day for 7 days after SAH. Hormone patterns and serum concentrations were compared to the severity of SAH, neurological condition at admission, clinical course and outcome of the patients. During the first week after SAH, all patients showed increased GH and IGF-1 concentrations. In the whole group, concentrations of TSH increased, whereas T3 and fT4 decreased. There were no relations of serum concentrations of IGF-1 or GH to clinical condition at admission, clinical course or outcome of the patients. Half of the patients showed low T3 serum concentrations. A complicated course was associated with a deeper fall in TSH and T3 concentrations. There were negative correlations for mean concentrations of TSH and T3 versus WFNS grade and a positive correlation for T3 versus GOS after 6 months, indicating that low concentrations of TSH and T3 were connected to worse SAH grade and poor outcome. All patients showed increased GH and IGF-1 concentrations irrespective of the grade of SAH or clinical course. Patients with a complicated clinical course showed a more pronounced fall in TSH and T3 concentrations and low serum T3 concentrations were related to a more serious SAH and poor patient outcome. These results need to be studied further and they may contribute to the accumulated knowledge needed to understand the complex mechanisms influencing the unpredictable clinical course after SAH.


Beyond the single-atom response in absorption line shapes: probing a dense, laser-dressed helium gas with attosecond pulse trains.
We investigate the absorption line shapes of laser-dressed atoms beyond the single-atom response, by using extreme ultraviolet (XUV) attosecond pulse trains to probe an optically thick helium target under the influence of a strong infrared (IR) field. We study the interplay between the IR-induced phase shift of the microscopic time-dependent dipole moment and the resonant-propagation-induced reshaping of the macroscopic XUV pulse. Our experimental and theoretical results show that as the optical depth increases, this interplay leads initially to a broadening of the IR-modified line shape, and subsequently, to the appearance of new, narrow features in the absorption line.


Lessons from microRNA mutants in worms, flies and mice.
It is apparent that microRNAs (miRNAs) are important components in the regulation of genetic networks in many biological contexts. Based on computational analysis, typical miRNAs are inferred to have tens to hundreds of conserved targets. Many miRNA-target interactions have been validated by various means, including heterologous tests in cultured cells and gain-of-function approaches that can yield striking phenotypes in whole animals. However, these strategies do not report on the endogenous importance of such miRNA activities. Likewise, studies of miRNA pathway mutants can suggest an endogenous role for miRNAs in a given setting, but do not identify roles for specific miRNAs. Therefore, these approaches must be complemented with the analysis of miRNA mutant alleles. In this review, we describe some of the lessons learned from studying miRNA gene deletions in worms, flies and mice, and discuss their implications for the control of endogenous regulatory networks.


Dust measurement of two organophosphorus flame retardants, resorcinol bis(diphenylphosphate) (RBDPP) and bisphenol A bis(diphenylphosphate) (BPA-BDPP), used as alternatives for BDE-209.
Resorcinol bis(diphenylphosphate) (RBDPP) and bisphenol A bis(diphenylphosphate) (BPA-BDPP) are two halogen-free organophosphorus flame retardant (PFRs) that are used as an alternative for the decabromodiphenyl ether (Deca-BDE) technical mixture in TV/flatscreen housing and other electronic consumer products. In this study, dust samples were collected from various microenvironments in The Netherlands (houses, cars), Greece (houses), and Sweden (apartments, cars, furniture stores, electronics stores) and analyzed for RBDPP and BPA-BDPP. Additionally, the dust samples from The Netherlands were analyzed for decabromodiphenyl ether (BDE-209) for comparison and for TPHP, which is a byproduct in the RBDPP and BPA-BDPP technical products. BPA-BDPP was detected in almost all dust samples from The Netherlands, Greece, and Sweden. Highest concentrations were found in dust samples collected on electronic equipment from all three countries with BPA-BDPP levels ranging from <0.1 to 1300 μg/g and RBDPP levels from <0.04 to 520 μg/g. RBDPP and BPA-BDPP levels in dust collected further away from the electronics (source) were usually lower. BDE-209 levels in The Netherlands dust samples collected on and around the electronics were similar and much lower than the BPA-BDPP/RBDPP levels, indicating that the electronics were not the source of BDE-209. Strong positive correlations were found between TPHP concentrations and those of RBDPP (r = 0.805) and BPA-BDPP (r = 0.924), probably due to TPHP being a byproduct in commercial RBDPP and BPA-BDPP mixtures in electronics. To our knowledge, this is the first time that RBDPP and BPA-BDPP were detected in dust samples from Europe.


Inhibition of the antidiuretic hormone hydroosmotic response by phospholipids and phospholipid metabolites.
Phospholipid metabolities and phospholipids containing arachidonic acid (AA) inhibited the antidiuretic hormone (ADH)-induced increase in transepithelial water flow in the toad urinary bladder, but had no effect on basal water flow when added to the serosal bathing solution. Other fatty acid-substituted phospholipid metabolites had no effect on osmotic water movement in the presence or absence of ADH. Indomethacin attenuated the inhibitory effects of the AA containing phospholipid metabolities (PMAA), suggesting that the PMAA response required AA release and prostaglandin (PG) formation. PMAA increased PGE formation as measured by radioimmunoassay. PG have been reported to inhibit ADH-stimulated water flow by inhibiting adenylcyclase. PGE2 (10(-8) M) had no effect on cyclic AMP-stimulated water flow, whereas exogenous AA and PMAA attenuated the hydroosmotic response to added cyclic AMP. Indomethacin only partially reversed the inhibition by AA of the cyclic AMP-associated water movement, suggesting that the inhibition by AA and PMAA may involve other metabolites of AA than PG. PG and the AA cascade have been implicated as cellular modulators of the ADH hydroosmotic response. The present results offer additional support to the theory that this system may regulate the intracellular events that are transduced following receptor activation by ADH.


Photoacoustic imaging using a Fourier transform technique.
The principles of Fourier transformation are applied to photoacoustic imaging. Advantages are threefold: reduction of the power density at the sample; improvement of signal to noise ratio due to multiplexing advantage; and increase of spatial resolution by additional measurements with masks corresponding to higher overtones. The compatibility of Fourier with other multiplex transform techniques is discussed.


Phenobarbital-induced alterations in the activities of the transport and hydrolytic components of the glucose-6-phosphatase system in smooth and rough subfractions of the rat hepatic endoplasmic reticulum.
We have examined the influence of the phenobarbital-induced proliferation of the hepatic endoplasmic reticulum (ER) on the activities of the components of the glucose-6-phosphatase system, i.e., the enzyme, the glucose-6-P translocase (T1), and the phosphate translocase (T2). Young male rats were injected ip twice daily for 4 days with 4 mg/100 g body wt of phenobarbital (PB) or an equivalent volume of saline solution. On the fifth day, the rats were killed and smooth (SER) and rough (RER) fractions of the ER were isolated from liver homogenates. Kinetic constants for glucose-6-P hydrolysis by the system and enzyme were determined and used to calculate the kinetic constants for glucose-6-P transport. T2 activity was approximated by assaying the pyrophosphatase activity at pH 6.0 in intact microsomes. Three times more SER protein was recovered from livers of PB-treated rats. PB-treatment did not alter total liver enzyme activity, but total liver T1 activity was decreased to 59% of the control value. Maximal specific activities of the system, enzyme and T1 were all reduced by PB treatment to 44% of control values in the RER and to 68% of control values in the SER. PB treatment reduced the apparent activity of T2 in RER and SER to 35 and 49% of the respective control values. In the SER from both groups of rats, T1 activity or apparent T2 activity divided by enzyme activity was about 55% of the corresponding ratio in the RER. Our analysis of these data suggests that the lower activities of T1 and T2 in the smooth ER are the results of suppression by some intrinsic component localized in the smooth membrane. Accordingly, the reduction in total liver T1 activity and, therefore, system activity in PB-treated rats reflects the redistribution of the glucose-6-P translocase from the RER to the more abundant SER membrane where it is less active. The possibility is discussed that a higher cholesterol content within the SER membrane is responsible for the lower transport activities.


Deacetylase inhibitors - focus on non-histone targets and effects.
Inhibitors of protein deacetylases have recently been established as a novel therapeutic principle for several human diseases, including cancer. The original notion of the mechanism of action of these compounds focused on the epigenetic control of transcriptional processes, especially of tumor suppressor genes, by interfering with the acetylation status of nuclear histone proteins, hence the name histone deacetylase inhibitors was coined. Yet, this view could not explain the high specificity for tumor cells and recent evidence now suggests that non-histone proteins represent major targets for protein deacetylase inhibitors and that the post-translational modification of the acetylome is involved in various cellular processes of differentiation, survival and cell death induction.


Is Next-Generation Sequencing the way to go for Residual Disease Monitoring in Acute Lymphoblastic Leukemia?
Minimal residual disease (MRD) is the most important independent prognostic factor in acute lymphoblastic leukemia (ALL). Since it has been implemented into in treatment stratification strategies, cure rates have improved significantly for all age groups. Real time quantitative (RQ)-PCR of clonal immunoglobulin and T-cell receptor gene rearrangements using allele-specific primers is currently regarded as the gold standard for MRD analysis in ALL, as it is not only highly sensitive and specific but also provides accurate MRD quantification. Following recent advances in next-generation sequencing (NGS), much attention has been devoted to the development of NGS-based MRD assays. This new technique can enhance sensitivity provided that sufficient numbers of cells are analyzed. Recent reports have shown that NGS-MRD also tends to be more specific for relapse prediction than RQ-PCR. In addition, NGS provides information on the physiological B- and T-cell repertoire during and after treatment, which has been shown to be prognostically relevant. However, before implementation of NGS-MRD detection in clinical practice, several issues must be addressed and the whole workflow needs to be standardized, including not only the analytical phase (spike-in calibrators, quality controls) but also the pre-analytical (e.g. sample preparation) and the post-analytical phases (e.g. bioinformatics pipeline, guidelines for correct data interpretation). These topics are currently addressed by a European network, the EuroClonality-NGS Consortium. In conclusion, NGS is a promising tool for MRD detection with the potential to overcome most of the limitations of RQ-PCR and to become the new gold standard for MRD detection in ALL.


Effect of exercise duration on pro-oxidants and pH in exhaled breath condensate in humans.
Exercise promotes pulmonary oxidative imbalance. In this regard, some evidence has been obtained from the study of exhaled breath condensate (EBC) during urban races, in which the factors involved in the occurrence of this process are still not characterized. In this paper, under laboratory conditions, both the role of time of exercise on the generation of pro-oxidants (H2O2, NO2 (-)) and pH have been assessed in EBC of 16 under-trained subjects who completed three tests of cycloergometric exercise at low intensity (30 % of VO2 max) with a duration of 10, 30, and 90 min. Samples were obtained as follows: immediately before and at 80 min post exertion in each test. In the 90-min test, an increase in H2O2, NO2 (-) concentration in EBC at 80 min post exertion with no changes in the pH was observed. Total O2 consumption and total ventilation weakly correlated with the changes in H2O2 and NO2 (-). In conclusion, the concentration of pro-oxidants in the EBC depends on the duration of the exercise when it is performed at low intensity under laboratory conditions.


The molybdenum--iron protein of Klebsiella pneumoniae nitrogenase. Evidence for non-identical subunits from peptide 'mapping'.
The molybdenum- and iron-containing protein components of nitrogenase purified from Klebsiella pneumoniae, Azotobacter vinelandii, Azotobacter chroococcum and Rhizobium japonicum bacteroids all gave either one or two protein-staining bands after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, depending on the commercial brand of sodium dodecyl sulphate used. The single band obtained with K. pneumoniae Mo-Fe protein when some commercial brands of sodium dodecyl sulphate were used in the preparation of the electrode buffer was resolved into two bands by the addition of 0.01% (v/v) dodecanol to the buffer. Protein extracted from the two bands obtained after electrophoresis of K. pneumoniae Mo-Fe protein gave unique and distinct peptide 'maps' after tryptic digestion. Undissociated Mo-Fe protein contained both sets of tryptic peptides. These data are consistent with Mo-Fe protein from K. pneumoniae being composed of non-identical subunits. Amino acid analyses of the subunit proteins revealed some clear differences in amino acid content, but the two subunits showed close compositional relatedness, with a different index [Metzer, H., Shapiro, M.B., Mosiman, J.E. & Vinton, J.G. (1968) Nature (London) 219, 1166-1168] of 4.7.


Relaxation strategies for patients during dermatologic surgery.
Patient stress and anxiety are common preoperatively and during dermatologic procedures and surgeries. Stress and anxiety can occasionally interfere with performance of procedures or surgery and can induce hemodynamic instability, such as elevated blood pressure or syncope, as well as producing considerable discomfort for some patients. Detection of excess stress and anxiety in patients can allow the opportunity for corrective or palliative measures. Slower breathing, biofeedback, progressive muscular relaxation, guided imagery, hypnosis, meditation and music can help calm and rebalance the patient's autonomic nervous system and immune functioning. Handheld miniaturized heart rate variability biofeedback devices are now available. The relaxation response can easily be taught. Guided imagery can be recorded or live. Live rapid induction hypnosis followed by deepening and then self-guided imagery requires no experience on the part of the patient but does require training and experience on the part of a provider. Recorded hypnosis inductions may also be used. Meditation generally requires more prior experience and training, but is useful when the patient already is skilled in it. Live, guided meditation or meditation recordings may be used. Relaxing recorded music from speakers or headphones or live performance music may also be employed to ease discomfort and improve the patient's attitude for dermatologic procedures and surgeries.


[Ecological characteristics of Arenicola marina L. (Annelida, Polychaeta) and its morphological and biochemical adaptation to burrowing].
Hydrochemical conditions developing in the burrows of lugworms (Arenicola marina L.) by the end of low-tide period are analyzed. The behavior of lugworms in the course of gradual decrease in the content of dissolved oxygen is described. Quantitative data on the hemoglobin contents in the blood of lugworms from different regions of the White Sea are presented. Morphological and biochemical adaptations facilitating the survival of these animals in their narrow burrows upon sharp fluctuations of environmental conditions, which are characteristic of the littoral zone, are discussed.


Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors.
Restrictive dermopathy (RD) is characterized by intrauterine growth retardation, tight and rigid skin with prominent superficial vessels, bone mineralization defects, dysplastic clavicles, arthrogryposis and early neonatal death. In two patients affected with RD, we recently reported two different heterozygous splicing mutations in the LMNA gene, leading to the production and accumulation of truncated Prelamin A. In other patients, a single nucleotide insertion was identified in ZMPSTE24. This variation is located in a homopolymeric repeat of thymines and introduces a premature termination codon. ZMPSTE24 encodes an endoprotease essential for the post-translational cleavage of the Lamin A precursor and the production of mature Lamin A. However, the autosomal recessive inheritance of RD suggested that a further molecular defect was present either in the second ZMPSTE24 allele or in another gene involved in Lamin A processing. Here, we report new findings in RD linked to ZMPSTE24 mutations. Ten RD patients were analyzed including seven from a previous series and three novel patients. All were found to be either homozygous or compound heterozygous for ZMPSTE24 mutations. We report three novel 'null' mutations as well as the recurrent thymine insertion. In all cases, we find a complete absence of both ZMPSTE24 and mature Lamin A associated with Prelamin A accumulation. Thus, RD is either a primary or a secondary laminopathy, caused by dominant de novo LMNA mutations or, more frequently, recessive null ZMPSTE24 mutations, most of which lie in a mutation hotspot within exon 9. The accumulation of truncated or normal length Prelamin A is, therefore, a shared pathophysiological feature in recessive and dominant RD. These findings have an important impact on our knowledge of the pathophysiology in Progeria and related disorders and will help direct the development of therapeutic approaches.


Predictive Role of Urinary Metabolic Profile for Abnormal MRI Score in Preterm Neonates.
Early identification of neonates at risk for brain injury is important to start appropriate intervention. Urinary metabolomics is a source of potential, noninvasive biomarkers of brain disease. We studied the urinary metabolic profile at 2 and 10 days in preterm neonates with normal/mild and moderate/severe MRI abnormalities at term equivalent age. Urine samples were collected at two and 10 days after birth in 30 extremely preterm infants and analyzed using proton magnetic resonance spectroscopy. A 3 T MRI was performed at term equivalent age, and images were scored for white matter (WM), cortical grey matter (cGM), deep GM, and cerebellar abnormalities. Infants were divided in two groups: normal/mild and moderately/severely abnormal MRI scores. No significant clustering was seen between normal/mild and moderate/severe MRI scores for all regions at both time points. The ROC curves distinguished neonates at 2 and 10 days who later developed a markedly less mature cGM score from the others (2 d: area under the curve (AUC) = 0.72, specificity (SP) = 65%, sensitivity (SE) = 75% and 10 d: AUC = 0.80, SP = 78%, SE = 80%) and a moderately to severely abnormal WM score (2 d: AUC = 0.71, specificity (SP) = 80%, sensitivity (SE) = 72% and 10 d: AUC = 0.69, SP = 64%, SE = 89%). Early urinary spectra of preterm infants were able to discriminate metabolic profiles in patients with moderately/severely abnormal cGM and WM scores at term equivalent age. Urine spectra are promising for early identification of neonates at risk of brain damage and allow understanding of the pathogenesis of altered brain development.


Persimmon highly galloylated-tannins in vitro mitigated α-amylase and α-glucosidase via statically binding with their catalytic-closed sides and altering their secondary structure elements.
Reticence of α-amylase (α-Amy) and α-glucosidase (α-Glu) is needed due to their mitigation potency on the glucose absorption. In this study, the anti-amylolytic effects of persimmon tannins (PT) on α-Amy and α-Glu and their interaction mechanisms were investigated. It was found that PT inhibited α-Amy and α-Glu with the half inhibitory concentration (IC50 ) values of 0.35 and 0.24 mg/ml, respectively. Fluorescence and FT-IR spectrometry results showed that PT could bind to enzymes and alter their conformations. Molecular docking showed that the structural units of PT interacted with the key sites (amino acids Glu233, Asp197, and Asp300) of α-Amy by H-bonds and π-π interactions, while they bound to the residues closed to the active sites of α-Glu. The whole results implied that PT was a promising mitigator of α-Amy and α-Glu. It might help to understand mechanisms of glycemic response inhibition of PT and develop certain therapeutic strategies against diabetes. PRACTICAL APPLICATIONS: α-Amy and α-Glu are the crucial starch digestive enzymes associated with type II diabetes mellitus in humans. Persimmon is an excellent source of bio-functional tannins which potentially mitigate the type II diabetes. This study showed that PT beneficially decreased the action of the carbohydrate digestion-related enzymes, namely α-Amy and α-Glu via interaction simultaneously, which could be used to formulate a functional food and natural medicine.


Overexpression of the Wild Soybean R2R3-MYB Transcription Factor GsMYB15 Enhances Resistance to Salt Stress and Helicoverpa Armigera in Transgenic Arabidopsis.
Plant R2R3-MYB transcription factors (TFs) have been suggested to play crucial roles in the response to diverse abiotic and biotic stress factors but there is little molecular evidence of this role in soybean plants. In this work, we identified and functionally characterized an R2R3-MYB TF, namely, GsMYB15, from the wild soybean ED059. Protein and promoter sequence analysis indicated that GsMYB15 is a typical R2R3-MYB TF and contains multiple stress-related cis-elements in the promoter region. GsMYB15 is located in the nucleus and exhibits transcriptional activation activity. QPCR assays suggested that the expression of GsMYB15 could be induced by NaCl, insect attacks and defense-related hormones (MeJA and SA). Furthermore, GsMYB15 exhibited highest expression in pods compared to other tissues. Functional analysis of GsMYB15 demonstrated that overexpression of GsMYB15 could increase salt tolerance and enhance the resistance to H. armigera larvae in transgenic Arabidopsis plants. Moreover, overexpression of GsMYB15 also affected the expression levels of salt stress- and defense-related genes in the transgenic plants. Feeding with transgenic Arabidopsis plant leaves could significantly suppress the expression levels of immunity-related genes in H. armigera larvae. Overexpression of GsMYB15 also increased mesophyll cell levels in transgenic plants. Taken together, these results provide evidence that GsMYB15 is a positive regulator of salt stress tolerance and insect resistance in transformed Arabidopsis plants.


Use of and attitudes toward complementary and alternative medicine among osteopathic medical students.
Complementary and alternative medicine (CAM) has grown into a huge health care industry in the United States, with 91.5 million people (38% of adults) using CAM in 2007. Given the increase in CAM use and the need for CAM education for health professionals, it is important to understand the baseline attitudes and beliefs of osteopathic medical students regarding CAM, as well as the factors that may have formed them. (1) To determine osteopathic medical students' use of different CAM modalities. (2) To assess osteopathic medical students' attitudes toward CAM using a previously validated instrument. A previously validated, 29-item Integrative Medicine Attitude Questionnaire and a 10-item CAM Health Belief Questionnaire were administered to osteopathic medical students. Demographic and other data were collected on student use of and recommendations for CAM modalities as well as student awareness and use of primary CAM information resources. Survey respondents were 635 osteopathic medical students from 7 osteopathic medical schools and additional locations in the United States. Osteopathic medical students demonstrated positive attitudes toward CAM use. A total of 527 osteopathic medical students (83.0%) self-reported the use of at least 1 CAM modality, whereas 69 students (10.9%) used just 1 CAM modality and 458 (72.1%) used 2 or more modalities. The most commonly used CAM modalities--meditation/yoga/relaxation/imagery, massage, and spirituality/prayer--were also most likely to be suggested to patients by osteopathic medical students. Sex, age, and the use of CAM modalities were significantly correlated with attitudes toward CAM modalities. Osteopathic medical students had a positive attitude toward CAM and had high levels of self-reported CAM knowledge and use. Osteopathic medical students who acquire professional training and have personal experience with CAM may be in a better position to discuss CAM with future patients.


Judicial Dilemmas of Female Domestic Violence Victims: An Empirical Study Based on Chinese Civil Judgments in 2020.
Women are the primary victims of domestic violence, but their experiences are often ignored in Chinese judicial judgments. Among 350 Chinese civil judgments on domestic violence in 2020, more than 96% involved female victims, and they faced various judicial dilemmas when seeking civil remedies. The court confirmed the existence of domestic violence in 26% of the cases, and 27% of applications for personal safety protection orders were rejected. More than two-thirds of female plaintiffs' divorce applications were not approved, and they received no compensation. This study analyzed the cause of these judicial dilemmas and proposed some solutions.


What happens during early outpatient palliative care consultations for persons with newly diagnosed advanced cancer? A qualitative analysis of provider documentation.
Early outpatient palliative care consultations are recommended by clinical oncology guidelines globally. Despite these recommendations, it is unclear which components should be included in these encounters. Describe the evaluation and treatment recommendations made in early outpatient palliative care consultations. Outpatient palliative care consultation chart notes were qualitatively coded and frequencies tabulated. Outpatient palliative care consultations were automatically triggered as part of an early versus delayed randomized controlled trial (November 2010 to April 2013) for patients newly diagnosed with advanced cancer living in the rural Northeastern US. In all, 142 patients (early = 70; delayed = 72) had outpatient palliative care consultations. The top areas addressed in these consultations were general evaluations-marital/partner status (81.7%), spirituality/emotional well-being (80.3%), and caregiver/family support (79.6%); symptoms-mood (81.7%), pain (73.9%), and cognitive/mental status (68.3%); general treatment recommendations-counseling (39.4%), maintaining current medications (34.5%), and initiating new medication (23.9%); and symptom-specific treatment recommendations-pain (22.5%), constipation (12.7%), depression (12.0%), advanced directive completion (43.0%), identifying a surrogate (21.8%), and discussing illness trajectory (21.1%). Compared to the early group, providers were more likely to evaluate general pain ( p = 0.035) and hospice awareness ( p = 0.005) and discuss/recommend hospice ( p = 0.002) in delayed group participants. Outpatient palliative care consultations for newly diagnosed advanced cancer patients can address patients' needs and provide recommendations on issues that might not otherwise be addressed early in the disease course. Future prospective studies should ascertain the value of early outpatient palliative care consultations that are automatically triggered based on diagnosis or documented symptom indicators versus reliance on oncologist referral.


Thyroid receptor β involvement in the effects of acute nicotine on hippocampus-dependent memory.
Cigarette smoking is common despite adverse health effects. Nicotine's effects on learning may contribute to addiction by enhancing drug-context associations. Effects of nicotine on learning could be direct or could occur by altering systems that modulate cognition. Because thyroid signaling can alter cognition and nicotine/smoking may change thyroid function, nicotine could affect learning through changes in thyroid signaling. These studies investigate the functional contributions of thyroid receptor (TR) subtypes β and α1 to nicotine-enhanced learning and characterize the effects of acute nicotine and learning on thyroid hormone levels. We conducted a high throughput screen of transcription factor activity to identify novel targets that may contribute to the effects of nicotine on learning. Based on these results, which showed that combined nicotine and learning uniquely acted to increase TR activation, we identified TRs as potential targets of nicotine. Further analyses were conducted to determine the individual and combined effects of nicotine and learning on thyroid hormone levels, but no changes were seen. Next, to determine the role of TRβ and TRα1 in the effects of nicotine on learning, mice lacking the TRβ or TRα1 gene and wildtype littermates were administered acute nicotine prior to fear conditioning. Nicotine enhanced contextual fear conditioning in TRα1 knockout mice and wildtypes from both lines but TRβ knockout mice did not show nicotine-enhanced learning. This finding supports involvement of TRβ signaling in the effect of acute nicotine on hippocampus-dependent memory. Acute nicotine enhances learning and these effects may involve processes regulated by the transcription factor TRβ.


Evaluation of response to chemotherapy with fiberoptic bronchoscopy in non-small cell lung cancer.
Fiberoptic bronchoscopy was performed before and during administration of chemotherapy in 32 patients with unresectable non-small cell carconoma of the lung. Pretreatment findings varied with the histologic cell type. Direct visual and/or pathologic evidence of cancer was obtained in 11 of 11 patients with epidermoid, in 5 of 7 with large cell, and in 9 of 14 with adenocarcinoma. In 5 of the 32 patients, intrathoracic tumor was documented at bronchoscopy but not by chest x-ray. During chemotherapy, one of five episodes of response and eight of 21 episodes of chest tumor progression were detected solely by bronchoscopy, while in an additional two objective responses and six progressions, bronchoscopic and radiographic findings simultaneously improved or deteriorated. The likelihood of documenting disease progression by bronchoscopy also depended upon the histologic type of cancer. Enlarging chest tumor found solely by chest x-ray occurred exclusively in patients with large cell carcinoma and adenocarcinoma. During chemotherapeutic treatment of our pateints, addition of serial bronchoscopic examinations to standard means of assessing tumor response frequently allowed the earlier discontinuation of an ineffective drug regimen.


Alterations in microbiota of patients with COVID-19: potential mechanisms and therapeutic interventions.
The global coronavirus disease 2019 (COVID-19) pandemic is currently ongoing. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high proportion of COVID-19 patients exhibit gastrointestinal manifestations such as diarrhea, nausea, or vomiting. Moreover, the respiratory and gastrointestinal tracts are the primary habitats of human microbiota and targets for SARS-CoV-2 infection as they express angiotensin-converting enzyme-2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) at high levels. There is accumulating evidence that the microbiota are significantly altered in patients with COVID-19 and post-acute COVID-19 syndrome (PACS). Microbiota are powerful immunomodulatory factors in various human diseases, such as diabetes, obesity, cancers, ulcerative colitis, Crohn's disease, and certain viral infections. In the present review, we explore the associations between host microbiota and COVID-19 in terms of their clinical relevance. Microbiota-derived metabolites or components are the main mediators of microbiota-host interactions that influence host immunity. Hence, we discuss the potential mechanisms by which microbiota-derived metabolites or components modulate the host immune responses to SARS-CoV-2 infection. Finally, we review and discuss a variety of possible microbiota-based prophylaxes and therapies for COVID-19 and PACS, including fecal microbiota transplantation (FMT), probiotics, prebiotics, microbiota-derived metabolites, and engineered symbiotic bacteria. This treatment strategy could modulate host microbiota and mitigate virus-induced inflammation.


Tetrahydrobiopterin corrects Escherichia coli endotoxin-induced endothelial dysfunction.
Acute inflammation causes endothelial dysfunction, which is partly mediated by oxidant stress and inactivation of nitric oxide. The contribution of depletion of tetrahydrobiopterin (BH(4)), the cofactor required for nitric oxide generation, is unclear. In this randomized, double-blind, three-way crossover study, forearm blood flow (FBF) responses to ACh and glyceryltrinitrate (GTN) were measured before and 3.5 h after infusion of Escherichia coli endotoxin (LPS, 20 IU/kg iv) in eight healthy men. The effect of intra-arterial BH(4) (500 microg/min), placebo, or vitamin C (24 mg/min) was studied on separate days 3.5 h after LPS infusion. In addition, human umbilical vein endothelial cells were incubated for 24 h with vitamin C and LPS. ACh and GTN caused dose-dependent forearm vasodilation. The FBF response to ACh, which was decreased by 23 +/- 17% (P < 0.05) by LPS infusion, was restored to baseline reactivity by BH(4) and vitamin C. FBF responses to GTN were not affected by BH(4) or vitamin C. LPS increased leukocyte count, high-sensitivity C-reactive protein, IL-6, IL-1beta, IFN-gamma, monocyte chemoattractant protein-1, pulse rate, and body temperature and decreased platelet count and vitamin C concentration. Vitamin C increased forearm plasma concentration of BH(4) by 32% (P < 0.02). Incubation with LPS and vitamin C, but not LPS alone, increased intracellular BH(4) concentration in human umbilical vein endothelial cells. Impaired endothelial function during acute inflammation can be restored by BH(4) or vitamin C. Vitamin C may exert some of its salutary effects by increasing BH(4) concentration.


Skin Wound Healing of the Adult Newt, Cynops pyrrhogaster: A Unique Re-Epithelialization and Scarless Model.
In surgical and cosmetic studies, scarless regeneration is an ideal method to heal skin wounds. To study the technologies that enable scarless skin wound healing in medicine, animal models are useful. However, four-limbed vertebrates, including humans, generally lose their competency of scarless regeneration as they transit to their terrestrial life-stages through metamorphosis, hatching or birth. Therefore, animals that serve as a model for postnatal humans must be an exception to this rule, such as the newt. Here, we evaluated the adult newt in detail for the first time. Using a Japanese fire-bellied newt, Cynops pyrrhogaster, we excised the full-thickness skin at various locations on the body, and surveyed their re-epithelialization, granulation or dermal fibrosis, and recovery of texture and appendages as well as color (hue, tone and pattern) for more than two years. We found that the skin of adult newts eventually regenerated exceptionally well through unique processes of re-epithelialization and the absence of fibrotic scar formation, except for the dorsal-lateral to ventral skin whose unique color patterns never recovered. Color pattern is species-specific. Consequently, the adult C. pyrrhogaster provides an ideal model system for studies aimed at perfect skin wound healing and regeneration in postnatal humans.


[Ethical problems experienced in a supervised curricular internship in nursing in an integrated curriculum].
An exploratory, qualitative study with the objective of analyzing repercussions of the supervised curricular internship in the development of the ethical dimension of competency in undergraduate nursing students. Semistructured interviews were performed with 28 students, professors and nurse preceptors of a public institution of higher education in the state of São Paulo, during the period of October of 2010 to March of 2011. The empirical result was subjected to the technique of discourse analysis and resulted in the empirical categories: preservation of autonomy; social responsibility and respect in interpersonal relations in health care delivery and in the teaching - learning process; treatment and care from the ethical dimension; and, public responsibility and social justice. It was concluded that the phase that uses problematization as a method of teaching and learning provides critical reflection about professional practice in the services and system of health.


Expansion of a clonal CD8+CD57+ large granular lymphocyte population after autologous stem cell transplant in multiple myeloma.
Clonal expansions of large granular lymphocytes (LGLs) have been identified in patients following stem cell transplants and may represent posttransplant LGL leukemias or reactive immune responses. To differentiate between these 2 possibilities, we assessed peripheral blood and bone marrow of patients with myeloma after autologous stem cell transplant. All patients examined shortly after autologous stem cell transplant had significant increases in the LGLs in the peripheral blood and bone marrow (71% of lymphocytes) as compared with controls (39%). This increase was detectable years after transplant. The LGLs had a reproducible immunophenotype of CD8+CD57+ T cells without phenotypic abnormalities in 19 of 20 patients. Sixty-five percent of the post-autologous stem cell transplant patients had clonal T-cell receptor gene rearrangements in the bone marrow, yet no patients had neutropenia or splenomegaly. Although the LGL expansions were clonal and persistent, the lack of clinical sequelae suggests the clonal LGL expansion is a reactive, potentially beneficial, immune response to autologous stem cell transplant.


Pneumonia and lower respiratory infections in nursing home residents: predictors of hospitalization and mortality.
To compare predictors of hospitalization and death in nursing home residents with pneumonia and other lower respiratory infections (LRIs). A nested cohort study. Nine nursing homes in southern Ontario. Three hundred fifty-three nursing home residents with LRIs (enrolled in the control arm of a clinical trial). Comorbidities, vaccination status, age, health-related quality of life, functional status, and vital statistics were evaluated as potential predictors of hospitalization and mortality at 30 days. Moderate to high disease severity score on a practical severity scale was a strong independent predictor of hospitalization (odds ratio (OR)=7.12, P<.001) and mortality (OR=5.04, P=.003). Diagnosis of pneumonia, established using chest radiograph, was also associated with hospitalization (OR=2.43, P=.008) and mortality (OR=2.35, P=.02). Oxygen saturation (<90%) was a strong independent predictor of hospitalization (OR=3.02, P=.004) but was not a significant predictor of mortality in multivariable analyses. Diagnosis of congestive heart failure (OR=2.26, P=.02) was an independent predictor of hospitalization, whereas receipt of pneumococcal vaccine (OR=0.36, P=.01) and greater functional independence (OR=0.92, P=.02) were negatively associated with hospitalization. In nursing home residents with LRI, severity of illness and radiographically confirmed pneumonia are predictive of death and hospitalization.


Specimen retrieval during elective laparoscopic cholecystectomy: is it safe not to use a retrieval bag?
Since the introduction of laparoscopic surgery for gallbladder disease different types of retrieval devices have been used to extract the gallbladder from the peritoneal cavity. These devises infer additional costs and may lead to associated risks and complications. We aimed to evaluate the safety of gallbladder retrieval without the use of a retrieval device. A prospective study was conducted across two teaching hospitals in the Republic of Ireland from July 2010-2013. Patients undergoing planed elective day case laparoscopic cholecystectomy in the two institutions were included in the study. Data were collected on patient demographics, the use of a bag, any need for extension of fascial incision, any unexpected over night stay, any 30-day post operative complications and presence of port site hernia within 1 year surgery. There were 373 planned elective day case laparoscopic cholecystectomy performed during the study period. A bag was not used to retrieve the gallbladder in 41 % (n = 152) patients. A retrieval bag was used in the majority of patients (71 %) who required over night stay due to pain. Overall wound infection rate was low (2.4 %), with 57 % of those being in patients where no retrieval bag was used. An increase incision in the fascia was required in 9.7 % of patients. The majority of these were in patients in whom a retrieval bag was used (75 %). At 1 year follow up, there were no recorded cases of port site hernia for the no retrieval bag group and two (0.9 %) cases of umbilical port site hernias in the group where retrieval bag was used. In cases of elective uncomplicated laparoscopic cholecystectomy for radiologically confirmed benign disease there was no benefit in using a retrieval bag. Furthermore, not using a bag was associated with less need for increasing the size of the fascial incision thereby reducing post operative pain and risk of port site hernia.


BCG promotes cord blood monocyte-derived dendritic cell maturation with nuclear Rel-B up-regulation and cytosolic I kappa B alpha and beta degradation.
Mycobacterium bovis bacillus Calmette-Guerin (BCG) is given to millions of neonates in developing countries as a vaccine against Mycobacterium tuberculosis; however, little is known about the initiation of response in neonatal dendritic cells (DCs) to BCG. To address this issue, the interaction of BCG with human cord blood monocyte-derived DCs was studied. We showed that BCG could promote cord blood monocyte-derived DC maturation by up-regulation of CD80, CD83, CD86, CD40, and MHC class II molecules and down-regulation of mannose receptor. BCG was able to induce similar levels of tumor necrosis factor-alpha and IL-10 but no bioactive IL-12p70 production from cord blood DCs as from adult blood DCs. Functionally BCG-treated cord blood DCs had higher ability to induce mixed lymphocyte reaction than non-BCG-treated cord blood DCs. Both non-BCG-treated and BCG-treated cord blood DCs efficiently induced a high level of IL-10, medium level of interferon-gamma, but little IL-4 production by cord blood naïve CD4+ T cells. Heat shock protein 65, a key component of BCG, had no effect on cord blood DC maturation in terms of CD86, MHC class II, and mannose receptor up-regulation. During the BCG-induced maturation process of cord blood DCs, nuclear transcription factor Rel-B was up-regulated and cytosolic Rel-B down-regulated with cytosolic IkappaB alpha and beta degradation. These results suggest that BCG can promote cord blood monocyte-derived DC maturation, and that the mechanism is through the up-regulation of nuclear Rel-B secondary to the degradation of cytosolic IkappaB alpha and beta.


Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites.
mirSVR is a new machine learning method for ranking microRNA target sites by a down-regulation score. The algorithm trains a regression model on sequence and contextual features extracted from miRanda-predicted target sites. In a large-scale evaluation, miRanda-mirSVR is competitive with other target prediction methods in identifying target genes and predicting the extent of their downregulation at the mRNA or protein levels. Importantly, the method identifies a significant number of experimentally determined non-canonical and non-conserved sites.


The Museum of Health Care at Kingston: its role in the preservation of the legacy of health care in Canada.
Beginning in the 16th century, museums were an important resource for medical education. By the mid 20th century, however, the perceived educational value of museum collections declined and museums adopted the strategy of turning collections into publicly accessible medical history. The Museum of Health Care at Kingston, governed by a Board of Directors, began in 1991. The collection reflective of health care in Canada is available as a research resource through the Museum website and Artefacts Canada. The Museum communicates the history and science of health and health care as it has occurred in Canada to the general public by means of special events, exhibits and educational programs. The outstanding challenge for the Museum, as a not-for-profit institution, is to meet the increasing demands of the annual operating budget and to establish an Endowment Fund to assure long-term financial stability of the Museum.


Influence of physical activity and maturation status on bone mass and geometry in early pubertal girls.
This study aimed to evaluate the influence of leisure-time physical activity on the development of bone mass and density in early pubertal girls. Scores of physical activity were obtained from 242 Finnish girls (10-12 years old within Tanner Stages I-II) using a questionnaire. Bone mass and density were assessed using different densitometric techniques. At Tanner Stage I, active girls had significantly higher bone mineral mass (BMC) and areal bone mineral density (aBMD) of the whole body and cortical volumetric BMD and thickness of the tibial shaft compared with sedentary girls (P<0.05). On the other hand, the active girls at Tanner Stage II showed significantly higher values only in BMC and aBMD at the lumbar spine (P=0.017 and P=0.007, respectively). These indicated that girls at Tanner Stage I with higher leisure-time physical activity level benefited more from physical activity in terms of their bone development than their less active counterparts. Our results provide evidence that the most beneficial time for physical exercise to exhibit its effect on bone development is in the earlier pubertal period for normal school children, but the positive effect on the lumbar spine is also demonstrated in Tanner Stage II.