Relative significance of different hydrocarbons for the carcinogenic potency of emissions from various incomplete combustion processes.
Animal experiments have shown that the carcinogenic activity of organic extracts of exhaust condensates is caused predominantly by PAHs containing 4-6 rings. The carcinogenic potency not only of PAH-containing extracts but also of the whole exhausts has often been estimated from their benzo[a]pyrene (BP) content. However, this simplified yardstick should not be applied for comparison of the carcinogenic potency of different types of PAH-containing exhausts. Epidemiological and experimental studies indicate that, for the induction of a certain tumour incidence, inhaled cigarette smoke contains about 100 times less BP and inhaled diesel exhaust contains about 1000 times less BP than the exhausts from coke ovens or heated tar pitch which yield the same results. This means that diesel exhaust and cigarette smoke contain--apart from PAHs--highly potent carcinogenic substances and/or they induce tumorigenic reactions which are very effective.


Safety of Oral Dofetilide Reloading for Treatment of Atrial Arrhythmias.
Although dofetilide labeling states that the drug must be initiated or reinitiated with continuous electrocardiographic monitoring and in the presence of trained personnel, the risks of dofetilide reloading justifying repeat hospitalization have not been investigated. Patients admitted for dofetilide reloading for atrial arrhythmias were retrospectively reviewed. The need for dose adjustment and the incidence of torsades de pointes (TdP) were identified. The incidence of TdP in dofetilide reloading was compared with patients admitted for dofetilide initial loading. Of 138 patients admitted for dofetilide reloading for atrial arrhythmias, 102 were reloaded at a previously tolerated dose, 30 with a higher dose from a previously tolerated dose and 2 at a lower dose; prior dosage was unknown in 4 patients. Dose adjustment or discontinuation was required in 44 patients (31.9%). No TdP occurred in the same dose reloading group, but TdP occurred in 2 patients admitted to increase dofetilide dosage (0% versus 6.7%; P=0.050). Dofetilide dose adjustment or discontinuation was required in 30 of 102 patients (29.4%) reloaded at a previously tolerated dose and in 11 of 30 patients (36.7%) admitted for an increase in dose. Although no TdP occurred in patients admitted to reload dofetilide at the same dose as previously tolerated, dosage adjustments or discontinuation was frequent and support the need for hospitalization for dofetilide reloading. Patients admitted for reloading with a higher dose tended to be at higher risk for TdP than patients reloaded at a prior tolerated dose.


Soft learning vector quantization and clustering algorithms based on ordered weighted aggregation operators.
This paper presents the development and investigates the properties of ordered weighted learning vector quantization (LVQ) and clustering algorithms. These algorithms are developed by using gradient descent to minimize reformulation functions based on aggregation operators. An axiomatic approach provides conditions for selecting aggregation operators that lead to admissible reformulation functions. Minimization of admissible reformulation functions based on ordered weighted aggregation operators produces a family of soft LVQ and clustering algorithms, which includes fuzzy LVQ and clustering algorithms as special cases. The proposed LVQ and clustering algorithms are used to perform segmentation of magnetic resonance (MR) images of the brain. The diagnostic value of the segmented MR images provides the basis for evaluating a variety of ordered weighted LVQ and clustering algorithms.


Chronic intestinal pseudo-obstruction in adults: A practical guide to identify patient subgroups that are suitable for more specific treatments.
Chronic intestinal pseudo-obstruction is a rare and heterogeneous syndrome characterized by recurrent symptoms of intestinal obstruction with radiological features of dilated small or large intestine with air/fluid levels in the absence of any mechanical occlusive lesion. Several diseases may be associated with chronic intestinal pseudo-obstruction and in these cases, the prognosis and treatment are related to the underlying disease. Also, in its "primary or idiopathic" form, two subgroups of patients should be determined as they require a more specific therapeutic approach: patients whose chronic intestinal pseudo-obstruction is due to sporadic autoimmune/inflammatory mechanisms and patients whose neuromuscular changes are genetically determined. In a context of a widely heterogeneous adult population presenting chronic intestinal pseudo-obstruction, this review aims to summarize a practical diagnostic workup for identifying definite subgroups of patients who might benefit from more specific treatments, based on the etiology of their underlying condition.


Demographics, aging and health care: is there a crisis?
Will the aging of Canada's population bankrupt the health care system? In this issue (see pages 1555 to 1560) Dr. Marie Demers reports that the increase in physician service costs for elderly people in Quebec from 1982 to 1992 resulted primarily from increased utilization and only secondarily from the growth of the elderly population. In this editorial the author argues that the common perception that masses of elderly people will soon swamp the system deflects attention from the crucial issue of utilization. Although a wide range of interventions for elderly people have demonstrable benefits, more research is needed to ensure that intensified services, especially for elderly people in good health, are effective and well targeted. It is not the aging of our population that threatens to precipitate a financial crisis in health care, but a failure to examine and make appropriate changes to our health care system, especially patterns of utilization.


Bilateral caudate infarct--a case report.
Caudate strokes comprise only a small proportion of all subtypes of strokes. Bilateral caudate infarcts are even rarer and only a few cases have been reported in the literature. We report an 86-year-old woman with bilateral caudate infarcts. She had no past medical history of note. She presented with headache for several days and drowsiness on day of admission. Clinical examination revealed abulia, inability to comprehend or verbalize (acute mutism), right-sided neglect and right-sided hemiparesis. Computed tomographic (CT) scan brain revealed decreased attenuation in both heads of both caudate nuclei with extension across the anterior limb of both internal capsules to involve the lentiform nuclei. Echocardiography showed aortic valve sclerosis, mild mitral and aortic regurgitation and normal left ventricular function. Carotid ultrasound revealed mild stenosis of proximal right internal carotid and left distal common carotid and adjacent proximal internal carotid arteries. She showed initial improvement in the first week, but subsequently had a progressive downward course despite rehabilitation and died 44 days after her stroke. A patient with bilateral caudate infarcts is likely to have poor prognosis for rehabilitation and survival.


Patient-reported outcome measures after periodontal surgery.
The present study aimed to explore the impact of different periodontal surgical treatments on the quality of life and postoperative morbidity. The present study is a single-center, prospective, observational cohort trial. One hundred fifty-five patients, referred to the Periodontal Department of Bologna University who needed periodontal surgical treatment, were recruited. The self-reported perception of the postoperative course was assessed using the following anonymous questionnaires: Italian oral health impact profile (I-OHIP-14), visual analog scale (VAS) to evaluate the intensity of the pain, and 5-point Likert scale. Patients reported a mean OHIP-14 total score of 9.87±8.5 (range 0-42), significantly influenced by the female sex, flap extension, and periodontal dressing. A mean VAS score of 2.96±2.39 (range 0-9) was calculated, and was found to be influenced by the presence of vertical releasing incisions and palatal flap extension. Of the 155 subjects, 40 (25.8%) patients reported bleeding as a post-surgical complication, 96 (61.9%) swelling, 105 (67.7%) eating discomfort, and 44 (28.4%) reported speech discomfort. Within the limitations of the nature of the present study, periodontal surgical procedures have a low impact on patients' quality of life evaluated through the OHIP-14 and VAS pain questionnaires. Periodontal surgical procedures are safe procedures, with a limited duration of postoperative discomfort as well as the incidence of complications.


The role of puberty in the developing adolescent brain.
Adolescence refers to the period of physical and psychological development between childhood and adulthood. The beginning of adolescence is loosely anchored to the onset of puberty, which brings dramatic alterations in hormone levels and a number of consequent physical changes. Puberty onset is also associated with profound changes in drives, motivations, psychology, and social life; these changes continue throughout adolescence. There is an increasing number of neuroimaging studies looking at the development of the brain, both structurally and functionally, during adolescence. Almost all of these studies have defined development by chronological age, which shows a strong-but not unitary-correlation with pubertal stage. Very few neuroimaging studies have associated brain development with pubertal stage, and yet there is tentative evidence to suggest that puberty might play an important role in some aspects of brain and cognitive development. In this paper we describe this research, and we suggest that, in the future, developmental neuroimaging studies of adolescence should consider the role of puberty.


Family stress and youth mental health problems: Self-efficacy and future orientation mediation.
The following study assessed whether future orientation and self-esteem mediated the relationship between family stress and mental health problems among African American youth. Data from this study included 638 African American adolescents purposively sampled from predominantly low-income neighborhoods. Major variables assessed were family stress, self-esteem, future orientation, mental health, and covariates (i.e., gender, sexual orientation, and socioeconomic proxy). Structural equation modeling computed direct and indirect (meditational) relationships between family stress and youth mental health. The average age of participants was 15.83 years old, slightly half of whom were female. The path model detected a significant relationship between family stress and mental health problems. Self-esteem and future orientation had a significant mediation effect on the relationship between family stress and mental health problems. Overall findings underscore the importance of strengthening resilience factors for African American youth, especially those who live in low-income communities. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Lanosterol 14alpha-demethylase (CYP51) and spermatogenesis.
CYP51 is the only gene of the cytochrome P450 (P450, or CYP) superfamily that is expressed in prokaryotes and eukaryotes. In animals, the gene product, P45014DM, catalyzes the lanosterol 14alpha-demethylase reaction, an essential step in cholesterol biosynthesis. P45014DM serves a housekeeping role, and it was surprising to find the highest level of CYP51 expression in the testes. This is a result of very high-level CYP51 expression in postmeiotic, haploid spermatids and results in elevated P45014DM activity in these cells. It is proposed that the elevated level of 14alpha-demethylase activity leads to production of signaling sterols by haploid germ cells, although the function of such sterols in males is unknown.


Genetic and cytological control of the asymmetric divisions that pattern the Volvox embryo.
The highly regular pattern in which approximately 2000 small somatic cells and 16 large reproductive cells (or 'gonidia') are arranged in a typical asexual adult of Volvox carteri can be traced back to a stereotyped program of embryonic cleavage divisions. After five symmetrical divisions have produced 32 cells of equal size, the anterior 16 cells cleave asymmetrically, to produce one small somatic cell initial and one larger gonidial initial each. The gonidial initials then cease dividing before the somatic cell initials do. The significance of the visibly asymmetric divisions is underscored by genetic and experimental evidence that differences in size--rather than differences in cytoplasmic quality--are causally important in activating the programs that cause small cells to become mortal somatic cells and large cells to differentiate as reproductive cells. A number of loci, including at least five mul ('multiple gonidia') loci, appear to be responsible for determining where and when asymmetric divisions will occur, since mutations at these loci result in modified temporal and/or spatial patterns of asymmetric division in one or more portions of the life cycle. But the capacity to divide asymmetrically at all appears to require a function encoded by the gls (gonidialess) locus, since gls mutants fail to execute any asymmetric divisions. Second-site suppressors of gls that have been identified may encode other functions required for asymmetric division. Cytological and immunocytochemical studies of dividing embryos are being undertaken in an attempt to elucidate the mechanisms by which cell-division planes are established--and shifted--under the influence of such pattern-specifying genes. Studies to date clearly indicate a central role for the basal body apparatus, and particularly its microtubular rootlets, in establishing the orientation of both the mitotic spindle and the cleavage furrow; but it remains to be determined how behavior of the division apparatus becomes modified during asymmetric division.


Multiple polymorphic sites at the ITS and ATAN loci in cultured isolates of Perkinsus marinus.
Sequence analysis of genomic DNA from the protozoan parasite Perkinsus marinus at two loci revealed genetic polymorphisms within and among different cultured isolates. Genomic DNA from 12 Perkinsus marinus isolates was amplified at the internal transcribed spacer region and at an anonymous locus previously identified to contain polymorphisms by restriction fragment length polymorphism analysis. Fourteen polymorphic nucleotide positions were identified at the internal transcribed spacer region; eight in internal transcribed spacer 1 and six in internal transcribed spacer 2. Thirteen polymorphic nucleotide sites were identified within the anonymous locus. In some instances, more than three different sequences were observed at both the internal transcribed spacer region and at the anonymous locus from a single clonal isolate, suggesting the possibility of recombination in cultured cells and/or strand jumping during the polymerase chain reaction. Intra-isolate sequence variation (3.46% for the anonymous locus and 3.08% for internal transcribed spacer 1) was in several cases as high as inter-isolate sequence variation, even in one isolate where recombination was not evident. High intra- and inter-isolate variation detected at both loci demonstrates the importance of determining the genetic variation of each locus prior to development of sequence-based molecular diagnostics.


Possible mechanism by which coenzyme Q10 improves reoxygenation-induced recovery of cardiac contractile force after hypoxia.
To elucidate possible mechanisms by which coenzyme Q10 enhances reoxygenation-induced recovery of cardiac contractile force after hypoxia, rabbit hearts were subjected to hypoxic perfusion for 20 min, followed by 45 min-reoxygenation with or without pretreatment with coenzyme Q10. Hypoxia induced a decline in cardiac contractile force, a decrease in myocardial high-energy phosphates and a release of ATP metabolites and creatine phosphokinase from the perfused heart. Upon reoxygenation the rate of release of ATP metabolites subsided, but no appreciable recovery of the loss of contractile force and the reduction of myocardial ATP content was seen, and the release of creatine phosphokinase was increased further. Pretreatment of rabbits with coenzyme Q10 resulted in an appreciable recovery of cardiac contractile force and of myocardial ATP content upon reoxygenation. The release of creatine phosphokinase from hearts during hypoxia and reoxygenation was inhibited completely by the pretreatment. Changes in the UV absorbance of the perfusate suggested that coenzyme Q10 reduced the loss of ATP metabolites from hypoxic hearts. Furthermore, high-performance liquid chromatographic analysis indicated that coenzyme Q10 attenuated the release of inosine and hypoxanthine from the hearts and decreased myocardial inosine and adenosine content of the hypoxic heart, suggesting that coenzyme Q10 retards the breakdown of ATP metabolites which are possible substrates for a salvage synthesis of ATP, when oxygen is replenished. This could account for an appreciable restoration of ATP, and eventually provide a significant recovery of cardiac contractile force upon reoxygenation.


Musculin/MyoR is expressed in kidney side population cells and can regulate their function.
Musculin/MyoR is a new member of basic helix-loop-helix transcription factors, and its expression is limited to skeletal muscle precursors. Here, we report that musculin/MyoR is expressed in adult kidney side population (SP) cells and can regulate their function. SP phenotype can be used to purify stem cell-rich fractions. Microarray analysis clarified that musculin/MyoR was exclusively expressed in kidney SP cells, and the cells resided in the renal interstitial space. Musculin/MyoR-positive cells were decreased in acute renal failure, but infusion of kidney SP cells increased musculin/MyoR-positive cells and improved renal function. Kidney SP cells in reversible acute renal failure expressed a high level of renoprotective factors and leukemia inhibitory factor (LIF), but not in irreversible chronic renal failure. In cultured kidney SP cells, LIF stimulated gene expression of renoprotective factors, and down-regulation of musculin/MyoR augmented LIF-induced gene expression. Our results suggest that musculin/MyoR may play important roles not only in developmental processes but also in regenerative processes in adult tissue.


Skeletal muscle channelopathies: nondystrophic myotonias and periodic paralysis.
The aim is to review the recent findings in relation to the genetics, pathophysiology, clinical phenotypes, investigation and treatment of the nondystrophic myotonias (NDMs) and periodic paralyses. The number of pathogenic mutations causing NDMs and periodic paralyses in known genes continues to expand. In addition, a mutation has been identified in the ryanodine receptor gene manifesting as an atypical periodic paralysis phenotype. Another recent study indicated that thyrotoxic hypokalaemic periodic paralysis is determined by mutations in a novel gene encoding an inwardly rectifying potassium channel, Kir2.6. Work studying molecular mechanisms indicates that 90% of the known mutations causing hypokalaemic periodic paralysis (HypoPP) result in loss of positively charged arginine residues in the S4 segments of either SCN4A or CACNA1S, possibly creating a gating-pore current that may be important in the pathogenesis of HypoPP. Recent studies evaluating clinical features and health status in NDM patients have provided more detailed insights into the significant morbidity associated with these diseases. Ultrasound has been successfully used to demonstrate muscle abnormalities in NDM patients and magnetic resonance spectroscopy studies applied to HypoPP patients suggest that this technique can demonstrate both disease-related and treatment-related changes. Recent discoveries in the skeletal muscle channelopathies have increased our understanding of the genetics and pathophysiology of these diseases. Studies reporting imaging techniques raise the possibility of improved disease monitoring and better outcome measures for clinical trials. Randomized controlled trials to establish an evidence base upon which to recommend standard treatments are required.


Gastrointestinal bleeding, angiodysplasia, cardiovascular disease, and acquired von Willebrand syndrome.
Recent evidence points to isolated deficiency of the largest multimers of von Willebrand factor (VWF)-known as von Willebrand syndrome type 2A (VWS-2A)-as a risk factor for bleeding from gastrointestinal (GI) angiodysplasia. This disorder is not widely recognized, perhaps because most patients do not exhibit generalized hemostatic impairment (bleeding is generally restricted to GI angiodysplasia) and because all but the largest multimers of VWF remain detectable in the plasma (thus, routine screening tests for VWS-2A are usually normal). The "Rosetta stone" for elucidating this syndrome was the enigma of Heyde's syndrome (aortic stenosis plus bleeding GI angiodysplasia), particularly the striking observation that aortic valve replacement generally cures GI bleeding and that preoperative deficiency of the largest VWF multimers undergoes long-term normalization after valve replacement. We critically review the evidence implicating VWS-2A as a risk factor for bleeding GI angiodysplasia. We hypothesize that VWS-2A secondary to cardiovascular disease other than severe aortic stenosis, such as peripheral arterial occlusive disease, could explain why elderly patients often develop recurrent GI bleeding or iron deficiency anemia from GI angiodysplasia.


Hormonal mediators of amino acid-induced glomerular hyperfiltration in humans.
It has been speculated that glucoregulatory hormones and/or renal autacoids mediate the increase in glomerular filtration rate (GFR) induced by the administration of protein or amino acids. Because infusion of a mixture of amino acids (AA mix), but not of branched-chain amino acids (BCAA) alone, increases GFR, we performed a crossover study in seven normal subjects in which the glomerular hemodynamic effects of separate 3-h infusions of these two amino acid solutions were compared with changes in potential mediators of this response, i.e., glucoregulatory hormones, renin, vasodilatory prostaglandins (PGs), and guanosine 3',5'-cyclic monophosphate (cGMP). As expected, infusion of the AA mix but not BCAA resulted in a prompt and sustained increase in GFR. Both infusions caused a significant increase in plasma insulin, whereas glucagon increased only with the AA mix. Plasma growth hormone was initially unchanged with both infusions but increased after 2 h of BCAA. Neither infusion significantly increased the urinary excretion of PGE2, 6-keto-PGF1 alpha, or cGMP. Both infusions resulted in a small but significant decrease in plasma renin activity. Infusion of BCAA but not the AA mix resulted in a progressive decrease in plasma glucose and potassium concentrations and an increase in renal sodium reabsorption that may have resulted from stimulation of insulin secretion that was not counterbalanced by a simultaneous increase in glucagon. Thus only changes in glucagon exhibited a significant temporal relationship with changes in GFR, lending further support to a role for glucagon as a mediator of amino acid-induced glomerular hyperfiltration.


Location and properties of two isoenzymes of cardiac adenylate kinase.
Adenylate kinase catalyses the equilibrium 2ADP = ATP + AMP. There are two isoenzymes of adenylate kinase in bovine ventricular tissue, one cytoplasmic, the other mitochondrial. Mitochondrial subfractionation locates this isoenzyme between the mitochondrial membranes with fatty acid-CoA ligase. The cytoplasmic and mitochondrial isoenzymes are distributed in ratio 3:2, and both forms were purified to homogeneity. They differ principally by charge, Km values for ATP, ADP and AMP, pH-stability and -activity profiles, and susceptibility to the inhibitor adenosine pentaphosphoadenosine. The forward and reverse reactions show similar energies of activation for the cytoplasmic enzyme, but differ for the mitochondrial enzyme. The molecular weights are indistinguishable. An integrated mechanism is formulated whereby one isoenzyme suppresses the activation of fatty acid and the other enhances carbohydrate utilization in hypoxic myocytes.


Effects of perinatal asphyxia on rat striatal cytoskeleton.
Perinatal asphyxia (PA) is a medical condition associated with a high short-term morbimortality and different long-term neurological diseases. In previous works, we have shown that neuronal and synaptic changes in rat striatum lead to ubi-protein accumulation in post-synaptic density (PSD) after six months of sub-severe PA. However, very little is known about the synaptic and related structural modifications induced by PA in young rats. In the present work, we studied neuronal cytoskeleton modifications in striatum induced by subsevere PA in 30-day-old rats. We observed a significant decrease in the number of neurons, in particular calbindin immunoreactive neurons after PA. In addition, it was also observed that actin cytoskeleton was highly modified in the PSD as well as an increment of F-actin staining by Phalloidin-alexa(488) in the striatum of PA rats. Using correlative fluorescence-electron microscopy photooxidation, we confirmed and extended confocal observations. F-actin staining augmentation was mostly related with an increment in the number of mushroom-shaped spines. Consistent with microscopic data, Western blot analysis revealed a β-actin increment in PSD in PA rats. On the other hand, MAP-2 immunostaining was decreased after PA, being NF-200 expression unmodified. Although neuronal death was observed, signs of generalized neurodegeneration were absent. Taken together these results showed early post-synaptic F-actin cytoskeleton changes induced by PA with slightly modifications in the other components of the neuronal cytoskeleton, suggesting that F-actin accumulation in the dendritic spines could be involved in the neuronal loss induced by PA.


Central venous access in pediatric patients.
Occlusion of traditional sites for central venous cannulation is a challenging problem in patients that require a permanent central venous line for chronic administration of nutrients or drugs. In rare cases, extensive central venous thrombosis of the superior and inferior vena cava may preclude catheterization, and uncommon routes should be used. We describe our approach for placement of chronic central venous lines in two pediatric patients with short bowel syndrome and extensive caval occlusion.


Sociodemographic characteristics of street children in Alexandria.
The sociodemographic characteristics of street children in the Egyptian city of Alexandria were studied. A cross-sectional descriptive study was designed. Difficulties in random sampling of street children meant that a non-random purposive sampling strategy was used. The final sample consisted of 100 street children (all boys) who were interviewed and medically examined. The study confirmed the findings of other studies that street children come from problematic family backgrounds. They are disproportionately victims of family breakdown, sexual and physical abuse. They suffer from increased health problems, malnutrition and lack of educational opportunities. Recommendations are made for programmes to address the challenging needs of street children in Alexandria.


CAM-ICU may not be the optimal screening tool for early delirium screening in older emergency department patients: a prospective cohort study.
Delirium is a frequent problem among older patients in the emergency department (ED) and early detection is important to prevent its associated adverse outcomes. Several screening tools for delirium have been proposed for the ED, such as the 6-Item Cognitive Impairment Test (6-CIT) and the Confusion Assessment Method-ICU (CAM-ICU). Previous validation of the CAM-ICU for use in the ED showed varying results, possibly because it was administered at different or unknown time points. The aim was to study the prevalence of delirium in older ( ≥ 70 years) ED patients using the CAM-ICU and 6-CIT. A prospective cohort study was carried out in one tertiary care and one secondary care hospital in the Netherlands. Patients aged 70 years and older attending the ED were included. Delirium screening was performed within 1 h after ED registration using the CAM-ICU. The 6-CIT was determined for comparison using a cut-off point of at least 14 points indicating possible delirium. A total of 997 patients were included in the study, with a median age of 78 years (interquartile range 74-84). Delirium as assessed with CAM-ICU was positive in only 13 (1.3%, 95% confidence interval: 0.8-2.2) patients. Ninety-five (9.5% 95% confidence interval: 7.9-11.5) patients had 6-CIT more than or equal to 14. We found a delirium prevalence of 1.3% using the CAM-ICU, which was much lower than the expected prevalence of around 10% as being frequently reported in the literature and what we found when using the 6-CIT. On the basis of these results, caution is warranted to use the CAM-ICU for early screening in the ED.


Study of the mechanism of rectal motility: the 'mass squeeze contraction'.
The motor physiology of the rectum has remained largely obscure, especially concerning the mechanism of rectal motility. In the current communication we tested the possibility of characterizing the mechanism of rectal motility during filling and evacuation through the study of the rectal electric activity in 16 healthy volunteers (mean age 43.6 +/- 10.8 years; 11 men). Two monopolar silver-silver chloride electrodes were introduced per annum and fixed to the rectal mucosa by suction. The rectum was distended in 10 ml increments of water by means of a balloon-ended catheter inserted into the rectum. The rectal pressure was measured by one catheter placed above and a second one below the rectal balloon, and the 2 catheters were connected to 2 strain gauge pressure transducers. Regular triphasic slow waves or pacesetter potentials (PPs) were recorded from the 2 electrodes at rest. PPs were superimposed or followed randomly by action potentials (APs). APs but not PPs were coupled with elevated rectal pressure. Rectal distension with 10 ml of water caused no significant changes of the rectal pressure or EMG activity. Distension with a mean volume of 27.3 +/- 4.7 ml effected a significant increase (p < 0.05) of the rectal electromechanical activity proximally to the balloon and a decrease distally (p < 0.05) to it. With progressive increase of the rectal distension, the electromechanical activity continued to increase proximally and to decrease distally to the balloon, until, at a mean distending volume of 76.3 +/- 3.7 ml, the balloon was dispelled to the exterior. In conclusion, the identification of the modality of rectal motility during defecation was feasible by recording the rectal electromechanical activity. The rectal contraction is suggested to occur in a 'mass squeeze manner' which squeezes the rectal contents aborally into the anal canal. The recognition of the rectal motor modality appears to be important for the understanding of rectal motility disorders. However, further studies are required to confirm these findings.


On-Farm Trials Reveal Significant but Uncertain Control of Botrytis cinerea by Aureobasidium pullulans and Potassium Bicarbonate in Organic Grapevines.
Botrytis cinerea, a fungal pathogen that causes gray mold on grapes, can decrease yield, substantially reduce wine quality, and therefore cause significant economic losses. In a context of increasing awareness of environmental and human health, biopesticides are a potential alternative to synthetic chemical treatments to produce grapes and wine in compliance with high food standards. However, the effectiveness of biopesticides is not well known and more research is needed to help winegrowers assess their ability to control wine diseases. Our study aims to assess the efficacy of two commercial biopesticides, based on potassium bicarbonate and Aureobasidium pullulans, in reducing the incidence of gray mold (i.e., the proportion of grape bunches that are diseased). We use data from an on-farm trial network managed over 3 years (from 2014 to 2016) in a major wine producing region located in Southwestern France, and fit Bayesian generalized linear multilevel models able to take the variability of treatment effect across trials into account. The fitted models were then used to estimate the efficacy on incidence as a function of the severity (i.e., the proportion of diseased grape berries in a bunch) in an untreated plot in order to determine if the effectiveness of the treatments depends on the disease pressure. At average disease severity (i.e., 3%), the efficacy on disease incidence at the network level was equal to 20% [95% CI = (-0.1; 37.3)] and 13% [95% CI = (0.2; 24.7)] for potassium bicarbonate and A. pullulans, respectively. For both biopesticides, the efficacy on incidence for a new site-year is highly uncertain, but potassium bicarbonate had a lower uncertainty and a lower application cost compared to A. pullulans. Our results confirm that potassium bicarbonate is an interesting biopesticide under farming conditions in organic vineyards in southwestern France, but the amount of uncertainty points to the need for further research.


In search of realistic optimism. Meaning, knowledge, and warm fuzziness.
Is it better to be realistic or optimistic? A realistic outlook improves chances to negotiate the environment successfully, whereas an optimistic outlook places priority on feeling good. But are realistic and optimistic outlooks necessarily in conflict? The author suggests that the fuzzy nature of accuracy typically places only loose boundaries on what it means to be realistic. As a result, there are many forms of optimism that do not, in principle, yield unrealistic assessments. Nevertheless, there remain numerous "optimistic biases" that do involve self-deception, or convincing oneself of desired beliefs without appropriate reality checks. The author describes several ways that realistic and unrealistic optimism can be differentiated and explores the impact of this distinction for current views of optimism. This critique reveals how positive psychology may benefit from a focus on personal meaning and knowledge as they relate to making the most of life.


Regenerative medicine regulatory policies: A systematic review and international comparison.
A small number of regenerative medicines (RMs) have received market authorization (MA) worldwide, relative to the large number of clinical trials currently being conducted. Regulatory issues constitute one major challenge for the MA of RMs. This study aimed to systematically review the regulation of RMs internationally, to identify the regulatory pathways for approved RMs, and to detail expedited programs to stimulate MA process. Official websites of regulatory authorities in 9 countries (United States (US), Japan, South Korea, Australia, Canada, New Zealand, Singapore, China, and India) and the European Union (EU) were systematically browsed, and was complemented by a systematic literature review in Medline and Embase database. Specific RM legislation/frameworks were available in the EU, US, Japan, South Korea and Australia. A risk-based approach exempting eligible RMs from MA regulations were adopted in the EU and 6 countries. All investigated regions have established accelerated review or approval programs to facilitate the MA of RMs. 55 RMs have received MA in 9 countries and the EU. Twenty-three RMs received Priority Medicine designation, 32 RMs received Regenerative Medicine Advanced Therapy designation, and 11 RMs received SAKIGAKE (fore-runner initiative) designation. Regulators have adopted proactive strategies to facilitate RM approval. However, addressing the discrepancies in regulatory requirements internationally remains challenging.


Localization of the adrenergic feeding system in the rat diencephalon.
Injection of 6 micrograms of aqueous norepinephrine elicits eating only when it takes place at sites within a limited region of the rat brain. The distribution of effective sites coincides with that of systems connected to an extrahypothalamic pathway between the limbic forebrain and tegmental motor systems. It does not correspond to those parts of the lateral hypothalamus thought to control normal feeding.


Transcriptional and genomic mayhem due to aging-induced nucleosome loss in budding yeast.
All eukaryotic genomes are assembled into a nucleoprotein structure termed chromatin, which is comprised of regular arrays of nucleosomes. Each nucleosome consists of eight core histone protein molecules around which the DNA is wrapped 1.75 times. The ultimate consequence of packaging the genome into chromatin is that the DNA sequences are relatively inaccessible. This allows the cell to use a comprehensive toolbox of chromatin-altering machineries to reveal access to the DNA sequence at the right time and right place in order to allow genomic processes, such as DNA repair, transcription and replication, to occur in a tightly-regulated manner. In other words, chromatin provides the framework that allows the regulation of all genomic processes, because the machineries that mediate transcription, repair and DNA replication themselves are relatively non-sequence specific and if the genome were naked, they would presumably perform their tasks in a random and unregulated manner. We recently provided support for this prediction in Zheng et al., [Genes and Development (2014) 28: 396-408] by investigating a physiologically relevant scenario in which we had found that cells lose half of the core histone proteins, that is, during the mitotic aging (also called replicative aging) of budding yeast. Using new spike-in normalization techniques, we found that the occupancy of nucleosomes at most DNA sequences is reduced by 50%, leading to transcriptional induction of every single gene. This loss of histones during aging was also accompanied by a significantly-increased frequency of genomic instability including DNA breaks, chromosomal translocations, retrotransposition, and transfer of mitochondrial DNA into the nuclear genome (Figure 1).


Outcome of surgical resection of pelvic osteosarcoma.
The aim of the following study is to evaluate the morbidity, oncologic results and functional outcome in nonmetastatic patients with primary osteosarcoma of the pelvis treated with surgical resection. Twelve cases of nonmetastatic osteosarcoma of pelvis were operated as part of their multimodality treatment regime between November 2003 and May 2011. There were 5 males and 7 females with a median age of 22 years (range 8-39 years). Ten patients underwent limb sparing resections while 2 had a hindquarter amputation. All 10 cases of limb sparing surgery included resection of the acetabulum. A pseudarthrosis was carried out in 7 cases. Extracorporeal radiation therapy and reimplantation of the bone followed by fixation with plates was used in 1 case and an ischiofemoral arthrodesis was carried out in 2 cases. Surgical margins were free in 11 patients. Seven patients had a poor histological response to chemotherapy while 4 patients had a good response to chemotherapy. In the patient reconstructed with radiated auto bone graft, the histological response to chemotherapy could not be assessed. Surgery related complications were seen in 8 out of 12 patients (67%). Three of these patients (25%) required additional surgical intervention for their complications. All patients were available for followup. The median followup of survivors was 56 months (range 24-102 months). Four patients (33%) developed a local recurrence. At 5 years, overall survival was 67%. Patients with a good response to chemotherapy had a better overall survival when compared with patients with a poor response to chemotherapy. The mean Musculoskeletal Tumor Society functional score was 22 (range12-27). Though complex and challenging, surgery provides good local control and oncologic outcomes with acceptable function in patients with osteosarcoma of the pelvis treated with appropriate surgical resection as part of their multimodality treatment.


Effect of Noninvasive Airway Management of Comatose Patients With Acute Poisoning: A Randomized Clinical Trial.
Tracheal intubation is recommended for coma patients and those with severe brain injury, but its use in patients with decreased levels of consciousness from acute poisoning is uncertain. To determine the effect of intubation withholding vs routine practice on clinical outcomes of comatose patients with acute poisoning and a Glasgow Coma Scale score less than 9. This was a multicenter, randomized trial conducted in 20 emergency departments and 1 intensive care unit (ICU) that included comatose patients with suspected acute poisoning and a Glasgow Coma Scale score less than 9 in France between May 16, 2021, and April 12, 2023, and followed up until May 12, 2023. Patients were randomized to undergo conservative airway strategy of intubation withholding vs routine practice. The primary outcome was a hierarchical composite end point of in-hospital death, length of ICU stay, and length of hospital stay. Key secondary outcomes included adverse events resulting from intubation as well as pneumonia within 48 hours. Among the 225 included patients (mean age, 33 years; 38% female), 116 (16%) were in the intervention group and 109 (58%) in the control group. No patients died during the in-hospital stay. There was a significant clinical benefit for the primary end point in the intervention group, with a win ratio of 1.85 (95% CI, 1.33 to 2.58). In the intervention group, there was a lower proportion with any adverse event (6% vs 14.7%; absolute risk difference, 8.6% [95% CI, -16.6% to -0.7%]) compared with the control group, and pneumonia occurred in 8 (6.9%) and 16 (14.7%) patients, respectively (absolute risk difference, -7.8% [95% CI, -15.9% to 0.3%]). Among comatose patients with suspected acute poisoning, a conservative strategy of withholding intubation was associated with a greater clinical benefit for the composite end point of in-hospital death, length of ICU stay, and length of hospital stay. ClinicalTrials.gov Identifier: NCT04653597.


Renal cell carcinoma in dialysis patients: a single center experience.
Renal cell carcinoma (RCC) is a life-threatening complication of end-stage renal disease with an unclear pathogenesis. We evaluated RCC developing in patients undergoing dialysis. In 2624 patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis at our hospital between July 1993 and March 2004, we performed annual screening for RCC using abdominal computed tomography and ultrasonography. Patients diagnosed with RCC underwent radical nephrectomy as well as clinical and pathologic evaluation. RCC was detected in 44 patients (1.68%; 31 males and 13 females). The age of RCC patients was 55.5 +/- 11.1 years. Dialysis duration before RCC diagnosis was 11.2 +/- 7.2 years. Most RCC were early stage and low stage by TNM classification, 43 patients had N0M0 RCC, whereas one had N1M0. Tumor size was 2.9 +/- 1.9 cm. The predominant histological type of RCC was common or conventional cell-type carcinoma (clear cell carcinoma and granular cell carcinoma). Of patients, 5(11.4%) had bilateral RCC, and satellite tumor lesions in RCC were detected in 13 (29.5%). In 36 patients (81.8%) RCC was accompanied by acquired cystic disease of the kidney. These patients had longer dialysis durations (P = 0.01) and smaller tumors (P = 0.048). RCC metastasized postoperatively in 4 patients (9.1%), while one (2.3%) died of cancer. Our dialysis patients showed a higher incidence of RCC than the general population. Prognosis was favorable because tumors were detected by screening when they were small. Therefore, periodical screening for RCC seems very important in dialysis patients.


The glycine-alanine repeating region is the major epitope of the Epstein-Barr nuclear antigen-1 (EBNA-1).
The Epstein-Barr nuclear antigen-1 (EBNA-1) is a protein containing a large glycine-alanine repeat that has been shown to be antigenic. Antibodies to EBNA-1 can be detected by means of immunoblotting. Preincubation of antisera with purified EBNA-1 protein inhibits the binding of IgG antibodies in this system, indicating that those epitopes detected by immunoblots are also accessible on the native molecule. A number of synthetic peptides the sequences of which were derived from the glycine-alanine repeating region of EBNA-1 and from regions adjacent to it also inhibited antibody binding to EBNA-1. These showed, however, a 1000-fold variation in their inhibitory activities. Peptides containing only glycine and alanine were the most effective inhibitors. The anti-EBNA-1 antibodies did not react with several other peptides representing sequences from unrelated proteins. At saturating concentrations of peptide 85 to 100% of anti-EBNA-1, antibody binding was inhibited in all sera tested with one exception. Similar results are obtained when antibody binding is assayed by an enzyme immunosorbent assay by using partially purified EBNA-1 to coat the plates. Thus the glycine-alanine region, either through its primary structure or through conformations assumed by this region, forms the major epitope(s) of the EBNA-1 molecule.


Prevalence of anatomical variants and coronary anomalies in 543 consecutive patients studied with 64-slice CT coronary angiography.
The aim of our study was to assess the prevalence of variants and anomalies of the coronary artery tree in patients who underwent 64-slice computed tomography coronary angiography (CT-CA) for suspected or known coronary artery disease. A total of 543 patients (389 male, mean age 60.5 +/- 10.9) were reviewed for coronary artery variants and anomalies including post-processing tools. The majority of segments were identified according to the American Heart Association scheme. The coronary dominance pattern results were: right, 86.6%; left, 9.2%; balanced, 4.2%. The left main coronary artery had a mean length of 112 +/- 55 mm. The intermediate branch was present in the 21.9%. A variable number of diagonals (one, 25%; two, 49.7%; more than two, 24%; none, 1.3%) and marginals (one, 35.2%; two, 46.2%; more than two, 18%; none, 0.6%) was visualized. Furthermore, CT-CA may visualize smaller branches such as the conus branch artery (98%), the sinus node artery (91.6%), and the septal branches (93%). Single or associated coronary anomalies occurred in 18.4% of the patients, with the following distribution: 43 anomalies of origin and course, 68 intrinsic anomalies (59 myocardial bridging, nine aneurisms), three fistulas. In conclusion, 64-slice CT-CA provides optimal visualization of the variable and complex anatomy of coronary arteries because of the improved isotropic spatial resolution and flexible post-processing tool.


Pediatric neurosurgeons' views regarding prenatal surgery for myelomeningocele and the management of hydrocephalus: a national survey.
The Management of Myelomeningocele Study (MOMS) compared prenatal with postnatal surgery for myelomeningocele (MMC). The present study sought to determine how MOMS influenced the clinical recommendations of pediatric neurosurgeons, how surgeons' risk tolerance affected their views, how their views compare to those of their colleagues in other specialties, and how their management of hydrocephalus compares to the guidelines used in the MOMS trial. A cross-sectional survey was sent to all 154 pediatric neurosurgeons in the American Society of Pediatric Neurosurgeons. The effect of surgeons' risk tolerance on opinions and counseling of prenatal closure was determined by using ordered logistic regression. Compared to postnatal closure, 71% of responding pediatric neurosurgeons viewed prenatal closure as either "very favorable" or "somewhat favorable," and 51% reported being more likely to recommend prenatal surgery in light of MOMS. Compared to pediatric surgeons, neonatologists, and maternal-fetal medicine specialists, pediatric neurosurgeons viewed prenatal MMC repair less favorably (p < 0.001). Responders who believed the surgical risks were high were less likely to view prenatal surgery favorably and were also less likely to recommend prenatal surgery (p < 0.001). The management of hydrocephalus was variable, with 60% of responders using endoscopic third ventriculostomy in addition to ventriculoperitoneal shunts. The majority of pediatric neurosurgeons have a favorable view of prenatal surgery for MMC following MOMS, although less so than in other specialties. The reported acceptability of surgical risks was strongly predictive of prenatal counseling. Variation in the management of hydrocephalus may impact outcomes following prenatal closure.


A Campylobacter jejuni Dps homolog has a role in intracellular survival and in the development of campylobacterosis in neonate piglets.
Iron acquisition is an absolute requirement by most microorganisms for host survival. In this work, we investigated the Campylobacter jejuni iron binding Dps protein for a potential role in virulence. In vitro assays using J774A.1 macrophage-like cells demonstrated a 2.5 log reduction in C. jejuni survival of the Dps mutant and a reduction of four logs in invasion of HEp-2 epithelial cells compared to the wild-type strain. To examine the role of the dps gene in host pathogenesis, the piglet model was used in C. jejuni challenge studies. In vivo inoculation studies of newborn piglets with wild-type C. jejuni demonstrated an 11-fold upregulation of the dps gene and intestinal lesion production typical of campylobacteriosis in humans. In contrast, piglets inoculated with the dps mutant were not colonized and remained normal throughout the study period. Mucosal lesion production was restored in piglets inoculated with the complemented Dps mutant strain. Based on these results, we conclude that the C. jejuni Dps homolog is a virulence factor in the production of campylobacteriosis, and warrants further investigation.


A multivariate approach to the prediction of no-show behavior in a primary care center.
To predict no-show behavior in a primary care center, we analyzed a wide range of factors in 376 patients. Of 1,181 appointments that were scheduled during a six-month follow-up period and that were not cancelled in advance, 968 (82%) were kept and 213 (18%) were no-shows. By multivariate logistic regression analysis based on two thirds of the patient sample, no-show behavior was independently correlated with the following four factors: the patient's age and race, the presence of any physician-identified psychosocial problems, and the percent of noncancelled and appointments that were kept during the prior 12 months. Neither patient satisfaction nor patient-physician concordance in problem identification were independent correlates of appointment keeping. When our four-factor logistic regression equation was independently tested on the other one third of the patients, it accurately predicted no-show behavior. We suggest that our predicted probability of no-show behavior can be used to guide changes in scheduling patterns or to recognize patients appropriate for interventions to change behavior.


A Novel Role for SIRT3 in Regulating Mediators Involved in the Terminal Pathways of Human Labor and Delivery.
Preterm birth remains the major cause of neonatal mortality and morbidity, mediated largely by an inflammatory process. The sirtuin (SIRT) family of cellular regulators has been implicated as key inhibitors of inflammation. We have previously reported a role for SIRT1, SIRT2, and SIRT6 in regulating inflammation-induced prolabor mediators. In this study, we determined the effect of term labor and pro-inflammatory cytokines on SIRT3, SIRT4, SIRT5, and SIRT7 expression in human myometrium. Functional studies were also used to investigate the effect of small interfering RNA (siRNA) knockdown of SIRTs in regulating inflammation-induced prolabor mediators. Western blot analysis and qRT-PCR were used to determine SIRT3, SIRT4, SIRT5, and SIRT7 mRNA and protein expression in human myometrium. Small interfering RNA knockdown of SIRT3 in myometrial primary cells determined its role in response to inflammatory stimuli IL1B and TNF. SIRT3 mRNA and protein expression levels were significantly lower in term laboring myometrium compared with term nonlaboring myometrium. There was no effect of labor on SIRT4, SIRT5 or SIRT7 protein expression. The pro-inflammatory cytokines IL1B and TNF significantly decreased levels of SIRT3 mRNA and protein expression. SIRT3 knockdown by siRNA significantly augmented IL1B- and TNF-stimulated IL6, CXCL8, and CCL2 mRNA expression and release; PTGS2 mRNA expression and subsequent PGF2alpha release; the mRNA expression and secretion of the adhesion molecule ICAM1 and the extracellular matrix remodeling enzyme MMP9; and nuclear factor kappa B1 (NFkappaB1) transcriptional activity. In human myometrium, SIRT3 expression decreases with term labor and regulates the mediators involved in the terminal effector pathways of human labor and delivery through the NFkappaB1 pathway.


mPulse Mobile Sensing Model for Passive Detection of Impulsive Behavior: Exploratory Prediction Study.
Mobile health technology has demonstrated the ability of smartphone apps and sensors to collect data pertaining to patient activity, behavior, and cognition. It also offers the opportunity to understand how everyday passive mobile metrics such as battery life and screen time relate to mental health outcomes through continuous sensing. Impulsivity is an underlying factor in numerous physical and mental health problems. However, few studies have been designed to help us understand how mobile sensors and self-report data can improve our understanding of impulsive behavior. The objective of this study was to explore the feasibility of using mobile sensor data to detect and monitor self-reported state impulsivity and impulsive behavior passively via a cross-platform mobile sensing application. We enrolled 26 participants who were part of a larger study of impulsivity to take part in a real-world, continuous mobile sensing study over 21 days on both Apple operating system (iOS) and Android platforms. The mobile sensing system (mPulse) collected data from call logs, battery charging, and screen checking. To validate the model, we used mobile sensing features to predict common self-reported impulsivity traits, objective mobile behavioral and cognitive measures, and ecological momentary assessment (EMA) of state impulsivity and constructs related to impulsive behavior (ie, risk-taking, attention, and affect). Overall, the findings suggested that passive measures of mobile phone use such as call logs, battery charging, and screen checking can predict different facets of trait and state impulsivity and impulsive behavior. For impulsivity traits, the models significantly explained variance in sensation seeking, planning, and lack of perseverance traits but failed to explain motor, urgency, lack of premeditation, and attention traits. Passive sensing features from call logs, battery charging, and screen checking were particularly useful in explaining and predicting trait-based sensation seeking. On a daily level, the model successfully predicted objective behavioral measures such as present bias in delay discounting tasks, commission and omission errors in a cognitive attention task, and total gains in a risk-taking task. Our models also predicted daily EMA questions on positivity, stress, productivity, healthiness, and emotion and affect. Perhaps most intriguingly, the model failed to predict daily EMA designed to measure previous-day impulsivity using face-valid questions. The study demonstrated the potential for developing trait and state impulsivity phenotypes and detecting impulsive behavior from everyday mobile phone sensors. Limitations of the current research and suggestions for building more precise passive sensing models are discussed. ClinicalTrials.gov NCT03006653; https://clinicaltrials.gov/ct2/show/NCT03006653.


A novel use of gentamicin in the ROS-mediated sensitization of NCI-H460 lung cancer cells to various anticancer agents.
Aminoglycosides are broad-spectrum antibiotics that are used for the treatment of severe Gram-negative and Gram-positive bacterial infections. While bactericidal effects of aminoglycosides are due to binding to the 30S subunit of the bacterial ribosome, aminoglycosides can affect protein synthesis, intracellular calcium levels, and levels of reactive oxygen species (ROS) in eukaryotic cells. While aminoglycosides can be cytotoxic at high concentrations, our results show that at much lower doses, gentamicin can be implemented as a sensitizing agent for the NSCLC cell line NCI-H460, increasing the efficacy of camptothecin, digitoxin, and vinblastine in vitro. We have also established that this sensitization is reliant on the ROS response generated by gentamicin.


Ramifications of Vorticity on Aggregation and Activation of Platelets in Bi-Leaflet Mechanical Heart Valve: Fluid-Structure-Interaction Study.
Bileaflet mechanical heart valves (BMHV) are widely implanted to replace diseased heart valves. Despite many improvements in design, these valves still suffer from various complications, such as valve dysfunction, tissue overgrowth, hemolysis, and thromboembolism. Thrombosis and thromboembolism are believed to be initiated by platelet activation due to contact with foreign surfaces and nonphysiological flow patterns. The implantation of the valve causes nonphysiological patterns of vortex shedding behind the leaflets. This study signifies the importance of vorticity in platelet activation and aggregation in BMHV implants. A two-phase model with the first Eulerian phase for blood and the second discrete phase for platelets is used here. The generalized cross model of viscosity has been used to simulate the non-Newtonian viscosity of blood. A fluid-structure-interaction model has been used to simulate the motion of leaflets. This study has also estimated the platelet activation state (PAS), which is the mathematical estimation of the degree of activation of platelets due to flow-induced shear stresses that cause thrombus formation. The regions in the fluid domain with a higher vorticity field have been found to contain platelets with relatively higher PAS than regions with relatively lower vorticity fields. Also, this study has quantitatively reported the effect of vorticity on platelet aggregation. Platelet densities in fluid areas with higher vorticity are higher than densities in fluid areas with lower vorticity, indicating that highly activated platelets aggregate in areas with stronger vorticity.


A phantom-motion aftereffect.
Motion aftereffects, typically found to result only from localized retinal stimulation, were obtained within regions of the visual field that had not been stimulated by moving contours. "Phantom" stripes are seen moving through a physically homogeneous (empty) region of the visual field when vertical stripes move above and below that region. Immediately afterward, stationary stripes in the previously empty region appear to move in the opposite direction. This phantom-motion aftereffect provides a novel instance of the way global structure affects processes that have been assumed to be influenced only by simpler local spatial and temporal variables.


MRI evaluation of nerve root avulsion in neonatal brachial plexus palsy: understanding the presence of isolated dorsal/ventral rootlet disruption.
The evaluation, treatment, and prognosis of neonatal brachial plexus palsy (NBPP) continues to have many areas of debate, including the use of ancillary testing. Given the continued improvement in imaging, it is important to revisit its utility. Nerve root avulsions have historically been identified by the presence of pseudomeningoceles or visible ruptures. This "all-or-none" definition of nerve root avulsions has many implications for the understanding and management of NBPP, especially as characterization of the proximal nerve root as a potential donor remains critical. This study examined the ability of high-resolution MRI to more specifically define the anatomy of nerve root avulsions by individually examining the ventral and dorsal rootlets as they exit the spinal cord. This is a retrospective review of patients who had undergone brachial plexus protocol MRI for clinical evaluation of NBPP at a single institution. Each MR image was independently reviewed by a board-certified neuroradiologist, who was blinded to both established diagnosis/surgical findings and laterality. Each dorsal and ventral nerve rootlet bilaterally from C5 to T1 was evaluated from the spinal cord to its exit in the neuroforamen. Each rootlet was classified as avulsed, intact, or undeterminable. Sixty infants underwent brachial plexus protocol MRI from 2010 to 2018. All infants were included in this study. Six hundred individual rootlets were analyzed. There were 49 avulsed nerve rootlets in this cohort. Twenty-nine (59%) combined dorsal/ventral avulsions involved both the ventral and dorsal rootlets, and 20 (41%) were either isolated ventral or isolated dorsal rootlet avulsions. Of the isolated avulsion injuries, 13 (65%) were dorsal only, meaning that the motor rootlets were intact. A closer look at nerve root avulsions with MRI demonstrates a significant prevalence (approximately 41%) of isolated dorsal or ventral nerve rootlet disruptions. This finding implies that nerve roots previously labeled as "avulsed" but with only isolated dorsal (sensory) rootlet avulsion can yet provide donor fascicles in reconstruction strategies. A majority (99%) of the rootlets can be clearly visualized with MRI. These findings may significantly impact the clinical understanding of neonatal brachial plexus injury and its treatment.


Hypertension Impact on Health-Related Quality of Life: A Cross-Sectional Survey among Middle-Aged Adults in Chongqing, China.
Hypertension is a major risk factor of cardiovascular disease in China, and yet little is known about health-related quality of life (HRQOL) and its associations with demographic and social-economic characteristics in middle-aged patients with hypertension. A cross-sectional survey was undertaken in Chongqing, China, using a multistage stratified random sampling methodology. Data was collected on 1,224 eligible adults, aged between 45 and 53 years, including the Medical Outcomes Survey Short Form-36 to measure HRQOL. Hypertension was associated with poor state of physical functioning, role-physical, bodily pain, general health, vitality, and social function (p < 0.05 for all). In multivariable analyses, education level, job conditions, average monthly income, smoking status, sleep quality, perception of relationship with family, childhood breastfeeding history, and body mass index were associated with domains of SF36 among those with hypertension (p < 0.05 for all). Hypertensive respondents with high education, marital status, breastfeeding, higher incomes, good quality of sleep, positive relationship with family, and higher body mass index have better HRQOL in middle-aged people with hypertension. Those unemployed had a better state of general health and had a poorer state of social function. Nonsmokers had a poorer state of bodily pain than smokers. This study provides detailed information of the implications for health care providers to gain a more complete picture of their hypertension patients' health.


Synthesis and Biological Evaluation of 6-[(1 R)-1-Hydroxyethyl]-2,4a( R),6( S),8a( R)-tetrahydropyrano-[3,2- b]-pyran-2-one and Structural Analogues of the Putative Structure of Diplopyrone.
The phytotoxin diplopyrone is considered to be the main phytotoxin in a fungus that is responsible for cork oak decline. A carbohydrate-based synthesis of the enantiomer of the structure proposed for diplopyrone has been developed from a commercially available derivative of d-galactose. Key steps in the synthesis are a highly stereoselective pyranose chain-extension based on methyltitanium, preparation of a vinyl glycoside via Isobe C-alkynylation-rearrangement/reduction, and RCM-based pyranopyran construction. Crystallographic and NMR analysis confirms an earlier report that the structure originally proposed for diplopyrone may require revision. Structural analogues were prepared for biological evaluation, the most promising being a pyranopyran nitrile synthesized from tri- O-acetyl-d-galactal by Ferrier cyanoglycosidation, Wittig chain extension, and lactonization. Biological assays revealed potent antibacterial activity for the nitrile analogue against common bacterial pathogens Edwardsiella ictaluri and Flavobacterium columnare that cause enteric septicemia (ESC) and columnaris disease, respectively, in catfish. The IC50 value of 0.002 against E. ictaluri indicates approximately 100 times greater potency than the antibiotic florfenicol used commercially for this disease. Phytotoxic activity for all three target compounds against duckweed was also observed. The antibiotic and phytotoxic activities of the new pyranopyrans synthesized in this study demonstrate the potential of such compounds as antibiotics and herbicides.


Association between alexithymia and impaired reward valuation in patients with fronto-insular damage.
Humans compute the anticipated reward value of stimuli in their environment in order to behave in an adaptive, goal-directed manner. This reward valuation ability is vital, and its disruption in a range of clinical populations has profound personal and social consequences. However, research has often failed to consider the reward-related functions of a central component of human emotion: conscious emotional experience. Alexithymia-a condition characterized by diminished conscious awareness of one's emotions-offers a unique opportunity to examine the link between emotional awareness and reward valuation. In the present study, we measured both acquired alexithymia and reward valuation ability in a large sample of patients with traumatic brain injuries (N = 112). Behavioral analyses provided evidence for a negative association between alexithymia and reward valuation ability. This association remained significant after controlling for several covariates in the model (anxiety, depression, posttraumatic stress disorder, and IQ). Voxel-based lesion-symptom mapping was carried out to identify brain regions-of-interest (ROIs) that, when damaged, lead to increased alexithymia and impaired reward valuation. Importantly, mediation models computed using the ROIs identified through the voxel-based lesion-symptom mapping revealed a specific indirect effect of left frontoinsular damage on impaired valuation that was mediated by increased levels of alexithymia. This indirect effect was not observed for any of the other candidate ROIs. The present study identifies a network of brain regions likely to be involved in the integration of subjective feelings and reward processes critical for the adaptive control of goal-directed behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


The importance of patient-reported outcome measures in reconstructive urology.
Patient-reported outcome measures (PROMs) are now recognised as the most appropriate instruments to assess the effectiveness of healthcare interventions from the patient's perspective. The purpose of this review was to identify recent publications describing the use of PROMs following reconstructive urological surgery. A wide systematic search identified only three original articles published in the last 2 years that prospectively assessed effectiveness using a patient-completed condition-specific or generic health-related quality of life (HRQoL) instrument. These publications illustrate the need to administer PROMs at a postoperative interval relevant to the anticipated recovery phase of individual procedures. They also highlight the difference in responsiveness of generic HRQoL instruments to symptomatic improvement between straightforward conditions such as pelviureteric junction obstruction and complex multidimensional conditions such as meningomyelocele. PROMs uptake and awareness is increasing in reconstructive urology but more work is required to demonstrate the effectiveness of surgical procedures for patients and healthcare funders alike. Healthcare policy-makers now rely on these measures to determine whether specific treatments are worth financing and to compare outcomes between institutions.


Exploring the effectiveness of occupational therapy interventions, other than the sensory integration approach, with children and adolescents experiencing difficulty processing and integrating sensory information.
This literature review was completed as part of the Evidence-Based Literature Review Project of the American Occupational Therapy Association to explore the effectiveness of occupational therapy interventions with children and adolescents experiencing difficulty processing and integrating sensory information. This part of the review focused on interventions other than the sensory integration approach. Twenty articles (reporting on 21 studies) met the inclusion criteria. This systematic review found that children with difficulty processing and integrating sensory information and difficulties with the performance of daily occupations can benefit from intervention. However, the great variability that characterizes this literature in terms of populations, interventions, and study quality precludes the formation of any firm conclusions regarding specific approaches. There is an urgent need for well-controlled studies examining the effectiveness of frequently used pediatric occupational therapy interventions with well-defined, homogeneous populations on outcomes that target participation in everyday life.


Diffusion MRI abnormalities in adolescent rats given repeated mild traumatic brain injury.
Mild traumatic brain injury (mTBI) is a serious health concern in the adolescent population. Repeated mTBI may result in more pronounced deficits, and has been associated with long-term neurological consequences including neurodegeneration. As such, there is a critical need for the development of objective mTBI biomarkers to help guide medical management. Diffusion-weighted imaging (DWI) is an advanced magnetic resonance imaging (MRI) technique that may detect brain abnormalities after mTBI. Diffusion tensor imaging (DTI) is the most commonly applied DWI method, and initial studies have reported DTI changes in mTBI patients. Furthermore, new DWI methods (e.g., track-weighted imaging; TWI) are being developed that may also be sensitive to mTBIs, but remain to be comprehensively studied. This study utilized the Awake Closed Head Injury (ACHI) model of mTBI to investigate changes in DTI and TWI following repeated mTBI in adolescent male and female rats. A total of four ACHI impacts, two/day over two consecutive days, were delivered beginning on postnatal day 25. At 1 day and 7 days postinjury, rats were euthanized and brains were collected for DWI analyses. Rats given repeated mTBI displayed changes in fractional anisotropy and radial diffusivity (i.e., DTI measures), as well as track density (i.e., TWI). These findings are consistent with initial DTI findings in mTBI patients, suggest that TWI may complement DTI, support the utility of DWI measures as biomarkers in mTBI, and further validate the ACHI rat model of mTBI.


[Parafoveolar scotomas in microinfarcts of the optic pathways (author's transl)].
Small parafoveolar scotomas in microinfarction of the optic pathways are often not demonstrated, or only inaccurately so, in conventional kinetic perimetry. By using Amsler's grid it is possible to determine accurately the shape and position of such visual field defects. Some remarkable variants of these scotomas are described.


Exploiting the plant secretory pathway to improve the anticancer activity of a plant-derived HPV16 E7 vaccine.
The human papillomavirus 16 (HPV16) E7 oncoprotein can be considered a "tumor-specific antigen", and therefore it represents a promising target for a therapeutic vaccine against HPV-associated tumors. Efficient production of E7 protein with a plant-based transient expression system has been already described and it was demonstrated that E7-containing crude plant extracts confer partial protection against tumor challenge in a mouse model system. Before adopting the plant-based system as a cost-effective method for the production of an E7-based anti-cancer vaccine, some aspects, such as the oncoprotein yield, need further investigation. In the present study, we report the transient expression, mediated by a potato virus X (PVX)-derived vector, of the E7 protein targeted to the secretory system of Nicotiana benthamiana plants by using a plant-derived signal sequence. Targeting the antigen to the secretory pathway enhanced the E7 protein expression levels about five-fold. Mice immunized by s.c. administration with crude foliar extracts containing E7 showed strong stimulation of cell-mediated immune response after five boosters, as detected by ELISPOT. After challenging with the E7-expressing C3 tumor cells, tumor growth was completely inhibited in 80% of the vaccinated animals and a drastic reduction of tumor burden was observed in the remaining tumor-affected mice. These data demonstrate that, by enhancing E7 yield, it is possible to improve the anti-cancer activity of the plant-based experimental vaccine and open the way for a large-scale production of the E7 protein which could be purified or used as in planta formulation, also suitable for oral therapeutic vaccination.


[Serotonin syndrome: four report cases and review of the literature].
The serotonin syndrome is a clinical condition associated with serotonin agonists. Is due to an overstimulation of central and peripheral serotonin receptors that leads to mental, autonomic and neuromuscular changes. Usually the disorder resolves within the first 24 hours after the medications are discontinued, however some patients progress to a multiple organ failure and die. We describe four elderly patients that presented with the classic triad. They presented the symptoms in average at the third day after the initiation or variation of the treatment with serotonin reuptake inhibitors. All had a favorable response with the suspension of medications and, in three cases, with the treatment with chlorpromazine. We believe it is a potentially fatal but reversible condition, probably underdiagnosed that requires a high index of suspicion.


Facioscapulohumeral dystrophy: case report and discussion.
Facioscapulohumeral dystrophy (FSHD) is often cited as the third most common form of muscular dystrophy. Therefore, it should be considered in patients with complaints of progressive weakness. We present the case of a man with facial, truncal, and leg weakness that initially sought medical attention for lower back pain. Electrodiagnostic testing revealed findings in the trapezius, serratus anterior, biceps, triceps, pectoralis major, tibialis anterior, and gastrocnemius muscles consistent with a myopathic disorder. Subsequent genetic testing identified a FSHD allele size consistent with a FSHD deletion mutation. Therefore, confirming the diagnosis of FSHD. Unfortunately, no effective treatments currently exist for FSHD. However, supportive measures involving physical therapy and the use of orthotics may aid in improving function and mobility.


Giardia lamblia infections in B-cell-deficient transgenic mice.
In the present study, we infected B-cell (and antibody-)-deficient transgenic mice with the Giardia lamblia clone GS/M-83-H7. These animals were inhibited in intestinal anti-Giardia immunoglobulin A (IgA) production and could not resolve the parasite infection, and antigenic diversification within the respective parasite populations occurred in an unusually slow manner. These findings indicate an important immunological function of local IgA antibodies which promotes antigenic variation of the parasite and is involved in control of the parasite infection.


Accumulation of trans C18:1 fatty acids in the rumen after dietary algal supplementation is associated with changes in the Butyrivibrio community.
Optimization of the fatty acid composition of ruminant milk and meat is desirable. Dietary supplementation of algae was previously shown to inhibit rumen biohydrogenation, resulting in an altered milk fatty acid profile. Bacteria involved in biohydrogenation belong to the Butyrivibrio group. This study was aimed at relating accumulation of biohydrogenation intermediates with shifts in Butyrivibrio spp. in the rumen of dairy cows. Therefore, an experiment was performed with three rumen-fistulated dairy cows receiving a concentrate containing algae (9.35 g/kg total dry matter [DM] intake) for 20 days. Supplementation of the diet with algae inhibited biohydrogenation of C(18:2) omega 6 (n-6) and C(18:3) n-3, resulting in increased concentrations of biohydrogenation intermediates, whereas C(18:0) decreased. Addition of algae increased ruminal C(18:1) trans fatty acid concentrations, mainly due to 6- and 20-fold increases in C(18:1) trans 11 (t11) and C(18:1) t10. The number of ciliates (5.37 log copies/g rumen digesta) and the composition of the ciliate community were unaffected by dietary algae. In contrast, supplementation of the diet with algae changed the composition of the bacterial community. Primers for the Butyrivibrio group, including the genera Butyrivibrio and Pseudobutyrivibrio, were specifically designed. Denaturing gradient gel electrophoresis showed community changes upon addition of algae without affecting the total amount of Butyrivibrio bacteria (7.06 log copies/g rumen DM). Clone libraries showed that algae affected noncultivated species, which cluster taxonomically between the genera Butyrivibrio and Pseudobutyrivibrio and might play a role in biohydrogenation. In addition, 20% of the clones from a randomly selected rumen sample were related to the C(18:0)-producing branch, although the associated C(18:0) concentration decreased through supplementation of the diet with algae.


Intracellular expression of RNA transcripts complementary to the human immunodeficiency virus type 1 gag gene inhibits viral replication in human CD4+ lymphocytes.
Intracellular expression of antisense transcripts was evaluated for its potential to interfere with human immunodeficiency virus type 1 (HIV-1) replication. Retroviral vectors encoding HIV-1 psi-gag complementary sequences downstream of a selectable gene (neo, puromycin gene, or Lyt2 gene) were stable and yielded high titers. Human CEMSS T cells were transduced with amphotropic retroviral vectors to express RNA complementary to the psi-gag sequence of HIV-1. Replication of laboratory-adapted HIV-1 strains was inhibited by more than 1 order of magnitude (log10) in these transduced cells even at high inoculation doses (4 x 10(4) 50% tissue culture infective doses). Antisense-mediated anti-HIV efficacy was further demonstrated by survival of CD4+ cells in these cultures relative to controls. The level of anti-HIV-1 activity of the psi-gag antisense sequence correlated with the length of the antisense transcript. Maximal anti-HIV efficacy was observed with complementary sequence more than 1,000 nucleotides long, whereas transcripts less than 400 nucleotides long failed to inhibit HIV-1 replication. Expression of psi-gag antisense RNA also reduced HIV-1 JR-CSF replication 10-fold in primary CD4+ lymphocytes. These results obtained with a T-cell line and primary peripheral blood lymphocytes indicate the potential of long antisense RNAs as an efficient anti-HIV-1 therapeutic agent for gene therapy.


Progressive image denoising.
Image denoising continues to be an active research topic. Although state-of-the-art denoising methods are numerically impressive and approch theoretical limits, they suffer from visible artifacts.While they produce acceptable results for natural images, human eyes are less forgiving when viewing synthetic images. At the same time, current methods are becoming more complex, making analysis, and implementation difficult. We propose image denoising as a simple physical process, which progressively reduces noise by deterministic annealing. The results of our implementation are numerically and visually excellent. We further demonstrate that our method is particularly suited for synthetic images. Finally, we offer a new perspective on image denoising using robust estimators.


The effects of tianeptine, olanzapine and fluoxetine on the cognitive behaviors of unpredictable chronic mild stress-exposed mice.
Strong evidence indicates that impaired cognition is a core element of depression, and antidepressant treatment may ameliorate cognitive impairments experienced by depressive patients. Present study was performed to investigate effects of chronic tianeptine (5 mg/kg) or olanzapine (2.5 mg/kg) administration on cognitive behaviors of unpredictable chronic mild stress (UCMS)-exposed mice and to compare these effects to those induced by widely used SSRI antidepressant fluoxetine (15 mg/kg) in mice. To investigate effects of these drugs, the Morris water maze test (MWM), elevated plus maze test (EPM) and radial arm maze test (RAM) were used. The effects of stress and drugs on gene expression in the hippocampus was determined by quantitative Real Time-PCR. In MWM test, fluoxetine significantly increased escape latency of non-stressed mice in acquisition sessions and decreased time spent in escape platform quadrant in probe trial; tianeptine and olanzapine decreased enhancement in escape latency, and only olanzapine significantly enhanced attenuation in time spent in the escape platform quadrant in UCMS-exposed mice. In EPM test, all drugs significantly decreased enhancement in transfer latency in UCMS-exposed mice. In RAM test, fluoxetine significantly increased number of errors made by both non-stressed and UCMS-exposed mice. Quantitative real-time PCR revealed that CREB and BDNF gene expression levels were significantly decreased in UCMS-exposed group, and this effect was significantly reversed by each of drugs tested. Our results seem to be test dependent and should be further investigated using different learning and memory tasks.


Sleep Duration and Sleep Quality in Caregivers of Patients With Dementia: A Systematic Review and Meta-analysis.
In the United States, 16 million family caregivers provide long-term care for patients with dementia. Although one's physical, mental, and cognitive health depends on sleep, many caregivers experience chronic stress, and stress is typically associated with worse sleep quantity and quality. To quantify the extent, nature, and treatability of sleep problems in dementia caregivers. PubMed and Scopus databases were systematically searched for articles published through June 2018 using the following keywords: caregiver or spouse or caretaker AND sleep or circadian AND dementia or Alzheimer. Backward citation tracking was performed, and corresponding authors were contacted for additional data to conduct meta-analyses and pooled analyses. Two reviewers independently screened 805 studies to identify those that reported sleep duration or sleep quality in caregivers of patients with dementia. Following the PRISMA guidelines, 2 reviewers independently extracted data from all studies and conducted National Heart, Lung, and Blood Institute study quality assessments. Meta-analyses with random-effects models were performed to evaluate sleep duration, sleep quality, and sleep interventions in dementia caregivers. Sleep quality and total sleep time were measured by polysomnography, actigraphy, and self-report. Thirty-five studies were analyzed with data from 3268 caregivers (pooled mean age [SD of sample means], 63.48 [5.99] years; 76.7% female) were analyzed. Relative to age-matched control noncaregiver adults, caregivers had lower sleep durations akin to losing 2.42 to 3.50 hours each week (Hedges g = -0.29; 95% CI, -0.48 to -0.09; P = .01). Sleep quality was significantly lower in caregivers (Hedges g = -0.66; 95% CI, -0.89 to -0.42; P < .001), but caregivers who underwent sleep intervention trials had better sleep quality than caregivers who did not receive a sleep intervention (Hedges g = 0.35; 95% CI, 0.20-0.49; P < .001). Sleep debt is known to have cumulative associations with physical, mental, and cognitive health; therefore, poor sleep quality in dementia caregivers should be recognized and addressed. Although the caregiving role is stressful and cognitively demanding by its nature, better sleep quality was observed in caregivers who received low-cost behavioral interventions.


A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is usually described as a pathological proliferation of prostatic fibroblasts/myofibroblasts and epithelial cells. In the present study of BPH samples, we have made a morphological and immunohistochemical study of BPH prostatic sections using markers of proliferation, apoptosis, hormone receptors, and TGF-beta signaling. We found no evidence of proliferation in the stroma but in the epithelium of some ducts; 0.7% of the basal and 0.4% of luminal cells were positive for Ki67 and PCNA. Androgen receptor and estrogen receptor beta (ERbeta)1 and ERbetacx were abundant in both stromal and epithelial compartments but cells expressing ERalpha were very rare. What was very common in all BPH samples was the following: (i) regions of the ductal epithelium where the epithelial cells did not express E-cadherin, had lost their polarization, and become spindle shaped (the nuclei of these cells were strongly positive for pSmad 3 and Snail); and (ii) regions where the walls of the blood vessels were extremely thick and there was loss of endothelial layer. Loss of E-cadherin, increased pSmad 3, and high expression of Snail are all characteristic of epithelial-mesenchymal transition (EMT). We conclude that BPH is not a disease of prostatic stromal proliferation but rather of accumulation of mesenchymal-like cells derived from the prostatic epithelium and the endothelium. TGF-beta is thought to play a key role in EMT. Our data suggests that TGF-beta/Smad should be considered as targets for treatment of BPH.


Protracted dendritic growth in the typically developing human amygdala and increased spine density in young ASD brains.
The amygdala is a medial temporal lobe structure implicated in social and emotional regulation. In typical development (TD), the amygdala continues to increase volumetrically throughout childhood and into adulthood, while other brain structures are stable or decreasing in volume. In autism spectrum disorder (ASD), the amygdala undergoes rapid early growth, making it volumetrically larger in children with ASD compared to TD children. Here we explore: (a) if dendritic arborization in the amygdala follows the pattern of protracted growth in TD and early overgrowth in ASD and (b), if spine density in the amygdala in ASD cases differs from TD from youth to adulthood. The amygdala from 32 postmortem human brains (7-46 years of age) were stained using a Golgi-Kopsch impregnation. Ten principal neurons per case were selected in the lateral nucleus and traced using Neurolucida software in their entirety. We found that both ASD and TD individuals show a similar pattern of increasing dendritic length with age well into adulthood. However, spine density is (a) greater in young ASD cases compared to age-matched TD controls (<18 years old) and (b) decreases in the amygdala as people with ASD age into adulthood, a phenomenon not found in TD. Therefore, by adulthood, there is no observable difference in spine density in the amygdala between ASD and TD age-matched adults (≥18 years old). Our findings highlight the unique growth trajectory of the amygdala and suggest that spine density may contribute to aberrant development and function of the amygdala in children with ASD.


Molecular effects of curcumin on the experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). Previous studies have shown that myelin degradation during MS and EAE resulted in reduced expression of some of the proteins, e.g., the MBP (myelin basic protein), and increased expression of genes such as iNOS (Inducible nitric oxide synthase) and NOGO-A in the affected patients. In the present study, EAE was induced by immunizing Wistar rats (n=12) with homogenized spinal cord of guinea pig and Freund's complete adjuvant. Curcumin is an active ingredient in turmeric with anti-inflammatory properties, which has been studied in this article. In this study, the effect of curcumin administration on the change of the expression of MBP, NOGO-A, and iNOS genes was evaluated using the RT-PCR (Reverse transcription-polymerase chain reaction) technique. The obtained results indicated it could be concluded that curcumin was able to improve EAE by increasing the amount of MBP gene expression and reducing the intensity of NOGO-A expression.


The influence of educational attainment on depression and risk of type 2 diabetes.
We investigated the association between major depressive disorder and type 2 diabetes, whether that association is explained by health behaviors, and whether it is influenced by educational attainment. We used discrete-time Cox proportional hazards models to determine the risk of type 2 diabetes associated with depression in a 23-year population-based cohort study. Major depressive disorder was associated with higher risk of type 2 diabetes (hazard ratio [HR]=1.62) after we controlled for age, gender, race, education, smoking status, alcohol use, social network size, and antidepressant use. This association was more pronounced after we controlled for body mass index, family history, and health behaviors (HR=2.04; 95% confidence interval=1.09, 3.81). In stratified analyses, the risk associated with major depressive disorder was elevated among those with 12 or fewer years of education compared with those with at least some education beyond high school. The risk of type 2 diabetes associated with major depressive disorder persists over the life course and is independent of the effects of health behaviors, body mass index, and family history. Education is an important moderator of this association.


Bioresorbable vascular scaffolds in STEMI patients: multimodality imaging comparison in mid-term perspective.
Bioresorbable vascular scaffolds (BVS) represent an exciting and novel coronary intervention technology. BVS implantation could play an important role in the acute ST elevation myocardial infarction (STEMI) setting, with mid- and long-term follow-up data still scarce. PRAGUE-19 is a prospective double-center single arm study that tests the performance and safety of BVS implantation during primary percutaneous coronary intervention (pPCI) in the STEMI setting. During the enrollment period 70 patients were included, quantitative coronary angiography (QCA) was done immediately after BVS implantation and optical coherence tomography (OCT) study was suggested but not mandatory; subsequently serial clinical follow-up was scheduled and research computed tomography (CT) angiography at 1 year was performed. The current study focused on a group of 22 patients who had complete multi-imaging data (QCA and OCT immediately post-procedure and CT at 1 year after implantation) and aimed to analyze the quantitative measurements of these different techniques. All 25 BVS implanted in 22 patients were widely patent at 1-year CT angiography. Immediately after pPCI, QCA measurements of vessel size were smaller than OCT with statistical significance: mean reference vessel diameter (RVD) was respectively 3.1±0.4 versus 3.4±0.5 mm (P<0.001), mean minimum lumen diameter (MLD) 2.5±0.3 versus 3.0±0.3 mm (P<0.001) and mean BVS diameter 2.8±0.3 versus 3.26±0.29 mm (P=0.001). Mean RVD and reference vessel area (RVA) were larger at 1 year CT angiography in comparison to baseline OCT (3.4±0.5 mm versus 3.76±0.45 mm, P=0.009, and 9.27±2.7 mm2 versus 11.28±2.62 mm2, P=0.01, respectively) and MLD was also larger at follow-up: 2.96±0.29 mm versus 3.09±0.53 (P=0.077). However, the mean percent area stenosis (parameter not influenced by possible difference between different methods) measured with OCT immediately after pPCI and with CT angiography at 1 year did not show any difference (20.2±23.9% versus 24.8±17.8%, P=0.478). In comparison with OCT, QCA largely underestimates luminal diameters and may interfere with BVS proper sizing. CT angiography did not identify any evidence of binary restenosis, confirming the effective anti-restenotic properties of BVS at mid-term follow-up.


Current and potential treatment of colorectal cancer metastasis to bone.
Colorectal cancer (CRC) with subsequent bone metastasis is associated with a poor prognosis compared with patients who do not develop bone metastasis. However, metastasis in bone is rare, contrasted with more common locations such as the liver and lungs. As a result, the treatment methods targeting CRC bone lesions are limited. This review aims to compile information regarding current and potential medical and surgical treatment methods for colorectal cancer with specific regard to bone metastasis. A computer-based literature review of animal- and human-based studies was conducted using multiple database searches. Case reports were excluded. Preliminary findings demonstrate that treatments specifically targeting bone metastasis due to colorectal cancer are categorized by local vs. systemic treatment. The primary goals are the alleviation of skeletal-related events and improvement in quality of life. Current options include: chemotherapy, radiation, monoclonal antibodies, and surgery. Emerging options include intratumoral mellitin, MRgFUS, and bone microenvironment targeting. Treatment of CRC metastasis to bone is necessary to slow down metastatic progression, alleviate symptoms, and improve quality of life. With a possible rise in bone metastasis due to increased overall CRC survival rates, more clinical trials should be performed to address this growing concern.


Optical Mapping of Virtual Electrode Polarization Pattern and Its Relationship with Pacemaker Location during Gastric Pacing.
Gastric rhythmic contractions are regulated by bioelectrical events known as slow waves (SW). Abnormal SW activity is associated with gastric motility disorders. Gastric pacing is a potential treatment method to restore rhythmic SW activity. However, to date, the efficacy of gastric pacing is inconsistent and the underlying mechanisms of gastric pacing are poorly understood. Optical mapping is widely used in cardiac electrophysiology studies. Its immunity to pacing artifacts offers a distinct advantage over conventional electrical mapping for studying pacing. In the present study, we first found that optical mapping can image pacing-induced virtual electrode polarization patterns in the stomach (adjacent regions of depolarized and hyperpolarized tissue). Second, we found that elicited SWs usually (15 of 16) originated from the depolarized areas of the stimulated region (virtual cathodes). To our knowledge, this is the first direct observation of virtual electrode polarization patterns in the stomach. Conclusions: Optical mapping can image virtual electrode polarization patterns during gastric pacing with high spatial resolution.Clinical Relevance- Gastric pacing is a potential therapeutic method for gastric motility disorders. This study provides direct observation of virtual electrode polarization pattern during gastric pacing and improves our understanding of the mechanisms underlying gastric pacing..


Structural motifs in the early metallation steps of Zn(II) and Cd(II) binding to apo-metallothionein 1a.
Many proteins require a metal cofactor to function and these metals are often involved in the protein folding process. The protein metallothionein (MT) has a dynamic structure capable of binding to a variety of metals with different stoichiometries. The most well-understood structure is the seven-metal, two domain structure formed upon metallation using Zn(II) or Cd(II). However, the partially metallated states and the pathways to form these clusters are less well-understood, although it is known that the pathways are pH dependent. Using stopped flow methods, it is shown that the metallation rates of the less cooperative Zn(II) binding pathway is much more impacted by low pH conditions that that of the more cooperative Cd(II) binding pathway. Electrospray ionization mass spectrometry (ESI-MS) methods reveal specific mixtures of bridging and terminally bound MxSy structures form in the first few metallation steps. Using a combination of methods, the data show that the result of unfolding this intrinsically disordered apo-MT structure using guanidinium chloride is that the formation of preliminary bridging structures that form in the first few metallation steps is impeded. The data show that more terminally bound structures form. Our conclusion is that the compact conformation of the native apo-MT at physiological pH allows for rapid formation of complex metal-thiolate structures with high affinity that provides protection from oxidation, a function that is suppressed upon unfolding. Overall, these results highlight both the importance of the apo-MT structure in the metallation pathway, but also the differences in Zn(II) and Cd(II) binding under different conditions.