Role of aminergic (serotonin and dopamine) systems in the embryogenesis and different embryonic behaviors of the pond snail, Lymnaea stagnalis.
A detailed biochemical and pharmacological analysis of the dopaminergic (DAergic) and serotonergic (5-HTergic) systems was performed during the embryogenesis of Lymnaea stagnalis, to monitor their role in development and different behaviors. The dopamine (DA) level and the synthesizing decarboxylase enzyme activity showed a continuous increase, whereas the serotonin (5-HT) concentration remained low until late postmetamorphic development, when they all showed a rapid and significant increase. Application of monoamine precursors increased, whereas enzyme inhibitors and neurotoxins reduced monoamine levels; all treatments resulting in a prolongation of embryogenesis. Following, p-chlorphenylalanine (pCPA) and 3-hydroxybenzylhydrazine (Nsd-1015) treatments, no 5-HT immunoreactivity could be detected in the embryonic nervous system. These findings suggest that changes of monoamine levels in either (negative or positive) direction cause slowing of embryogenesis. Embryonic rotation and radula protrusion rate was enhanced following both serotonin and dopamine application, whereas frequency of gliding was increased by serotonin treatment. These results clearly indicate the involvement of 5-HT and DA in the regulation of a broad range of embryonic behaviors. Pharmacological characterization of a 5-HT receptor associated with the L. stagnalis embryonic behaviors studied revealed that a mammalian 5-HT(1)-like receptor type is involved in the 5-HTergic regulation of locomotion activity.


Characterization of antisperm antibody binding patterns in relation to sperm phenotypic attributes and field fertility in dairy bulls.
To test our hypothesis that antisperm antibodies (ASA) might alter sperm phenotypic attributes thus leading to sub-fertility/infertility in bulls, ASA were generated in crossbred male calves by immunizing with sperm two times. Cryopreserved spermatozoa from crossbred bulls (n = 24) with different field fertility ratings were incubated with ASA and different patterns of ASA immunolocalization were studied. In addition, sperm membrane integrity, acrosomal integrity and cryo-capacitation status were also assessed. Immunolocalization of sperm antigens using antisperm antibody revealed three major patterns (Acrosomal-AR, apical-AP and, acrosome and tail-AT). The proportion of ASA reactive spermatozoa was significantly (P < 0.05) higher in low- and medium-fertile bulls compared to high-fertile bulls. Among the three patterns, the proportion of spermatozoa with AR pattern was significantly (P < 0.05) higher in low- and medium-fertile bulls compared to high-fertile bulls. The proportion of membrane and acrosome intact spermatozoa was significantly (P < 0.05) higher in high-fertile bulls compared to medium- and low-fertile bulls. There were no significant differences in the proportion of cryo-capacitated spermatozoa among high-, medium- and low-fertile bulls. The relationship between ASA reactive spermatozoa and conception rates (CR) of bulls was highly (P < 0.01) significant and negative. Similarly, AR and AT pattern were also significantly (P < 0.01) and negatively related to CR of bulls. The reactivity of spermatozoa with ASA was also significantly (P < 0.01) and negatively related to the membrane and acrosome integrity of spermatozoa. It was concluded that the proportion of spermatozoa responding to ASA was higher in low-compared to high-fertile bulls and ASA localization in sperm acrosomal area was negatively related to sperm membrane and acrosomal integrity and bull fertility.


Occurrence and prevalence of bot flies, Metacuterebra apicalis (Diptera: Cuterebridae), in rodents of cerrado from central Brazil.
The occurrence and prevalence of Metacuterebra apicalis (Diptera: Cuterebridae) in natural populations of Oryzomys subflavus, Bolomys lasiurus, and Thalpomys cerradensis (Rodentia: Muridae) from August 1990 to July 1992 in the cerrado, a common savanna-like vegetation type of central Brazil, are reported. An increase in bot infection in the 3 rodent species between October 1991 and July 1992 without correlation to precipitation was detected. The prevalence was lower than in neotropical forest formations. Mean intensity was 1.3 bots (range 1-2) for T. cerradensis and 1 bot for B. lasiurus and O. subflavus. This is the first record of T. cerradensis as host of bot flies.


Sputum and pulmonary function in asthma.
To assess the relevance of sputum production to pulmonary function, in particular, persistent obstruction in patients with a primary clinical diagnosis of asthma. Cross-sectional study of all patients currently followed up in secondary care in a defined locality. National Health Service and private clinics in north-east England. All attenders, aged 18 years or older, with asthma, confirmed by reversibility of peak expiratory flow (PEF) by > or =15% and to > or =200 L/min. Pro forma history. Pulmonary function at attendance. Assessment of best function according to protocol. Measurement of actual FEV1, FVC, and PEF at attendance. We studied 772 subjects; 387 (50%) were male; mean age was 55 years; atopic, 51%; current smokers, 11.5%; ex-smokers, 36%; and never smokers, 52.5%. Best pulmonary function was lower in chronic sputum producers (PEF, 83.2 vs 95.8; FVC, 67.9 vs 81.7% predicted). Chronic sputum production and its negative relationship with best function was strongly associated with smoking. There was little relationship between chronic sputum and persistent obstruction in nonsmokers. There were no univariate associations between sputum during attacks, or its color, and pulmonary function, but after allowing for demographic factors, including smoking, green sputum was associated with persistent obstruction. There was little relationship between sputum and actual/best function at attendance. Chronic sputum production is associated with persistent obstruction principally in those who have smoked, suggesting that the association reflects smoking rather than asthma. There is no interaction with atopy. After allowance for cigarette smoking, there is an association between green sputum production during exacerbations and persistent obstruction. Green sputum during relapse in asthma may indicate inflammation that is relevant to prognosis.


Tension pneumopericardium: a case report and a review of the literature.
Pneumopericardium, or air within the pericardial sack, generally occurs after high-speed blunt deceleration injuries. Although it is generally relatively benign, in rare instances, it can become hemodynamically significant. The diagnosis is easily made on plain chest radiography. More recently, chest computed tomography has been helpful in making the diagnosis. Injury to vital structures such as the tracheobronchial tree or esophageal tears require operative fixation. However, in most instances, pneumopericardium is secondary to dissection of air through the adjacent structures to the pericardial space. The air is trapped as a one-way valve. The pneumopericardium is usually self-limited, requiring no specific therapy. In patients where there is a concomitant pneumothorax, chest tube drainage suffices. We present a case of hemodynamically significant tension pneumopericardium that occurred in association with blunt carotid injury and aortic


Empirically testing determinants of hospital BPR success.
Business process reengineering has been touted in the literature as a dramatic improvement necessary for organization competitiveness, but in practice there are many unsuccessful cases. Thus, there is need for a more systematic and rigorous assessment of the factors deemed important to project success. The main objective of this study is to examine this issue. For this research, success has been defined as the benefits the hospital has derived from the BPR project, according to top managers' opinions. A sample of 192 hospital administrators shared their organizations' experience with their last BPR project implementation, where the changes have been operational for at least one year. Based on the results, recommendations are made for hospital managers to focus attention and resources on factors important to BPR project success. In general, hospitals are not emphasizing some of the most important activities and tasks recommended in the BPR literature, such as changes to customer/market-related business processes, the value-added element of every business activity, and applying the right innovative technology. Based on the findings as a whole, it behoves top managers not to engage in BPR before ensuring the presence of the success factors found to be important.


Wetting behavior and nanotribological properties of silicon nanopatterns combined with diamond-like carbon and perfluoropolyether films.
A large number of silicon (Si) patterns consisting of nanopillars of varying diameter and pitch have been fabricated and further coated with diamond-like carbon (DLC) and perfluoropolyether (Z-DOL) films. The wetting behavior and nano-adhesion/friction of the patterns are investigated experimentally in relation to the nanostructures and the hydrophobicity of the materials. Measurements of water contact angle illustrate that the patterning-enhanced wettability of the Si flat surface, along with two distinct wettings which are in good agreement with the Wenzel and hemi-wicking states, depended on the value of the pitch-over-diameter ratio. In the case of the coated patterns, three wetting states are observed: the Cassie-Baxter, the Wenzel, and a transition from the Cassie-Baxter into the Wenzel, which varies with regard to the hydrophobic properties of the DLC and Z-DOL. In terms of tribological properties, it is demonstrated that a combination of the nanopatterns and the films is effective in reducing adhesive and frictional forces. In addition, the pitch and diameter of the patterns are found to significantly influence their adhesion/friction behaviors.


Alpha male replacements and delayed dispersal in crested macaques (Macaca nigra).
In species with a high male reproductive skew, competition between males for the top dominant position is high and escalated fights are common between competitors. As a consequence, challenges incur potentially high costs. Selection should favor males who time an alpha male challenge to maximize chances of a successful outcome minimizing costs. Despite the importance of alpha male replacements for individual males, we know little about the timing of challenges and the condition of the challenger. We investigated the timing and process of alpha male replacements in a species living in multi-male groups with high male reproductive skew, the crested macaque. We studied four wild groups over 6 years in the Tangkoko Reserve, North Sulawesi, Indonesia, during which 16 alpha male replacements occurred. Although unusual for cercopithecines, male crested macaques delayed their natal dispersal until they attained maximum body mass and therefore fighting ability whereupon they emigrated and challenged the alpha male in another group. Accordingly, all observed alpha male replacements were from outside males. Ours is the first report of such a pattern in a primate species living in multi-male groups. Although the majority of alpha male replacements occurred through direct male-male challenges, many also took place opportunistically (i.e., after the alpha male had already been injured or had left the group). Furthermore, alpha male tenures were very short (averaging ca. 12 months). We hypothesize that this unusual pattern of alpha male replacements in crested macaques is related to the species-specific combination of high male reproductive skew with a large number of males per group. Am. J. Primatol. 79:e22448, 2017. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc.


Clinical observations on a newly designed electronic apex locator.
The introduction of alternative electronic principles and circuitry has produced the next generation of electronic apex locators, which have fewer clinical limitations and greater ease of use, on a routine basis, than their predecessors. The history of how the electronic apex locator was developed over the past 30 years and the limitations of the machines designed on earlier principles are reviewed. Clinical examples of root canal systems measured using a newly-designed, frequency-dependent apex locator are presented in order to illustrate the spectrum of cases that can be read. All measurements were made on canals irrigated previously with electro-conducting solutions, which would have made readings from earlier machines problematic. Single-rooted and molar teeth as well as teeth with vital tissue in the root canal system or with necrotic pulp tissue and periapical lesions have been treated with equal ease and results. The electronic apex locator is being advocated to supplement instrumentation technique and to improve the identification of the apical terminus of the root canal system. The routine use of these devices is advocated to ensure an accurate placement of root canal fillings rather than to eliminate the need for radiographs.


Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents.
Retrograde and anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was studied in 7 squirrel monkeys with discrete injections of the subthalamic nucleus (STN). Injections labeled: (1) the lateral two-thirds of the nucleus (63% and 47%), (2) ventrolateral parts caudally (20%), (3) dorsomedial parts caudally (18%), (4) rostromedial parts (21%), (5) the medial third (38%) and (6) the lateral pole of the nucleus (9%). Afferents to the lateral two-thirds of the STN originated from two parallel cellular arrays in dorsal parts of the middle third of the lateral pallidal segment (LPS) and a single array in the rostral third of the LPS. Medial regions of the STN received input from cells in the rostral LPS. Small numbers of cells were retrogradely labeled in the centromedian-parafascicular (CM-PF) and the pedunculopontine (PPN) nuclei. No cells were labeled in the frontal cortex, the striatum, the substantia innominata (SI), the substantia nigra (SN) or the dorsal nucleus of the raphe. Virtually all pallidal neurons, including identified pallidosubthalamic neurons, were immunoreactive (IR) for gamma-aminobutyric acid (GABA). Pallidosubthalamic neurons were most numerous in regions of the LPS with the lowest density of leucine enkephalin-IR fibers. Substance P-IR fibers, found mainly in the medial pallidal segment, bore no relationship to pallidal afferents to the STN. Choline acetyltransferase-IR cells in the SI and the PPN were not retrogradely labeled with WGA-HRP granules. Anterograde transport in fibers and terminal fields surrounded retrogradely labeled cells in the LPS, suggesting a reciprocal relationship. The caudal third of the LPS and ventral region of the middle third of this nucleus, appeared to project few fibers to, or to receive few fibers from, the STN. A small number of STN efferents entered the medial border of the putamen, but no terminal fields were identified. STN projections to the pars reticulata of the SN appeared to represent about 10% of the projection to the LPS. No STN efferents were identified in the frontal cortex, the SI or the PPN. The hypothesis that STN afferents from the frontal cortex and CM-PF may represent collaterals of projections to other loci is discussed.


A Systematic Analysis of the Binding Affinity between the Pim-1 Kinase and Its Inhibitors Based on the MM/3D-RISM/KH Method.
A systematic study of the binding affinities of 16 lead compounds targeting the Pim-1 kinase based on the 3D-RISM/KH theory and MD simulations is reported. The results show a correlation coefficient R = 0.69 between the theoretical and experimental values of the binding free energy. This demonstrates that the method is applicable to the problem of compound screening and lead optimization, for which relative values of the free energy among the compounds have significance. We elucidate the contribution of the ligand fragments to the binding free energy. Our results indicate that the interactions between the residues and the triazolo[4,3-b]pyridazine scaffold as well as the phenyl ring of the ligand molecule make significant contributions to stabilization of the complex. Using the 3D-RISM/KH theory, we further analyze the probability distribution of a ligand fragment around the protein-ligand complex in which the substituent around the phenyl ring is removed from the ligand. The results demonstrate that the 3D-RISM/KH theory is capable of predicting the position of substitution on a ligand that has a higher affinity to a target protein.


Human immunodeficiency virus and the outcome of treatment for new and recurrent pulmonary tuberculosis in African patients.
The purpose of this study was to evaluate the impact of human immunodeficiency virus (HIV) infection on treatment for tuberculosis (TB). The study population comprised 28,522 black Southern African gold miners. Patients with sputum culture-positive new or recurrent pulmonary TB diagnosed in 1995 were prospectively enrolled in the cohort. Directly observed therapy (DOT) was practiced and outcomes were assessed at 6 mo after treatment was begun. There were 376 cases of TB (incidence 1,318 per 100,000), of which 190 (50%) were HIV positive and 82 (22%) had recurrent TB. There was no association between HIV status and history of previous TB or drug resistance. Neither the treatment interruption rate (2%) nor the rate at which patients transferred out of the treatment program (1.6%) were associated with HIV status. Excluding deaths, cure rates were similar for HIV-positive and HIV-negative patients (89% versus 88%), but significantly lower in those with recurrent than in those with new TB (77% versus 92%). Mortality was 0.5% in HIV-negative patients versus 13.7% in HIV-positive patients, and in the latter group was associated with CD4(+) lymphocyte depletion. Autopsy examination showed that in HIV-positive patients, early mortality was due to TB whereas late deaths were most commonly due to cryptococcal pneumonia. The study showed that a well-run TB control program can result in acceptable cure rates even in a population with a very high incidence of TB and HIV infection. Particular vigilance is needed for concurrent infections, which may contribute significantly to mortality during treatment of TB in HIV-positive patients.


Longitudinal pathways linking racial discrimination and Chinese American mothers' parenting.
Racial discrimination is a salient and chronic stressor for ethnic minority parents that can negatively impact their parenting. The present study used a short-term longitudinal design to examine the link between Chinese American mothers' stressful experiences of racial discrimination and their authoritarian parenting practices, the mediating role of mothers' depressive symptoms, and the moderating role of their behavioral acculturation toward American and Chinese cultures in these associations (i.e., behavioral participation in the American culture and behavioral maintenance of Chinese culture). Participants were 143 first-generation Chinese American mothers (Mage = 38.0 years) with preschool-age children (Mage = 4.6 years; 50% girls). Mothers reported their racial discrimination stress, depressive symptoms, American and Chinese behavioral acculturation, and authoritarian parenting across two time points over a 6-month interval. A moderated mediation model was conducted using structural equation modeling to test the hypothesized associations. Chinese American mothers' depressive symptoms mediated the association between racial discrimination stress and authoritarian parenting. The path between racial discrimination stress and depressive symptoms and the indirect effect of racial discrimination stress on authoritarian parenting were buffered by mothers' behavioral acculturation toward American culture and exacerbated by their behavioral acculturation toward Chinese culture. This study provides the first longitudinal evidence linking Chinese American mothers' experiences of racial discrimination and their negative parenting over time as well as mediating and moderating factors underlying this process. Our findings highlight the need for systemic efforts addressing racial inequalities and fostering positive development in Asian Americans and other marginalized families. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin.
Survivors of a cardiac arrest often have persistent cardiovascular derangements following cardiopulmonary resuscitation including decreased cardiac output, arrhythmias and morphological myocardial damage. These cardiovascular derangements may lead to an increased susceptibility towards the external and internal environment of the cardiovascular system as compared to the healthy situation. Here we tested the hypothesis that the cardiovascular system in healthy rats and rats resuscitated from a cardiac arrest may be differentially affected by a transient receptor potential vanilloid type 1 agonist, by continuous intravenous infusion of dihydrocapsaicin (DHC). Compared to baseline, infusion of DHC caused an initial increase in mean arterial blood pressure in both healthy and resuscitated rats of 25% and 10%, respectively. Also, we observed an initial response of tachycardia in both healthy and resuscitated rats of 30% and 20%, respectively. Then, at high levels of DHC infusion (> 2.0 mg/kg/hr) we observed two single episodes of transient bradycardia and hypotension in 33% of the healthy rats, which was consistent with a TRPV1 agonist induced Bezold-Jarisch reflex. In contrast, in resuscitated rats we observed multiple episodes of bradycardia/hypotension in 100% of the rats and at a dose of DHC of 0.65 mg/kg/hr. Notably, this DHC effect could be completely blocked in the resuscitated rats by pre-treatment with atropine, a muscarinic acetylcholine antagonist. Our results indicate that the susceptibility of the rats towards TRPV1 agonist induced Bezold-Jarisch reflex is increased in those resuscitated from cardiac arrest compared to the healthy situation.


Associations between neuropeptide Y nerve terminals and intraparenchymal microvessels in rat and human cerebral cortex.
Neuropeptide Y (NPY) can influence local brain perfusion, possibly via direct relationships with the microvascular bed. To evaluate this possibility, the authors quantitatively analyzed by light and electron microscopy the morphological associations between immunostained NPY neuronal elements and intraparenchymal microvessels in the rat and human cerebral cortex. At the light microscopic level in the rat frontoparietal cortex, about 16% of NPY neurons and large proximal processes as well as a subset of nerve terminals not affected by double sympathectomy were associated with penetrating arterioles and local microvessels. In human temporal cortex, a dense network of NPY nerve fibers was observed, many of which approached and/or contacted intracortical vessels. At the ultrastructural level, 14% of NPY axonal varicosities in the rat cerebral cortex were considered perivascular and associated with capillaries (approximately 70%) or microarterioles (approximately 30%). They were particularly enriched in the immediate vicinity (< 0.25 micron) of the microvessels, where the perivascular astrocytic leaflets represented a frequent target. In human cerebral cortex, NPY varicosities were observed in proximity to microvessels corresponding primarily to capillaries. Perivascular NPY varicosities never established synaptic junctions with vascular or astroglial elements. The results show that central NPY nerve terminals associate with microvessels and perivascular astroglial cells in the rat and human cerebral cortex. Thus, NPY released from these nerves could possibly influence (via a parasynaptic mode of action) vascular and/or astrocytic functions depending on the distribution of NPY receptors in these cellular compartments. These results provide morphological support for the effects of NPY on brain perfusion and homeostasis.


Essential References for Structural Analysis of the Peripheral Nervous System for Pathologists and Toxicologists.
Toxicologic neuropathology for the peripheral nervous system (PNS) is a vital but often underappreciated element of basic translational research and safety assessment. Evaluation of the PNS may be complicated by unfamiliarity with normal nerve and ganglion biology, which differs to some degree among species; the presence of confounding artifacts related to suboptimal sampling and processing; and limited experience with differentiating such artifacts from genuine disease manifestations and incidental background changes. This compilation of key PNS neurobiology, neuropathology, and neurotoxicology references is designed to allow pathologists and toxicologists to readily access essential information that is needed to enhance their proficiency in evaluating and interpreting toxic changes in PNS tissues from many species.


Neuroradiological features of intraosseous cavernous hemangioma--case report.
A 40-year-old man presented to our hospital because of a painless lump on his right forehead. Radiography showed a radiolucent defect in the frontal bone. Bone window computed tomography demonstrated a lucent mass which expanded externally from the diploë destroying and passing through the outer plate. T1-weighted magnetic resonance imaging revealed the lesion as non-homogeneously isointense, and T2-weighted imaging as non-homogeneously hyperintense. The lesion was enhanced non-homogeneously after contrast administration. The lesion was subtotally removed. Histological examination suggested cavernous hemangioma. Preoperative examinations could not provide a definitive diagnosis, which was established by the operative finding. Because of the difficulty of diagnosis in the early stage, surgical treatment in the early stage is recommended for total removal and definitive diagnosis of intraosseous tumor.


Short-term variability and nocturnal decline in ambulatory blood pressure in normotension, white-coat hypertension, masked hypertension and sustained hypertension: a population-based study of older individuals in Spain.
Blood pressure (BP) variability and nocturnal decline in blood pressure are associated with cardiovascular outcomes. However, little is known about whether these indexes are associated with white-coat and masked hypertension. We performed a cross-sectional analysis of 1047 community-dwelling individuals aged ⩾60 years in Spain in 2012. Three observer-measured home BPs and 24-h ambulatory blood pressure monitoring (ABPM) were performed under standardized conditions. BP variability was defined as BP s.d. and coefficient of variation. Differences in BP variability and nocturnal BP decrease between groups were adjusted for sociodemographic and clinical covariates using generalized linear models. Of the cohort, 21.7% had white-coat hypertension, 7.0% had masked hypertension, 21.4% had sustained hypertension, and 49.9% were normotensive. Twenty-four hour, daytime and night-time systolic BP s.d. and coefficients of variation were significantly higher in subjects with white-coat hypertension than those with normotension (P<0.05) and were similar to subjects with sustained hypertension. In untreated subjects, 24-h but not daytime or night-time BP variability indexes were significantly higher in subjects with white-coat hypertension than in those with normotension (P<0.05). Percentage decrease in nocturnal systolic and diastolic BP was greatest in the white-coat hypertension group and lowest in the masked hypertension group in all patients and untreated patients (P<0.05). Lack of nocturnal decline in systolic blood pressure was observed in 70.2% of subjects with normotension, 57.8% of subjects with white-coat hypertension, 78.1% of subjects with masked hypertension, and 72.2% of subjects with sustained hypertension (P<0.001). In conclusion, 24-h BP variability was higher in subjects with white-coat hypertension and blunted nocturnal BP decrease was observed more frequently in subjects with masked hypertension. These findings may help to explain the reports of increased cardiovascular risk in patients with white-coat hypertension and poor prognosis in those with masked hypertension, highlighting the importance of ABPM.


Effects of soluble factors and extracellular matrix components on vascular cell behavior in vitro and in vivo: models of de-endothelialization and repair.
Vessel walls are comprised of several different cell populations residing in and on complex extracellular matrices. Each of the vascular cell types has diverse and sometimes unique functions and morphologies, and each has roles in repair processes following injury. Large vessel endothelial cells are known to respond to denudation injury by sheet migration and proliferation. This is in contrast to the migration through soft tissues with tube formation and subsequent lumen formation exhibited by microvascular endothelial cells in response to injury. Vascular smooth muscle cells of larger vessels respond to injury by migration from the arterial media into the intima, proliferation, and matrix biosynthesis, ultimately causing intimal thickening. Both these cell types exhibit "dysfunctional" phenotypes during their responses to injury. Microvascular cell responses to injury, while extremely variable, are less well documented. Specifically, responses to injury by microvascular endothelial vascular cells appear to be modulated, in part, by the composition and organization of the surrounding matrix as well as by the various soluble factors and cytokines found at sites of injury, suggesting that the extracellular matrix and soluble factors modulate each other's effects on local vascular cell populations following injury.


The Glomeromycota in the Neotropics.
Arbuscular mycorrhizal fungi (AMF-Glomeromycota) are a group of soil fungi with a widespread occurrence in terrestrial ecosystems where they play important roles that influence plant growth and ecosystem processes. The aim of this paper is to reveal AMF distribution in the Neotropics based on an extensive biogeography database with literature data from the last five decades. All four orders and 11 families were reported in the Neotropics. 221 species (69% of the total number of species for the phylum) were registered in the Neotropics pertaining to 37 genera. Acaulospora, Glomus, Scutellospora, and Funneliformis were the most speciose genera and represented by 47, 29, 15, and 13 species, respectively. Seventy-six species were originally described from Neotropics, which represents 24% of the total diversity of Glomeromycota. The most representative families were Gigasporaceae, Ambisporaceae, and Acaulosporaceae with 89%, 80%, and 79% of species within each family detected in the Neotropics, respectively. AMF were detected in 11 biomes and 52 ecological regions in 19 countries. Biomes with the largest number of species were Tropical and Subtropical Moist Forests (186 species), Tropical and Subtropical Dry Broadleaf forests (127 species), and Tropical and Subtropical Grasslands (124 species), and Jaccard's similarity among them was 53-57%. Mean annual temperature and precipitation were not correlated with total AMF species richness. The Neotropics biomes shelter a large amount of the total diversity of Glomeromycota and studies of occurrence of these fungi should be encouraged considering their importance in maintaining terrestrial ecosystems.


Targeting the metabolism of cancer stem cells by energy disruptor molecules.
Cancer stem cells (CSCs) have been identified in various tumor types. CSCs are believed to contribute to tumor metastasis and resistance to conventional therapy. So targeting these cells could be an effective strategy to eliminate tumors and a promising new type of cancer treatment. Alterations in metabolism play an essential role in CSC biology and their resistance to treatment. The metabolic properties pathways in CSCs are different from normal cells, and to some extent, are different from regular tumor cells. Interestingly, CSCs can use other nutrients for their metabolism and growth. The different metabolism causes increased sensitivity of CSCs to agents that disrupt cellular homeostasis. Compounds that interfere with the central metabolic pathways are known as energy disruptors and can reduce CSC survival. This review highlights the differences between regular cancer cells and CSC metabolism and discusses the action mechanisms of energy disruptors at the cellular and molecular levels.


WSO Leadership in Stroke Medicine Award Lecture Vienna, September 26, 2008: functional imaging correlates to disturbance and recovery of language function.
Disturbance of neurologic function in disorders of the central nervous system is expressed as an altered activation pattern in functional networks used by specific tasks and can be studied by functional imaging modalities, e.g., positron emission tomography and functional magnetic resonance imaging. Language, a complex brain function, is based on the interplay of a distributed network in which partial functions are executed in various centers, the primary language areas. These areas are hierarchically organized and activated according to the complexity of the specific language task. The specialization of different centers and the lateralization of integrative functions into the dominant (usually left) hemisphere are achieved by collateral and transcallosal inhibition of secondary language areas that are not used normally for performance of a specific language task. Changes in the interaction within the functional network of language are important for the recovery from aphasia after stroke. In particular, studies of changes in the activation patterns during speech tasks have demonstrated that patients with favorable recovery predominantly activate structures in the ipsilateral hemisphere, but some activation was also seen in the right hemisphere. Increased activation within the right hemisphere may be a marker of failed or faulty recovery attempts in the sense of maladaptive plasticity or the breakdown of normal interhemispheric control within the distributed neural network. The role of activation in the right hemisphere for residual language performance can be investigated by combining repetitive transcranial magnetic stimulation (rTMS) with functional imaging [e.g., positron emission tomography (PET)]. These studies suggested a less effective compensatory potential of right-sided network areas. Overactivation of right language homologues may represent a maladaptive strategy by paradoxical functional facilitation as a result of decreased transcallosal inhibition attributable to damage of specialized and lateralized speech areas. Suppression of this paradoxical activation might therefore improve aphasic deficits.


Advances in the synthesis, characterisation, and mechanistic understanding of active sites in Fe-zeolites for redox catalysts.
The recent research developments on the active sites in Fe-zeolites for redox catalysis are discussed. Building on the characterisation of the α-Fe/α-O active sites in the beta and chabazite zeolites, we demonstrate a bottom-up approach to successfully understand and develop Fe-zeolite catalysts. We use the room temperature benzene to phenol reaction as a relevant example. We then suggest how the spectroscopic identification of other monomeric and dimeric iron sites could be tackled. The challenges in the characterisation of active sites and intermediates in NOX selective catalytic reduction catalysts and further development of catalysts for mild partial methane oxidation are briefly discussed.


Interictal epileptiform discharges induce hippocampal-cortical coupling in temporal lobe epilepsy.
Interactions between the hippocampus and the cortex are critical for memory. Interictal epileptiform discharges (IEDs) identify epileptic brain regions and can impair memory, but the mechanisms by which they interact with physiological patterns of network activity are mostly undefined. We show in a rat model of temporal lobe epilepsy that spontaneous hippocampal IEDs correlate with impaired memory consolidation, and that they are precisely coordinated with spindle oscillations in the prefrontal cortex during nonrapid-eye-movement (NREM) sleep. This coordination surpasses the normal physiological ripple-spindle coupling and is accompanied by decreased ripple occurrence. IEDs also induce spindles during rapid-eye movement (REM) sleep and wakefulness-behavioral states that do not naturally express these oscillations-by generating a cortical 'down' state. In a pilot clinical examination of four subjects with focal epilepsy, we confirm a similar correlation of temporofrontal IEDs with spindles over anatomically restricted cortical regions. These findings imply that IEDs may impair memory via the misappropriation of physiological mechanisms for hippocampal-cortical coupling, which suggests a target for the treatment of memory impairment in epilepsy.


Novel solid-phase synthesis of thiol-terminated-poly(alpha-amino acid)-drug conjugate.
A new method using a controlled pore glass solid support for the preparation of a thiol-terminated-polymerdrug, notably poly-L-glutamate-daunomycin having a terminal thiol group, is described. The method consists of first polymerizing an ester-protected glutamic acid onto an amino-disulfide functionalized controlled pore glass support. The ester protecting group is then removed, freeing the gamma-carboxyl groups of the grafted polymer which then allows it to react with daunomycin. Finally, the disulfide bond linking the conjugated polymer-drug to the solid support is broken by thiolysis, thus releasing the desired product. The final product consists of only polymer-drug conjugates with terminal thiol groups (global yield 26%). This novel method is much simpler and more elegant than more conventional preparation methods requiring solution phase techniques.


Levels of persistent organic pollutants (POPs) in a coastal northern Norwegian population with high fish-liver intake.
Recent research has again raised the issue regarding the potential health effects of long term exposure to persistent organic pollutants (POPs) in the context of a risk-benefit analysis. There remains clear evidence of the beneficial effects of fish consumption on public health and in particular fatty fish with its essential fatty acids. In addition to providing fatty acids, fish fat constitutes an essential source to vitamin D for the northern Norwegian population. Norwegian Food Control Authorities have recommended that children and women of childbearing age should not consume fish liver due to the risk associated with high intake of POPs. The aim of this study was to assess the influence of fish liver intake on the levels of PCBs and chlorinated pesticides in a rural coastal community (n = 31) in northern Norway, applying a cross-sectional design. The geometric mean plasma levels of sum of PCBs (14 congeners) and p,p'-DDE was found to be 558 microg kg(-1) lipids and 179 microg kg(-1) lipids, respectively. These levels were not significantly affected by the reported intake of fish liver, when age and gender were considered. Age in particular, but also gender were significant predictors for most compounds. When merging the dataset with an urban population with considerable lower intake of fish liver, the intake of cod liver still did not significantly affect the levels of PCBs and p,p'-DDE when adjusted for age and gender. Age and gender remain the strongest predictors of plasma levels of POPs in this study whereas fish liver intake was not significantly associated with the POPs.


[Ni(H2O)6]2[Na(H2O)3]2[V10O28].4H2O, bis(nickel hexahydrate) bis(sodium trihydrate) decavanadate tetrahydrate.
Polyoxometallates are capable of including transition metals in their crystal structures as either discrete cations or heteroatoms. The title compound crystallizes with triclinic symmetry and consists of a centrosymmetric [V(10)O(28)](6-) anion, a trimeric [Na(H(2)O)(3)][Ni(H(2)O)(6)][Na(H(2)O)(3)](4+) cation, an [Ni(H(2)O)(6)](2+) cation and four water molecules of crystallization. The compound possesses two Ni atoms (each on independent inversion centres), one as a discrete cation and one in a disodium-nickel trimeric cation involved in the one-dimensional polycation-polyanion hybrid polymer. The polymers are bound together via hydrogen bonds to the water molecules and the nickel(II) hexahydrate cation. Several structures of decavanadate compounds having transition metal atoms, monovalent cations and [V(10)O(28)](6-) anions in the ratio 2:2:1 have been reported previously. However, the present compound differs from these in its arrangement of monovalent cations and transition metal atoms.


Photocatalytic Oxidation of Bromide to Bromine.
Three consecutive bimolecular reactions are employed to photocatalyze bromide oxidation to bromine. The system consists of a ruthenium(II) complex, [Ru(deeb)2(dmbpy)]2+ (deeb = 4,4'-diethylester-2,2'-bipyridine; dmbpy = 4,4'-dimethyl-2,2'-bipyridine), 4-bromobenzenediazonium tetrafluoroborate (ArN2BF4), and Br-. Varying reagent concentrations allowed us to optimize the sequence of reactions for product formation. The electronically excited ruthenium complex (*Ru) reacts first with ArN2BF4 to produce a ruthenium(III) (RuIII) intermediate, triggering a subsequent reaction with Br-. Transient absorption measured at 486 and 380 nm provides insight into the time-dependent concentrations of *Ru, RuIII, and Br2•-. Without interference of back-electron transfer, the rate constant for an equal concentration bimolecular reaction of Br2•- was determined to be 5 × 109 M-1 s-1. The final products, bromine and tribromide, were spectroscopically characterized, and the turnover number (TON) was 230.


Differences in Manifestations and Gut Microbiota Composition Between Patients With Different Henoch-Schonlein Purpura Phenotypes.
Gut microbiota plays an important role in the pathogenesis of immune-mediated diseases. However, the complex pathogenesis of Henoch-Schonlein Purpura (HSP) remains elusive. This study aimed to characterize the gut microbiota in HSP patients and explore the potential association between gut microbiota composition and phenotypic changes in HSP. 16SrRNA gene sequencing and bioinformatic analyses were performed using total DNA extracted from the fecal microbiota of 34 children with HSP, including 18 primary cases, 16 recurrent cases, and 23 healthy children. The diversity indexes showed significant differences in the microbial community among the primary HSP groups, the recurrent HSP group and healthy controls. The abundance of Escherichia-Shigella in the recurrent HSP group was significantly higher than that in the primary HSP group, and the constructed ROC curve had an AUC value of 0.750. According to the Spearman correlation analysis, the abundance of Bacteroides was positively associated with the serum IgG level in children with HSP, while the abundance of Lachnoclostridium was negatively correlated with the complement component 3 (C3). The diversity indexes of gut microbiota in the HSP group with abdominal symptoms were higher than those in the HSP group without GI involvement, and also higher than those in the healthy control group. In the HSP group with GI involvement, the abundance of Faecalibacterium was decreased, while the abundance of Streptococcus and Fusobacteria was increased, compared to the HSP group without GI involvement. The gut microbiota of children with HSP was different from that of healthy children. The genus Escherichia-Shigella has a diagnostic value for HSP recurrence. Bacteroides and Lachnoclostridium may affect IgG and complement C3 levels in children with HSP. Abdominal symptoms in HSP children were related to gut microbiota (Streptococcus and butyric acid-producing bacteria).


Phospholipid furan fatty acids and ubiquinone-8: lipid biomarkers that may protect dehalococcoides strains from free radicals.
Dehalococcoides species have a highly restricted lifestyle and are only known to derive energy from reductive dehalogenation reactions. The lipid fraction of two Dehalococcoides isolates, strains BAV1 and FL2, and a tetrachloroethene-to-ethene-dechlorinating Dehalococcoides-containing consortium were analyzed for neutral lipids and phospholipid fatty acids. Unusual phospholipid modifications, including the replacement of unsaturated fatty acids with furan fatty acids, were detected in both Dehalococcoides isolates and the mixed culture. The following three furan fatty acids are reported as present in bacterial phospholipids for the first time: 9-(5-pentyl-2-furyl)-nonanoate (Fu18:2omega6), 9-(5-butyl-2-furyl)-nonanoate (Fu17:2omega5), and 8-(5-pentyl-2-furyl)-octanoate (Fu17:2omega6). The neutral lipids of the Dehalococcoides cultures contained unusually large amounts of benzoquinones (i.e., ubiquinones [UQ]), which is unusual for anaerobes. In particular, the UQ-8 content of Dehalococcoides was 5- to 20-fold greater than that generated in aerobically grown Escherichia coli cultures relative to the phospholipid fatty acid content. Naphthoquinone isoprenologues (MK), which are often found in anaerobically grown bacteria and archaea, were also detected. Dehalococcoides shows a difference in isoprenologue pattern between UQ-8 and MK-5 that is atypical of other bacteria capable of producing both quinone types. The difference in UQ-8 and MK-5 isoprenologue patterns strongly suggests a special function for UQ in Dehalococcoides, and Dehalococcoides may utilize structural modifications in its lipid armamentarium to protect against free radicals that are generated in the process of reductive dechlorination.


A study of HTLV-I and its associated risk factors in Trinidad and Tobago.
Seroprevalence of human T-lymphotropic virus type 1 (HTLV-I) among a sample of persons selected from a government register of businesses in Trinidad was 3.2% in 1,025 persons of African descent compared to 0.2% among 487 persons of Asian descent and 0% among 46 persons of European-descent. In Tobago, from a coastal village, among persons of African ancestry ascertained as part of a cardiovascular survey, the rate was 11.4%, which was significantly higher when corrected for age and race than the rate in Trinidad. The seroprevalence rate of antibodies to hepatitis A and B was also significantly elevated in Tobago compared to Trinidad. HTLV-I seroprevalence rates were higher in females than males while hepatitis A and B rates were not significantly different in the two sexes. For males, age was a significant determinant of HTLV-I seropositivity, while for females, age, markers of poor sanitation, and hepatitis B were each independently linked to HTLV-I seropositivity. The frequent occurrence of multiple infectious exposures in persons of lower socioeconomic circumstances in this tropical environment may result in immune activation that heightens susceptibility to HTLV-I infection.


Hydrothermal synthesis and characterization of two cobalt phosphates based on double-four-ring units with fluorine-occlusion and phosphite-substitution modifications.
Two new fluorinated microporous cobalt phosphates, (H2en)0.5[F(0.25)Co(H(0.5)PO4)0.5(PO4)0.5].0.25H2O (1) and (H2en)0.5[Fx(H2O)0.25(-x)Co(HPO3)x(PO4)1-x].0.25H2O (x = 0.17; 2), have been synthesized from different P sources, H3PO4 and H3PO3, in the presence of ethylenediamine and F ions. Both structures of 1 and 2 are based on the similar secondary building unit of a double four ring (D4R). 1 crystallizes in the orthorhombic space group Cmcm with a = 14.895(1) A, b = 9.7133(9) A, c = 13.688(1) A, V = 1980.4(3) A(3), and Z = 16 and is built up from fully F-occluded double-four-ring units via corner-sharing Co and P polyhedra and edge-sharing Co polyhedra. 2 crystallizes in the tetragonal space group /42m with a = 10.2033(4) A, c = 9.5545(9) A, V = 994.7(1) A(3), and Z = 8 and adopts an ACO-type framework with strict alternation of corner-sharing Co and P polyhedra. On the basis of the evidence from ion chromatography studies and elemental analyses, 2 contains both phosphate and phosphite ions, and the amount of F ions in 2 is the same as the amount of phosphite ions. This implies that some PO4(3-) groups in 2 are substituted by HPO3(2-) groups with the same amount of F(-) occlusion in the center of D4R as charge compensation. Magnetic susceptibility measurements of both 1 and 2 appear that they contain mainly antiferromagnetic interaction (theta = -27.8 K for 1 and -35.0 K for 2). However, the magnetic coupling is much more complicated in compound 1 because of the Co-O-Co linkages in it. Low-field temperature-dependent magnetization curves of 1 showed spontaneous magnetization in the form of two continuous bumps, one sharp and one broad. This may be related to the temperature dependence of two related but different types of spin canting. At 2 K, 1 also showed a large coercive field of about 5000 Oe.


"Am I going crazy, doc?": a self psychology approach to therapeutic assessment.
In this case study, we explore the effectiveness of Therapeutic Assessment with a severely disturbed 25-year-old man, referred by his therapist, following Finn's (2007; Finn & Tonsager, 1992, 1997) model. This patient-therapist pair had been working together for approximately 2 months, but the therapy had ceased to progress. The therapist requested a clearer picture of his patient's affective functioning, interpersonal functioning, and self-functioning that might facilitate more effective treatment. Through a collaborative assessment process informed by the principles of Kohutian self psychology, the evaluator and patient slowly formed a working alliance that proved useful for the eventual communication to the patient of his psychologically tenuous reality. This case illustrates the utility of a collaborative, multimethod Therapeutic Assessment with a severely ill patient and the use of Therapeutic Assessment by a less experienced clinician.


Is the biological antioxidant system integrated and regulated?
It is proposed that there is biological regulation of the low molecular weight antioxidant (LMWA) status of the body, and that these different antioxidants work in concert and in homeostasis as a system analogous to the regulation of acid-base status (pH). The theoretical design characteristics for such a system include regulation, inducibility, interactivity and balance with the beneficial properties of reactive oxygen species. Testing the hypothesis requires developing suitable methodologies (such as measurement of the redox state) for assessing the total ratio of antioxidant to oxidant activity of both tissues and biological fluids, since it is not clear whether plasma antioxidant status reflects that of the tissues as well. This concept, if accepted, may help explain the contradictions relating to antioxidant therapy and lead to more rational recommendations for dietary intake. It may also help explain the effects of manipulating (increasing/decreasing) specific antioxidants on the overall antioxidant status in health and disease.


Protein synthesis associated with quiescence and senescence in auxin-starved pear cells.
Pear fruit cells (Pyrus communis L. cv Passe Crassane) stopped dividing when subcultured in a bioreactor under auxin starvation in the presence of 0.37 molar mannitol. The cessation of cell division was preceded by the accumulation of a specific basic polypeptide of 24 kilodalton. Readdition of 2.3 micromolar 2,4-dichlorophenoxyacetic acid (2,4-D) neither caused a resumption of cell division nor depressed the accumulation of this polypeptide. Under complete auxin starvation, cells began to die at day 18. In vivo radioactive labeling of proteins followed by two-dimensional electrophoresis showed that during auxin starvation the synthesis of some polypeptides including the 24 kilodalton one (referred to as homeostasis-related proteins, HRPs) was decreased while the synthesis of some others (referred as senescence-related proteins, SRPs) was increased. Readdition of 2.3 micromolar 2,4-D postponed the onset of cell death by 10 to 15 days while supplementation with 7.6 micromolar abscisic acid advanced cell death by 8 days. Two-dimensional analysis of protein synthesis indicated that both hormones interact on the synthesis of these two groups of polypeptides. The levels of most HRPs were maintained or increased in the presence of auxin, while the levels of the SRPs were decreased by auxin and increased by abscisic acid. Short and long-term effects of 2,4-D and abscisic acid on the synthesis of specific polypeptides were observed, allowing a discrimination between the direct and indirect effect of both hormones on the development of cell senescence.


Mutagenesis analysis of functionally important domains within the C-terminal end of smooth muscle caldesmon.
The ability of chicken gizzard smooth muscle caldesmon (CaD) to inhibit actomyosin ATPase activity is due mainly to an inhibitory domain that resides within the C-terminal 67 amino acid residues of the CaD molecule. In the present study, a series of C-terminal truncation and internal deletion mutants of chicken gizzard smooth muscle CaD were systematically designed using a site-directed mutagenesis approach, and these mutant proteins were overexpressed in a baculovirus expression system. Analysis of actin binding and inhibition of actomyosin ATPase activity using these mutants identified a strong actin-binding motif of 6 amino acid residues (from Lys718 to Glu723), which also form the core sequence for CaD-induced inhibition of actomyosin ATPase. However, maximal inhibition by CaD requires the presence of residues 728-731, which are not associated with actin binding. Our data provide direct evidence for the requirement of actin binding to a specific region in CaD for CaD-induced inhibition of actin activation of smooth muscle myosin ATPase. Furthermore, our findings also show that the region between residues 690 and 717 is responsible for the weak inhibition of actomyosin ATPase and reveal that the inhibitory determinants located in the regions between residues 690 and 717 and residues 718 and 756 can function independently.


Constructing a Sr2+-Substituted Surface Hydroxyapatite Hexagon-Like Microarray on 3D-Plotted Hydroxyapatite Scaffold to Regulate Osteogenic Differentiation.
Surface topography and chemical characteristics can regulate stem cell proliferation and differentiation, and decrease the bone-healing time. However, the synergetic function of the surface structure and chemical cues in bone-regeneration repair was rarely studied. Herein, a strontium ion (Sr2+)-substituted surface hydroxyapatite (HA) hexagon-like microarray was successfully constructed on 3D-plotted HA porous scaffold through hydrothermal reaction to generate topography and chemical dual cues. The crystal phase of the Sr2+-substituted surface microarray was HA, while the lattice constant of the Sr2+-substituted microarray increased with increasing Sr2+-substituted amount. Sr2+-substituted microarray could achieve the sustainable release of Sr2+, which could effectively promote osteogenic differentiation of human adipose-derived stem cells (ADSCs) even without osteogenic-induced media. Osteogenic characteristics were optimally enhanced using the higher Sr2+-substituted surface microarray (8Sr-HA). Sr2+-substituted microarray on the scaffold surface could future improve the osteogenic performance of HA porous scaffold. These results indicated that the Sr2+-substituted HA surface hexagon-like microarray on 3D-plotted HA scaffolds had promising biological performance for bone-regeneration repair scaffold.


The Size and Shape Effects on the Melting Point of Nanoparticles Based on the Lennard-Jones Potential Function.
A model is proposed to calculate the melting points of nanoparticles based on the Lennard-Jones (L-J) potential function. The effects of the size, the shape, and the atomic volume and surface packing of the nanoparticles are considered in the model. The model, based on the L-J potential function for spherical nanoparticles, agrees with the experimental values of gold (Au) and lead (Pb) nanoparticles. The model, based on the L-J potential function, is consistent with Qi and Wang's model that predicts the Gibbs-Thompson relation. Moreover, the model based on the non-integer L-J potential function can be used to predict the melting points Tm of nanoparticles.


A new anatomically based nomenclature for the roots and root canals-part 1: maxillary molars.
Numerous terminologies have been employed in the dental literature to describe the roots and root canal systems of maxillary molars. This multiplicity in naming of roots and canals makes the reader susceptible to misinterpretation and confusion. No consensus thus far has been arrived at for defining the names of roots and root canals in maxillary molars, including their various morphological aberrations. The anatomical relation of roots and their root canals were identified and were subsequently named based on definite sets of criteria. A new method for identification and naming of roots and root canal anatomy in maxillary molars, based on their root and canal relationship, was formulated and is presented in this paper. The nomenclature makes certain essential modifications to the traditional approach to accommodate naming of the various aberrations presented in the maxillary molars. A simple, yet extensive, nomenclature system has been proposed that appropriately names the internal and external morphology of maxillary molars.


Philodryas chamissonis (Reptilia: Squamata: Colubridae) preys on the arboreal marsupial Dromiciops gliroides (Mammalia: Microbiotheria: Microbiotheriidae).
Philodryas chamissonis, the Chilean long-tailed snake, is a diurnal predator mainly of Liolaemus lizards, but also of amphibians, birds, rodents and juvenile rabbits. Dromiciops gliroides (Colocolo opossum) is an arboreal marsupial endemic of temperate rainforest of southern South America. Little information is available about this marsupial's biology and ecology. Here we report the predation of one Colocolo opossum by an adult female P. chamissonis in a mixed Nothofagus forest, composed mainly by N. dombeyi, N. glauca and N. alpina trees, in the "Huemules de Niblinto" National Reserve, Nevados de Chillán, Chile. Since these two species have different activity and habitat use patterns, we discuss how this encounter may have occurred. Although it could just have been an opportunistic event, this finding provides insights into the different components of food chains in forest ecosystems of Chile.


A new L-type calcium channel isoform required for normal patterning of the developing neuromuscular junction.
One of the earliest steps in the development of the neuromuscular junction (NMJ) is the pre-patterning of acetylcholine receptors (AChR) in the center of muscle fibers. This process has recently been proposed to depend on L-type calcium currents. But its feeble current properties make the skeletal muscle calcium channel (Ca(v)1.1) a poor candidate for this function. Independently a new Ca(v)1.1e splice variant with greatly distinct current properties has been described. But so far this channel lacked a function. Could this orphan channel be responsible for regulating AChR pre-patterning? Here we compare the properties of the two splice variants and argue that the newly discovered variant Ca(v)1.1e, is dominantly expressed at the proper time in development and has the essential current properties to accomplish the proposed role in the formation of the NMJ.


Comparison of observed and expected levels of genetic diversity based on surname frequencies: An example from historical Massachusetts.
The inverse of random inbreeding based on surname frequencies (1/Fr ) is an estimate of genetic diversity, and its expectation is a function of the number of migrants into a population. Observed and expected values of (1/Fr ) were compared to determine if observed diversity matches theoretical expectations under conditions of rapid demographic change using data from historical Massachusetts. Data on migration and surnames were taken from 6,038 marriage records from the eighteenth and nineteenth centuries from five towns in north-central Massachusetts. Data for each town were broken down into a number of time cohorts defined by year of marriage, giving 33 samples based on town and year of marriage. The number of migrants (M) and the inverse of the random component of inbreeding (1/Fr ) were derived for each sample based on surname frequencies. There was no significant difference between observed and expected values of 1/Fr in samples where there were 100 or more migrants. However, 1/Fr was significantly higher in samples where M < 100, which is possibly due to these samples not having reached equilibrium, resulting in higher than expected values of 1/Fr . Regression of residual values of 1/Fr (observed-expected) on the number of years since settlement supports this interpretation. The number of migrants affects the level of genetic diversity inferred from surname frequencies, and the relationship between observed and expected measures depends on the number of migrants and the proximity of a given sample to an equilibrium state.


The Ets-1 transcription factor is required for complete pre-T cell receptor function and allelic exclusion at the T cell receptor beta locus.
The pre-T cell receptor (TCR) functions as a critical checkpoint during alphabeta T cell development. Signaling through the pre-TCR controls the differentiation of immature CD4(-)CD8(-)CD25(+)CD44(-) [double-negative (DN)3] thymocytes into CD4(+)CD8(+) double-positive (DP) cells through the CD4(-)CD8(-)CD25(-)CD44(-)(DN4) stage. In addition, pre-TCR activity triggers expansion and survival of thymocytes and inhibits TCRbeta gene rearrangement through a process referred to as allelic exclusion. Whereas many proteins involved in the pre-TCR transduction cascade have been identified, little is known about the nuclear factors associated with receptor function. Here, we use gene targeting to inactivate the Ets-1 transcription factor in mice and analyze pre-TCR function in developing Ets-1-deficient (Ets-1(-/-)) thymocytes. We find that inactivation of Ets-1 impairs the development of DN3 into DP thymocytes and induces an elevated rate of cell death in the DN4 subset. This defect appears specific to the alphabeta lineage because gammadelta T cells maturate efficiently. Finally, the percentage of thymocytes coexpressing two different TCRbeta chains is increased in the Ets-1(-/-) background and, in contrast with wild type, forced activation of pre-TCR signaling does not block endogenous TCRbeta gene rearrangement. These data identify Ets-1 as a critical transcription factor for pre-TCR functioning and for allelic exclusion at the TCRbeta locus.


The Pairwise Variability Index and coexisting rhythms in language.
The Pairwise Variability Index (PVI) has been widely used as a metric for quantifying rhythm in languages, often with a view to placing them on a continuum between notional categories of stress-timing and syllable-timing. We review the history of and rationale for the PVI, and point out three potential anomalies in the way the PVI has been applied. Following up one of these we apply the PVI to the level of the foot, and argue that stress-timing and syllable-timing are not points at either end of a continuum but orthogonal dimensions, so that a language can be (for instance) both syllable-timed and stress-timed. Results from Estonian, English, Mexican Spanish, and Castilian Spanish are presented which give some support for this view.


Neurovirulence of influenza A virus.
Infection of mouse brain with influenza A virus has provided a valuable model for investigating viral adaptation and virulence. These studies have indicated important roles for the neuraminidase (NA), matrix (M), non-structural (NS) and haemagglutinin (HA) genes of the virus in determining neurovirulence. For the NA, three changes close to the active site have been identified in the neurovirulent strains, which also display altered enzyme properties, including changes in specificity. In the M gene, two specific amino acid substitutions in the M1 protein have been observed, Ala41-->Val and Thr139-->Ala, which correlate with increased virulence for mouse. Such changes are likely to affect the pH-dependent association/dissociation of M1 with the viral ribonucleoprotein, as well as growth and virulence. The changes in the NS gene in the neurovirulent strains cause alterations in the mRNA secondary structure to mask the 3' splice site, and correlate with reduced splicing of the NS gene in these strains. Finally, the increased virulence of the HA gene occurs by at least three different mechanisms: loss of a glycosylation site, a change at the cleavage site, and a substitution which may increase the pH of fusion. These observations define a useful set of parameters with which to analyse epidemic virus strains that have been associated with elevated CNS symptoms in humans. In addition, the changes present in the neurovirulent influenza strains show interesting parallels to those in the neurovirulent derivatives of other viruses, suggesting different viruses utilise common strategies to permit replication in the brain.


[Genetics of asthma and atopy: how many genes?].
Asthma is a complex and heterogeneous disease involving many genes and environmental factors. Numerous genetic association studies of asthma, atopy and bronchial hyper-responsiveness have consistently implicated a small number of genes, most of which are involved in immune responses. Genome-wide screens of various populations in the past three years have identified six asthma and/or atopy susceptibility genes by means of positional cloning. However, the precise functions of these genes are unclear. Recent advances in molecular methods for genotyping thousands of polymorphisms in candidate regions (and, very soon, across the entire genome), together with new statistical methods applicable to complex biological systems, will rapidly identify new culprit genes as well as gene-gene and gene-environment interactions. A better knowledge of asthma susceptibility will lead to better diagnosis, prevention and treatment of this increasingly frequent disease.


Biodiverse Histoplasma Species Elicit Distinct Patterns of Pulmonary Inflammation following Sublethal Infection.
Histoplasma is an endemic dimorphic fungus that can cause disease in healthy and immunocompromised individuals after the transition of inhaled spores into the facultative intracellular yeast form. There is substantial diversity among Histoplasma species, but it is not clear how this heterogeneity impacts the progression of pathology and cellular immune responses during acute respiratory infection, which represents the vast majority of histoplasmosis disease burden. After inoculating mice intranasally with a sublethal inoculum, we characterized the immune response to Histoplasma capsulatum (strain G186A) and Histoplasma ohiense (strain G217B) using comprehensive flow cytometric and single-cell analyses. Within 8 days after inoculation, H. ohiense induced a significantly higher infiltration of neutrophils and inflammatory monocytes into the lung compared to H. capsulatum Microscopic analysis of infected lung tissue revealed that although the total number of fungi was similar within inflamed lung lesions, we observed different species-dependent intracellular yeast distribution patterns. Inoculation with gfp-expressing strains indicated that H. ohiense, but not H. capsulatum, was associated primarily with alveolar macrophages early after infection. Interestingly, we observed a significant reduction in the total number of alveolar macrophages 12 to 16 days after H. ohiense, but not H. capsulatum infection, despite similar intracellular growth dynamics within AMJ2-C11 alveolar macrophages in vitro Together, our data suggest that H. ohiense, but not H. capsulatum, preferentially interacts with alveolar macrophages early after infection, which may lead to a different course of inflammation and resolution despite similar rates of fungal clearance.IMPORTANCE Acute pulmonary histoplasmosis in healthy individuals comprises most of the disease burden caused by the fungal pathogen Histoplasma Fungal pneumonia is frequently delayed in diagnosis and treatment due to a prolonged period of quiescence early during infection. In this study, we used a murine respiratory model of histoplasmosis to investigate how different Histoplasma species modulate lung inflammation throughout the complete course of infection. We propose that a relatively low, sublethal inoculum is ideal to model acute pulmonary histoplasmosis in humans, primarily due to the quiescent stage of fungal growth that occurs in the lungs of mice prior to the initiation of inflammation. Our results reveal the unique course of lung immunity associated with divergent species of Histoplasma and imply that the progression of clinical disease is considerably more heterogeneous than previously recognized.


New APJCP impact factor for 2012 is 1.271--time to make a major effort to break through the 2.0 barrier.
The APJCP Impact Factor for 2012 is 1.271, returning from 0.659 for 2011 (1.240 for 2010 and 1.108 for 2009). For an Asian Pacific journal publishing over 100 papers a month from countries with very varied resources it is heartening and we thank all those who continued to submit papers and cite references in the APJCP through our difficult period. However, we still have very much room for improvement. As Chief Editors it is our shared responsibility to act for the benefit of the cancer control research community who utilize the journal in our region of over four billion people and provide a prestigious forum for publication of research findings which can be freely shared by all. The motivation for the APOCP/APJCP has never been financial profit but a firm financial base is nevertheless essential. Although we have kind support from the Korean National Cancer Center for our Managing Editor and the website, our ability to maintain our Chinese and Thai offices is totally dependent on the processing charges paid by the authors. In order to expand our staff to cope with increased submissions and provide greater assistance in ensuring comprehensive reference coverage and dissemination of findings published in the APJCP to the worldwide research community, a joint decision has been made to increase formatting charges by 50% from July. We ask for author understanding. In addition, we appeal to scientists to positively consider our requests to make their reference lists as comprehensive as possible, including papers from the APJCP where appropriate. The future of the journal and the APOCP is largely in your own hands.


X-ray reflectometer for optical efficiency and scatter measurements.
An instrument has been developed to determine the reflection efficiency and scatter characteristics of optical samples at x-ray wavelengths from 1.5 to 113 A. The reflectometer operates in an oil-free vacuum chamber and measures the reflection efficiency and scatter characteristics as a function of the angle of incidence. The reflection efficiency is given for lambda=8.34 A incident on a fused silica sample finished to a flatness of lambda/10. The experimental reflection efficiency is compared to the theoretical data. The scatter curves are given for the direct x-ray beam and for the beam reflected from the fused silica sample at theta=50 arc minutes. The full-width-at-half-maximum (FWHM) resolution of the instrument is approximately 13 arc seconds as determined by a least-squares smoothing of the experimental data.


Induction of the estrogen receptor by growth hormone and glucocorticoid substitution in primary cultures of rat hepatocytes.
Hepatic estrogen receptors (ER) mediate estrogenic effects on mammalian liver metabolism and are thereby involved in the regulation of important physiological/pathological processes, such as coagulation, atherosclerosis, and hypertension. The regulation of the formation of the ER in primary cultures of rat hepatocytes was studied by assaying ER and ER mRNA under different endocrine conditions. The ER concentration was measured using two different methods, a ligand-binding technique and an ER enzyme immunoassay. The results obtained by the two methods showed good correlation, and linear regression analysis gave a correlation coefficient of 0.95. ER concentrations fell to low steady state levels within 16 h after establishing the cell culture and remained low in the absence of hormonal substitution. Upon medium supplementation with pituitary GH and the glucocorticoid dexamethasone (DEX) in combination, the ER concentration increased 6-fold from 4.2 +/- 1.0 to 25.8 +/- 7.0 fmol/mg cytosolic protein. ER mRNA was measured by solution hybridization. Substitution with GH and DEX in combination increased ER mRNA to 210 +/- 14% of control levels. No effect on ER mRNA stability was seen after hormone treatment. It is concluded that the regulatory effects of GH and DEX on the hepatic ER in this in vitro system are very similar to the effects of these hormones under in vivo conditions. The inducible expression of the ER has never before, to our knowledge, been demonstrated in any mammalian liver cell culture system.


Public Willingness to Pay for and Participate in Sanitation Infrastructure Improvement in Western China's Rural Areas.
The suitability and feasibility of public-private partnership (PPP) patterns in a rural context have not been well-documented and understood. To address this research gap and practical plight, this study aims to analyze the rural resident's willingness to pay for and participate in the improvement of rural sanitation facilities, and further explore the drivers and barriers affecting their decisions. This study was performed in rural areas of three western provinces, including Shaanxi, Ningxia, and Inner Mongolia, of western China's rural areas by conducting a survey on 1,248 rural residents. In Inner Mongolia, the proportion of respondents who were willing to pay was highest, while the proportion of respondents who may provide labor was lowest among the three provinces. Respondents from Ningxia had the least willing to pay, and respondents from Shaanxi had the highest willingness to participate. Overall, respondents' rural (living) duration time, personal interest in local government notice, and the latest time when the sanitation facilities were improved could significantly affect their willingness. In Inner Mongolia, occupation and water availability could significantly influence respondents' willingness, and both gender and health conditions had significant impacts. In Ningxia, respondents' personal interest in local government notice had a notable impact on willingness, and low-income respondents showed a more notable willingness to pay and participate. In Shaanxi, occupation and water availability could significantly influence respondents' willingness. Respondents' personal interest in local government notice had a notable impact on their willingness. This study is of significant importance to understand rural resident's participation in sanitation infrastructure improvement to support relevant PPP projects, and is important to solve poverty-caused dilemmas.


[Skin improvement and cosmetic facial surgery].
Intensive skin treatments are gaining an ever more prominent place in the treatment of facial aging. The goal of these treatments is to cause selective damage to the skin surface, after which the healing process begins, the so-called 'resurfacing' of the skin. During the healing period fibroblasts are stimulated to produce new collagen and elastin, by means of which a rejuvenating effect is achieved. Resurfacing treatments can be divided into chemical peels, dermabrasia and laser treatments. The wishes and expectations of the patient, the skin type and the experience of the physician play an important role in choosing the treatment type. In addition, skin enhancement products are being used to an increasing degree in both the preparatory phase and the recovery phase of skin treatments, again to optimize treatment results. Complications from intensive skin treatments are rare and are usually due to a suboptimal indication or carelessness.


A Review of the Dermatological Manifestations of Coronavirus Disease 2019 (COVID-19).
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected 210 countries and territories around the world. The virus has spread rapidly, and the disease is still extending up to now. The pathophysiology for SARS-CoV-2 has not been well elucidated, and diverse hypotheses to date have been proposed. Initially, no skin manifestations were observed among patients with COVID-19, but recently a few cases have been described. In this review, we discuss these various cutaneous manifestations and skin problems related to personal protective equipment, as well as different cutaneous anti-COVID-19 drug-associated reactions. We also focus on the currently proposed managements of these rare manifestations.


[Characteristics of dark-adapted and light-adapted oscillatory potentials in human electroretinogram].
To characterize dark-adapted and light-adapted oscillatory potentials (OPs) in human electroretinogram (EGR) elicited by flashing light stimulation of the same intensity. Dark- and light-adapted ERGs of normal eyes were studied. The frequency spectra of the extracted dark-adapted OPs and light-adapted OPs were analyzed by a fast Fourier transform. The peak frequency, latency and total power of the OPs were determined. The averaged peak frequency, latency, and power of the dark-adapted OPs was 125.3∓9.93 Hz, 41.7∓3.56 ms, and 9.25∓5.55 (V·s)(2), as compared with 79.5∓6.79 Hz, 50.8∓5.36 ms, and 3.56∓2.18 (V·s)(2) for light-adapted Ops, respectively, showing significant differences in the parameters between dark- and light-adapted Ops (P<0.001). Compared with dark-adapted OPs, light-adapted Ops is characterized by a lower peak frequency and a lower power with a prolonged latency.


The occurrence of parasitic arthropods in two groups of European bison in the Białowieza primeval forest.
Within 1992-2000, a total of 181 Białowieza Forest bison were examined from two winter herds. Twelf parasitic arthropod species were observed, a high infestation being typical of Demodex bisonianius, Chorioptes bovis, Ixodes ricinus, Dermacentor reticulatus, and Bisonicola sedecimdecembrii. The infestation in section 422 herd being higher for B. sedecimdecembrii, I. ricinus, D. reticulatus, Ch. bovis. D. bisonianus was slightly more prevalent in the section 391 herd, the intensity being, however, lower than that in the other herd. Among the remaining arthropods found in the Bialowieza Forest European bison, some Lipoptena cervi occurred in both herds, Demodex sp. and Sarcoptes scabiei were recorded only in the section 422 herd, Ixodes persulcatus was present only in the section 391 bison and those kept in the reservation, while D. bovis, Psoroptes ovis, and Melophagus ovinus were found in the reserve bison only. In the present study, the largest differences in the extent of infestation involved the hair-dwelling arthropods (B. sedecimdecembrii, I. rixinus).


Pros and cons of quitting, self-efficacy, and the stages of change in smoking cessation.
In The Netherlands, 34% of the population smoke, and 70% of these smokers are not planning to quit. The lower percentages in the U.S. population seem to reflect a difference in smoking culture. This study analyzes the pros and cons of quitting and self-efficacy expectation in the 5 stages of change in the Dutch population. The results are compared with the pattern of the pros and cons of smoking and self-efficacy expectations found in U.S. samples. The data show the hypothesized pattern: In the first 2 stages, the expected positive outcomes of quitting discriminated better between the stages than self-efficacy, whereas for later stages, self-efficacy was the better discriminator. This study shows that the stage typology is applicable to the Dutch population and that the pattern of the pros, cons, and self-efficacy is very similar to the pattern found in the U.S. populations.


Case study: developing product lines using ICD-9-CM codes.
In this marketing case study, Thomas Jefferson University Hospital used a product line approach to maximize the use of its resources. The method used, based on ICD-9-CM codes, fulfilled the demands of increased efficiency by encouraging customer-oriented thinking, enhancing communication with physicians and patients, and helping the institution to compete more effectively.


MicroRNA detection using light-up aptamer amplification based on nuclease protection transcription.
The quantification of microRNAs (miRNAs) is important because the miRNA expression level is closely associated with the occurrence and development of diseases. Here, we report a simple nuclease protection transcription assay which combines nuclease protection assays and transcription-assisted light-up aptamer amplification for detecting miRNAs with great sensitivity.


Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays.
Glioblastomas are cytogenetically heterogeneous tumors that frequently display alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single-nucleotide polymorphism arrays to investigate genome-wide copy number alterations and loss of heterozygosity in 35 primary glioblastomas. We focused on the identification and detailed characterization of alterations involving the most frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns of alteration for these chromosomes, and validation of their prognostic impact in a larger series of tumors from public databases. Gains of chromosome 7 (97%), with or without epidermal growth factor receptor (EGFR) amplification, and losses of chromosomes 9p (83%) and 10 (91%) were the most frequent alterations. Such alterations defined five different cytogenetic groups with a significant effect on patient survival; notably, EGFR amplification (29%) was associated with a better survival among older patients, as confirmed by multivariate analysis of a larger series of glioblastomas from the literature. In addition, our results provide further evidence about the relevance of other genes (eg, EGFR, CDKN2A/B, MTAP) in the pathogenesis of glioblastomas. Altogether, our results confirm the cytogenetic heterogeneity of glioblastomas and suggest that their stratification based on combined assessment of cytogenetic alterations involving chromosomes 7, 9, and 10 may contribute to the prognostic evaluation of glioblastomas.


Effects of essential amino acids on lipid metabolism in mice and humans.
Eight amino acids are considered essential for human nutrition, and three of them, including leucine, isoleucine and valine, are called as branched-chain amino acids (BCAAs). We recently discovered that dietary deficiency of any BCAA for 7 days rapidly reduces the abdominal fat mass in mice. The goal of this study was to investigate (1) whether dietary deficiency of the other five essential amino acids (EAAs), including phenylalanine, threonine, tryptophan, methionine and lysine, would produce similar effects and (2) whether an association between serum AAs and obesity was observed in humans in Chinese Han population. Similar to BCAAs deprivation, dietary deficiency of any of these five EAAs for 7 days significantly reduced abdominal fat mass, which is likely caused by increased energy expenditure. Expression of genes and proteins related to lipolysis, however, were differentially regulated by different EAAs. These results suggest a crucial role of EAAs deprivation on lipid metabolism in mice. Our human studies revealed that levels of four EAAs (leucine, isoleucine, valine and phenylalanine) were elevated in obese humans compared with those in lean controls in Chinese Han population. Based on the results obtained from mice, we speculate that these four EAAs might play important roles in human obesity.


Erythrocyte nitric oxide synthase as a surrogate marker for mercury-induced vascular damage: the modulatory effects of naringin.
In this study, endothelial nitric oxide synthase activity and nitric oxide (NO) production by human erythrocytes in the presence and absence of mercuric chloride (HgCl2 ), L-arginine (L-ARG), N ω- nitro-L-arginine methyl ester (L-NAME), and naringin (NAR) were investigated. In addition, the levels of reduced glutathione (GSH) and related enzymes were estimated in erythrocytes hemolysate. The protein carbonyl content (PCC) and thiobarbituric acid-reactive substances (TBARS) levels were also determined. The results of this study revealed that the treatment of erythrocytes with either HgCl2 or L-NAME induced a significant decrease in NOS activity and nitrite levels compared with control cells. Furthermore, mercury exposure significantly increased the levels of PCC and TBARS but reduced the GSH level. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase (GST) were inhibited. The exposure of erythrocytes to HgCl2 in combination with L-ARG, NAR, or both ameliorated the investigated parameters compared with erythrocytes incubated with HgCl2 alone. These results indicate that mercury exposure decreased both erythrocyte NOS activity and nitrite production, and that these parameters might be indicative of mercury exposure. The data also suggest that concomitant treatment with NAR can restore NO bioavailability through either its metal-chelating properties or its antioxidant activity.


Clinical significance of oxidative stress for untreated patients with diffuse large B-cell lymphoma.
Oxidative stress serves an important role in carcinogenesis. The present study investigated the clinical significance of oxidative stress as a prognostic factor for diffuse large B-cell lymphoma (DLBCL). The participants comprised 55 consecutive patients with DLBCL. A commercially available derivatives of reactive oxygen metabolites (d-ROMs) test kit was used to assess oxidant levels. Similarly, a commercially available biological antioxidant potential (BAP) test was used to assess antioxidant levels. The antioxidative/oxidative stress ratio was calculated as d-ROMs/BAP. The median serum concentration of d-ROMs was 425 µM. The levels of d-ROMs were significantly higher in patients with DLBCL than in healthy volunteers (P<0.01). The complete remission (CR) rates in patients with d-ROMs <425 and ≥425 µM were 81.5 and 85.7%, respectively [not significant (NS)]. The 3-year overall survival (OS) rates for patients with d-ROMs <425 and ≥425 µM were 67.2 and 72.0%, respectively (NS). The median BAP was 2,002 µM. The CR rates of patients with BAP <2,002 and ≥2,002 µM were 77.8 and 88.9%, respectively (NS). The 3-year OS rates of patients with BAP <2,002 and ≥2,002 µM were 60.9 and 75.9%, respectively (NS). No significant difference in the d-ROMs/BAP ratio was observed between groups. Multivariate analysis revealed that d-ROMs were an independent prognostic factor for progression-free survival.


Evaluation of acepromazine-induced hemodynamic alterations and reversal with norepinephrine infusion in standing horses.
The effects of norepinephrine (NOR) infusion on hemodynamic alterations induced with sedative doses of acepromazine (ACP) were evaluated. Infusion of NOR at 1 μg/kg body weight (BW)/minute for 15 min was administered to 5 standing horses 45 min (T45) after intravenous injection of ACP at 0.1 mg/kg BW. Systolic arterial blood pressure (SAP) and hemodynamic parameters were evaluated on the median artery. Parameters were evaluated every 5 min from 45 to 65 min (T65) at 75 (T75), 90 (T90), and 105 (T105) minutes after ACP administration, and the vessel's surface (SURF), diameter (DIAM), circumference (CIRC), peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (MV), volumetric flow (VF) and resistivity index (RI) of the flow were calculated. Acepromazine induced hypotension and vasodilation with a significant rise in SURF, DIAM, CIRC, PSV, EDV, MV, and VF and a reduction in RI and SAP, which were significantly counteracted from T50 to T60 for EDV, VF, MV and RI, and to T65 for SAP, from T50 to T90 for CIRC and SURF and to T60 for DIAM. These findings demonstrate that a 1 μg/kg BW/minute NOR infusion can reverse ACP's vasodilatory effects, restoring hemodynamic parameters and blood pressure in horses.


MRI findings in a case of a superficial siderosis associated with an ependymoma.
We present the imaging findings of superficial siderosis of the central nervous system associated with an ependymoma of the posterior fossa in a patient who presented with progressive bilateral sensorineural hearing loss and cerebellar ataxia. The ependymoma was a homogeneous well-defined mass of the fourth ventricle without hydrocephalus. Secondary siderosis due to chronic bleeding from the ependymoma appeared as linear hypointensity delineating the surface of the cortex, thin and subtle on spin-echo T2-weighted images, thick and obvious on gradient-echo T2-weighted images.


A Cross-Sectional Study of Sub-Basal Corneal Nerve Reduction Following Neurotoxic Chemotherapy.
Sub-basal corneal nerves have been shown to change during neurotoxic chemotherapy treatment. This cross-sectional study investigated corneal nerve morphology in patients who have completed neurotoxic chemotherapy well after treatment cessation and its association with peripheral nerve function. Central corneal nerve fiber length (CNFL) and inferior whorl length (IWL), average nerve fiber length (ANFL), corneal nerve fiber density (CNFD) and corneal nerve branch density (CNBD), and nerve fiber area (CNFA) were examined using in vivo corneal confocal microscopy in patients with cancer who had completed treatment with either paclitaxel or oxaliplatin between 3 and 24 months prior to assessment in comparison with 2 separate groups of healthy controls. Neurological assessments were conducted including clinician- and patient-reported outcomes, and neurological grading scales. Both paclitaxel- (n = 40) and oxaliplatin-treated (n = 30) groups had reduced IWL and ANFL compared to the respective healthy control groups (n = 15 in each group) (paclitaxel: IWL = P = 0.02, ANFL = P = 0.009; and oxaliplatin: IWL = P = 0.008, ANFL P = 0.02). CNFL and CNFD reduction were observed only in the paclitaxel-treated group compared with healthy controls (P = 0.008 and P = 0.02, respectively), whereas CNFA was reduced in the oxaliplatin-treated group (P = 0.04). IWL reduction correlated with worse fine hand dexterity in chemotherapy-treated patients (r = -0.33, P = 0.007). There is evidence of corneal nerve loss in patients with cancer who have been treated with paclitaxel and oxaliplatin well after treatment cessation associated with worse upper limb function. Sub-basal corneal nerve reduction is evident even after cessation of neurotoxic treatment. In vivo corneal confocal microscopy may be useful in the monitoring of nerve function in patients receiving chemotherapy.


Biomimetic Nanoparticles Enabled by Cascade Cell Membrane Coating for Direct Cross-Priming of T Cells.
Despite the activation of T lymphocytes by antigen-presenting cells being responsible for eliciting antigen-specific immune responses, their crosstalking suffers from temporospatial limitations and endogenous influencing factors, which restrict the generation of a strong antitumor immunity. Here, cascade cell membrane coating is reported to prepare biomimetic nanoparticles (BNs) that can manipulate the cross-priming of T cells. BNs are obtained from coating nanoparticulate substrates with cell membranes extracted from dendritic cells (DCs) that are pre-pulsed with cancer cell membrane-coated nanoparticles. With a DC membrane that presents an array of cancer cell membrane antigen epitopes, BNs inherit the intrinsic membrane function of DCs, which can directly cross-prime T cells and provoke robust yet antigen-specific antitumor responses in multiple mouse models. Combination with clinical anti-programmed death-1 antibodies demonstrates a robust way of BNs to achieve desirable tumor regression and survival rate. This work spotlights the impact of nanoparticles on direct cross-priming of T cells and supports a unique yet modulate platform for boosting an effective adaptive immunity for immunotherapy.


Structural characterization and molecular order of rodlike mesogens with three- and four-ring core by XRD and 13C NMR spectroscopy.
Structural characterizations using XRD and (13)C NMR spectroscopy of two rodlike mesogens consisting of (i) three phenyl ring core with a polar cyano terminal and (ii) four phenyl ring core with flexible dodecyl terminal chain are presented. The three-ring-core mesogen with cyano terminal exhibits enantiotropic smectic A phase while the four-ring mesogen reveals polymesomorphism and shows enantiotropic nematic, smectic C, and tilted hexatic phases. The molecular organization in the three-ring mesogen is found to be partial bilayer smectic Ad type, and the interdigitation of the molecules in the neighboring layers is attributed to the presence of the polar terminal group. For the four-ring mesogen, the XRD results confirm the existence of the smectic C and the tilted hexatic mesophases. A thermal variation of the layer spacing across the smectic C phase followed by a discrete jump at the transition to the tilted hexatic phase is also observed. The tilt angles have been estimated to be about 45° in the smectic C phase and about 40° in tilted hexatic phase. (13)C NMR results indicate that in the mesophase the molecules are aligned parallel to the magnetic field. From the (13)C-(1)H dipolar couplings determined from the 2D experiments, the overall order parameter for the three-ring mesogen in its smectic A phase has been estimated to be 0.72 while values ranging from 0.88 to 0.44 have been obtained for the four-ring mesogen as it passes from the tilted hexatic to the nematic phase. The orientations of the different rings of the core unit with respect to each other and also with respect to the long axis of the molecule have also been obtained.


The fibrinolytic response to venous occlusion and the natural anticoagulants in patients with antiphospholipid antibodies both with and without systemic lupus erythematosus.
Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis and this is increased in the presence of antiphospholipid antibodies (APA). These APA are also associated with thrombosis in patients who do not have SLE. We compared haemostatic parameters in SLE patients with and without APA, and also compared patients who had APA but not SLE with healthy normal controls. No relationships between the natural anticoagulants, antithrombin III, heparin cofactor II, protein C and protein S, and the presence of APA were found. In the patients with SLE both tissue plasminogen activator antigen and plasminogen activator inhibitor (PAI) were increased, but these changes were not due to APA which had no effect on fibrinolysis in these patients. In the patients with APA who did not have SLE the fibrinolytic response to venous occlusion was reduced due to raised levels of PAI; similar changes have, however, been reported in some patients with idiopathic thrombosis.


Study design synopsis: Bias can cast a dark shadow over studies.
The study of free-living populations is important to generate knowledge related to the epidemiology of disease and other health outcomes. These studies are unable to provide the same level of control as is possible in laboratory studies and thus are susceptible to certain errors. The primary categories of study errors are random and systematic. Random errors cause imprecision and can be quantified using statistical methods including the calculation of confidence intervals. Systematic errors cause bias, which is typically difficult to quantify within the context of an individual study. The three main categories of systematic errors are selection, information, and confounding bias. Selection bias occurs when enrolled animals are not representative of the target population of interest in respect to characteristics important to the primary study objective. Information bias occurs when data collected from enrolled animals deviates from the true value. Information bias is most damaging when errors vary among comparison groups. Both selection and information bias are prevented through the application of good study design procedures. Researchers should select study animals after careful consideration of the primary study objective and desired target population. Investigators can reduce information bias through standardised data collection procedures and the use of blinding. Confounding bias occurs when the measured association between a predictor and an outcome ignores the influential effect of an additional variable. Confounding is common and analysts must implement the appropriate statistical adjustments to reduce the associated bias. All studies will have some errors and biased data with high precision are the most damaging to the validity of study conclusions. Authors can facilitate the critical evaluation of their research by providing text related to the limitations and potential sources of bias within the discussion section of their manuscripts.


Encoding multielement scenes: statistical learning of visual feature hierarchies.
The authors investigated how human adults encode and remember parts of multielement scenes composed of recursively embedded visual shape combinations. The authors found that shape combinations that are parts of larger configurations are less well remembered than shape combinations of the same kind that are not embedded. Combined with basic mechanisms of statistical learning, this embeddedness constraint enables the development of complex new features for acquiring internal representations efficiently without being computationally intractable. The resulting representations also encode parts and wholes by chunking the visual input into components according to the statistical coherence of their constituents. These results suggest that a bootstrapping approach of constrained statistical learning offers a unified framework for investigating the formation of different internal representations in pattern and scene perception.