Investigation of the human serotonin 6 [5-HT6] receptor gene in bipolar affective disorder and schizophrenia.
Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that mediates a wide range of central nervous functions by activating multiple 5-HT receptor subtypes. A possible irregularity of serotonergic neurotransmission has been implicated in a variety of neuropsychiatric diseases. In the present study, we performed a systematic mutation scan of the complete coding region and splice junctions of the 5-HT(6) receptor gene to explore the contribution of this gene to the development of bipolar affective disorder and schizophrenia. Investigating 137 unrelated individuals (including 45 bipolar affective patients, 46 schizophrenic patients, and 46 unrelated controls), we identified six single base substitutions (126G/T, 267C/T, 873+30C/T, 873+128A/C, 1128G/C, 1376T/G). Comparing frequencies between patients and controls, we observed a significant overrepresentation of the 267C allele among bipolar patients (P=0. 023 not corrected for multiple testing). This finding was followed up in an independent sample of 105 bipolar family trios using a family-based association design. Fifty-one transmissions could be examined. In 30 cases allele 267C and in 21 cases allele 267T were transmitted to the affected offspring. Although this result was far from statistical significance (transmission disequilibrium test=1.59, P=0.208), the limited number of possible transmissions may have prevented detection of smaller effects. Our preliminary data suggest that bipolar affective disorder may be associated with variation in the 5-HT(6) gene. It will be important to extend the present analysis to larger samples. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:217-221, 2000.


Recruiting a transcription factor in the liver to prevent atherosclerosis.
Hypertriglyceridemia is associated with obesity, diabetes, and atherosclerosis. While lipoprotein lipase (LPL) hydrolyzes triglyceride (TG) cargo into remnant lipoproteins with atherogenic properties, how remnant lipoprotein clearance relates to atherosclerosis in people with diabetes remains unclear. In this issue of the JCI, Shimizu-Albergine et al. examined the effects of the basic leucine zipper transcription factor CREBH, which induces genes that activate LPL in mouse models of type I diabetes. Overexpression of a CREBH fragment reduced apolipoprotein C3 (APOC3) levels, which reduced plasma TGs. Notably, the TGs were lowered by a mechanism that was independent of LPL, and atherosclerosis was alleviated by enhanced lipoprotein remnant clearance as opposed to increased lipolysis of TG-rich lipoprotein precursors. A proinflammatory mechanism likely underlies the atherogenicity of remnant lipoproteins. These findings suggest that modifying CREBH expression in the liver may ameliorate atherosclerosis and, perhaps, other diabetes complications.


Tensor renormalization group: local magnetizations, correlation functions, and phase diagrams of systems with quenched randomness.
The tensor renormalization-group method, developed by Levin and Nave, brings systematic improvability to the position-space renormalization-group method and yields essentially exact results for phase diagrams and entire thermodynamic functions. The method, previously used on systems with no quenched randomness, is extended in this study to systems with quenched randomness. Local magnetizations and correlation functions as a function of spin separation are calculated as tensor products subject to renormalization-group transformation. Phase diagrams are extracted from the long-distance behavior of the correlation functions. The approach is illustrated with the quenched bond-diluted Ising model on the triangular lattice. An accurate phase diagram is obtained in temperature and bond-dilution probability for the entire temperature range down to the percolation threshold at zero temperature.


Osteoblast cell adhesion on a laser modified zirconia based bioceramic.
Due to their attractive mechanical properties, bioinert zirconia bioceramics are frequently used in the high load-bearing sites such as orthopaedic and dental implants, but they are chemically inert and do not naturally form a direct bond with bone and thus do not provide osseointegration. A CO2 laser was used to modify the surface properties with the aim to achieve osseointegration between bioinert zirconia and bone. The surface characterisation revealed that the surface roughness decreased and solidified microstructure occurred after laser treatment. Higher wettability characteristics generated by the CO2 laser treatment was primarily due to the enhancement of the surface energy, particularly the polar component, determined by microstructural changes. An in vitro test using human fetal osteoblast cells (hFOB) revealed that osteoblast cells adhere better on the laser treated sample than the untreated sample. The change in the wettability characteristics could be the main mechanism governing the osteoblast cell adhesion on the YPSZ.


Nucleation and Growth of Amyloid Fibrils.
The formation of amyloid fibrils is a complex phenomenon that remains poorly understood at the atomic scale. Herein, we perform extended unbiased all-atom simulations in explicit solvent of a short amphipathic peptide to shed light on the three mechanisms accounting for fibril formation, namely, nucleation via primary and secondary mechanisms, and fibril growth. We find that primary nucleation takes place via the formation of an intermediate state made of two laminated β-sheets oriented perpendicular to each other. The amyloid fibril spine subsequently emerges from the rotation of these β-sheets to account for peptides that are parallel to each other and perpendicular to the main axis of the fibril. Growth of this spine, in turn, takes place via a dock-and-lock mechanism. We find that peptides dock onto the fibril tip either from bulk solution or after diffusing on the fibril surface. The latter docking pathway contributes significantly to populate the fibril tip with peptides. We also find that side chain interactions drive the motion of peptides in the lock phase during growth, enabling them to adopt the structure imposed by the fibril tip with atomic fidelity. Conversely, the docked peptide becomes trapped in a local free energy minimum when docked-conformations are sampled randomly. Our simulations also highlight the role played by nonpolar fibril surface patches in catalyzing and orienting the formation of small cross-β structures. More broadly, our simulations provide important new insights into the pathways and interactions accounting for primary and secondary nucleation as well as the growth of amyloid fibrils.


Multiparametric MRI for the improved diagnostic accuracy of Alzheimer's disease and mild cognitive impairment: Research protocol of a case-control study design.
Alzheimer's disease (AD) is a major neurocognitive disorder identified by memory loss and a significant cognitive decline based on previous level of performance in one or more cognitive domains that interferes in the independence of everyday activities. The accuracy of imaging helps to identify the neuropathological features that differentiate AD from its common precursor, mild cognitive impairment (MCI). Identification of early signs will aid in risk stratification of disease and ensures proper management is instituted to reduce the morbidity and mortality associated with AD. Magnetic resonance imaging (MRI) using structural MRI (sMRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (1H-MRS) performed alone is inadequate. Thus, the combination of multiparametric MRI is proposed to increase the accuracy of diagnosing MCI and AD when compared to elderly healthy controls. This protocol describes a non-interventional case control study. The AD and MCI patients and the healthy elderly controls will undergo multi-parametric MRI. The protocol consists of sMRI, fMRI, DTI, and single-voxel proton MRS sequences. An eco-planar imaging (EPI) will be used to perform resting-state fMRI sequence. The structural images will be analysed using Computational Anatomy Toolbox-12, functional images will be analysed using Statistical Parametric Mapping-12, DPABI (Data Processing & Analysis for Brain Imaging), and Conn software, while DTI and 1H-MRS will be analysed using the FSL (FMRIB's Software Library) and Tarquin respectively. Correlation of the MRI results and the data acquired from the APOE genotyping, neuropsychological evaluations (i.e. Montreal Cognitive Assessment [MoCA], and Mini-Mental State Examination [MMSE] scores) will be performed. The imaging results will also be correlated with the sociodemographic factors. The diagnosis of AD and MCI will be standardized and based on the DSM-5 criteria and the neuropsychological scores. The combination of sMRI, fMRI, DTI, and MRS sequences can provide information on the anatomical and functional changes in the brain such as regional grey matter volume atrophy, impaired functional connectivity among brain regions, and decreased metabolite levels specifically at the posterior cingulate cortex/precuneus. The combination of multiparametric MRI sequences can be used to stratify the management of MCI and AD patients. Accurate imaging can decide on the frequency of follow-up at memory clinics and select classifiers for machine learning that may aid in the disease identification and prognostication. Reliable and consistent quantification, using standardised protocols, are crucial to establish an optimal diagnostic capability in the early detection of Alzheimer's disease.


Camurati-Engelmann disease in a family from Croatian Island: an old bone scan confirmed pattern of inheritance.
34-year old patient had history of muscular wasting, easy fatigability, pain in extremities and waddling gait since age of four. During the time, neuromuscular disease was suspected, but not confirmed. Elevated bone alkaline phosphatase as well as other bone turnover markers (osteocalcin, procollagen, telopeptide) indicated further skeletal evaluation. Symmetrical enhanced uptake on technetium methylene diphosphonate [99mTc]MPD bone scintigraphy at diaphyses of longitudinal bones and scull matched cortical thickening of long bones and sclerosis of the scull seen at radiograms. Those findings pointed to Camurati-Engelmann disease misdiagnosed for the long time. This rare genetic autosomal dominant disorder was retrospectively diagnosed in asymptomatic father too on the basis of bone scans done long time ago. Old family member scans confirmed heredity pattern of the disease.


Fibreoptic bronchoscopy: ten years on.
Fibreoptic bronchoscopy was introduced more than 10 years ago and is now in many centres a routine diagnostic procedure, having superseded rigid bronchoscopy. Its major role is in the diagnosis of bronchial carcinoma, where the results are as good as, if not better than, results with the rigid instrument. Other major applications have been found in investigating haemoptysis, transbronchial lung biopsy in interstitial lung disease, and in the critically ill patient in the intensive care unit. More recently, the instrument has been used to perform bronchoalveolar lavage in investigating interstitial lung diseases and to enable lobar and segmental lung function studies to be performed. Fibreoptic bronchoscopy is a major advance in the diagnosis of pulmonary diseases, but there will always be times when rigid bronchoscopy is preferable.


Cinacalcet therapy in a child with novel homozygous CASR p.Glu353Lys mutation causing familial hypocalciuric hypercalcemia type 1: case report and review of the literature.
Familial hypocalciuric hypercalcemia (FHH) is one of the conditions that should be considered in the differential diagnosis of hypercalcemia and normo-hypophosphatemia in childhood. Heterozygous Calcium-sensing receptor (CASR) gene mutations cause FHH, and homozygous CASR gene mutations cause neonatal severe primary hyperparathyroidism (NSHPT). Cinacalcet is an allosteric modulator of Calciumsensing receptor (CaSR), and has been used in the treatment of these clinical entities in recent years. A 26-month-old boy was examined for a recurrent rash. During the evaluation, hypercalcemia (13.3 mg/ dL), hypophosphatemia (2.3 mg/dL) and inappropriately normal PTH level (67 pg/mL) were observed. Neck and renal ultrasonography were normal. The parathyroid scintigraphy was unremarkable. The patient`s family members were also evaluated, and hypocalciuria (fractional excretion of calcium were 0.01%, 0.04% on two separate tests) was detected concurrently with the patient`s hypercalcemia. The mother`s serum calcium was 10.2 mg/dL, the father`s was 10.6 mg/dL, and the brother`s was 12.8 mg/dL. CASR gene sequencing showed a novel homozygous mutation in exon 4 (c.1057G > A), which had generated a substitution of the amino acid glutamate to lysine at codon 353 (p.Glu353Lys). This mutation was homozygous in the children and heterozygous in the parents. Fluid hydration, furosemide, oral phosphorus, prednisolone, pamidronate and cinacalcet treatments were used in the management of hypercalcemia of the proband. A longer and more effective control was achieved with cinacalcet treatment. FHH can be seen in heterozygous as well as homozygous CASR gene mutations. Different clinical findings may occur in different individuals from the same family. Cinacalcet therapy can be used successfully in the treatment of individuals with FHH.


IgG from patients with pulmonary arterial hypertension and/or systemic sclerosis binds to vascular smooth muscle cells and induces cell contraction.
Pulmonary arterial hypertension (PAH) is characterised by remodelling of pulmonary arteries with enhanced vascular smooth muscle cell (VSMC) contraction, migration and proliferation. The authors investigated the presence of antibodies to human VSMCs in the serum of patients with systemic sclerosis with or without PAH and idiopathic PAH (iPAH). Antibodies to VSMCs were detected by immunofluorescence in sera from healthy controls and patients with scleroderma without PAH, scleroderma-associated PAH and iPAH. Serum IgG from these patients induced contraction of VSMCs in a collagen matrix in contrast with IgG from healthy controls. Several protein spots of interest and target antigens were identified by two-dimensional immunoblotting and MS, including stress-induced phosphoprotein 1 and α-enolase. Finally, antibodies to stress-induced phosphoprotein 1 were detected by ELISA in sera from 84%, 76% and 24% of patients with scleroderma without PAH, scleroderma-associated PAH and iPAH, respectively, compared with only 3% of healthy controls. The authors have identified IgG that binds to VSMCs in the serum of patients with scleroderma and iPAH. These antibodies may be pathogenic by modulating vascular contraction. The target antigens of these antibodies are stress-induced phosphoprotein 1 and α-enolase.


Etomidate depresses lumbar dorsal horn neuronal responses to noxious thermal stimulation in rats.
Etomidate is a widely used IV anesthetic, but little is known about its analgesic properties, in particular, its effects on spinal cord neuronal responses to noxious stimuli. We hypothesized that etomidate would depress lumbar neuronal responses to noxious heat. Rats (n = 15) were anesthetized with isoflurane (1.2%) and laminectomy was performed to record single unit activity. Lumbar neuronal responses to noxious thermal (52 degrees C, 12 s) stimulation of the hindpaw were recorded before and every 2 min (up to 13 min postinjection) after administration of etomidate. The responses at peak effect of etomidate (as a percentage of the control response) were 63% +/- 16%, 63% +/- 16%, 38% +/- 25%, 36% +/- 30%, and 41% +/- 26% for the 0.125, 0.25, 0.5, 1 and 2 mg/kg doses, respectively. The responses quickly recovered, usually by the 10-min period postinjection. Similar responses were obtained in decerebrate, isoflurane-free rats administered etomidate and in isoflurane-anesthetized rats administered propofol. These data demonstrate that etomidate depresses spinal cord neuronal responses to noxious stimulation and is a possible mechanism by which this drug might produce analgesia.


How Personal Perspectives Shape Health Professionals' Perceptions of Fetal Alcohol Spectrum Disorder and Risk.
This article examines how health, allied health and social service professionals' personal perspectives about alcohol and the risks associated with alcohol consumption become non-clinical factors that may influence their professional practice responses in relation to fetal alcohol spectrum disorder (FASD). It presents findings derived from a qualitative, interview-based study of professionals from a range of health, allied health and social service professions in New Zealand. The data derived from these interviews revealed four frames of reference that practitioners use when thinking about alcohol and risk: reflection on personal experience; experiences of friends, relatives and colleagues; social constructions of alcohol use and misuse; and comparisons to other types of drug use. The article concludes that these non-clinical factors are important considerations in professional decision making about FASD.


Radial mobility and cytotoxic function of retroviral replicating vector transduced, non-adherent alloresponsive T lymphocytes.
We report a novel adaptation of the Radial Monolayer Cell Migration assay, first reported to measure the radial migration of adherent tumor cells on extracellular matrix proteins, for measuring the motility of fluorescently-labeled, non-adherent human or murine effector immune cells. This technique employs a stainless steel manifold and 10-well Teflon slide to focally deposit non-adherent T cells into wells prepared with either confluent tumor cell monolayers or extracellular matrix proteins. Light and/or multi-channel fluorescence microscopy is used to track the movement and behavior of the effector cells over time. Fluorescent dyes and/or viral vectors that code for fluorescent transgenes are used to differentially label the cell types for imaging. This method is distinct from similar-type in vitro assays that track horizontal or vertical migration/invasion utilizing slide chambers, agar or transwell plates. The assay allows detailed imaging data to be collected with different cell types distinguished by specific fluorescent markers; even specific subpopulations of cells (i.e., transduced/nontransduced) can be monitored. Surface intensity fluorescence plots are generated using specific fluorescence channels that correspond to the migrating cell type. This allows for better visualization of the non-adherent immune cell mobility at specific times. It is possible to gather evidence of other effector cell functions, such as cytotoxicity or transfer of viral vectors from effector to target cells, as well. Thus, the method allows researchers to microscopically document cell-to-cell interactions of differentially-labeled, non-adherent with adherent cells of various types. Such information may be especially relevant in the assessment of biologically-manipulated or activated immune cell types, where visual proof of functionality is desired with tumor target cells before their use for cancer therapy.


Enduring Changes in Decision Making in Patients with Full Remission from Anorexia Nervosa.
Deficits in neuropsychological functioning have consistently been identified in patients with anorexia nervosa (AN). However, little is known on how decision making in AN patients evolves in response to treatment or whether impairments are reversible. AN patients (n = 42) completed the Iowa Gambling Task (IGT) upon admission to a 3-month day-hospital treatment programme and at a 1-year follow-up. Patient IGT performance was compared to age-matched controls (n = 46). AN patients displayed poorer performance on the IGT at admission compared to controls (p < .001). Patients with full remission (n = 31; 73.9%) at the 1-year follow-up improved IGT performance (p = 0.007), and scores were similar compared to controls (p = 0.557). AN patients with partial/no remission at follow-up (n = 11; 26.1%) did not improve IGT scores (p = 0.867). These findings uphold that enduring remission from AN can reverse decision-making impairments, and they might be most likely explained by clinical state rather than a trait vulnerability. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.


Probing Single-Cell Fermentation Fluxes and Exchange Networks via pH-Sensing Hybrid Nanofibers.
The homeostatic control of their environment is an essential task of living cells. It has been hypothesized that, when microenvironmental pH inhomogeneities are induced by high cellular metabolic activity, diffusing protons act as signaling molecules, driving the establishment of exchange networks sustained by the cell-to-cell shuttling of overflow products such as lactate. Despite their fundamental role, the extent and dynamics of such networks is largely unknown due to the lack of methods in single-cell flux analysis. In this study, we provide direct experimental characterization of such exchange networks. We devise a method to quantify single-cell fermentation fluxes over time by integrating high-resolution pH microenvironment sensing via ratiometric nanofibers with constraint-based inverse modeling. We apply our method to cell cultures with mixed populations of cancer cells and fibroblasts. We find that the proton trafficking underlying bulk acidification is strongly heterogeneous, with maximal single-cell fluxes exceeding typical values by up to 3 orders of magnitude. In addition, a crossover in time from a networked phase sustained by densely connected "hubs" (corresponding to cells with high activity) to a sparse phase dominated by isolated dipolar motifs (i.e., by pairwise cell-to-cell exchanges) is uncovered, which parallels the time course of bulk acidification. Our method addresses issues ranging from the homeostatic function of proton exchange to the metabolic coupling of cells with different energetic demands, allowing for real-time noninvasive single-cell metabolic flux analysis.


Noninvasive assessment of impaired endothelial function in psoriasis.
The objectives of this study are noninvasive assessment of endothelial dysfunction (ED) and diagnosing the possible early vascular development of atherosclerosis in psoriasis disease (PD). Twenty-eight PD patients (study group) without any obstructive vascular involvement were compared with 28 healthy controls (control group) in terms of ED utilizing endothelium-dependent dilation as well as endothelium-independent dilation, which was assessed by measuring changes in brachial artery diameter following sublingual glyceryl trinitrate (400 microg Nitrolingual spray). All patients underwent a complete transthoracic echocardiographic and tissue Doppler study. A standard form was utilized for the documentation of the presence or absence of the known risk factors for atherosclerotic vascular disease. Statistical analysis was performed by utilizing SPSS version 11. There was no difference between patients and controls in terms of echocardiographic and tissue Doppler parameters as well as baseline brachial artery diameters. Flow-mediated dilation showed 37% impairment in study group compared with control (p < 0.05). Endothelium-independent NTG dilatation did not differ in both groups. Noninvasive methods such as ultrasonography, saving time and cost-effective, can be utilized for following outpatient PD patients for the risk of ED, which may preclude to atherosclerosis.


An outbreak of adenovirus type 8 keratoconjunctivitis in a nursing home in Madrid.
This work describes and analyses an outbreak of epidemic keratoconjunctivitis which occurred in 2001 and 2002 in a nursing home for the elderly in Leganes (an area of Madrid). This is the first such published case in Spain with these characteristics and this serotype identification. Sociodemographic characteristics, epidemic curve and attack rates are described. Comparisons of the data were carried out using a chi2 test for qualitative variable and t-test for quantitative. Factors associated with the illness are explored by means of contingency tables and logistic regression models. One hundred and two cases were detected, with an attack rate of 36.4% for residents, and 12.9% for workers, not considering spatial or professional differences. The epidemic curve showed an interpersonal transmission pattern. Multivariate analysis identified the following risk factors in the residents: able to wander freely through the building, urinary incontinence and use of shared bathroom. In 34.6% of the conjunctival samples, adenovirus serotype 8 was detected with identical genomic sequence. Establishment of hygienic sanitary guidance adapted for the cleaning of such establishments and contact with residents as well as early diagnosis and good coordination of human and material resources are key factors in the prevention and control of these outbreaks in closed communities.


Batch cultivation of Methylosinus trichosporium OB3b: II. Production of particulate methane monooxygenase.
The obligatory methanotroph, Methylosinus trichosporium OB3b, was studied to optimize the batch culture conditions for the formation of particulate methane monooxygenase (pMMO) in a nitrate minimal salts medium. The important medium components investigated were copper, carbon dioxide, and nitrate. The whole-cell specific pMMO activity decreased sharply with increasing copper concentrations in the range of 10-40 microM and remained constant upon further increases of the copper concentration to 120 microM. The cell growth rate (micro), on the other hand, decreased over the entire range (10-120 microM) of copper concentrations tested. When pMMO was produced in a bioreactor with an optimal initial copper concentration of 10 microM, M. trichosporium OB3b exhibited a much faster overall growth rate and a higher whole-cell propene epoxidation activity compared to our earlier study, in which soluble methane monooxygenase (sMMO) was produced with copper-deficient medium. The addition of external carbon dioxide to the bioreactor culture eliminated an initial lag period in the cell growth. When the standard culture medium nitrate concentration (10 mM) was depleted, the pMMO activity, but not the growth rate, decreased rapidly. The whole-cell specific pMMO activity could be maintained by subsequent supplementation of nitrate. A 4-fold higher initial culture medium nitrate concentration of 40 mM, however, resulted in slower cell growth and lower pMMO activity. These observations demonstrate that, in addition to affecting the exclusive production of pMMO, copper also has an important previously unrecognized role in enhancing the growth rate of M. trichosporium OB3b. They also indicate that for the optimal batch production of pMMO with the minimal medium under study, nitrate should be supplied intermittently during the course of cultivation until other culture medium components become growth-limiting.


Maize streak virus coat protein binds single- and double-stranded DNA in vitro.
Maize streak virus (MSV) coat protein (CP) is required for virus movement within the plant. Deletion or mutation of MSV CP does not prevent virus replication in single cells or protoplasts but leads to a loss of infectivity in the inoculated plant. The mechanism by which MSV CP mediates the transfer of MSV DNA from cell to cell and through the vascular bundle is still unknown. Towards understanding the role of MSV CP in virus movement, the interaction of the CP with viral DNA was investigated using the 'south-western' assay. Wild-type and truncated MSV CPs were expressed in E. coli and the expressed CPs were used to investigate interactions with single-stranded (ss) and double-stranded (ds) DNA. The results showed that MSV CP bound ss and ds viral and plasmid DNA in a sequence non-specific manner. The binding domain was mapped to within the 104 N-terminal amino acids of the MSV CP. We propose that the binding of CP to MSV DNA is involved in viral DNA nuclear transport as well as encapsidation and thus may have a role in intra- and inter-cellular movement as well as systemic infection.


Effect of routine claw trimming on claw temperature in dairy cows measured by infrared thermography.
Infrared thermography (IRT) was used to assess the effect of routine claw trimming on claw temperature. In total, 648 IRT observations each were collected from 81 cows housed in 6 tiestalls before and 3 wk after claw trimming. The feet were classified as either healthy (nonlesion group, n = 182) or affected with infectious foot disorders (group IFD, n = 142). The maximal surface temperatures of the coronary band and skin and the difference of the maximal temperatures (ΔT) between the lateral and medial claws of the respective foot were assessed. Linear mixed models, correcting for the hierarchical structure of the data, ambient temperature, and infectious status of the claws, were developed to evaluate the effect of time in relation to the trimming event (d 0 versus d 21) and claw (medial versus lateral). Front feet and hind feet were analyzed separately. Ambient temperature and infectious foot status were identified as external and internal factors, respectively, that significantly affected claw temperature. Before claw trimming, the lateral claws of the hind feet were significantly warmer compared with the medial claws, whereas such a difference was not evident for the claws of the front feet. At d 21, ΔT of the hind feet was reduced by ≥ 0.25 °C, whereas it was increased by ≤ 0.13 °C in the front feet compared with d 0. Therefore, trimming was associated with a remarkable decrease of ΔT of the hind claws. Equalizing the weight bearing of the hind feet by routine claw trimming is associated with a measurable reduction of ΔT between the paired hind claws.


Short-term effects of video gaming on brain response during working memory performance.
Breaks filled with different break activities often interrupt cognitive performance in everyday life. Previous studies have reported that both enhancing and deteriorating effects on challenging ongoing tasks such as working memory updating, depend on the type of break activity. However, neural mechanisms of these break-related alterations in working memory performance have not been studied, to date. Therefore, we conducted a brain imaging study to identify the neurobiological correlates of effects on the n-back working memory task related to different break activities. Before performing the n-back task in the magnetic resonance imaging (MRI) scanner, young adults were exposed to break activities in the MRI scanner involving (i) eyes-open resting, (ii) listening to music, and (iii) playing the video game "Angry Birds". Heart rate was measured by a pulse oximeter during the experiment. We found that increased heart rate during gaming as well as decreased relaxation levels after a video gaming break was related to poorer n-back task performance, as compared to listening to music. On the neural level, video gaming reduced supplementary motor area activation during working memory performance. These results may indicate that video gaming during a break may affect working memory performance by interfering with arousal state and frontal cognitive control functions.


The effect of an eucaloric high carbohydrate diet on circulating levels of glucose, fructose and non-esterified fatty acids in patients with cirrhosis.
Twelve cirrhotic patients and six controls were fed an eucaloric high carbohydrate (CHO) diet for 3 days. Fasting serum triglyceride (TG), non-esterified fatty acids (NEFA), glucose, insulin and glycerol were estimated daily. On the 3rd day of the study we measured NEFA, glucose, insulin, and fructose every 45 min from 07:45 h until 19:45 h, and then every 4 h until 07:45 h the next day. The patients were divided into two groups of six on the basis of plasma lecithin-cholesterol acyltransferase (LCAT) activity: group A cirrhotics (with good liver function--LCAT activity: 40.6-65.7 nmol.ml-1.h-1; mean 48.5), and group B (poor liver function--LCAT: 23.7-32.3; mean 27.4). On the high CHO diet there was an increase in the fasting serum TG with a peak after 2 or 3 days. The increase in serum TG in controls was greater (p less than 0.01) than in either group of cirrhotics. In the controls and in group A most of the extra TG was carried in VLDL; in group B only 39% of the TG increment was found in VLDL. Fasting NEFA fell with 3 days of CHO feeding in the control group (p less than 0.01); they were unchanged in group A, and rose in group B to a significantly higher level than in controls (p less than 0.01). During day 3 when a high CHO diet was fed plasma NEFA levels fell in cirrhotics, and for most of the day the mean NEFA concentration in group B patients was significantly (p less than 0.05) lower than in normals. On day 3 glucose and fructose levels rose after each meal--much more in cirrhotics than in controls (and more in group B than in group A), and for most of the day they were significantly higher in group B patients as compared to the controls (glucose p less than 0.01, fructose p less than 0.001). Our results supported the hypothesis that plasma NEFA would be lower following high CHO meals in cirrhotics than in controls. This suggests that a high NEFA utilisation, which occurs in fasting cirrhotics, is not present throughout the day. Following a CHO meal, we suggest that tissues derive energy directly from the dietary sugars which are present in high concentration during the period of absorption and that this reduces the post prandial requirement for NEFA.


Medicare and Medicaid programs; conditions for coverage for end-stage renal disease facilities. Final rule.
This rule finalizes the February 4, 2005 proposed rule entitled "Medicare Program; Conditions for Coverage for End-Stage Renal Disease Facilities." It establishes new conditions for coverage that dialysis facilities must meet to be certified under the Medicare program. This final rule focuses on the patient and the results of care provided to the patient, establishes performance expectations for facilities, encourages patients to participate in their plan of care and treatment, eliminates many procedural requirements from the previous conditions for coverage, preserves strong process measures when necessary to promote meaningful patient safety, well-being, and continuous quality improvement. This final rule reflects the advances in dialysis technology and standard care practices since the requirements were last revised in their entirety in 1976.


Trans-arterial chemo-embolization (TACE), with either lipiodol (traditional TACE) or drug-eluting microspheres (precision TACE, pTACE) in the treatment of hepatocellular carcinoma: efficacy and safety results from a large mono-institutional analysis.
More data about TACE and pTACE seem necessary to better define the global treatment strategy for HCC. Aim of our analysis was to evaluate the role of TACE, either with lipiodol (traditional) or drug-eluting microspheres in terms of response rate (RR), time to progression (TTP), overall survival (OS) and toxicity in HCC.Patients with HCC undergoing traditional TACE or pTACE (either alone or in combination with other treatment options) were eligibleOne hundred and fifty patients were analyzed. In the global patient population median OS was 46 months for lipiodol TACE and 19 months for pTACE (p < 0.0001), TTP was 30 months versus 16 months for patients receiving TACE or pTACE respectively (p = 0.003). These results were confirmed also among the group of patients who received exclusive TACE or pTACE. Neither RR nor toxicity was different between TACE or pTACE.At multivariate analysis, age, the Okuda stage, type of TACE and number of TACE proved to be independent prognostic factors influencing overall survival.In our experience, lipiodol TACE showed a better OS and TTP over pTACE, without difference in toxicity profile and RR. Among the staging systems analyzed only the Okuda stage seemed able to reliably predict patients outcome.


Acetate promotes microbial reductive debromination of tetrabromobisphenol A during the startup phase of anaerobic wastewater sludge bioreactors.
The detection of increasing concentrations of tetrabromobisphenol A (TBBPA) in wastewater treatment plants is raising concerns as TBBPA has been identified as a potentially toxic flame retardant. The objectives of this study were to evaluate the effect of acetate biostimulation on TBBPA microbial reductive debromination, and the response of anaerobic sludge associated microbial communities repeatedly exposed to TBBPA. Results indicate that the bulk of the microbial community did not experience significant shifts as a result of TBBPA exposure, and that only a small fraction of the community responded to the presence of TBBPA. Taxa most likely responsible for TBBPA transformation affiliated to Clostridiales and the wastewater sludge group Blvii28. The biostimulating effect of acetate was only observed during reactor startup, when acetogenesis was likely not yet occurring. However, when acetate likely started to be microbially generated in the reactor, acetate addition resulted in a slight but significant inhibiting effect on TBBPA transformation. A significant increase of hydrogenotrophic methanogens in the TBBPA-spiked reactor overtime implies that TBBPA degraders were not in direct competition with methanogens for H2. These results strongly suggest that TBBPA degrading taxa might have been primarily using acetate as an electron donor for the reductive debromination of TBBPA.


Micro-CT image gallery visually presenting the effects of ocean warming and acidification on marine gastropod shells.
Digitisation of specimens (e.g. zoological, botanical) can provide access to advanced morphological and anatomical information and promote new research opportunities. The micro-CT technology may support the development of "virtual museums" or "virtual laboratories" where digital 3D imaging data are shared widely and freely. There is currently a lack of universal standards concerning the publication and curation of micro-CT datasets. The aim of the current project was to create a virtual gallery with micro-CT scans of individuals of the marine gastropod Hexaplextrunculus, which were maintained under a combination of increased temperature and low pH conditions, thus simulating future climate change scenarios. The 3D volume-rendering models created were used to visualise the structure properties of the gastropods shells. Finally, the 3D analysis performed on the micro-CT scans was used to investigate potential changes in the shell properties of the gastropods. The derived micro-CT 3D images were annotated with detailed metadata and can be interactively displayed and manipulated using online tools through the micro-CT virtual laboratory, which was developed under the LifeWatchGreece Research Infrastructure for the dissemination of virtual image galleries collection supporting the principles of FAIR data.


Mycobacterium avium bacilli grow saprozoically in coculture with Acanthamoeba polyphaga and survive within cyst walls.
Protozoans are gaining recognition as environmental hosts for a variety of waterborne pathogens. We compared the growth of Mycobacterium avium, a human pathogen associated with domestic water supplies, in coculture with the free-living amoeba Acanthamoeba polyphaga with the growth of M. avium when it was separated from amoebae by a 0.1-micron-pore-size polycarbonate membrane (in a parachamber). Although viable mycobacteria were observed within amoebal vacuoles, there was no significant difference between bacterial growth in coculture and bacterial growth in the parachamber. This suggests that M. avium is able to grow saprozoically on products secreted by the amoebae. In contrast, Legionella pneumophila, a well-studied intracellular parasite of amoebae, multiplied only in coculture. A comparison of amoebae infected with L. pneumophila and amoebae infected with M. avium by electron microscopy demonstrated that there were striking differences in the locations of the bacteria within amoebal cysts. While L. pneumophila resided within the cysts, M. avium was found within the outer walls of the double-walled cysts of A. polyphaga. These locations may provide a reservoir for the bacteria when environmental conditions become unfavorable.


The aryl hydrocarbon receptor affects mouse ovarian follicle growth via mechanisms involving estradiol regulation and responsiveness.
The aryl hydrocarbon receptor (AHR) is a known transcription factor. Although studies indicate that Ahr-deficient (AhRKO) mice have defects in female reproduction, only a few studies have examined the role of AHR in the ovary. Previous studies have suggested, without directly testing, that AhRKO mice have slower follicular growth than wild-type (WT) mice. Therefore, the first objective of the present study was to examine whether AhRKO follicles grow slower than WT follicles and if so, to determine whether the mechanism by which Ahr affects follicular growth is through effects on antrum size, granulosa cell proliferation, and regulators of cell cycle progression. Since estradiol (E(2)) is critical for the normal growth of ovarian follicles, the second objective of the present study was to determine the role of Ahr in regulating E(2) production and responsiveness. The third objective of the present study was to determine whether E(2) replacement restores follicular growth of AhRKO follicles to WT levels in vitro. We found that AhRKO follicles grew slower than WT follicles in vitro. While AhRKO and WT follicles had similar antrum sizes, AhRKO follicles showed decreased granulosa cell proliferation and reduced mRNA and protein levels of cell cycle regulators, as compared to WT follicles. Furthermore, the AhRKO mice had lower serum and follicle-produced E(2) levels and showed decreased Esr1 and Esr2 mRNA levels compared to WT mice. Finally, E(2) treatment of AhRKO follicles restored follicular growth to WT levels in vitro. Collectively, these findings suggest that the AHR affects follicular growth via mechanisms that involve E(2) regulation and responsiveness.


Low-copy-number molecules are produced by recombination, actively maintained and can be amplified in the mitochondrial genome of Brassicaceae: relationship to reversion of the male sterile phenotype in some cybrids.
A PCR analysis of mitochondrial (mt) genomes of cybrid rapeseed plants revealed substoichiometric concentrations of molecules bearing different configurations of the gene (orf138) responsible for Ogura cytoplasmic male sterility (CMS). These substoichiometric molecules are also present in plants bearing the unmodified Ogura cytoplasm. In one cybrid family, which shows reversion of the male sterile phenotype, we observed changes in the respective proportions of these molecules. The phenotypic (sterility-fertility) reversion occurs as a result of a modification of the equilibrium state between the different forms of the orf138 gene and is very probably determined by the level of expression of this gene. Stable situations are always characterized by one predominant form; the others, when present, exist in substoichiometric amounts. We report results indicating that the different forms of the orf138 gene are continuously interconverted by recombination and that an active mechanism is involved in the maintenance of some substoichiometric molecules.


Intrinsic and extrinsic pathway signaling during neuronal apoptosis: lessons from the analysis of mutant mice.
Trophic factor deprivation (TFD)-induced apoptosis in sympathetic neurons requires macromolecular synthesis-dependent BAX translocation, cytochrome c (cyt c) release, and caspase activation. Here, we report the contributions of other intrinsic and extrinsic pathway signals to these processes. Sympathetic neurons expressed all antiapoptotic BCL-2 proteins examined, yet expressed only certain BH3-only and multidomain proapoptotic BCL-2 family members. All coexpressed proapoptotic proteins did not, however, exhibit functional redundancy or compensatory expression, at least in the Bax-/-, Bak-/-, Bim-/-, Bid-/-, and Bad-/- neurons examined. Although the subcellular distribution or posttranslational modification of certain BCL-2 proteins changed with TFD, neither transcriptional nor posttranslational mechanisms regulated the expression or subcellular localization of BID, BAD, or BAK in this paradigm. Despite modest induction of Fas and FasL expression, Fas-mediated signaling did not contribute to TFD-induced apoptosis in sympathetic neurons. Similar findings were obtained with K+ withdrawal-induced apoptosis in cerebellar granule neurons, a model for activity-dependent neuronal survival in the CNS. Thus, expression alone does not guarantee functional redundancy (or compensation) among BCL-2 family members, and, at least in some cells, extrinsic pathway signaling and certain BH3-only proteins (i.e., BID and BAD) do not contribute to BAX-dependent cyt c release or apoptosis caused by TFD.


Treatment of advanced prostatic cancer.
Many treatment modalities are available to patients with disseminated adenocarcinoma of the prostate. Although no single therapeutic approach can be advocated for all patients at the present time, delay of endocrine manipulation until the onset of symptoms is the recommended approach because it maintains the most normal lifestyle in these patients. With the onset of symptoms such as bone pain or urinary retention, or perhaps as disease progression becomes apparent, orchiectomy is recommended to patients with increased cardiovascular risks as well as to those patients who are judged irresponsible in taking oral estrogens. A dose of 1 mg of diethylstilbestrol three times daily achieves a castrate level of serum testosterone and may not increase cardiovascular mortality. Because of the relative safety and lack of side effects, GnRH analogues represent an alternative treatment in selected patients, particularly in those who refuse orchiectomy or have an increased risk of developing cardiovascular complications. Hormonal manipulation with androgen deprivation remains the cornerstone of treatment and provides clinical remission in the majority of patients with advanced prostate cancer. The prognosis is poor once tumor has recurred. Several secondary forms of endocrine therapy are available, but it would help to be able to select those patients with hormonally sensitive tumors that would respond favorably to these modalities. Transurethral surgery and radiotherapy are effective in palliating patients with bladder outlet obstruction and bony metastases unresponsive to hormonal therapy. Nonhormonal cytotoxic agents are available, but well-controlled studies are required to determine the value of specific agents, whether used alone or in combination.


Insights into the structure of sunscreen lotions: a small-angle neutron scattering study.
Sunscreen lotions and creams are arguably the most popular products used to protect the skin against harmful UV radiation. Several studies have been conducted to untangle the internal microstructure of creams and lotions. However, the effect of UV filters and other materials such as preservatives, on the internal microstructure and the aesthetics of these products is not yet fully understood. Using small-angle neutron scattering (SANS), we were able to investigate the effect of adding the commonly used organic UV filters (avobenzone (AVB), ethylhexyl methoxycinnamate (EMC), ethylhexyl triazone (EHT) and bemotrizinol (BMT)) and the water soluble preservatives (1,5-pentanediol (1,5-PD) and 1,2-hexanediol (1,2-HD)), on the internal architecture and microstructure of an oil-in-water (o/w) based sunscreen lotion. Our findings highlight the complexities of these formulations, and how the introduction of different additives could influence their structure and possibly their performance.


[Fundamental bases of biological rhythms].
The data and theoretical points given in the paper mould basically new views of molecular relationships underlying the function of living beings and biological rhythms. The authors' procedure for wedge biological fluid dehydration reveals a wide autowave spectrum that is clearly detectable when the fluid passes into the solid phase. A hypothesis of the autowave interaction of biologically active molecules is forwarded, which considers autowaves as a basis of organization of physiological and pathological processes occurring in the body.


A scalable architecture for real-time synthetic-focus imaging.
A scalable architecture for forming real-time synthetic focus images is described and the design of a 256-channel system using currently-available technology is presented as an example implementation of the architecture. The parallelism of the system scales directly with the number of array elements and the image computation rate for a given image size (in pixels) stays constant as the number of array elements is increased. The system leverages earlier work in the real-time generation of the required time-of-flight surfaces and allows either real-time image generation or iterative adaptive image generation from a single complete data set.


The molecular weight-dependent distribution of urinary glycosaminoglycans in Werner's syndrome.
The macromolecular AGAG in the urine of patients with Werner's syndrome were analyzed by enzymatic methods after digestion with chondroitinases and Streptomyces hyaluronidase. The molecular weight-dependent distribution of the urinary AGAG has been determined by gel filtration on a Sephadex G-100 column. The distribution of HA and HS was predominant in the macromolecular fractions. Chondroitin sulfate isomers were prominent in the low molecular weight fractions but the ratio of the 4-type to the 6-type increased with decreasing molecular weight. These observations indicated that Werner's syndrome is a metabolic disorder of the molecular weight-dependent AGAG composition.


Adult idiopatic occlusion of Monro foramina: intraoperative endoscopic reinterpretation of radiological data and review of the literature.
Adult idiopathic occlusion of the foramen of Monro (AIOFM) is a rare condition, with only few cases described in the modern literature. We propose that AIOFM may result from unilateral or bilateral occlusion of Monro foramina, as well as from progression of a monolateral hydrocephalus. Different surgical strategies may be required for effective treatment according to the type of occlusion. To date, only 12 cases of AIOFM have been reported in the literature. We report the cases of two patients, aged 20 and 47 years respectively, who presented with intracranial hypertension secondary to bilateral ventricular dilatation due to obstruction at the level of the foramen of Monro. Both patients were successfully treated with endoscopic fenestration of the primarily obstructed foramen of Monro and, in one patient, fenestration of the septum. We propose that septum pellucidum displacement could play a role in the occlusion of the second foramen of Monro. AIOFM can, therefore, result also from unilateral stenosis of Monro. The difference in AIOFM (i.e. unilateral vs bilateral) will be useful in guiding the most suitable surgical approach in this rare condition.


New phenolic inhibitors of yeast homoserine dehydrogenase.
A relatively unexploited potential target for antimicrobial agents is the biosynthesis of essential amino acids. Homoserine dehydrogenase, which reduces aspartate semi-aldehyde to homoserine in a NAD(P)H-dependent reaction, is one such target that is required for the biosynthesis of Met, Thr, and Ile from Asp. We report a small molecule screen of yeast homoserine dehydrogenase that has identified a new class of phenolic inhibitors of this class of enzyme. X-ray crystal structural analysis of one of the inhibitors in complex with homoserine dehydrogenase reveals that these molecules bind in the amino acid binding region of the active site and that the phenolic hydroxyl group interacts specifically with the backbone amide of Gly175. These results provide the first nonamino acid inhibitors of this class of enzyme and have the potential to be exploited as leads in antifungal compound design.


The reflex effects of spinal somatic nerve stimulation on visceral function.
This paper studies somatovisceral reflex responses in the cardiovascular organ, gastrointestinal tract, urinary bladder and adrenal medulla in anesthetized animals after eliminating emotional factors following somatic sensory stimulations. Various somatic sensory stimulations, including cutaneous, muscle and articular sensory stimulations, can produce differing autonomic reflex responses, depending on which visceral organs and somatic afferents are stimulated. Some responses have dominant sympathetic efferent involvement, whereas others have dominant parasympathetic efferent involvement. Some responses have propriospinal and segmental characteristics, while others have supraspinal and generalized characteristics in their reflex nature. These somatovisceral reflex responses may be functioning during spinal manipulative therapy in conscious humans.


A multifactorial role for P. falciparum malaria in endemic Burkitt's lymphoma pathogenesis.
Endemic Burkitt's lymphoma (eBL) arises from the germinal center (GC). It is a common tumor of young children in tropical Africa and its occurrence is closely linked geographically with the incidence of P. falciparum malaria. This association was noted more than 50 years ago. Since then we have learned that eBL contains the oncogenic herpes virus Epstein-Barr virus (EBV) and a defining translocation that activates the c-myc oncogene. However the link to malaria has never been explained. Here we provide evidence for a mechanism arising in the GC to explain this association. Accumulated evidence suggests that eBL arises in the GC when deregulated expression of AID (Activation-induced cytidine deaminase) causes a c-myc translocation in a cell latently infected with Epstein-Barr virus (EBV). Here we show that P. falciparum targets GC B cells via multiple pathways to increase the risk of eBL. 1. It causes deregulated expression of AID, thereby increasing the risk of a c-myc translocation. 2. It increases the number of B cells transiting the GC. 3. It dramatically increases the frequency of these cells that are infected with EBV and therefore protected from c-myc induced apoptosis. We propose that these activities combine synergistically to dramatically increase the incidence of eBL in individuals infected with malaria.


Application of continuous incisional infusion of local anesthetic after major pediatric urological surgery: prospective randomized controlled trial.
The aim of the study was to determine efficacy of continuous incisional infusion of local anesthetic, ON-Q® pain relief system (Kimberly-Clark, Georgia), in improving postoperative pain, reducing narcotic requirement, and shortening recovery time after major pediatric urological surgery. Prospective open-labeled randomized controlled trial comparing the ON-Q® pain relief system to standard of care pain management. Pain was assessed by nurses using the Visual Analog Scale or the Face, Legs, Activity, Cry, Consolability Scale depending on the child's age. Information regarding analgesic consumption and recovery parameters such as temperature, start of oral nutrition, and length of hospitalization were prospectively collected. Patient's demographic, clinical, and surgical characteristics were similar in both groups. The ON-Q® group experienced significantly lower scores of maximal daily pain episodes compared to the control on the day of surgery (1.9±1.8 vs. 4.2±2.2 p=0.009) and first postoperative day (2.28±3.2 vs. 5.47±2.45 p=0.004). Mean number of narcotic doses was significantly lower in treatment group compared to control [Total (2.21 vs. 4.6 p=0.02), POD0 (0.7 vs. 1.7 p=0.02) and POD1 (1.3 vs. 2.8 p=0.04)]. The ON-Q® system is a viable option for postoperative pain management in children undergoing urological surgeries. This technology significantly decreases the amount of maximal pain, and the need for systemic narcotic consumption.


Acute and subacute hematologic effects of multi-colony stimulating factor in combination with granulocyte colony-stimulating factor in vivo.
Multi-colony stimulating factor (Multi-CSF, interleukin-3, IL-3) and granulocyte-CSF (G-CSF) administered concurrently as an intravenous (IV) injection induce a peripheral neutrophilia that is approximately additive in comparison with the neutrophilia induced by IL-3 and G-CSF individually. The bone marrow (BM) at 12 hours is depleted of mature neutrophils and shows a left-shifted myeloid hyperplasia, consistent with the neutrophil-releasing and myeloproliferative activities of both IL-3 and G-CSF individually. The BM at 24 hours shows a replenished reserve of mature neutrophils and a synergistic left-shifted myeloid hyperplasia as compared with IL-3 and G-CSF alone. Daily IV injections of IL-3 plus G-CSF for 1 week also induce an approximately additive daily peripheral neutrophilia. The BM after a week's administration of IL-3 plus G-CSF shows a generalized myeloid hyperplasia with a synergistic increase in mature neutrophils as compared with IL-3 or G-CSF alone. Daily injection of IL-3 plus G-CSF induced a significant decrease in erythroid, lymphoid, and eosinophilic marrow precursors, possibly owing to a myelophthisic effect of the myeloid hyperplasia and despite the fact that IL-3 alone induced a significant erythroid hyperplasia.


Excessive ethanol drinking following a history of dependence: animal model of allostasis.
Alcohol withdrawal symptoms, particularly negative emotional states, can persist for months following the removal of alcohol. These protracted withdrawal symptoms have been implicated as an important trigger of relapse to excessive drinking in alcoholics and may represent a long lasting shift in affective tone as a result of chronic alcohol exposure. It was shown previously that ethanol-dependent rats increased their operant responding for ethanol when tested during the first 12 hr after withdrawal. The purpose of the present experiments was to determine the persistence of this finding by examining operant oral ethanol self-administration in rats with a history of physical dependence upon ethanol, detoxified and then allowed a two week period of protracted abstinence. The results of these experiments indicate that operant responding for ethanol was enhanced during protracted abstinence by 30-100% and remained elevated for 4-8 weeks post acute withdrawal. These results have important implications for understanding the characteristics and mechanisms underlying vulnerability to relapse.


The prevalence and interventions of xerosis cutis among older adults: A systematic review and meta-analysis.
Xerosis cutis in older adults is a geriatric public health issue that severely affects healthy aging, associated with adverse outcomes and increased nursing burden. Skin care plays a significant role in the management of xerosis cutis. To assess the pooled prevalence and interventions of xerosis cutis among older adults. We searched ten databases systematically from inception to August 29, 2023. We estimated pooled prevalence of xerosis cutis using Stata 15.0. 28 articles were included in this review. The pooled prevalence of xerosis cutis was 53 %(95 %CI:36-69 %). We found the prevalence of xerosis cutis was highest in nursing homes and developed countries. The prevalence of xerosis cutis was similar in males and females. The prevalence of mild xerosis cutis and xerosis cutis at lower limbs was relatively high. Regular use of humectant-containing leave-on skin care products and structured skin care regimens were helpful in alleviating xerosis cutis. Older adults are at high risk for xerosis cutis. The research provides health professionals with a basic framework for the prevention and management of xerosis cutis.


"I do the best I can": caregivers' perceptions of informal caregiving for older adults in Belize.
In this first study of informal caregiving for older adults in Belize, 29 caregivers described their experiences of caregiving, how they perceived and managed the role, and what critical resources they needed. The three main themes identified in the caregiver interviews were the experiences of caregivers, the rewards of caregiving, and navigating the caregiver role. Caregivers identified positively with the role of care provider and they did not describe it as burdensome nor did they describe role strain. However, caregivers' complaints of poor physical health might be construed as somatic expressions of strain. The caregivers' religiosity was salient to how they viewed and coped with their caregiver role. In conclusion, culture appears to influence positively caregivers' beliefs and perceptions of caregiving in Belize. However, the expected increase in the older population and current circumstances of many caregivers and care recipients means there is a critical need for resources to support caregivers and promote aging in place.


Spheroidal Fabry-Perot microcavities in optical fibers for high-sensitivity sensing.
All-optical-fiber Fabry-Perot interferometers (FPIs) with microcavities of different shapes were investigated. It was found that the size and shape of the cavity plays an important role on the performance of these interferometers. To corroborate the analysis, FPIs with spheroidal cavities were fabricated by splicing a photonic crystal fiber (PCF) with large voids and a conventional single mode fiber (SMF), using an ad hoc splicing program. It was found that the strain sensitivity of FPIs with spheroidal cavities can be controlled through the dimensions of the spheroid. For example, a FPI whose cavity had a size of ~10x60 μm exhibited strain sensitivity of ~10.3 pm/με and fringe contrast of ~38 dB. Such strain sensitivity is ~10 times larger than that of the popular fiber Bragg gratings (~1.2 pm/με) and higher than that of most low-finesse FPIs. The thermal sensitivity of our FPIs is extremely low (~1pm/°C) due to the air cavities. Thus, a number of temperature-independent ultra-sensitive microscopic sensors can be devised with the interferometers here proposed since many parameters can be converted to strain. To this end, simple vibration sensors are demonstrated.


Glucose activates ChREBP by increasing its rate of nuclear entry and relieving repression of its transcriptional activity.
Carbohydrate response element-binding protein (ChREBP) is a glucose-responsive transcription factor that activates genes involved in de novo lipogenesis in mammals. The current model for glucose activation of ChREBP proposes that increased glucose metabolism triggers a cytoplasmic to nuclear translocation of ChREBP that is critical for activation. However, we find that ChREBP actively shuttles between the cytoplasm and nucleus in both low and high glucose in the glucose-sensitive beta cell-derived line, 832/13. Glucose stimulates a 3-fold increase in the rate of ChREBP nuclear entry, but trapping ChREBP in the nucleus by mutagenesis or with a nuclear export inhibitor does not lead to constitutive activation. In fact, mutational studies targeting the nuclear export signal of ChREBP also identified a distinct function essential for glucose-dependent transcriptional activation. From this, we conclude that an additional event independent of nuclear translocation is required for activation. The N-terminal segment of ChREBP (amino acids 1-298) has previously been shown to repress activity under basal conditions. This segment has five highly conserved regions, Mondo conserved regions 1-5 (MCR1 to -5). Based on activating mutations in MCR2 and MCR5, we propose that these two regions act coordinately to repress ChREBP in low glucose. In addition, other mutations in MCR2 and mutations in MCR3 were found to prevent glucose activation. Hence, we conclude that both relief of repression and adoption of an activating form are required for ChREBP activation.


Does exercise program of endurance and strength improve health-related quality of life in persons living with HIV-related distal symmetrical polyneuropathy? A randomized controlled trial.
The most common HIV neurological comorbidity, Distal Symmetrical Peripheral Neuropathy (DSPN), is characterized by severe symptoms and reduced quality of life. Exercise has consistently been mentioned as one of the non-pharmacological therapies for the rehabilitation of individuals with HIV, but little is known about an exercise program to recommend to people living with HIV (PLWHIV)-related DSPN. The purpose of this study was to investigate the effectiveness of aerobic (AE) or progressive resisted exercise (PRE) on quality of life (QOL) in a person living with HIV-related DSPN. A randomized controlled trial was conducted with 136 persons living with HIV-related Neuropathy, including 6 domains of QOL within WHOQOL-BREF, 45 in the AE (used ergometer), 44 in the PRE (used quadriceps bench), and 47 in the control group (CG). The outcome measures (QOL) data were analyzed using the inferential statistic of Friedman for within-group with post hoc analysis of Wilcoxon signed Test. A Kruskal-Wallis test was carried out for between-groups with post hoc analysis of Mann-Whitney to find where significant differences exist. The results indicated significant differences within experimental groups in all six domains p < 0.05. Similarly, the result indicated significant differences within the CG in Physical, level of independence, and Spirituality/Religions domains (p = 0.002, p = 0.035, p = 0.006). However, the results indicated significant differences between experimental groups and CG. These findings indicated that strength and endurance exercise of moderate intensity have a positive effect on QOL in PLWHIV-related DSPN. Clinical trial No. http://apps.who.int/trialsearch/default.aspx (PACTR201707002173240).


Role of PARP inhibitors in cancer biology and therapy.
Deeper understanding of DNA repair mechanisms and their potential value as therapeutic targets in oncology heralded the clinical development of poly(ADP-ribose) polymerase (PARP) inhibitors. Although initially developed to exploit synthetic lethality in models of cancer associated with defective DNA repair, our burgeoning knowledge of PARP biology has resulted in these agents being exploited both in cancer with select chemotherapeutic agents and in non-malignant diseases. In this review article, we briefly review the mechanisms of DNA repair and pre-clinical development of PARP inhibitors before discussing the clinical development of the various PARP inhibitors in depth.


[The medical social characteristics of health of the early age children and their families].
The results of the comparative analysis of the life and health conditions of 1236 families of various types with early age children are presented. The data used consisted of medical documentation excerpts and mothers' sociological questioning. It is established that children from the families from risk group.


Molecular and pathological insights into Chlamydia pecorum-associated sporadic bovine encephalomyelitis (SBE) in Western Australia.
Despite its global recognition as a ruminant pathogen, cases of Chlamydia pecorum infection in Australian livestock are poorly documented. In this report, a C. pecorum specific Multi Locus Sequence Analysis scheme was used to characterise the C. pecorum strains implicated in two cases of sporadic bovine encephalomyelitis confirmed by necropsy, histopathology and immunohistochemistry. This report provides the first molecular evidence for the presence of mixed infections of C. pecorum strains in Australian cattle. Affected animals were two markedly depressed, dehydrated and blind calves, 12 and 16 weeks old. The calves were euthanized and necropsied. In one calf, a severe fibrinous polyserositis was noted with excess joint fluid in all joints whereas in the other, no significant lesions were seen. No gross abnormalities were noted in the brain of either calf. Histopathological lesions seen in both calves included: multifocal, severe, subacute meningoencephalitis with vasculitis, fibrinocellular thrombosis and malacia; diffuse, mild, acute interstitial pneumonia; and diffuse, subacute epicarditis, severe in the calf with gross serositis. Immunohistochemical labelling of chlamydial antigen in brain, spleen and lung from the two affected calves and brain from two archived cases, localised the antigen to the cytoplasm of endothelium, mesothelium and macrophages. C. pecorum specific qPCR, showed dissemination of the pathogen to multiple organs. Phylogenetic comparisons with other C. pecorum bovine strains from Australia, Europe and the USA revealed the presence of two genetically distinct sequence types (ST). The predominant ST detected in the brain, heart, lung and liver of both calves was identical to the C. pecorum ST previously described in cases of SBE. A second ST detected in an ileal tissue sample from one of the calves, clustered with previously typed faecal bovine isolates. This report provides the first data to suggest that identical C. pecorum STs may be associated with SBE in geographically separated countries and that these may be distinct from those found in the gastrointestinal tract. This report provides a platform for further investigations into SBE and for understanding the genetic relationships that exist between C. pecorum strains detected in association with other infectious diseases in livestock.


Factors affecting mortality of critical care trauma patients.
Critically-ill trauma patients have a high mortality. To study the factors affecting the mortality of ICU trauma patients treated at Al-Ain Hospital, United Arab Emirates (UAE). All trauma patients who were admitted to the ICU were prospectively collected over three years (2003-2006). Univariate and multivariate analysis were used to compare patients who died and who did not. Gender, age, nationality, mechanism of injury, systolic blood pressure and GCS on arrival, the need for ventilation, presence of head or chest injuries, AIS for the chest and head injuries and the ISS were studied. There were 202 patients (181 males). The most common mechanism of injury was road traffic collisions (72.3 %). The overall mortality was 13.9%. A direct logistic regression model has shown that factors that affected mortality were decreased GCS (p < 0.0001), mechanism of injury (p = 0.004) with burns having the highest mortality, increased age (p = 0.004), and increased ISS (p = 0.02). The best GCS that predicted mortality was 5.5 while the best ISS that predicted mortality was 13.5. Road traffic collision is the most common cause of serious trauma in UAE followed by falls. Decreased GCS was the most significant factor that predicted mortality in the ICU trauma patients.


Observational pain assessment scales for people with dementia: a review.
Dementia may alter the experience of pain and the ability to communicate it; this will, in turn, result in poor pain detection and inadequate treatment. The aim of this literature review is to identify the observational pain scales that have clinical utility and feasibility for use with people living with dementia in the community by district nurses in their daily practice. It was found that a consensus could not be reached on which tool to use in clinical practice. A further evaluation of the Non-communicative Patients Pain Assessment Instrument has improved its feasibility for use in the community environment, as it can be administered by family carers. This literature review concludes that observational pain scales need to be validated for use in the community and that there is a need to consider the involvement of the informal carer in the assessment of pain.


Assembly of influenza hemagglutinin trimers and its role in intracellular transport.
The hemagglutinin (HA) of influenza virus is a homotrimeric integral membrane glycoprotein. It is cotranslationally inserted into the endoplasmic reticulum as a precursor called HA0 and transported to the cell surface via the Golgi complex. We have, in this study, investigated the kinetics and cellular location of the assembly reaction that results in HA0 trimerization. Three independent criteria were used for determining the formation of quaternary structure: the appearance of an epitope recognized by trimer-specific monoclonal antibodies; the acquisition of trypsin resistance, a characteristic of trimers; and the formation of stable complexes which cosedimented with the mature HA0 trimer (9S20,w) in sucrose gradients containing Triton X-100. The results showed that oligomer formation is a posttranslational event, occurring with a half time of approximately 7.5 min after completion of synthesis. Assembly occurs in the endoplasmic reticulum, followed almost immediately by transport to the Golgi complex. A stabilization event in trimer structure occurs when HA0 leaves the Golgi complex or reaches the plasma membrane. Approximately 10% of the newly synthesized HA0 formed aberrant trimers which were not transported from the endoplasmic reticulum to the Golgi complex or the plasma membrane. Taken together the results suggested that formation of correctly folded quaternary structure constitutes a key event regulating the transport of the protein out of the endoplasmic reticulum. Further changes in subunit interactions occur as the trimers move along the secretory pathway.


[Magnesium homeostasis and its disturbances].
Magnesium homeostasis is maintained through normal functions of the kidney, intestine, and bone. In the kidney, approximately 80% magnesium is filtered by the glomeruli. In general, 95% filtered magnesium is collectively reabsorbed in the proximal tubule (15%-20%) , thick ascending limb of Henle (TAL, 65%-75%) , and the distal convoluted tubule (DCT, 5%-10%) . In the TAL, magnesium reabsorption regulated by the paracellular pathway via claudin-16 is driven by electrochemical voltage. Chloride channel Kb and renal outer medullary potassium channels control this lumen-positive voltage. In the DCT, the transcellular pathway via transient receptor potential melastatin 6 (TRPM6) plays a fundamental role in the final 5%-10% magnesium reabsorption. The functions of TRPM6 depend on Na-Cl co-transporters and Na( + )-K( + )-ATPase. Defects in these regulatory proteins may cause inherited or drug-induced disorders of magnesium metabolism. Recently, some proteins have been confirmed to be responsible for magnesium homeostasis ; however, further research is required to elucidate the mechanisms underlying the maintenance of magnesium homeostasis.


[Toxicity thresholds and predicted model of Pb added to soils with various properties and its leaching factors as determined by barley root-elongation test].
Ten field soils with various properties were added with Pb at 8 levels, and treated with or without leaching using simulated rain to test the Pb toxicity threshold (EC10, EC50) according to the ISO 11269-1 root elongation toxicity testing method. The leaching factors of Pb toxicity to barley root elongation were determined and the predicted models of Pb toxicity thresholds in soils with various properties were developed. The results indicated that the determined toxicity threshold (EC10, EC50) of Pb varied significantly (P<0.01) among the soils, and the EC10 and EC50 of Pb to barley in the soils ranged from 300-4130 mg . kg-1 and 55-633 mg . kg-1, respectively. The Pb toxicity decreased sharply after leaching treatment. The determined leaching factors (LF) ranged from 0.96-1.96 (LFEC50) and 1.03-1.81 (LFEC10) respectively, and the obvious effect was observed for the Pb toxicity decreasing in the soils with pH<6.81. The predicted models for Pb toxicity thresholds in soils were developed based on main soil properties (soil pH, organic carbon content and cation exchange capacity), and the determined Pb toxicity thresholds (ECx, x = 10,50) in soils fell in the range of mean values with ± 2 standard error (SD) prediction interval for the leached and unleached soils except for the red soil of Jiangxi Province, which indicated that the models based on the main soil properties could well predict the Pb toxicity in soils with various soil properties.


The discrepancy between actigraphic and sleep diary measures of sleep in adolescents.
To explore the discrepancy between sleep diary and actigraphic measures of sleep in adolescents and to ascertain whether these discrepancies may vary according to characteristics of the participant. Participants were 385 adolescents aged 13-18years (X=15.6, standard deviation [SD]=0.95; 60% male) from eight high schools in South Australia. Adolescents completed the School Sleep Habits Survey and Pediatric Daytime Sleepiness Scale during class time, followed by an 8-day sleep diary and wrist actigraphy. The Flinders Fatigue Scale was completed on the final day of the study. Parents completed a sleep, medical, education, and family history survey. Actigraphic estimates of wake after sleep onset (WASO) were substantially greater than sleep diary estimates (74min actigraphy vs. 7min sleep diary) and actigraphic estimates of total sleep time were substantially less than sleep diary and parent report (6h 51min actigraphy vs. 8h 16min sleep diary vs. 8h 51 parent report). Actigraphy displayed no significant relationship with daytime functioning and weak relationships with concomitantly recorded sleep diary variables. Sex and puberty-related differences in actigraphic scoring were found, with more WASO and less sleep scored in boys compared to girls and more WASO scored amongst pubertally-mature boys than boys of less advanced pubertal development. There may be differences in the sleep of adolescents that result in less actigraphic total sleep scored than perceived, particularly in boys, possibly because of increased sleep motor activity in adolescents that actigraphic algorithms score as wake. This is a significant concern that requires further examination with polysomnography.


Survival and Progression in Synucleinopathy Phenotypes With Parkinsonism: A Population-Based Study.
To compare survival by the presenting parkinsonism symptoms at diagnosis among patients with incident clinically diagnosed synucleinopathies. Using the Rochester Epidemiology Project medical records-linkage system, we identified all persons residing in Olmsted County, Minnesota, who received a diagnostic code of parkinsonism from January 1, 1991, through December 31, 2010. A movement disorder specialist reviewed the complete medical records of each individual to confirm the presence of parkinsonism, determine the type of synucleinopathy, and identify the onset dates of each cardinal symptom (tremor at rest, bradykinesia, rigidity, and impaired postural reflexes). We determined the median time from age at diagnosis to death or censoring (June 30, 2015) for each presenting symptom and the age- and sex-adjusted risk of death. From 1991 through 2010, a total of 433 individuals had a synucleinopathy diagnosed (301 [69.5%], Parkinson disease; 68 [15.7%], dementia with Lewy bodies; 52 [12.0%], Parkinson disease dementia; and 12 [2.8%], multiple systems atrophy with parkinsonism). Overall, the risk of death in the tremor-predominant group was less than that in the bradykinesia/rigidity-only group (hazard ratio [HR], 0.59; 95% CI, 0.40-0.87; P=.007). Similarly, risk of death in the bradykinesia/rigidity-only group was significantly greater than in the tremor-predominant group (HR, 1.75; 95% CI, 1.23-2.51; P=.002) and compared with tremor before bradykinesia (HR, 1.75; 95% CI, 1.24-2.47; P=.001). Patients with tremor as a presenting symptom have longer survival. In contrast, the presence of bradykinesia/rigidity as a presenting symptom correlates with reduced survival across all types of synucleinopathies.


Role of guanine-nucleotide exchange factor Epac in renal physiology and pathophysiology.
Exchange proteins directly activated by cAMP [Epac(s)] were discovered more than a decade ago as new sensors for the second messenger cAMP. The Epac family members, including Epac1 and Epac2, are guanine nucleotide exchange factors for the Ras-like small GTPases Rap1 and Rap2, and they function independently of protein kinase A. Given the importance of cAMP in kidney homeostasis, several molecular and cellular studies using specific Epac agonists have analyzed the role and regulation of Epac proteins in renal physiology and pathophysiology. The specificity of the functions of Epac proteins may depend upon their expression and localization in the kidney as well as their abundance in the microcellular environment. This review discusses recent literature data concerning the involvement of Epac in renal tubular transport physiology and renal glomerular cells where various signaling pathways are known to be operative. In addition, the potential role of Epac in kidney disorders, such as diabetic kidney disease and ischemic kidney injury, is discussed.


Exploiting class activation mappings as prior to generate fetal brain ultrasound images with GANs.
The identification of fetal-head standard planes (FHSPs) from ultrasound (US) images is of fundamental importance to visualize cerebral structures and diagnose neural anomalies during gestation in a standardized way. To support the activity of healthcare operators, deep-learning algorithms have been proposed to classify these planes. To date, the translation of such algorithms in clinical practice is hampered by several factors, including the lack of large annotated datasets to train robust and generalizable algorithms. This paper proposes an approach to generate synthetic FHSP images with conditional generative adversarial network (cGAN), using class activation maps (CAMs) obtained from FHSP classification algorithms as cGAN conditional prior. Using the largest publicly available FHSP dataset, we generated realistic images of the three common FHSPs: trans-cerebellum, trans-thalamic and trans-ventricular. The evaluation through t-SNE shows the potential of the proposed approach to attenuate the problem of limited availability of annotated FHSP images.


Subcutaneous administration of drugs in palliative care: results of a systematic observational study.
Especially in palliative care, safe and manageable administration of medication is essential. Subcutaneous drug administration is a possible alternative, when oral intake is hampered. However, evidence for this method is rare. This observational study assessed the clinical practice of subcutaneous drug administration, focusing on the evaluation of local reactions or complications to further develop recommendations. Over 14 months, patients in a specialized inpatient palliative care unit treated by the subcutaneous route were invited to participate in this clinical study. All subcutaneous medications including dosage and volume of injection, type of needles, and injection site were documented. The injection sites were systematically assessed including the subjective perceptions of patients for analysis of patient tolerability and acceptability. T-tests and Chi-squared tests of these variables were performed to calculate group differences between needles with vs. without complications (P < 0.05). In 120 patients, 3957 applications were administered via 243 needles. The needles were placed in thighs (38.7%) and upper arms (28.8%). Most frequently used medications were hydromorphone (59.0%), haloperidol (12.3%), and midazolam (8.3%). Complications were diagnosed most often on the third or fourth day of the needle in situ and occurred significantly more often in (fully) active patients and patients transferred or discharged at the end of treatment. The mean time of needle in situ was significantly lower (4.1 vs. 5.0 days) in complication cases than in noncomplication cases (t-test: P = 0.027). The results of this study acknowledge the clinical practice of subcutaneous administration of medication as a very flexible, broadly feasible, rather safe, and nonburdensome method. Nevertheless, this practice is not free from complications, needs appropriate nursing care, and requires standardized policies and procedures.


Are schools shortchanging boys or girls? The answer rests on methods and assumptions: reply to Card (2014) and Penner (2014).
Our target article (Robinson-Cimpian, Lubienski, Ganley, & Copur-Gencturk, 2014) used nationally representative data to examine the development of gender gaps in math achievement. We found that when boys and girls demonstrate equivalent math test performance and are perceived by their teachers to be equally well behaved and engaged with the material, teachers tend to rate girls as less proficient in math than boys (Study 1). Moreover, this underrating of girls' proficiency appeared to contribute substantially to a widening gender gap in early elementary school (Study 2). In this response, we use the thoughtful comments of Card (2014) and Penner (2014) as a springboard for discussing the methodologies and assumptions of some of the most recent research using nationally representative data to explore gender inequities. In the process, we shed light on how recent works using the same data reach different conclusions. We also make recommendations regarding the use of such data for understanding the development of the gender gap and for designing effective interventions.


A small-molecule screen identifies new functions for the plant hormone strigolactone.
Parasitic weeds of the genera Striga and Orobanche are considered the most damaging agricultural agents in the developing world. An essential step in parasitic seed germination is sensing a group of structurally related compounds called strigolactones that are released by host plants. Although this makes strigolactone synthesis and action a major target of biotechnology, little fundamental information is known about this hormone. Chemical genetic screening using Arabidopsis thaliana as a platform identified a collection of related small molecules, cotylimides, which perturb strigolactone accumulation. Suppressor screens against select cotylimides identified light-signaling genes as positive regulators of strigolactone levels. Molecular analysis showed strigolactones regulate the nuclear localization of the COP1 ubiquitin ligase, which in part determines the levels of light regulators such as HY5. This information not only uncovers new functions for strigolactones but was also used to identify rice cultivars with reduced capacity to germinate parasitic seed.


Differential sensitivity to lung tumorigenesis following transplacental exposure of mice to polycyclic hydrocarbons, heterocyclic amines, and lung tumor promoters.
Research conducted by this laboratory over the past decade has demonstrated the high susceptibility of the fetus to lung tumor formation following in utero exposure of the resistant C57BL/6 and DBA/2N strains of mice to 3-methylcholanthrene (MC). In this review, we describe our more recent studies on the effects of MC and cotreatment with the lung tumor promoter, butylated hydroxytoluene (BHT), on lung tumor formation in the intermediately susceptible BALB/c strain of mice, and the determination of the potential carcinogenicity of the heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in resistant mouse strains. BALB/c mice showed a similar incidence of lung tumors, both in terms of percentage of mice with tumors and number of tumors per mouse, as found in the resistant [D2 x B6D2F1]F2 mice. Ki-ras point mutations were found in 56% (20/36) of BALB/c lung lesions compared with an incidence of 79% in [D2 x B6D2F1]F2 mice. BALB/c lung lesions demonstrated a similar association of Ki-ras mutations with tumor stage. Interestingly, a strain-dependent difference was observed in the mutational spectrum, where 62% and 38% of the lesions in BALB/c mice exhibited G-->C and G-->T transversions, respectively, in contrast with the 16% and 84% incidences observed in [D2 x B6D2F1]F2 mice. BHT had no statistically significant effect on tumor incidence, multiplicity, or Ki-ras mutational spectrum in BALB/c mice treated in utero with MC, although a trend toward increased tumor multiplicity was observed. Finally, experiments initiated to assess the transplacental carcinogenicity of IQ in D2B6F1 mice demonstrated that 1 year after birth, no macroscopically or microscopically visible liver, lung, or colon tumors were found in the transplacentally treated offspring, nor was induction of Cyp1a1, Cyp1b1, or glutathione S-transferases (GSTs) in fetal lung and liver tissues observed. This implies that at least under these experimental conditions, IQ may not be an important transplacental carcinogen. Overall, these data demonstrate that mutagenic damage to Ki-ras is a critical early event mediating murine lung tumorigenesis in both sensitive and resistant strains. Strain-dependent differences in the Ki-ras mutational spectrum may be associated with their differential susceptibility to lung tumor initiation.


Loss of DNA mismatch repair protein hMSH6 in ovarian cancer is histotype-specific.
Microsatellite instability (MSI) due to defects in DNA mismatch repair genes may be involved in the development of a subset of human ovarian carcinomas. The role of one such gene, hMSH6, in ovarian cancer is not well documented. We investigated the expression of hMSH6 protein in different histotypes of ovarian carcinoma and the associations between loss of hMSH6 protein and tumor grade, disease stage, familial history of cancer and patient survival. We stained an ovarian carcinoma tissue microarray consisting of formalin-fixed, paraffin-embedded tissue samples from 322 patients with an anti-hMSH6 antibody and scored the results semiquantitatively as negative or positive. Twelve cases were excluded owing to loss of cores during staining. Absence of hMSH6 protein was noted in 20 of 230 serous carcinomas (8.7%), in 7 of 16 clear cell carcinomas (43.7%), in 4 of 34 endometrioid carcinomas (11.7%), in 1 of 14 malignant mixed Müllerian tumors, 2 of 6 mucinous carcinomas, 0 of 2 transitional cell carcinomas and in 0 of 8 undifferentiated carcinomas. Loss of hMSH6 protein was not associated with survival, patient age, tumor grade, or disease stage but was associated with clear cell, mucinous and endometrioid carcinoma histology (P<0.007). These findings indicate that loss of hMSH6 expression in ovarian carcinoma is more common in certain histologic subtypes, particularly in clear cell, endometrioid, and mucinous carcinoma, suggesting that loss of hMSH6 function may participate in the pathogenesis of these subtypes of cancer. Loss of hMSH6 expression did not predict survival and was not associated with disease stage, tumor grade, patient age or family history of cancer.


T-derived colony-inhibiting activity: partial characterization and mechanism of action.
A soluble inhibitor of granulocyte macrophage colony growth, to which we shall refer to as T-derived colony-inhibiting activity (Td/CIA), was obtained from the supernatant of T cells from 5 healthy donors and 5 patients with severe aplastic anemia (SAA) in remission, following immunosuppressive therapy. The supernatants were purified by an ACA 44 column and the suppressor activity found in fractions of 70,000-80,000 daltons. Experiments were then performed to test for endogenous productions of Td/CIA in normal marrow cells (NBM), reversibility of suppression, and competitive inhibition with human placenta-conditioned medium (HPCM). The results of this study can be summarized as follows: the endogenous production of Td/CIA can be elicited by addition of mitogens to NBM, and is prevented if the marrow is T-depleted or treated with cyclosporin A; suppression is completely reversible if Td/CIA is removed from NBM by washing at 1, 48, 72 and 96 h; CFU-c which have been exposed to Td/CIA once, and freed from Td/CIA by washing, are still sensitive to a second exposure of Td/CIA; there is no clear competitive inhibition between Td/CIA and HPCM. These experiments represent an in vitro model of a lymphokine-mediated regulation of CFU-c growth not associated with death of progenitor cells.


Relief of gastrointestinal symptoms by correcting insulin excess.
Persons with diabetes mellitus often have disordered gastrointestinal function, usually attributed to autonomic neuropathy. Hypoglycemia in persons taking insulin has been considered a possible result of anorexia and gastric atony, but not a potential cause of gastrointestinal symptoms. Three patients with diabetes developing before age 30 yr and of long duration had severe gastrointestinal complaints for 1-9 mo, with symptoms suggesting nocturnal hypoglycemia. All recovered rapidly with no specific treatment other than reduction of insulin doses. Studies identified no gastrointestinal pathology. These patients may represent a subgroup of persons with diabetic enteropathy, in whom recurrent hypoglycemia provokes a reversible derangement of gut function with accompanying symptoms.


Neonatal jaundice among Nigerian preterm infants.
Jaundice among Nigerian preterm infants under special care was studied to determine the incidence of clinical jaundice, the predisposing factors and outcome among those with significant hyperbilirubinaemia (SBR greater than or equal to 10mg/dl). The incidence of jaundice among 292 preterm infants over an 18-month period was 71.2%. The male: female ratio was 1:1.04. Of the 74 infants with serum bilirubin 10mg/dl or more, prematurity alone was the identified cause in 44 (59.5%), Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and septicaemia were the only additional factors in 13 (17.6%) and 7 (9.5%) respectively, while multiple aetiological factors (prematurity, septicaemia and G-6-PD deficiency) were identified in six (8.1%) of the babies. Septicaemia was associated with higher mean bilirubin levels and the highest mortality. The two kernicteric infants in the study had septicaemia. Thus, the single most important cause of jaundice was prematurity. G-6-PD deficiency alone did not appear to increase the incidence and severity of hyperbilirubinaemia in this study. Septicaemia should be suspected and promptly treated in order to reduce mortality and risk of kernicterus among preterm infants with hyperbilirubinaemia.


Inhibition of Aurora A and Aurora B Is Required for the Sensitivity of HPV-Driven Cervical Cancers to Aurora Kinase Inhibitors.
The activity and efficacy of Aurora inhibitors have been reported in a wide range of cancer types. The most prominent Aurora inhibitor is alisertib, an investigational Aurora inhibitor that has been the subject of more than 30 clinical trials. Alisertib has inhibitory activity against both Aurora A and B, although it is considered to be primarily an Aurora A inhibitor in vivo Here, we show that alisertib inhibits both Aurora A and B in vivo in preclinical models of HPV-driven cervical cancer, and that it is the inhibition of Aurora A and B that provides the selectivity and efficacy of this drug in vivo in this disease setting. We also present formal evidence that alisertib requires progression through mitosis for its efficacy, and that it is unlikely to combine with drugs that promote a G2 DNA damage checkpoint response. This work demonstrates that inhibition of Aurora A and B is required for effective control of HPV-driven cancers by Aurora kinase inhibitors. Mol Cancer Ther; 16(9); 1934-41. ©2017 AACR.


The relationship between second language acquisition and nonverbal cognitive abilities.
We monitored the progress of 40 children when they first started to acquire a second language (L2) implicitly through immersion. Employing a longitudinal design, we tested them before they had any notions of an L2 (Time 0) and after 1 school year of L2 exposure (Time 1) to determine whether cognitive abilities can predict the success of L2 learning. Task administration included measures of intelligence, cognitive control, and language skills. Initial scores on measures of inhibitory control seemed predictive of L2 Dutch vocabulary acquisition. At the same time, progress on IQ, inhibitory control, attentional shifting, and working memory were also identified as contributing factors, suggesting a more intricate relationship between cognitive abilities and L2 learning than previously assumed. Furthermore, L1 development was mainly predicted by performance on inhibitory control and working memory. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Data access for the 1,000 Plants (1KP) project.
The 1,000 plants (1KP) project is an international multi-disciplinary consortium that has generated transcriptome data from over 1,000 plant species, with exemplars for all of the major lineages across the Viridiplantae (green plants) clade. Here, we describe how to access the data used in a phylogenomics analysis of the first 85 species, and how to visualize our gene and species trees. Users can develop computational pipelines to analyse these data, in conjunction with data of their own that they can upload. Computationally estimated protein-protein interactions and biochemical pathways can be visualized at another site. Finally, we comment on our future plans and how they fit within this scalable system for the dissemination, visualization, and analysis of large multi-species data sets.


Hyperspectral fluorescence lidar imaging at the Colosseum, Rome: elucidating past conservation interventions.
Fluorescence lidar techniques offer considerable potential for remote, non-invasive diagnostics of stone cultural heritage in the outdoor environment. Here we present the results of a joint Italian-Swedish experiment, deploying two hyperspectral fluorescence lidar imaging systems, for the documentation of past conservation interventions on the Colosseum, Rome. Several portions of the monument were scanned and we show that it was possible to discriminate among masonry materials, reinforcement structures and protective coatings inserted during past conservation interventions, on the basis of their fluorescence signatures, providing useful information for a first quick, large-scale in situ screening of the monument.