Effects of a culturally tailored physical activity promotion program on selected self-regulation skills and attitudes in adolescents of an underserved, multiethnic milieu.
To implement a culturally tailored physical activity (PA) promotion program (FunAction) and to assess its impact on five self-regulation skills and attitudes in adolescents. Design . The design and implementation of the FunAction program were informed by social marketing principles. The study used a quasi-experimental approach to assess the impact of the program on specific outcome variables. A multiethnic, underserved middle school in Montreal, Quebec, Canada. The intervention group was made up of grade 8 students (n = 165) and the control group was made up of grade 7 students (n = 137). During the 16-week intervention, adolescents were able to choose from a variety of 45-minute cardiovascular PAs offered daily during their school lunch period. Adolescents participated in the activities on a voluntary basis. A self-report questionnaire was administered preintervention and postintervention to measure adolescents' scores on the following self-regulation skills and attitudes: self-control, self-esteem, attention/concentration, social competence, and interethnic relationships. Three-way repeated measures analyses of variance and correlational analyses were used. Results . A significant improvement was observed only in attention/concentration. Girls' attention/concentration scores improved significantly in the intervention group compared to the control group (F(1,127) = 16.26, p < .001). The improvement in attention/concentration scores for boys in the intervention group was correlated with their frequency of participation in the program PAs (r = .24, p = .008). Using social marketing principles can help encourage adolescents from underserved, multiethnic milieus to participate in PA during their school lunch hour. Furthermore, voluntary participation in a culturally tailored PA program can improve youths' attention/concentration.


Calmodulin inhibitor trifluoperazine attenuates the development and expression of morphine-induced conditioned place preference in rats.
The effect of trifluoperazine, a calmodulin inhibitor, on morphine-induced conditioned place preference was examined in rats. Morphine (5, 10 mg/kg, i.p.) produced significant place preference for the drug-associated place. Trifluoperazine significantly suppressed the development as well as the expression of morphine-induced place preference in a dose-dependent manner, but it neither produced place preference or aversion, nor affected locomotor activity. Injection of 0.5 and 1.0 mg/kg apomorphine, a dopamine receptor agonist, did not alter the inhibition by trifluoperazine of morphine-induced place preference. Verapamil, at the dose that failed to change the place preference induced by morphine, enhanced the inhibition by trifluoperazine of morphine-induced place preference. These findings provide the first demonstration that trifluoperazine attenuates morphine-induced conditioned place preference in rats. The action of trifluoperazine might be produced through its inhibition of calmodulin, but is probably not related to dopamine receptor blockade.


Inhaled corticosteroid use and outcomes in pregnancy.
Current asthma management guidelines recommend aggressive asthma treatment for women who are pregnant. To examine asthma medication use and asthma-related health care use before and during pregnancy. Women aged 15 to 45 years with a pregnancy claim (index event) and an asthma claim (diagnosis or asthma medication prescription) were identified from a database of US managed care organizations (PharMetrics Patient-Centric Database). Medical claims 6 months before and after the index event were studied to determine the impact of pregnancy on asthma medication use (ie, prescription claims) and asthma-related physician visits, emergency department (ED) visits, and hospitalizations. Of 7,235 women with a pregnancy claim and 6 months of preindex and postindex data, 633 had an asthma claim (334 had an asthma-related medication claim and 299 had no asthma-related medication claim before the index event). During the preindex period, 142 patients were using asthma controller medications, with inhaled corticosteroids (ICSs) the most commonly used controller (n = 101); 283 were using short-acting beta2-adrenergic agonists (SABAs) with or without controllers. Among the 334 patients using asthma medication before pregnancy, the number using any controller decreased from 142 to 94 (-34%), those using ICSs decreased from 101 to 65 (-36%), and those using SABAs decreased from 283 to 137 (-52%) after the pregnancy claim. For these 334 patients, the number with an asthma-related ED visit increased from 14 to 17 (21%) after the pregnancy claim. Among those without a pharmacy record of medication use before pregnancy (n = 299), the number with an asthma-related ED visit increased from 4 to 7 (75%) after the pregnancy claim. For the 101 patients using ICSs before pregnancy, the number with an asthma-related physician visit decreased from 39 to 25 (-36%) and the number with an ED visit was unchanged. For the 532 patients not using an ICS before pregnancy, the number with an asthma-related physician visit increased from 84 to 107 (27%) and the number with an ED visit increased from 12 to 18 (50%). For patients using an ICS before pregnancy, the rate of asthma-related physician visits decreased and the number of ED visits was unchanged after pregnancy, whereas physician and ED visits increased after pregnancy for patients not using an ICS before pregnancy. Overall, the data suggest that asthma is undertreated in women contemplating pregnancy and in those who are pregnant.


Optimization of Salmonella detection in garlic, onion, cinnamon, red chili pepper powders and green tea.
Salmonella is the causative agent of many outbreaks related to spice consumption. However, because of the antimicrobial properties of various spices which hinders recovery and detection, Salmonella detection in spices remains a challenge. The objective of this study was to optimize an enrichment broth for Salmonella growth in different spices and tea, in order to maintain an adequate pH and decrease the antimicrobial effects of spices during Salmonella enrichment and subsequent detection. Salmonella contaminated spice and tea dried samples were prepared and the detection of Salmonella was assessed using the developed broth and automated DNA extraction and RT-PCR. Double strength Buffered Peptone Water (BPW) was used to maintain pH, and L-cysteine and DL-serine were added to the broth to reduce the effects of antimicrobial compounds in spices. The modified enrichment broth allowed the growth of Salmonella from each spice sample. Sample to broth ratios varied from 1:9 (garlic powder, chili peppers and tea), to 1:20 (cinnamon). The pH value of each enrichment varied but remained above 4.8. The addition of L-cysteine (30 mmol/L) allowed Salmonella recovery and growth in garlic and onion samples and the addition of DL-serine (11.23 mmol/L) allowed the recovery and growth in cinnamon. The results indicated that Salmonella detection was achieved in <24 h in the modified (BPW + L-cysteine and DL-serine) enrichment broth followed by detection by RT-PCR. This protocol could allow for a more rapid, robust, and sensitive enrichment method for Salmonella in spices.


Reduction of vasoconstriction mediated by neuropeptide Y Y2 receptors in arterioles of the guinea-pig small intestine.
Brief applications of a high-K+ solution were used to evoke transient constrictions of arterioles from the guinea-pig small intestine. Analogues of neuropeptide Y (NPY) selective for Y2-receptors reduced the constrictions, whereas NPY or a Y1-selective analogue potentiated the constrictions. We conclude that arteriolar smooth muscle has both Y1 and Y2 receptors, and suggest that Y2 receptors inhibit vasoconstriction by modulating the opening of voltage-sensitive Ca2+ channels. This may be related to the role of NPY that is present in some vasodilator nerves.


Phosphorylation of branched-chain 2-oxo acid dehydrogenase complex in isolated hepatocytes.
Hepatocytes, isolated from rats fed a low-protein diet, were incubated with [32P]Pi and the phosphoproteins analysed. Immunoprecipitation using antibody against El of branched-chain 2-oxo acid dehydrogenase complex demonstrated phosphorylation of the alpha-subunit of El. Analysis of the tryptic phosphopeptides from the alpha-subunit indicated that two sites were phosphorylated. 4-methyl 2-oxopentanoate and DL-2-chloro 4-methylpentanoate decreased labelling of both sites. No major direct effects of several hormones on phosphorylation of branched-chain 2-oxo acid dehydrogenase was observed.


A transformer-based hierarchical registration framework for multimodality deformable image registration.
Deformable image registration (DIR) between daily and reference images is fundamentally important for adaptive radiotherapy. In the last decade, deep learning-based image registration methods have been developed with faster computation time and improved robustness compared to traditional methods. However, the registration performance is often degraded in extra-cranial sites with large volume containing multiple anatomic regions, such as Computed Tomography (CT)/Magnetic Resonance (MR) images used in head and neck (HN) radiotherapy. In this study, we developed a hierarchical deformable image registration (DIR) framework, Patch-based Registration Network (Patch-RegNet), to improve the accuracy and speed of CT-MR and MR-MR registration for head-and-neck MR-Linac treatments. Patch-RegNet includes three steps: a whole volume global registration, a patch-based local registration, and a patch-based deformable registration. Following a whole-volume rigid registration, the input images were divided into overlapping patches. Then a patch-based rigid registration was applied to achieve accurate local alignment for subsequent DIR. We developed a ViT-Morph model, a combination of a convolutional neural network (CNN) and the Vision Transformer (ViT), for the patch-based DIR. A modality independent neighborhood descriptor was adopted in our model as the similarity metric to account for both inter-modality and intra-modality registration. The CT-MR and MR-MR DIR models were trained with 242 CT-MR and 213 MR-MR image pairs from 36 patients, respectively, and both tested with 24 image pairs (CT-MR and MR-MR) from 6 other patients. The registration performance was evaluated with 7 manually contoured organs (brainstem, spinal cord, mandible, left/right parotids, left/right submandibular glands) by comparing with the traditional registration methods in Monaco treatment planning system and the popular deep learning-based DIR framework, Voxelmorph. Evaluation results show that our method outperformed VoxelMorph by 6 % for CT-MR registration, and 4 % for MR-MR registration based on DSC measurements. Our hierarchical registration framework has been demonstrated achieving significantly improved DIR accuracy of both CT-MR and MR-MR registration for head-and-neck MR-guided adaptive radiotherapy.


Neural representations of ensemble coding in the occipital and parietal cortices.
The human visual system is able to extract summary statistics from sets of similar items, but the underlying neural mechanism remains poorly understood. Using functional magnetic resonance imaging (fMRI) and an encoding model, we examined how the neural representation of ensemble coding is constructed by manipulating the task-relevance of ensemble features. We found a gradual increase in orientation-selective responses to the mean orientation of multiple stimuli along the visual hierarchy only when these orientations were task-relevant. Such responses to the ensemble orientation were present in the extrastriate area, V3, even when the mean orientation was not task-relevant, indicating that the ensemble representation can co-exist with the task-relevant individual feature representation. Ensemble orientations were also represented in frontal regions, but those representations were robust only when each mean orientation was linked to a motor response dimension. Together, our findings suggest that the neural representation of the ensemble percept is formed by pooling signals at multiple levels of the visual processing stream.


Neurons in the deep layers of superior colliculus play a critical role in the neuronal network for audiogenic seizures: mechanisms for production of wild running behavior.
Recent investigations suggest that the deep layers of superior colliculus (DLSC) play a role in the neuronal network for audiogenic seizures (AGS). The present study examined DLSC neuronal firing and convulsive behavior simultaneously in freely-moving genetically epilepsy-prone rats (GEPR-9s) using chronically implanted microwire electrodes. An abrupt onset of acoustically-evoked firing at approximately 80-90 dB was observed in DLSC neurons of GEPR-9s, which was significantly above the normal threshold. DLSC neurons began to exhibit rapid tonic burst firing 1-2 s prior to the onset of the wild running behavior at the beginning of AGS. As the tonic phase of the seizure began, DLSC firing ceased, and only returned towards normal following post-ictal depression. These neuronal mechanisms may be relevant to other seizure models in which the DLSC is implicated. The temporal pattern of neuronal firing during AGS is specific to DLSC and differs markedly from those observed elsewhere in the AGS neuronal network. The temporal firing pattern suggests that the DLSC plays a primary role in the generation of the wild running phase of AGS. Previous studies indicate that the inferior colliculus is dominant during AGS initiation, and the pontine reticular formation is dominant during the tonic extension phase of AGS. Taken together these data suggest that the neurons in the neuronal network undergo a dominance shift as each specific convulsive behavior of AGS is elaborated.


Collection and transportation system construction of potentially viral municipal solid waste during the COVID-19 pandemic in China.
The transmission route of COVID-19 through municipal solid waste (MSW) has been confirmed and receives increasing attention. Potentially viral municipal solid waste (PVMSW) refers to the domestic waste generated by risky areas and epidemic-related populations under a major epidemic in their daily lives or in activities that provide services for their daily lives. For its potential infectivity, PVMSW should be properly collected and transported. This study aimed to standardize the collection and transportation of PVMSW and proposed specific construction schemes of PVMSW collection and transportation systems for three situations which were city-wide lockdown status, medium and high-risk area, and home quarantine separately. In the cases of city-wide lockdown status and home quarantine, PVMSW collection and transportation systems were constructed qualitatively with the examples of Wuhan and Shanghai respectively, and in the case of medium and high-risk area, the systems were constructed quantitatively through the development of a waste collection and transportation costs model. To reduce the risks of virus transmission during the collection and transportation process, the collection and transportation links should be minimized. For the disposal of PVMSW, medical waste treatment facilities and MSW incineration plants should be prioritized. Furthermore, the results showed that the total number of people and the transfer capacity of MSW transfer facility were the two main influencing factors for the selection of PVMSW collection and transportation systems in medium and high-risk area. This article could help manage MSW for preventing virus transmission during the COVID-19 pandemic or similar future epidemics.


Identification of a novel pathogenic deep intronic variant in PTEN resulting in pseudoexon inclusion in a patient with juvenile polyps.
Colorectal, hamartomatous juvenile polyps occur as part of different hereditary syndromes, including Juvenile polyposis syndrome and PTEN-hamartoma tumour syndrome. However, based on clinical manifestations alone, it is difficult to differentiate between the syndromes, and genetic analysis with an NGS-panel is often used to aid diagnostics. We report a 59-year-old male with colorectal juvenile polyps, who had been referred to genetic testing but had normal genetic analysis. He did not fulfil the clinical criteria of PTEN- hamartoma tumour syndrome, but the clinical criteria of Juvenile polyposis syndrome. With Whole Genome Sequencing we detected a novel intronic variant of unknown significance in PTEN (NC_000010.11:g.89687361 A > G(chr10, hg19), NM_000314.8:c.209 + 2047 A > G). RNA analysis classified the variant as likely pathogenic as it results in a pseudoexon inclusion introducing a frameshift and a premature stop codon. The patient was then diagnosed with PTEN-hamartoma Tumour syndrome. To our knowledge this is the first report of a variant resulting in pseudoexon inclusion in PTEN.


An old story with a new twist: do NMDAR1 mRNA binding proteins regulate expression of the NMDAR1 receptor in the presence of alcohol?
NMDA receptors not only play a pivotal role in normal physiological processes in the central nervous system (CNS), but have been identified as an important target of ethanol. Chronic exposure to ethanol induces a number of adaptive processes in the CNS, including an upregulation of NMDA receptor number and function. The increase in NMDA receptor number in response to chronic ethanol exposure both in vivo and in vitro is accompanied by an increase in NMDAR1 and NMDAR2B polypeptide levels. It is widely believed that these adaptive changes play an important role in the development of alcohol dependence and withdrawal syndrome. At the molecular level, chronic ethanol exposure of fetal cortical neurons selectively increases expression of NMDAR1 splice variants lacking exon 5 and exon 22. Chronic ethanol exposure of fetal cortical neurons also increases NMDAR1 mRNA half-life in these neurons. However, when new protein synthesis is inhibited, the half-life of NR1 mRNA in these neurons returns to control values, strongly suggesting that ethanol induces the synthesis of protein(s) that may regulate the decay of NR1 mRNA. In recent years, it has become apparent that regulation of mRNA stability is an important aspect of regulation of gene expression. Changes in mRNA stability can be accomplished by interaction between cis-acting sequences in the 3' untranslated region (3'UTR) of mRNAs and trans-acting proteins expressed in cells. Such interactions may protect RNAs from degradation by ribonucleases, thereby increasing the half-life of mRNAs.


Effects of procaine and oxyphenylbutazone on interferon-mediated inhibition of murine leukemia virus production.
Treatment of murine NIH/MOL, C cells which are chronically infected with Moloney murine leukemia virus (MuLV), with mouse interferon (IFN), causes inhibition of extracellular MuLV production. We tested the effect of procaine, a drug that is known to expand cellular membranes and to increase their fluidity, on IFN-mediated inhibition of MuLV production. We observed that procaine did not alleviate this inhibition when IFN was present during procaine treatment. However, if IFN was removed from the culture medium before procaine treatment, the inhibition of MuLV production was partially reversed. We also observed that procaine treatment caused an increase in the amount of MuLV production by cells which had not been treated with IFN. Oxyphenylbutazone (OPB) is an inhibitor of cyclooxygenase, a key enzyme in prostaglandin biosynthesis. New synthesis of prostaglandins is thought to be needed for the antiviral actions of IFN. We observed that OPB did not prevent the antiretroviral action of IFN on NIH/MOL, C cells. OPB also failed to alleviate the IFN-mediated inhibition of replication of vesicular stomatitis virus either in NIH/MOL, C cells or in the L929 cells.


Suppurative peritonitis by Klebsiella pneumoniae in captive gold-handed tamarin (Saguinus midas midas).
This report describes an outbreak of suppurative peritonitis caused by Klebsiella pneumoniae in an adult female of captive golden-handed tamarin (Saguinus midas midas). Two virulent and multidrug-resistant strains were isolated and classified through MLST as ST60 and ST1263. The microbiological diagnosis works as a support tool for preventive measures.


Filtering structures and particle size selection in coexisting Cladocera.
Five commonly co-occurring cladocerans, Holopedium gibberum, Daphnia longispina, Ceriodaphnia quadrangula, Bosmina longispina, Diaphanosoma brachyurum and the calanoid copepod Eudiaptomus gracilis were fed monodisperse fluorescent latex beads (0.5, 1,5 μm) to reveal clearance rates and particle size selection. The results were compared to those obtained with labelled bacteria and yeast. All cladoceran species ingested the beads, and particle size selection varied from a strong predominance of the largest particles in Holopedium, to an almost non selective particle retention in Diaphanosoma. The results indicated a strong correlation between morphology of the filtering combs, measured by Scanning electron microscopy, and ability to retain the smallest particles.


Long noncoding RNAs (lncRNAs) dynamics evidence immunomodulation during ISAV-Infected Atlantic salmon (Salmo salar).
Despite evidence for participation in the host response to infection, the roles of many long non-coding RNAs (lncRNAs) remain unknown. Therefore, the aims of this study were to identify lncRNAs in Atlantic salmon (Salmo salar) and evaluate their transcriptomic regulation during ISA virus (ISAV) infection, an Orthomyxoviridae virus associated with high mortalities in salmonid aquaculture. Using next-generation sequencing, whole-transcriptome analysis of the Salmo salar response to ISAV infection was performed, identifying 5,636 putative lncRNAs with a mean length of 695 base pairs. The transcriptional modulation evidenced a similar number of differentially expressed lncRNAs in the gills (3,294), head-kidney (3,275), and liver (3,325) over the course of the infection. Moreover, analysis of a subset of these lncRNAs showed the following: (i) Most were similarly regulated in response to ISA virus infection; (ii) The transcript subsets were uniquely modulated in each tissue (gills, liver, and head-kidney); and (iii) A subset of lncRNAs were upregulated for each tissue and time analysed, indicating potential markers for ISAV infection. These findings represent the first discovery of widespread differential expression of lncRNAs in response to virus infection in non-model species, suggesting that lncRNAs could be involved in regulating the host response during ISAV infection.


Developmental expression patterns of Arabidopsis XTH genes reported by transgenes and Genevestigator.
The plant cell wall is the structural basis of cellular form and thus forms a foundation on which morphogenesis builds organs and tissues. Enzymes capable of modifying major wall components are prominent candidates for regulating wall form and function. Xyloglucan endotransglucosylases/hydrolases (XTHs) are predicted to participate in xyloglucan integration and/or restructuring. XTHs are encoded by large gene families in plants; the Arabidopsis genome encodes 33 XTHs. To gain insight into the potential physiological relevance of the distinct members of this family, GUS reporter fusion genes were constructed, and plants expressing these transgenes were characterized to reveal spatial and temporal patterns of expression. In addition, Genevestigator sources were mined for comprehensive and comparative XTH expression regulation analysis. These data reveal that the Arabidopsis XTHs are likely expressed in every developmental stage from seed germination through flowering. All organs show XTH::GUS expression and most, if not all, are found to express multiple XTH::GUS genes. These data suggest that XTHs may contribute to morphogenesis at every developmental stage and in every plant organ. Different XTHs have remarkably diverse and distinct expression patterns indicating that paralogous genes have evolved differential expression regulation perhaps contributing to the maintenance of the large gene family. Extensive overlap in XTH expression patterns is evident; thus, XTHs may act combinatorially in determining wall properties of specific tissues or organs. Knowledge of gene-specific expression among family members yields evidence of where and when gene products may function and provides insights to guide rational approaches to investigate function through reverse genetics.


Subcutaneous adipose tissue alteration in aging process associated with thyroid hormone signaling.
Functional changes in subcutaneous adipose tissue (SAT) occur earlier in the aging process and play an important role in the occurrence and development of age-related metabolic diseases. The mechanism of this phenomenon is still unclear, and the change in adipose tissue with age is poorly understood. We used transcriptome sequencing (RNA seq) to screen differentially expressed genes at the mRNA level, and analyzed the functional characteristics of the differential genes through GO and KEGG analysis in human SAT of all ages. In order to clarify the specific mechanism of the functional change, we analyzed the chromatin accessibility in the promoter region in the same SAT used in the RNA seq by the assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and obtained the functional genes in SAT changed with age. To verify these changes, we enlarged our sample content of human SAT. The primary mice adipocytes were extracted and stimulated by thyroid hormone of different concentration to construct an animal model, and the expression of the genes were determined through real-time Polymerase Chain Reaction(RT-PCR). The oxygen consumption test and immunofluorescence staining were used to determine the mitochondrial function of SAT. RNA-seq showed characteristic gene expression of young and old human SAT, in which 331 genes were up-regulated and 349 genes were down-regulated. ATAC-seq, RNA-seq, combined with the mouse prediction model, determined the functional changed characteristics of seven genes. All these genes expressed differently in SAT of different ages, in which, NCF1, NLRP3, DUOX1 showed positive correlation with age; The expression of IFI30, P2RX1, P2RX6, PRODH, however, decreased with age. And all these genes showed dose dependent alternations under treatment of triiodothyroxine in mice SAT. The oxygen consumption rate revealed significant changes of the mitochondrial function and ROS accumulation in human SAT of different ages. In elderly individuals, the function, in addition to distribution, of SAT undergoes significant changes, primarily in mitochondria, which may be due to insensitivity to thyroid hormone signaling. These results identified seven novel genes regulated by thyroid hormone, exhibiting significant changes in SAT of different age, and are probably related to the dysfunction of the aged SAT due to the mitochondrial damage and ROS accumulation.


Ectopic expression of eIF4E-transporter triggers the movement of eIF4E into P-bodies, inhibiting steady-state translation but not the pioneer round of translation.
Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism; this process removes faulty mRNAs harboring premature termination codons (PTCs). NMD targets newly synthesized mRNAs bound by nuclear cap-binding proteins 80/20 (CBP80/20) and exon junction complex (EJC), the former of which is thought to recruit the ribosome to initiate the pioneer round of translation. After completion of the pioneer round of translation, CBP80/20 is replaced by the cytoplasmic cap-binding protein eIF4E, which mediates steady-state translation in the cytoplasm. Here, we show that overexpression of eIF4E-T preferentially inhibits cap-dependent steady-state translation, but not the pioneer round of translation. We also demonstrate that overexpression of eIF4E-T or Dcp1a triggers the movement of eIF4E into the processing bodies. These results suggest that the pioneer round of translation differs from steady-state translation in terms of ribosome recruitment.


Sirolimus: the evidence for clinical pharmacokinetic monitoring.
This review seeks to apply a decision-making algorithm to establish whether clinical pharmacokinetic monitoring (CPM) of sirolimus (rapamycin) in solid organ transplantation is indicated in specific patient populations. The need for CPM of sirolimus, although a regulatory requirement in Europe, has not yet been firmly established in North America and other parts of the world. Sirolimus has demonstrated immunosuppressive efficacy in renal, pancreatic islet cell, liver and heart transplant recipients. The pharmacological response of immunosuppressive therapy with sirolimus cannot be readily evaluated; however, a relationship between trough blood sirolimus concentrations, area under the plasma concentration-time curve (AUC) and the incidence of rejection has been proposed. Furthermore, sirolimus can be measured in whole blood by several assays--high-performance liquid chromatography with detection by tandem mass spectrometry, or with ultraviolet detection, radioreceptor assay or microparticle enzyme immunoassay. Both experimental animal and clinical data suggest that adverse events and their associated severity are correlated with blood concentrations. To prevent rejection and minimise toxicity, a therapeutic range of 4-12 microg/L (measured via chromatographic assays) is recommended when sirolimus is used in conjunction with ciclosporin. If ciclosporin therapy is discontinued, a target trough range of 12-20 microg/L is recommended. Sirolimus pharmacokinetics display large inter- and intrapatient variability, which may change in specific patient populations due to disease states or concurrent immunosuppressants or other interacting drugs. Due to the long half-life of sirolimus, dosage adjustments would ideally be based on trough levels obtained more than 5-7 days after initiation of therapy or dosage change. Once the initial dose titration is complete, monitoring sirolimus trough concentrations weekly for the first month and every 2 weeks for the second month appears to be appropriate. After the first 2 months of dose titration, routine CPM of sirolimus is not necessary in all patients, but may be warranted to achieve target concentrations in certain populations of patients, but the frequency of further monitoring remains to be determined and should be individualised.


Dispersal of the Ponto-Caspian amphipod Echinogammarus ischnus: invasion waves from the Pleistocene to the present.
The geographical range of the amphipod crustacean Echinogammarus ischnus has expanded over the past century from the Ponto-Caspian region to Western Europe, the Baltic Sea, and the Great Lakes of North America. The present study explores the phylogeographic patterns of this amphipod across its current distribution, based on an examination of nucleotide diversity in the mitochondrial cytochrome c oxidase subunit I (COI) gene. Marked genetic divergence exists among populations of E. ischnus from the Black and Caspian Seas, as well as those from the drainage system of the Black Sea. This divergence suggests the prolonged geographic isolation of these native populations, reflecting the limited dispersal capability of E. ischnus. By contrast, invading populations are characterized by a lack of genetic variation; a single mitochondrial genotype of Black Sea origin has colonized sites from the Rhine River to North America. The dispersal pattern in E. ischnus is very similar to that in the Ponto-Caspian cladoceran Cercopagis pengoi. Despite their contrasting life history strategies, these invading species followed the same route of invasion from the northern Black Sea to the Baltic Sea region, and subsequently to North America.


Considerations of diversity, equity, and inclusion in mental health apps: A scoping review of evaluation frameworks.
Mental health applications or apps are a promising approach to reduce the pervasive unmet mental health need observed among marginalized groups. However, these groups face unique challenges to engage in and benefit from these interventions, and apps that consider issues of diversity, equity, and inclusion (DEI) may be better positioned to reach them. App evaluation frameworks emerge as crucial tools for researchers, clinicians, and users to select evidence-based apps. Nevertheless, it is unclear the extent to which existing assessment tools capture DEI factors. The present scoping review identified 68 studies that employed one or more assessment tools to evaluate a mental health app, leading to 44 unique app evaluation frameworks. Results showed that most frameworks were developed after 2015, and only 58% of them considered at least one DEI criterion. Frameworks that performed exceptionally well were those that combined multiple standardized and validated measures. This lack of consideration for DEI variables may limit the ability of app-based interventions to serve marginalized communities, or even worse, create new disparities. Therefore, we provide recommendations to improve current app evaluation frameworks' cultural robustness and clinical utility, maximizing their effectiveness when working with individuals from marginalized communities.


Clinical science workshop: targeting the gut-liver-brain axis.
A clinical science workshop was held at the ISHEN meeting in London on Friday 11th September 2014 with the aim of thrashing out how we might translate what we know about the central role of the gut-liver-brain axis into targets which we can use in the treatment of hepatic encephalopathy (HE). This review summarises the integral role that inter-organ ammonia metabolism plays in the pathogenesis of HE with specific discussion of the roles that the small and large intestine, liver, brain, kidney and muscle assume in ammonia and glutamine metabolism. Most recently, the salivary and gut microbiome have been shown to underpin the pathophysiological changes which culminate in HE and patients with advanced cirrhosis present with enteric dysbiosis with small bowel bacterial overgrowth and translocation of bacteria and their products across a leaky gut epithelial barrier. Resident macrophages within the liver are able to sense bacterial degradation products initiating a pro-inflammatory response within the hepatic parenchyma and release of cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-8 into the systemic circulation. The endotoxemia and systemic inflammatory response that are generated predispose both to the development of infection as well as the manifestation of covert and overt HE. Co-morbidities such as diabetes and insulin resistance, which commonly accompany cirrhosis, may promote slow gut transit, promote bacterial overgrowth and increase glutaminase activity and may need to be acknowledged in HE risk stratification assessments and therapeutic regimens. Therapies are discussed which target ammonia production, utilisation or excretion at an individual organ level, or which reduce systemic inflammation and endotoxemia which are known to exacerbate the cerebral effects of ammonia in HE. The ideal therapeutic strategy would be to use an agent that can reduce hyperammonemia and reduce systemic inflammation or perhaps to adopt a combination of therapies that can address both.


Microglial activation during epileptogenesis in a mouse model of tuberous sclerosis complex.
Tuberous sclerosis complex (TSC) is a genetic disorder, characterized by tumor formation in multiple organs and severe neurologic manifestations, including epilepsy, intellectual disability, and autism. Abnormalities of both neurons and astrocytes have been implicated in contributing to the neurologic phenotype of TSC, but the role of microglia in TSC has not been investigated. The objectives of this study were to characterize microglial activation in a mouse model of TSC, involving conditional inactivation of the Tsc1 gene predominantly in glial cells (Tsc1(GFAP) CKO mice), and to test the hypothesis that microglial activation contributes to epileptogenesis in this mouse model. Microglial and astrocyte activation was examined in Tsc1(GFAP) CKO mice by ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein immunohistochemistry. Cytokine and chemokine expression was evaluated with quantitative polymerase chain reaction. Seizures were monitored by video-electroencephalography (EEG). The effect of minocycline in inhibiting microglial and astrocyte activation, cytokine expression, and seizures was tested. Microglial cell number and size were increased in cortex and hippocampus of 3- to 4-week-old Tsc1(GFAP) CKO mice, which correlated with the onset of seizures. Minocycline treatment prevented the increase in number and cell size of microglia in 4-week-old Tsc1(GFAP) CKO mice. However, minocycline treatment had no effect on astrocyte proliferation and cytokine/chemokine expression and the progression of seizures in Tsc1(GFAP) CKO mice. Microglia cell number and size are abnormal in Tsc1(GFAP) CKO mice, and minocycline treatment inhibits this microglia activation, but does not suppress seizures. Microglia may play a role in the neurologic manifestations of TSC, but additional studies are needed in other models and human studies to determine whether microglia are critical for epileptogenesis in TSC.


Surveillance of Zika virus in field-caught Aedes aegypti and Aedes albopictus suggests important role of male mosquitoes in viral populations maintenance in Medellín, Colombia.
Due to the rapid spread of Zika virus (ZIKV) infection after its emergence in the Americas in 2015 and its relationship with birth defects, it became declared a Public Health Emergency of International Concern (WHO). The main mechanism by which this virus circulates in nature is horizontal transmission between vectors and humans. However, it has been suggested that vertical transmission (parent to offspring infection) or venereal mosquito-mosquito transmission may have an important role in viral populations maintenance during inter-epidemic periods. In this study we evaluate the presence of ZIKV in males and females of Aedes aegypti and Ae. albopictus in Medellín, Colombia, throughout the post-epidemic period of 2017 and 2018. A total of 7986 mosquitoes Aedes sp. resting within houses were captured and grouped in 2768 pools; 146 of these were RT-PCR positive for ZIKV, of which 38 (26%) were male mosquito pools (36 of Ae. aegypti and 2 of Ae. albopictus). The partial NS5 gene was sequenced in all ZIKV PCR-positive pools to confirm the ZIKV presence throughout spatial and temporal sampling. The results suggest a vector role of ZIKV by Ae. Albopictus; and because it is well known that male mosquitoes are not hematophagous, the high rate detection of ZIKV in male Aedes mosquitoes pools supports the existence of vertical or venereal transmission in Medellín, which can contribute to ZIKV maintenance during low transmission periods. This study provides a better understanding of the population dynamics of ZIKV in an endemic region during an inter-epidemic period and supports alternative transmission pathways as a mechanism to maintain endemism of this arbovirus.


Mistaken diagnosis of optic neuritis and the possible role of phosphodiasterase-5 inhibitors (Sildenafil/Viagra).
The diagnosis of optic neuritis and particularly retrobulbar optic neuritis when atypical and not responsive to corticosteroid treatment may need to be revised. This is now especially so in male patients who should be questioned regarding their taking a phosphodiasterase-5 inhibitor in particular Viagra. The case history of such a patient is presented who sustained posterior ischaemic optic neuropathy mistaken for retrobulbar neuritis resulting in bilateral severe visual loss.


Waste to wealth: Synthesis of hydrocalumite from Moroccan phosphogypsum and aluminum wastes.
Each year, the phosphate industries in Morocco discard over 20 million tons of phosphogypsum into the Atlantic Ocean, posing a significant threat to aquatic life and causing potential long-term damage to ecosystems due to the accumulation of harmful substances. Hence, developing eco-friendly and cost-effective strategies to valorize phosphogypsum is vital to protect ecosystems and human health. This study aims to provide a concrete and efficient strategy for exploiting phosphogypsum and aluminum wastes in the preparation of hydrocalumite using the co-precipitation method. The synthesis strategy's effectiveness was assessed through a comprehensive analysis of the phosphogypsum-based hydrocalumite using various techniques, including FT-IR spectroscopy, X-ray powder diffraction, scanning electron microscopy (SEM), Energy-Dispersive X-Ray (EDX) analysis, X-ray fluorescence (XRF), and inductively coupled plasma optical emission spectrometry (ICP-OES). In addition, the structure was refined to discuss the arrangement of the polyhedrons occupied by the different ions in the hydrocalumite framework. It was found that the phosphogypsum-based hydrocalumite exhibited chemical and structural properties comparable to those of conventionally synthesized hydrocalumite, suggesting its potential applicability in diverse fields, including catalysis, cement and concrete production, polymer additives, medicine, and environmental remediation. Overall, in this work, the Moroccan phosphogypsum and aluminum wastes proved to be effective precursors of hydrocalumite, with structural and chemical properties presumably close to the conventional hydrocalumite.


Bioaccumulation and Quantitative Variations of Microcystins in the Swartspruit River, South Africa.
The bioaccumulation and quantitative variations of cyanobacterial peptide hepatotoxin intracellular microcystin in floating scums of cyanobacterium microcystis flos aquae collected from predetermined sampling sites in the Swartspruit River was investigated. Three distinct MCs variants (MC-YR, MC-LR, and MC-RR) were isolated, identified, and quantified. Additionally, two minor microcystin congeners (MC-(H4) YR), (D-Asp(3), Dha(7))MC-RR) also were identified but were not quantified. Quantitative analysis was achieved using peak areas substituted on linear regression equations: Y = 10085x - 19698 (R (2) = 0.9998), Y = 201387x + 20328 (R (2) = 0.9929), Y = 2506x + 15659 (R (2) = 0.9999), and 9859x + 208694 (R (2) = 0.9929) of standard curves for 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 μg/mL MC-LR, MC-RR, MC-YR respectively. Variant dominance followed the order MC-LR > MC-RR > MC-YR across the sampling sites. Analysis of maximum and minimum concentrations of quantified MCs variants showed 270.7, 14.10 (µg/g), 141.5, 1.43 (µg/g), and 72.28, 0.15 (µg/g) for MC-LR, MC-RR, and MC-YR, respectively. This implies there was quantitative variations of microcystin congeners across the sampled sites. Significant differences between means were assessed by an analysis of variance with P < 0.05 being considered significant. Results showed that there were no significant difference between mean MCs concentrations across the sampling periods (P > 0.05) and significant difference between mean MCs concentrations across sampling sites (P < 0.05).


Auriculasin sensitizes primary prostate cancer cells to TRAIL-mediated apoptosis through up-regulation of the DR5-dependent pathway.
Primary prostate cancer cells frequently develop resistance toward chemotherapy as well as most chemotherapeutics have been reported to induce undesirable cytotoxicity in normal cells. In this study, we performed sensitizing activity analysis of auriculasin (AC) to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in RC-58T/h/SA#4 primary prostate cancer cells without significant cytotoxicity in RWPE-1 prostate epithelial cells. Combined treatment with AC and TRAIL at optimal concentrations resulted in tumor-specific apoptotic cell death in RC-58T/h/SA#4 cells, characterized by DNA fragmentation, accumulation of apoptotic cell population, and nuclear condensation. Compared to single treatment with AC or TRAIL, co-treatment with AC and TRAIL significantly increased expression of Bax, cleaved PARP, AIF, endo G, and cytochrome c but decreased expression of phosphorylation of AKT and mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K), Bcl-2 and caspases-9, -8, -3, and -10. The sensitizing effect of AC to TRAIL was well correlated with inhibition of death receptor 5 (DR5) CHOP, and p53 expression. Moreover, pre-treatment with a chimeric blocking antibody for DR5 effectively reduced AC-TRAIL-induced cell death and apoptosis-related protein expression. These results suggest that non-toxic concentrations of AC sensitize TRAIL-resistant primary prostate cancer cells to TRAIL-mediated apoptosis via up-regulation of DR5 and downstream signaling pathways.


(A lack of) effects of acute social stress on attentional bias to threat.
Attentional biases toward or away from emotionally evocative stimuli have been well documented and are known to be clinically relevant, making it important to understand how various factors contribute to them. Some work has suggested that acute stress modulates attentional biases, but this work has produced inconsistent results. For example, many studies have found that stress enhances attentional bias, others that stress decreases attentional bias, and others still that there is no effect of stress at all. Methodological differences may explain these inconsistencies. For example, discrepancies exist between studies in participant sex (e.g., mixed sample vs. all men) and in the type of attentional bias paradigm. We addressed these gaps by examining the effects of an acute social stressor (vs. control) on attentional bias assessed via facial dot probe, focusing on potential sex differences in these effects (N = 141). We found that, overall, participants were significantly biased towards threat, but biases did not differ by stress condition or sex. These findings help to clarify the existing discrepancy in the literature, as we found that stress exerts little if any effect on attentional bias assessed via a facial dot probe.


Neonatal seizures.
Epileptic seizures are more frequent in the neonate than at any other time. The incidence of neonatal seizures (NNS) is estimated to be between 1.5 and 5.5/1000 living births, its onset being during the first week in 80% of cases. Mortality rate remains very high (20-45%). Not all paroxysmal manifestations are epileptic, and differential diagnosis remains an important challenge. Neonates may present with different types of seizures: clonic, tonic, myoclonic (axial, focal, erratic), epileptic spasms, and subtle seizures, including autonomic signs or automatisms. The main etiology is hypoxic-ischemic encephalopathy (40-45%) with a very early onset, and variable semiology including all seizure types. An EEG is necessary to recognize the seizures, and interictal tracing may help in assessing prognosis. Ischemic stroke is associated with seizures of early onset, being focal or unilateral. Interictal EEG is asymmetrical, with focal or unilateral patterns. Other etiologies less often linked to epileptic seizures must be looked for such as brain infection, metabolic disorders, chromosomal abnormalities, inborn errors of metabolism, brain malformations, and vitamin B6 dependency. Neonatal epilepsy syndromes may have favorable (benign familial neonatal seizures) or poor (early infantile encephalopathy with epilepsy, early myoclonic encephalopathy, and migrating partial seizures in infancy) prognosis.


Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma.
To analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC). Specimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC. Another 95 blood samples taken from individuals with no history of cancer were also analysed. After DNA extraction and PCR amplification, microsatellite instability (MSI) was determined using the Bethesda microsatellite panel, two exonic microsatellites of the TGFbRII and BAX genes, and the microsatellite D3S1611. The promoter methylation status of hMLH1 was investigated using the HpaII and MspI restriction enzymes. In addition, a sequencing analysis of complete coding region of hMLH1 and hMSH2 genes was performed. MSI and promoter hypermethylation of hMLH1 were not detected. Interestingly, loss of heterozygosity (LOH) was common among patients with RCC, particularly in microsatellite D3S1611 (34.9%). Mutations were identified in eight patients: K618A and V716M in gene hMLH1; and I145V, G322D, and the novel mutation P349A, in gene hMSH2. The mutations also appeared in healthy renal tissue and therefore, were considered as germline DNA sequence variations. There were G322D and K618A changes in >1% of the healthy control subjects, suggesting that they are DNA polymorphisms. Our data show that loss of function of both hMLH1 and hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation in their exons. However, LOH indicated that chromosomal instability affecting large fragments of DNA was the main genetic alteration we detected associated with RCC.


Percutaneous repair of the Achilles tendon rupture in athletic population.
This review was designed in order to study the percutaneous repair of Achilles tendon rupture in athletic population. We present a comprehensive description of clinical, functional outcomes, complications, with emphasis on patients' level, and time of return to sports. We proceeded to a systematic search of Medline (PubMED), Cochrane, and Scopus databases using keywords "Achilles Tendon", "Percutaneous Repair", "Percutaneous suturing", "Subcutaneous repair", "Subcutaneous suturing", "Athletes", and "Athletic" to identify articles or abstracts written in English. Thirteen studies, including 670 patients, could be identified. A variety of percutaneous repair techniques were performed. Re-rupture rate was very low. The most frequent complication was sural nerve damage. Average functional outcomes were satisfying. Up to 91.4% continued practicing sports after surgery. Furthermore, 78-84% returned to the same or higher sports level. Average time of return was 18 weeks in 9 studies. Percutaneous repair of Achilles tendon rupture is an excellent perspective for athletic population. Low re-rupture rate and impressing level of return to sports allow athletes to continue their recreational activities or careers.


Salt tide affecting algae-laden micropolluted surface water treatment and membrane performance based on BDD electro-oxidation coupled with ceramic membrane process.
Harmful algal blooms pose an emerging threat to freshwater ecological security and human health, necessitating further study in offshore areas. In this work, boron-doped diamond electro-oxidation (BDD/EO) coupled with a ceramic membrane filtration was employed aiming to assess the salt tide affecting algae-laden water treatment involving with various natural organic matters (e.g., HA, SA, and BSA). The results have demonstrated that BDD/EO remove chlorophyll from the algae-laden water effectively due to the inactivation of algal cells. Moreover, considering the influence of salt tide, NH3-N would be mainly oxidized through the in-situ generated active chlorine at the electrode-liquid interface. In addition, in three kinds of salt tide affecting algae-laden water, TOC content in BSA group was decreasing remarkably after BDD/EO with TOC removal efficiency above 80%; while those in HA and SA groups had no obvious reducing due to the more algae cells breakage synchronous with HA and SA removal. Based on the fluorescent characteristics and particle size distribution, the generated small molecular organics after electro-oxidation might raise the pore blockage probability and the hydrophobic organic and fluorescent substances were preferentially oxidized in BDD/EO process being beneficial to reducing membrane fouling. Besides, the membrane special flux in three groups were decreasing significantly and the irreversible fouling resistance in SA group accounted for a larger proportion of the total resistance than those of HA and BSA. At last, in BDD/EO-CM process, macromolecular substances degradation rate was greater than that of small molecules based on the molecular weight distribution in three groups of salt tide affected algae-laden water treatment. In a word, this work provides effective and innovative strategies for the harmful algal bloom control and contributes interesting insights of membrane fouling performance of electrochemical coupled ultrafiltration membrane process.


Cell-Specific α-Tubulin Isotype Regulates Ciliary Microtubule Ultrastructure, Intraflagellar Transport, and Extracellular Vesicle Biology.
Cilia are found on most non-dividing cells in the human body and, when faulty, cause a wide range of pathologies called ciliopathies. Ciliary specialization in form and function is observed throughout the animal kingdom, yet mechanisms generating ciliary diversity are poorly understood. The "tubulin code"-a combination of tubulin isotypes and tubulin post-translational modifications-can generate microtubule diversity. Using C. elegans, we show that α-tubulin isotype TBA-6 sculpts 18 A- and B-tubule singlets from nine ciliary A-B doublet microtubules in cephalic male (CEM) neurons. In CEM cilia, tba-6 regulates velocities and cargoes of intraflagellar transport (IFT) kinesin-2 motors kinesin-II and OSM-3/KIF17 without affecting kinesin-3 KLP-6 motility. In addition to their unique ultrastructure and accessory kinesin-3 motor, CEM cilia are specialized to produce extracellular vesicles. tba-6 also influences several aspects of extracellular vesicle biology, including cargo sorting, release, and bioactivity. We conclude that this cell-specific α-tubulin isotype dictates the hallmarks of CEM cilia specialization. These findings provide insight into mechanisms generating ciliary diversity and lay a foundation for further understanding the tubulin code.


Rivaroxaban Related Bilateral Adrenal Hemorrhage: A Rare Complications of Direct Oral Anticoagulants - A Case Reports.
BACKGROUND Adrenal hemorrhage is an uncommon and under-recognized disorder with a wide array of etiologies ranging from pregnancy to septic shock. It is one of the complications of anticoagulation therapy, including direct anticoagulant medications. CASE REPORT Here, we present a case of a 68-year-old female with recent right knee arthroplasty who was on rivaroxaban for deep vein thrombosis (DVT) prophylaxis presented to the emergency department (ED) for severe acute onset abdominal pain, computed tomography (CT) of abdomen and pelvis revealed possible left adrenal hemorrhage that was confirmed with magnetic resonance imaging (MRI). On repeat CT, her unilateral adrenal hemorrhage converted to a bilateral adrenal hemorrhage (BAH) and, as a result, the patient developed adrenal insufficiency. CONCLUSIONS An undiagnosed and untreated adrenal hemorrhage can have catastrophic consequences, leading to adrenal insufficiency with potential shock and death. Therefore, it is important for clinicians to have an increased awareness and knowledge about adrenal hemorrhage.


Structural language impairment in Autism Spectrum Disorder versus Loss of Autism Diagnosis: Behavioral and neural characteristics.
This study probed for structural language impairment using behavioral and functional neuroimaging methods in individuals with Autism Spectrum Disorder (ASD) and those diagnosed with ASD in childhood who no longer meet criteria for ASD, referred to as Loss of Autism Diagnosis (LAD1). Participants were drawn from Fein et al. (2013): ASD (n = 35), LAD (n = 31), and Neurotypical (NT; n = 34). Criteria for structural language impairment were: Scores ≤ 82 on Clinical Evaluation of Language Fundamentals-4 (CELF) Core Language, an omnibus measure of language; and scores ≤ 7 on CELF Recalling Sentences, a clinical marker of structural language impairment. Task-based fMRI examined lateralization of significantly activated language-related brain regions in groups with structural language impairment (LI2) versus normal-range language (LN3), collapsed across ASD, LAD1, and NT status. Results showed no ASD versus LAD group differences in the proportion of participants with structural language impairment according to either metric (Recalling Sentences or Core Language). Functional MRI results indicated greater left hemisphere lateralization within significantly activated regions in the LI2 group. Structural language abilities were not meaningfully associated with either social abilities or lifetime ADHD symptoms in LI2 subgroups, further suggesting the presence of structural language impairment. Findings indicate the presence of persistent structural language difficulty even in the absence of ASD symptoms in some individuals within the LAD1 group and unique patterns of language-related neural specialization for language function in LI2 relative to LN3.


Incidence of acute respiratory distress syndrome: a comparison of two definitions.
To determine the incidence and outcome of acute respiratory distress syndrome (ARDS) in children by comparing two commonly used definitions: the lung injury score and the American-European Consensus Conference definition. The causes and risk for developing ARDS were also studied. Part prospective and retrospective analysis of 8100 consecutive hospital admissions from 1 June 1995 to 1 April 1997. Twenty one patients fulfilled the criteria for ARDS. Both definitions identified the same group of patients. The incidence was 2.8/1000 hospital admissions or 4.2% of paediatric intensive care unit admissions. The main causes were sepsis and pneumonia. Mortality was 13 of 21. Factors predicting death were a high admission paediatric risk of mortality (PRISM) score (30.38 v 18.75) and the presence of multiple organ dysfunction syndrome (92% v 25%). Both definitions identified similar groups of patients. The incidence in this population was higher than that reported elsewhere, but mortality and cause were similar to those in developed countries. Poor outcome was associated with sepsis, a high admission PRISM score, and simultaneous occurrence of other organ dysfunction.


Free amino acids in the pre-retinal vitreous space. Effect of high potassium and nipecotic acid.
The pre-retinal vitreous space of the eye of albino rabbits was perfused in vivo via a dialysis probe in order to measure the concentration of endogenous amino acids. Studies of isotope concentrations in the vitreal effluent following intracarotid injections of 3HOH and [14C]mannitol demonstrated that entrance of 3HOH into the dialysis probe occurred within a few minutes whereas [14C]mannitol was almost completely excluded. Among the amino acids, analysed with high-pressure liquid chromatography (HPLC), glutamine had a concentration similar to that in plasma and cerebrospinal fluid (CSF). Taurine was four times higher than in the CSF. Perfusion with 125 mM KCl media increased particularly the taurine and phosphoethanolamine content. Nipecotic acid, a potent inhibitor of gamma-aminobutyric acid (GABA) uptake, increased GABA concentration over 60 times. In addition, it increased taurine levels by almost 10 times.


[Promoting citizen participation in healthcare through PyDEsalud.com].
This project supports the initiative promoted by the Spanish National Health System to provide informational materials, in printed or interactive format, to encourage public participation in decision making and healthcare. We present the newly created PyDEsalud.com, a web platform aimed at people with chronic diseases with a high socioeconomic impact, such as breast cancer, depression, and diabetes. This platform uses scientific methodology and contains three information service modules (Patients' experiences, Shared decision making, and Research needs), aimed at promoting health education for patients and families.


[Age-specific features of hypothalamus-hypophysis-suprarenal gland action on liver cells of rats (author's transl)].
Relevant studies show that there is a reduction in the regulation of hormonal stimulation of the genetic system in the cells and tissues at old age, which results in the early appearance of the "fatigue" reaction at old age and in reduced stimulation of the ferments tested. In the hypothalamus-hypophysis-suprarenal gland system the hypothalamus has the smallest regulation range; it reveals manifest changes due to ageing.


Right brain-to-right brain psychotherapy: recent scientific and clinical advances.
This article overviews my recent acceptance of a Lifetime Achievement Award from Sapienza University of Rome, in which I discussed three decades of my work on the right brain in development, psychopathogenesis, and psychotherapy. In the following, I offer current brain laterality and hemispheric asymmetry research indicating that right brain emotional and relational processes operate beneath conscious awareness not only in early human development, but over the lifespan. I discuss recent interdisciplinary studies on the central role of ultrarapid right brain-to-right brain intersubjective communications of face, voice, and gesture and the implicit regulation of emotion in nonverbal attachment dynamics. Special emphasis is on the fundamental psychobiological process of interpersonal synchrony, and on the evolutionary mechanism of attachment, the interactive regulation of biological synchrony within and between organisms. I then present some clinical applications, suggesting that effective therapeutic work with "primitive" nonverbal emotional attachment dynamics focuses not on conscious verbal insight but on the formation of an unconscious emotion-communicating and regulating bond within the therapeutic relationship. Lastly, I review recent hyperscanning research of the patient's and therapist's brains during a face-to-face, emotionally focused psychotherapy session that supports the right brain-to-right brain communication model. I end suggesting that the right brain is dominant in both short-term symptom-reducing and long-term growth-promoting deep psychotherapy.


Nano-Graphene Layer from Facile, Scalable and Eco-Friendly Liquid Phase Exfoliation Strategy as Effective Barrier Layer for High-Performance and Durable Direct Liquid Alcohol Fuel Cells.
Graphene, in spite of exceptional physio-chemical properties, still faces great limitations in its use and industrial scale-up as highly selective membranes (enhanced ratio of proton conductivity to fuel cross-over) in liquid alcohol fuel cells (LAFCs), due to complexity and high cost of prevailing production methods. To resolve these issues, a facile, low-cost and eco-friendly approach of liquid phase exfoliation (bath sonication) of graphite to obtain graphene and spray depositing the prepared graphene flakes, above anode catalyst layer (near the membrane in the membrane electrode assembly (MEA)) as barrier layer at different weight percentages relative to the base membrane Nafion 115 was utilized in this work. The 5 wt.% nano-graphene layer raises 1 M methanol/oxygen fuel cell power density by 38% to 91 mW·cm-2, compared to standard membrane electrode assembly (MEA) performance of 63 mW·cm-2, owing to less methanol crossover with mild decrease in proton conductivity, showing negligible voltage decays over 20 h of operation at 50 mA·cm-2. Overall, this work opens three prominent favorable prospects: exploring the usage of nano-materials prepared by liquid phase exfoliation approach, their effective usage in ion-transport membrane region of MEA and enhancing fuel cell power performance.


Systemically wound-responsive genes in poplar trees encode proteins similar to sweet potato sporamins and legume Kunitz trypsin inhibitors.
When the lower leaves of hybrid poplar trees are mechanically wounded, several novel mRNAs accumulate in the unwounded upper leaves (Parsons TJ, Bradshaw HD, Gordon MP: Systemic accumulation of specific mRNAs in response to wounding in poplar trees, Proc Natl Acad Sci USA, in press). A partial cDNA clone corresponding to a transcript from the wound-responsive gene designated win 3 (wound-inducible) has been cloned by differential hybridization to 32P-labelled cDNA from the leaves of wounded trees. Northern blots show a large accumulation of win 3 transcripts in the unwounded leaves of wounded trees. Southern blot analysis of poplar DNA suggests that win 3 is a member of a multigene family. The nucleotide sequences of several win 3 cDNA clones have been determined, indicating that at least three win 3 gene family members are transcribed. A genomic clone of a win 3 gene family member has been isolated and a 1.5 kb Hind III fragment containing the predicted protein-coding and 5' upstream regions has been sequenced. The putative win 3 gene product is similar to the major soluble proteins of sweet potato tubers, sporamin A and sporamin B. Both Win3 and the sporamins share significant amino acid sequence identity with Kunitz-type trypsin inhibitors from legume seeds. The Kunitz family of proteinase inhibitors thus joints three other proteinase inhibitor families which are systemically responsive to wounding.


Heart infarction-like effect induced by natural catecholamines in vitro.
Isolated rat hearts were perfused using retrograde technique under constant perfusion pressure or under constant coronary flow. The addition of L-epinephrine or L-nor-epinephrine (1 microgram per ml) into the perfusion medium for one hour caused visible and irreversible morphological changes. They became apparent usually after 4 hours of perfusion in the form of small, pale, opaque spots of streaks gradually enlarging on the surface or on the transverse section of myocardium. Light microscope and electron microscope examination showed the disintegration process analogous to myocardial infarction but lacking the infiltration with blood elements. The structural changes were preceeded by increased release of lactate dehydrogenase into the effluent, the most characteristic metabolic change a accompanying myocardial injury. Although the underlying mechanism of cardiotoxic action catecholamines remains to be clarified, several factors under consideration could be eliminated like hyperlipidemia, thrombogenic process or reduced total coronary inflow rate.


Internal structure of the Community Assessment of Psychic Experiences-Positive (CAPE-P15) scale: Evidence for a general factor.
Psychotic-like experiences (PLEs) are prevalent in the general population and are associated with poor mental health and a higher risk of psychiatric disorders. The Community Assessment of Psychic Experiences-Positive (CAPE-P15) scale is a self-screening questionnaire to address subclinical positive psychotic symptoms (PPEs) in community contexts. Although its psychometric properties seem to be adequate to screen PLEs, further research is needed to evaluate certain validity aspects, particularly its internal structure and its functioning in different populations. To uncover the optimal factor structure of the CAPE-P15 scale in adolescents aged 13 to 18 years using factorial analysis methods suitable to manage categorical variables. A sample of 727 students from six secondary public schools and 245 university students completed the CAPE-P15. The dimensionality of the CAPE-P15 was tested through exploratory structural equation models (ESEMs). Based on the ESEM results, we conducted a confirmatory factor analysis (CFA) to contrast two factorial structures that potentially underlie the symptoms described by the scale: a) three correlated factors and b) a hierarchical model composed of a general PLE factor plus three specific factors (persecutory ideation, bizarre experiences, and perceptual abnormalities). The underlying structure of PLEs assessed by the CAPE-P15 is consistent with both multidimensional and hierarchical solutions. However, the latter show the best fit. Our findings reveal the existence of a strong general factor underlying scale scores. Compared with the specific factors, the general factor explains most of the common variance observed in subjects' responses. The findings suggest that the factor structure of subthreshold psychotic experiences addressed by the CAPE-P15 can be adequately represented by a general factor and three separable specific traits, supporting the hypothesis according to which there might be a common source underlying PLEs.


[Urinary incontinence after radical prostatectomy: risk factors and utilisation of care].
Stress urinary incontinence is a relevant risk of radical prostatectomy (RP), which significantly affects patients' quality of life. The risk of developing stress urinary incontinence depends on pre-, intra- and postoperative factors. In particular, intraoperative factors regarding different surgical techniques are often focused on in order to improve continence rates. If stress urinary incontinence develops after RPE, patients affected should be treated adequately. In this respect, there are indications of healthcare insufficiencies in Germany. On the one hand, these include deficits in the use of incontinence materials. On the other hand, surgical treatment of stress urinary incontinence after RPE is insufficient.


Hydrophobic interactions of relaxin family peptide receptor 3 with ligands identified using a NanoBiT-based binding assay.
Relaxin family peptide receptor 3 (RXFP3) is a G protein-coupled receptor implicated in the regulation of food intake and stress response upon activation by the neuropeptide relaxin-3. In recent studies, interactions of RXFP3 with some natural or synthetic ligands have been investigated. In the present study, we identified the hydrophobic interactions of human RXFP3 with the chimeric agonist R3/I5 and the chimeric antagonist R3(ΔB23-27)R/I5 using a newly developed NanoBiT-based homogenous binding assay. We first demonstrated that the conserved large aliphatic B15Ile and B19Ile were important for the binding of the agonist and antagonist to RXFP3, because alanine replacement significantly decreased their receptor-binding potency. Thereafter, we demonstrated that the conserved large aliphatic Leu246 and Leu248 in extracellular loop 2 were important for RXFP3 binding to the agonist and antagonist, because alanine replacement significantly decreased the binding affinity of RXFP3 for both ligands. Finally, we deduced probable hydrophobic interactions based on the ability of RXFP3 mutants to distinguish the wild-type and mutant ligands: Leu246 of RXFP3 interacted with B15Ile of both ligands, while Leu248 of RXFP3 interacted with both B15Ile and B19Ile of the agonist and antagonist. The present results not only provided new insights into the interaction mechanism of RXFP3 with agonists and antagonists, but also demonstrated usefulness of the NanoBiT-based homogenous binding assay to study the interaction mechanism of certain receptors with their ligands.


Pharmacological characterization of vanilloid receptor located in the brain.
Specific [3H]resiniferatoxin (RTX) binding detects the vanilloid receptor type I (VR1). In the present study we demonstrate specific, high-affinity, saturable [3H]RTX binding in various areas of monkey brain not known to be innervated by primary afferent neurons as well as in spinal cord and dorsal root ganglion neurons of the same origin. Detailed pharmacological characterization and comparison revealed no major difference in binding affinities between the peripheral and the central sites as measured by K(d)/K(i) values. In general, lower receptor density was measured in selected brain areas than in the periphery. Areas with higher receptor density were detected in the locus ceruleus, preoptic area, and medial basal hypothalamus of the brain. Both capsaicin and the competitive antagonist capsazepine inhibited the specific binding of [3H]RTX to membrane preparations of the dorsal horn of the spinal cord and dorsal root ganglia with K(i) values of 4.3+/-0.32 microM and 2.7+/-0.33 microM, respectively. Inhibition was observed in the central areas (hypothalamus) with K(i) values of 0.95+/-0.1 microM for capsaicin and 0.86+/-0.11 microM for capsazepine. Previous biological and pharmacological evidence suggested that vanilloid receptors were present in the brain. Our results demonstrate that the pharmacological properties of both the peripheral and central receptor sites display appropriate pharmacological similarity to represent the same receptor class. The modest differences in ligand affinities for the vanilloid receptor expressed in the brain nuclei and the dorsal root ganglion neurons may correspond to differences in sequence, modification or associated proteins.


Preliminary observations on maternal rating of health of children: data from three subspecialty clinics.
Although routinely used in health surveys, the factors affecting maternal perceptions of health in children, especially those with health problems, have received little examination. This question has been addressed using a telephone interview of families of 483 children followed in one of three clinics at Children's Hospital of Philadelphia: the Neonatal Follow-up Program, the Pediatric Rheumatology Center and the Spina Bifida Program. Limitations in activities of daily living due to the health of the child, medical care use and variables indicative of socio-economic disadvantage were associated with a maternal rating of child health as fair/poor in all groups. The relationship was strongest in the rheumatologic group and less strong in the other two, suggesting that mothers may distinguish between a chronic active disease in a previously healthy child and the disability following a neonatal event in conceptualizing health. The results add to our information about maternal perceptions in assessing child health and suggest ways in which such ratings may prove useful in assessing health and health services for children with health problems.


Durability and efficacy of the ELVeS® Radial® 2ring slim fiber for multiple ablations.
To prove that the ELVeS® Radial® 2ring slim fiber (Biolitec AG, Wien, Austria) is safe and effective, with a reliable fiber durability. This prospective, non-randomized, registry recruited patients with venous incompetence of the great saphenous vein, with or without concomitant incompetence of the small, anterior accessory and posterior accessory saphenous veins. Anatomic success, clinical success and pain were assessed. 150 patients (410 veins) underwent endovenous laser ablation (EVLA). Mean number of veins treated was 2.7 (1-7) with a mean total length of 80.7 cm. 98.3% occlusions were observed after 12 months. Clinical improvement was significant with reduced venous clinical severity scores at 1 month (1.7 ±1.9; p < .0001) and 12 months (0.7 ±1.3; p < .0001) versus pre-operation (4.4 ± 2.2). Mean pain level after 1-week was 5.8/100. No major surgery- or device-related complications occurred. 1470-nm EVLA with the 2ring slim fiber is a highly effective treatment option well tolerated by patients. Despite intensive use, fiber integrity was preserved. The study protocol was registered in clinicaltrials.gov (NCT03810677).


The use of digital technologies to support home-based prehabilitation prior to major surgery: A systematic review.
Prehabilitation is a multidimensional and multidisciplinary approach, to prepare patients for surgery, with the aim of improving postoperative outcomes. Worldwide, healthcare systems are facing challenges with a gap between demand and supply of healthcare services. Telehealth is seen as a solution for delivering sustainable and efficient treatments. The effect of providing prehabilitation using telehealth solutions is unclear. This systematic review investigated the existing literature regarding the effects and feasibility of technologies for remotely supporting home-based prehabilitation compared to standard care on pre- and postoperative outcomes in adults undergoing elective major surgery. A literature search identified relevant studies published between 1 January 2012 and December 2022 in PubMed, PsychInfo, Cinahl and the Cochrane Library. We included RCTs, feasibility and pilot studies. The quality of studies was evaluated using Cochrane's Risk of bias assessment and by narratively rating the certainty of evidence. Six randomized controlled trials and 20 pilot/feasibility studies were included. The number and content of the interventions varied, depending on context and resources. Multiple approaches in the use of digital healthcare solutions were applied and the results highlight the potential of providing health services remotely. The use of technologies to support remote home-based prehabilitation in patients undergoing elective major surgery is feasible and has high acceptability, though telehealth is a broad term and wide-ranging strategies are used. Digital technologies for supporting home-based prehabilitation are likely to play an essential role in future health care as resources are scarce and innovative solutions are needed.


Tadalafil-associated priapism.
A healthy 46-year-old man presented to the Emergency Department with a 36-hour history of persistent, painful erection after taking the cyclic guanylyl monophosphate-specific phosphodiesterase 5 inhibitor tadalafil. He had no other identified contributing factors for priapism. After confirmation of ischemic priapism and failure of bedside management in the Emergency Department, the patient underwent operative caverno-spongiosal shunting. Postoperatively, the erection initially rebounded but gradually receded with manual compression over 48 hours. At outpatient follow-up, the patient remained flaccid without erections. To our knowledge, this is the first report of tadalafil-associated priapism.


Periodontal status of mandibular central incisors after orthodontic proclination in adults.
Some animal and human studies showed that periodontal recession occurs after incisor proclination, but other authors disagree. The purpose of this study was to assess the periodontal status of mandibular central incisors that were proclined during orthodontic treatment. The sample comprised 34 adults who had completed treatment over periods of 7 months to 3 years 11 months. The proclination and vertical movement of these teeth were analyzed by 6 measurements from lateral cephalometric radiographs taken before and after treatment. The thickness and height of the symphysis were recorded from pretreatment lateral cephalometric films. Crowding was determined based on the irregularity index from the initial cast. The following periodontal clinical parameters were assessed: plaque and gingival bleeding indexes, probing pocket depth, clinical levels of attachment, and recession of selected teeth and of the mandibular central incisors. The height of the keratinized tissue and the thickness of the facial gingival margin of these incisors were also measured. The Pearson and Spearman correlation analyses, the Fisher exact test, and the Kruskal-Wallis test were applied. Statistical analyses showed no correlation between recession and the plaque and gingival bleeding indexes, probing pocket depth, and total quantity of labial movement (P >.05). Recession was negatively correlated with keratinized gingival height and thickness of the facial gingival margin on the mandibular central incisors. Final inclination (>95 degrees ) and free gingival-margin thickness (>0.5 mm) showed greater and more severe recession on the mandibular central incisors. Nevertheless, when comparing thickness to the final inclination, thickness had greater relevance to recession.


Ultrasound guided pulmonary artery catheter insertion: An alternative to fluoroscopic guidance.
Pulmonary artery catheters (PACs) can provide extremely valuable objective data in select patients. They are usually advanced by floatation of balloon tip along the normal blood flow and their placement is confirmed under pressure waveform guidance. Imaging such as fluoroscopy is often employed in low flow states and in cardiac catheterization suite to reduce the failure rate and time to wedge; but is not readily available at bedside. In critically ill patient, bedside insertion is feasible but can be complicated by repeated attempts to float the balloon tip through various cardiac chambers. Point of care ultrasound can be used to visualize the balloon tip of PAC inside the cardiac chambers alongside the confirmatory pressure waveform changes.


Comparison of phosphorylated TDP-43-positive inclusions in oculomotor neurons in patients with non-ALS and ALS disorders.
TDP-43 has been identified as a major component of the pathological inclusions in most forms of frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis (ALS). In the present study, paraffin sections of the midbrain in 112 patients with various non-ALS disorders and 27 patients with sporadic ALS were immunostained with antibody against phosphorylated TDP-43 (pTDP-43). pTDP-43-positive inclusions in oculomotor neurons were detected in 18 of 112 patients with non-ALS disorders (16.1%). The appearance of the inclusions showed fine filamentous structures rather than the skein-like inclusions seen in the anterior horn cells of ALS spinal cords. The incidence was increased in the age range of 80-89 years old (10/37 cases; 27.0%), in which 6 of 10 cases demonstrated AD pathology in the temporal lobes. Twenty-seven ALS patients were examined and the findings were compared with those of non-ALS patients. There were 13 cases demonstrating pTDP-43-positive inclusions (48.1%) which showed stronger immunoreactivities in ALS cases. This is the first report demonstrating fine filamentous pTDP-43-positive inclusions in oculomotor neurons in non-ALS disorders. Although the mechanisms underlying pTDP-43 in oculomotor neurons are currently unknown, its detection is of interest, and the expression may occur not only in ALS but also during the aging process.


IL-27 receptor-regulated stress myelopoiesis drives abdominal aortic aneurysm development.
Abdominal aortic aneurysm (AAA) is a prevalent life-threatening disease, where aortic wall degradation is mediated by accumulated immune cells. Although cytokines regulate inflammation within the aorta, their contribution to AAA via distant alterations, particularly in the control of hematopoietic stem cell (HSC) differentiation, remains poorly defined. Here we report a pathogenic role for the interleukin-27 receptor (IL-27R) in AAA, as genetic ablation of IL-27R protects mice from the disease development. Mitigation of AAA is associated with a blunted accumulation of myeloid cells in the aorta due to the attenuation of Angiotensin II (Ang II)-induced HSC expansion. IL-27R signaling is required to induce transcriptional programming to overcome HSC quiescence and increase differentiation and output of mature myeloid cells in response to stress stimuli to promote their accumulation in the diseased aorta. Overall, our studies illuminate how a prominent vascular disease can be distantly driven by a cytokine-dependent regulation of bone marrow precursors.


Evaluation of MODIS surrogates for meteorological humidity data in east Africa.
Satellite remote sensing technology has shown promising results in characterizing the environment in which plants and animals thrive. Remote sensing scientists, biologists, and epidemiologists are adopting remotely sensed imagery to compensate for the paucity of weather information measured by weather stations. With measured humidity from three stations as baselines, our study reveals that Normalised Difference Vegetation Index (NDVI) and atmosphere saturation deficits at the 780 hPa pressure level (DMODIS), both of which were derived from the MODerate-resolution Imaging Spectroradiometer (MODIS) sensor, were significantly correlated with station saturation deficits (Dstn)(ȣrȣ = 0.42-0.63, p < 0.001). These metrics have the potential to estimate saturation deficits over east Africa. Four to nine days of lags were found in the NDVI responding to Dstn. For the daily estimations of Dstn, DMODIS had a better performance than the NDVI. However, both of them poorly explained the variances in daily Dstn using simple regression models (adj. R2 = 0.17-0.39). When the estimation temporal scale was changed to 16-day, their performances were similar, and both were better than daily estimations. For Dstn estimations at coarser geographic scales, given that many factors such as soil, vegetation, slope, aspect, and wind speed might complicate the NDVI response lags and model construction, DMODIS is more favourable as a proxy of the saturation deficit over ground due to its simple relationship with Dstn.


Heat-shock induces abnormalities in the cellular distribution of amyloid precursor protein (APP) and APP fusion proteins.
The heat shock or stress response may play a role in the pathogenesis of Alzheimer's disease. We conducted experiments to visualize microscopically the distribution of wild type amyloid precursor protein (APP) and the behavior of an APP deletion mutant under stress. This was achieved by heat-shock treatment of cells expressing fusion recombinant APP proteins tagged with secreted placental alkaline phosphatase (SEAP). The fusion proteins were cleaved and secreted in a manner similar to wild type APP in unstressed control cells. SEAP activity was detected by cytochemical methods within the cytoplasm in less than 10% of transfected unstressed cells. Heat shocked cells showed a striking difference from the control cells in that over 90% of the stressed cells displayed strong intracytoplasmic SEAP activity occurring with Golgi-like pattern and/or membranous distribution. The effects of heat shock were not due to a peculiar behavior of the clones and depended on the APP portion of the constructs. This study shows miscompartmentalization of APP under stress. Such cellular changes may bear important implications in the processing of APP.


Postischemic regulation of central histamine receptors.
This study characterizes changes occurring in the central histaminergic system associated with ischemia-reperfusion pathology in the rat. Specifically, after a postocclusion time period of 48 h, we have analyzed histamine H(1) receptor mRNA expression, histamine H(2) receptor protein amount and binding densities, and histamine H(3) receptor mRNA expression and binding densities in brain regions that have been suggested to be selectively vulnerable to transient global ischemia, i.e. hippocampus, thalamus, caudate-putamen, and cerebral cortex. We found an increase in H(1) receptor mRNA expression in the caudate-putamen: given that ischemia reduces glucose uptake and H(1) receptor activation has been shown to decrease this effect, an increase of expression levels may result in mitigating tissue damage due to energy failure observed in ischemia. A decrease in H(2) receptor binding densities in the caudate-putamen was also observed; the ischemia-induced decrease in H(2) receptor protein was also detectable by Western blot analysis. This phenomenon may underlie the previously reported ischemia induced striatal dopamine release. H(3) receptor mRNA expression was increased in the caudate putamen of the postischemic brain but was decreased in the globus pallidus and the thalamus; in association with this, H(3) receptor binding densities were increased in the cortex, caudate-putamen, globus pallidus, and hippocampus. The upregulation of H(3) receptor ligand binding may be involved in the previously reported continuous neuronal histamine release. Our data suggest that central histamine receptor expression and ligand binding are altered in brain ischemia in distinct areas, and may participate in neuroprotection and/or ischemia-associated neuronal damage.


Preparation of galactose oxidase functional phosphorescent quantum dots and detection of D-galactose.
Environmental friendly nano biosensor can improve the detection performance of traditional biomolecular sensors and have important application value in practical applications. In this study, a kind of room temperature phosphorescence (RTP) quantum dots (QDs) (GOX RTP QDs) nanobiosensor was prepared by mineralization at room temperature (25 °C), using galactose oxidase (GOX) as template, which improved the catalytic ability of traditional GOx to D-Galactose. The specific enzyme substrate reaction between GOx and D-Galactose and photoinduced electron transfer (Piet) were used to detect the RTP of D-galactose. The linear range of D-galactose detection is 0.02-0.8 mM, and the detection limit of the method is 0.008 mM. This method is based on the RTP property of QDs, which can effectively avoid the interference of background fluorescence of biological samples, and does not need complex sample pretreatment process. Therefore, this method is more suitable for the quantitative detection of D-Galactose in biological samples.


CCL21/CCR7 axis as a therapeutic target for autoimmune diseases.
Chemokine receptor 7 (CCR7) is a G protein-coupled receptor containing 7 transmembrane domains that is expressed on various cells, such as naive T/B cells, central memory T cells, regulatory T cells, immature/mature dendritic cells (DCs), natural killer cells, and a minority of tumor cells. Chemokine ligand 21 (CCL21) is the known high-affinity ligand that binds to CCR7 and drives cell migration in tissues. CCL21 is mainly produced by stromal cells and lymphatic endothelial cells, and its expression is significantly increased under inflammatory conditions. Genome-wide association studies (GWAS) have shown a strong association between CCL21/CCR7 axis and disease severity in patients with rheumatoid arthritis, sjogren's syndrome, systemic lupus erythematosus, polymyositis, ankylosing spondylitis, and asthma. Disrupting CCL21/CCR7 interaction with antibodies or inhibitors prevents the migration of CCR7-expressing immune and non-immune cells at the site of inflammation and reduces disease severity. This review emphasizes the importance of the CCL21 /CCR7 axis in autoimmune diseases and evaluates its potential as a novel therapeutic target for these conditions.


Reversal of Rous sarcoma-specific immunoglobulin phosphorylation on tyrosine (ADP as phosphate acceptor) catalyzed by the src gene kinase.
To determine the equilibrium constant of the reaction between ATP and protein-bound tyrosine we used as catalyst the highly purified Rous sarcoma src gene transcript. J. M. Sturtevant had earlier found (personal communication) that free tyrosine O-phosphate, upon hydrolysis with alkaline phosphatase in a calorimeter (37 degrees C, pH 9), yielded a delta H degrees of -2.8 kcal/mol (1 kcal = 4.18 kJ), less than half of that found in ATP hydrolysis. Experience with protein-bound serine phosphate (in phosvitin) had shown it to be energy rich [Rabinowitz, M. & Lipmann, F. (1960) J. Biol. Chem. 235, 1043-1050]. We wondered if the same is true for tyrosine phosphate when it is protein bound. From the equilibrium constant of 2.62 (at pH 6.5 and 5 mM Mg2+), we calculate a delta G degrees' of -9.48 kcal/mol for hydrolysis of protein-bound tyrosine phosphate, assuming an approximate delta G degrees' of -10 kcal/mol for hydrolysis of ATP. The experiments show that protein-bound tyrosine phosphate is energy rich, like serine phosphate in phosvitin.


Carpal tunnel syndrome due to heterotopic ossification.
We report a rare case of carpal tunnel syndrome due to heterotopic ossification in the carpal tunnel in a 34-year-old woman without antecedents of neurological injury, musculoskeletal trauma, or metabolic disorder. To our knowledge, this is the first reported case. Incomplete excision of heterotopic ossification resulted in partial relief of symptoms.


Clinicopathologic significance of histologic vascular invasion in papillary and follicular thyroid carcinomas.
The association of angioinvasion with tumor aggressiveness in follicular and papillary thyroid carcinoma remains unclear. This study addresses this problem focusing on clinicopathologic relevance of angioinvasion in the treatment of papillary thyroid carcinoma and follicular thyroid carcinoma. From a university hospital database, 358 patients with papillary thyroid carcinoma or follicular thyroid carcinoma were randomly selected. Their charts were retrospectively analyzed and divided into papillary thyroid carcinoma and follicular thyroid carcinoma groups. Each group was subdivided into angioinvasive and nonangioinvasive tumor subgroups. All data were analyzed using Student's t-test, Mann-Whitney rank sum test, chi-square test, and Fisher's exact test. There were 289 women and 69 men, ages 18 to 89 years. Papillary thyroid carcinoma (86%) was more frequent than follicular thyroid carcinoma. Most patients had nonangioinvasive tumor (90.2%). After a mean followup of 43.6 months, there were no significant differences between papillary thyroid carcinoma subgroups for local recurrence (p = 0.69), persistent elevated serum thyroglobulin (p = 0.568), and distant metastasis rates (p = 0.422). No death related to the cancer was observed in both papillary thyroid carcinoma subgroups (p = 1), except for one death resulting from a concomitant nasopharyngeal cancer. The longterm prognosis was less favorable for angioinvasive papillary thyroid carcinoma based on AJCC (American Joint Committee on Cancer staging), AMES (age, distant metastasis, tumor extent, and size), and MACIS (distant metastasis, age, completeness of primary tumor resection, local invasion, and tumor size), but the angioinvasive papillary thyroid carcinoma were larger than nonangioinvasive papillary thyroid carcinomas. The short-term clinical outcomes in both follicular thyroid carcinoma, after a mean followup of 72.3 months, were comparable in terms of local recurrence (p = 0.34), persistent elevated serum thyroglobulin (p = 1), and distant metastasis (p = 0.597). There was no death related to cancer in both follicular thyroid carcinoma subgroups (p = 1). There were no significant differences between both follicular thyroid carcinoma subgroups for longterm prognosis. Our results indicate that angioinvasion does not adversely influence short-term outcomes or longterm prognosis in follicular thyroid carcinoma and short-term outcomes in papillary thyroid carcinoma. Angioinvasion is a postoperative pathologic finding that does not justify an ominous prognosis or drastic therapeutic measures.


Effects of acute tryptophan depletion on executive function in healthy male volunteers.
Neurocognitive impairment is frequently described in a number of psychiatric disorders and may be a direct consequence of serotonergic dysfunction. As impairments in executive functions are some of the most frequently described, the purpose of this study was to examine the performance of normal volunteers on a range of executive tasks following a transient reduction of central serotonin (5-HT) levels using the method of acute tryptophan depletion (ATD). Fifteen healthy male subjects participated in a within-subject, double-blind, counterbalanced crossover study. ATD was induced by ingestion of a 100 g amino-acid drink. Executive function was evaluated using the Wisconsin Card Sorting Test, Stroop, Verbal Fluency and Trail Making. Visual analogue scales were administered to assess mood. Plasma free and total tryptophan concentrations were significantly reduced by the depleting drink (P < 0.001). ATD selectively improved motor speed/ attention on the Trails A test (P = 0.027), with no effect on subjective ratings of mood. Interaction effects between drink and the order of drink administration were observed on most neurocognitive tests. The improvement in simple motor speed/ attention following ATD is in keeping with the ascribed role of 5-HT in the cortex, however performance on tests of executive function is not robustly altered. The presence of interaction effects on most tasks suggests that subtle changes may occur but are masked, possibly by simple learning effects, in the context of a crossover design. This has implications for the design of future studies, particularly those examining executive functions.


Corrigendum: Chlamydia pneumoniae CdsL regulates CdsN ATPase activity, and disruption with a peptide mimetic prevents bacterial invasion.
[This corrects the article DOI: 10.3389/fmicb.2011.00021.].


Distribution of opiate-like substances in rat tissues.
Rat tissues were tested for their ability to inhibit the binding of [3H]dihydromorphine or [3H]naloxone to membrane-bound opiate receptors. By this criterion, morphine-like substances were found in lung, heart, liver, and kidney as well as in brain. The relative activity of the extracts, based on initial tissue weight, differed with the radioactive lignand employed. With dihydromorphine, the order was as above. With naloxone, lung was most active, followed by heart, brain, liver, and kidney. The ability of all tissue extracts to inhibit opiate binding was reduced by 100 mM NaC1 and slightly reduced by 1 mM MnC1(2). Gel filtration using Sephadex G-25 indicated that the inhibitory substances were heterogeneous in molecular weight. Only with brain and kidney extracts was there significant activity at the elution volume where enkephalins would be expected. Fractionation using Amberlite XAD-2, a resin which selectively absorbs hydrophobic materials, again indicated that the major protion of activity in all tissue extracts was due to substances other than enkephalins.