Thermal stability of type I and type III procollagens from normal human fibroblasts and from a patient with osteogenesis imperfecta.
Type I and type III procollagens were isolated from the medium of human fibroblast cultures in amounts adequate for examination by circular dichroism. Type I procollagen had a spectrum similar to that of type I procollagen and collagen from chicken embryos. The human type III procollagen showed a red shift not seen in type III collagen from calf skin. The midpoint (tm) for the helix-to-coil transition for both human procollagens was 40 degrees C. the same tm values were obtained with type I and type III procollagens synthesized by fibroblasts from a patient with osteogenesis imperfecta. Type I procollagen synthesized by the patient's fibroblasts, however, tended to aggregate more readily than type I procollagen from normal human fibroblasts, apparently because of a structural alteration of the protein.


Hemoglobin Wayne Trait with Incidental Polycythemia.
Hemoglobinopathies, caused by mutations in the globin genes, are one of the most common inherited disorders. Many of the hemoglobin variants can be identified by hemoglobin analysis using conventional electrophoresis and high performance liquid chromatography; however hemoglobin DNA analysis may be necessary in other cases for confirmation. Here, we report a case of a rare alpha chain hemoglobin variant, hemoglobin Wayne, in a 47-year-old man who presented with secondary polycythemia. Capillary zone electrophoresis and high performance liquid chromatography revealed a significant amount of a hemoglobin variant, which was further confirmed by hemoglobin DNA sequencing as hemoglobin Wayne. Since the patient was not homozygous for hemoglobin Wayne, which is associated with secondary polycythemia, the laboratory diagnosis in this case was critical in ruling out hemoglobinopathy as the etiology of his polycythemia.


Regulating the onset of mitosis.
In eukaryotes, G2/M progression is mediated by activation of mitosis promoting factor (MPF). To ensure faithful chromosome segregation, the activity of key mitotic inducers and inhibitors are coupled with chromosome replication, spindle pole duplication, morphogenesis, and DNA damage. Evidence gathered in the past two years has underscored the importance of positioning MPF and its regulators in the proper place at the proper time to ensure orderly progression through the G2/M transition. Altering the spatial organization of G2/M regulators also contributes to prevention of mitosis following DNA damage.


Changes in the networks of complex posttraumatic stress disorder symptoms among Chinese college students with childhood trauma.
To advance understanding of the development of complex posttraumatic stress disorder (CPTSD) symptoms longitudinally and facilitate future treatments, the present study investigated changes in the network of CPTSD symptoms among Chinese college students with childhood trauma. A longitudinal study was conducted with college students, following them three times at 3-month intervals. CPTSD symptoms were measured using the International Trauma Questionnaire, and childhood trauma was assessed by the revised Adverse Childhood Experiences Scale. The final sample consisted of 294 participants with childhood trauma at baseline measurement (28.9% were males, Mage = 20.76 years). Comparisons of cross-sectional networks and cross-lagged panel network (CLPN) analysis were performed to characterize the features and changes of interactions among CPTSD symptoms. Sense of failure and isolation were the core symptoms in the cross-sectional networks of CPTSD symptoms. The comparison of cross-sectional networks indicated that the global network strength was stable, and no node's strength centrality and only one edge weight changed significantly from Time 1 (T1) to Time 3 (T3). The findings of the CLPN model reveal that worthlessness, difficulties with intimacy, and flashbacks have the highest out-expected influence. In the T1-T3 network, the strongest edge was from worthlessness to sense of failure. Cross-sectional network analyses and comparisons revealed the characteristics of CPTSD networks at multiple time points, while the CLPN analysis identified the longitudinal dynamics of CPTSD symptoms. These provide insights for designing more targeted intervention plans for college students with childhood trauma. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


The dyadic effects of subclinical paranoia on relationship satisfaction in roommate relationships and college adjustment.
Subclinical paranoia is associated with negative psychological and general health consequences including poorer social functioning. Despite extensive research on the outcomes of individuals with greater paranoia, the consequences of interacting with someone who is paranoid are less clear. As social functioning involves interactions between individuals, investigating associations between paranoia and relationship outcomes from a dyadic perspective may aid in elucidating the mechanisms underlying social dysfunction in subclinical paranoia. This study examined the trajectory of new roommate relationships over the course of the college semester. One hundred three same-sex roommate dyads were assessed on pathological personality traits at the beginning of the semester and on roommate relationship satisfaction and college adjustment at 2-week intervals. Individuals who were more paranoid reported lower satisfaction in their roommate relationship and poorer overall college adjustment. Importantly, individuals who lived with a more paranoid roommate also reported lower satisfaction in their roommate relationship. In contrast, elevated psychoticism, in either the individual or their roommate, was not associated with lower roommate relationship satisfaction. These findings demonstrate that the effects of subclinical paranoia extend beyond the paranoid individual to social partners as well. Further, poorer relationship satisfaction appears specifically related to paranoia and does not seem to be associated with increased psychoticism. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Pathological Cerebrospinal Fluid Findings in Patients With Neuralgic Amyotrophy and Acute Hepatitis E Virus Infection.
There is growing evidence that hepatitis E virus (HEV) infection can present with extrahepatic manifestations including neurological disorders. Among these, neuralgic amyotrophy (NA) has been reported to occur in some industrialized countries. We investigated 35 patients with NA and a control group for markers of HEV infection. Acute HEV infection was found in NA patients only and was associated with an inflammatory response in the central nervous system. Shedding of HEV RNA into the cerebrospinal fluid and intrathecal production of anti-HEV immunoglobulin M occurred in 1 patient, suggesting that HEV is neurotropic.


Rescue of yeast defective in mitochondrial ATP synthase subunit 8 by a heterologous gene from Aspergillus nidulans.
Mitochondrial ATP synthase subunit 8 of the yeast Saccharomyces cerevisiae and of the filamentous fungus Aspergillus nidulans have the same length and similar structural motifs. However, the two proteins share only 50% identical residues, with the conserved residues being concentrated in the N- and C-terminal domains. We have investigated whether it is amino acid sequence or overall structural motifs that are required for subunit 8 function. PCR was used to construct a gene encoding A. nidulans subunit 8 fused to an N-terminal cleavable mitochondrial targeting sequence. Following expression in the nucleus of a yeast strain deficient in subunit 8, the chimaeric precursor targeted the subunit 8 protein back to the mitochondrion. The A. nidulans subunit 8 was found to be able to restore growth on non-fermentable substrate at 18 degrees C and 28 degrees C, but not at 36 degrees C. Given the sequence divergence between subunit 8 of A. nidulans and that of S. cerevisiae, this finding suggests that common structural motifs are important for subunit 8 function.


Type 1 diabetes structured education: What are the core self-management behaviours?
Study aims were to (1) describe and compare the way diabetes structured education courses have evolved in the UK, (2) identify and agree components of course curricula perceived as core across courses and (3) identify and classify self-care behaviours in order to develop a questionnaire assessment tool. Structured education courses were selected through the Type 1 diabetes education network. Curricula from five courses were examined and nine educators from those courses were interviewed. Transcripts were analysed using framework analysis. Fourteen key stakeholders attended a consensus meeting, to identify and classify Type 1 diabetes self-care behaviours. Eighty-three courses were identified. Components of course curricula perceived as core by all diabetes educators were: carbohydrate counting and insulin dose adjustment, hypoglycaemia management, group work, goal setting and empowerment, confidence and control. The broad areas of self-management behaviour identified at the consensus meeting were carbohydrate counting and awareness, insulin dose adjustment, self-monitoring of blood glucose, managing hypoglycaemia, managing equipment and injection sites; and accessing health care. Specific self-care behaviours within each area were identified. Planned future work will develop an updated questionnaire tool to access self-care behaviours. This will enable assessment of the effectiveness of existing structured education programmes at producing desired changes in behaviour. It will also help people with diabetes and their healthcare team identify areas where additional support is needed to initiate or maintain changes in behaviour. Provision of such support may improve glycaemia and reduce diabetes-related complications and severe hypoglycaemia.


The Role of Discoidin Domain Receptor 1 in Inflammation, Fibrosis and Renal Disease.
Discoidin domain receptors (DDRs) are a family of 2 non-integrin collagen receptors, DDR1 and DDR2, which display a tyrosine kinase activity. They are mainly expressed during embryonic development and their role during adulthood is very limited. DDR1 has been widely studied in several types of cancers, in atherosclerosis and fibrosis, but also in chronic kidney disease (CKD). This review focuses on the role of DDR1 in chronic nephropathies and on the effect of its deletion in the pathological processes involved in renal disease progression. DDR1 was shown to be de novo expressed in several models of experimental CKD. Its genetic or pharmaco-genetic inhibition led to the preservation of renal structure and function, and to decreased inflammatory influx and fibrosis. Furthermore, delayed pharmaco-genetic inhibition of DDR1 led to significant protection in models of renal disease. These results demonstrate the involvement of DDR1 in inflammatory and fibrotic processes occurring during CKD and the beneficial effect of its inhibition. Thus, DDR1 could be an interesting therapeutic target to treat renal pathologies.


Drug resistance in tuberculosis--a reinfection model.
There is increasing recognition that reinfection is an important component of TB transmission. Moreover, it has been shown that partial immunity has significant epidemiological consequences, particularly in what concerns disease prevalence and effectiveness of control measures. We address the problem of drug resistance as a competition between two types of strains of Mycobacterium tuberculosis: those that are sensitive to anti-tuberculosis drugs and those that are resistant. Our objective is to characterise the role of reinfection in the transmission of drug-resistant tuberculosis. The long-term behaviour of our model reflects how reinfection modifies the conditions for coexistence of sensitive and resistant strains. This sets the scene for discussing how strain prevalence is affected by different control strategies. It is shown that intervention effectiveness is highly sensitive to the baseline epidemiological setting.


Social determinants of health: present status, unanswered questions, and future directions.
This article reviews the current status of theory and research concerning the social determinants of health. It provides an overview of current conceptualizations and evidence on the impact of various social determinants of health. The contributions of different disciplines--epidemiology, sociology, political economy, and the human rights perspective--to the field are acknowledged, but profound gaps persist in our understanding of the forces that drive the quality of various social determinants of health and why research is too infrequently translated into action. Many of these gaps in knowledge concern the political, economic, and social forces that make implementation of public policy agendas focused on strengthening the social determinants of health problematic. The author identifies the areas of inquiry needed to help translate knowledge into action.


The parents', hospitalized child's, and health care providers' perceptions and experiences of family centered care within a pediatric critical care setting: a metasynthesis of qualitative research.
The delivery of family centered care (FCC) occurs within varied pediatric care settings with a belief that this model of care meets the psychosocial, emotional, and physical needs of the hospitalized child and family. The aim of this review was to explore the attitudes, experiences, and implementation of FCC from many studies and to facilitate a wider and more thorough understanding of this practice from a diverse sample of parents, hospitalized children, and their health care providers within a pediatric critical care setting. A metasynthesis is an integration of qualitative research findings based on a systematic review of the literature. Thirty original research articles focusing on family-centered care experiences from the hospitalized child's, parents', and health care providers' perception published between 1998 and 2011 met the criteria for the review. Nine syntheses from 17 themes emerged from the synthesis of the literature: Prehospital, Entry into the Hospital, Journeying Through Unknown Waters, Information, Relationships, The hospital Environment, The Possibility of Death, Religion and Spirituality, and The Journey Home. The individual cultures of the critical care units helped create and reinforce the context of parental needs where satisfaction with communication, information, and relationships were interconnecting factors that helped maintain the positive or negative experiences for the parent, hospitalized child, and/or health care providers.


Is there a doctor in the house? Availability of Israeli physicians to the workforce.
Israeli policymakers have expressed serious concerns about being able to meet the growing demand for physician services. For this reason, the Israel Ministry of Health (MoH) undertook studies based on 2008 and then 2012 data to obtain an accurate assessment of the size, specialty mix, demographic and geographic composition of the physician workforce. This paper highlights the findings from these studies about the number and percentage of licensed physicians in Israel who were not available, were only partially available, or were about to leave the Israeli healthcare workforce. The two studies cross-linked administrative files of the entire physician population in Israel. The two sources were the MoH registry of licensed physicians, which contains demographic, medical education and specialty information, and the Israel Tax Authority income file on employment data. A third source, used only for the study of 2008 data, was the CBS Population Census Data 2008 which was based on a large representative sample of the population (14%), along with the updated Population Registry, which provided data on physicians whose occupation was in medical care as well as the number of work-hours. By linking the files we could also assess the population of licensed Israeli physicians living abroad. Only 74% of licensed physicians of all ages in 2012 were active in the Israeli workforce. Of physicians under the age of 70, 87% were living and working in Israel. Female physicians tended to retire from the workforce earlier than males and were more likely to work fewer hours during their working years. The rate of physicians who worked longer hours declined in both genders as age rose. About 10% of licensees had been living abroad for at least a year and the majority of these were older. Approximately 7% of licensed physicians, ages 30-44, were abroad and most are presumed to be doing additional clinical training or gaining research experience. In some specialty fields young physicians were not replacing retirees at a compensatory rate; anesthesiologists, a specialty in short supply in Israel were more likely to be living abroad than other specialists. Assessment of the medical workforce pool and personnel planning require not just the number of licensed physicians but also information about the employment mix of license holders and their level of professional activity in Israel. For planning future workforce needs, it is important to keep in mind that the average female vs. male physician has lower clinical productivity due to shorter hours and earlier retirement and that a group of young physicians will predictably be abroad at any point in time; however major "brain drain" is not evident. Furthermore, extrapolating from the findings in the current studies, we believe that a potential shortage of physicians within Israel can be mitigated by better administrative support of physicians, use of physician extenders, and careful attention to improving physician satisfaction in certain specialties.


Sentinel visits in emergency department patients with diabetes mellitus as a warning sign for hyperglycemic emergencies.
Patients with poorly controlled diabetes mellitus may have a sentinel emergency department (ED) visit for a precipitating condition prior to presenting for a hyperglycemic emergency, such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS). This study's objective was to describe the epidemiology and outcomes of patients with a sentinel ED visit prior to their hyperglycemic emergency visit. This was a 1-year health records review of patients≥18 years old presenting to one of four tertiary care EDs with a discharge diagnosis of hyperglycemia, DKA, or HHS. Trained research personnel collected data on patient characteristics, management, disposition, and determined whether patients came to the ED within the 14 days prior to their hyperglycemia visit. Descriptive statistics were used to summarize the data. Of 833 visits for hyperglycemia, 142 (17.0%; 95% CI: 14.5% to 19.6%) had a sentinel ED presentation within the preceding 14 days. Mean (SD) age was 50.5 (19.0) years and 54.4% were male; 104 (73.2%) were discharged from this initial visit, and 98/104 (94.2%) were discharged either without their glucose checked or with an elevated blood glucose (>11.0 mmol/L). Of the sentinel visits, 93 (65.5%) were for hyperglycemia and 22 (15.5%) for infection. Upon returning to the ED, 61/142 (43.0%) were admitted for severe hyperglycemia, DKA, or HHS. In this unique ED-based study, diabetic patients with a sentinel ED visit often returned and required subsequent admission for hyperglycemia. Clinicians should be vigilant in checking blood glucose and provide clear discharge instructions for follow-up and glucose management to prevent further hyperglycemic emergencies from occurring.


Hypnozoites in Bradford.
We present two paediatric cases of a condition that should be considered when a child of an immigrant family presents to the A&E department with a pyrexia with no obvious focus of infection.


Expression of RON Proto-oncogene in Renal Oncocytoma and Chromophobe Renal Cell Carcinoma.
Recently, it was reported that RON proto-oncogene, encoding a receptor tyrosine kinase, was strongly expressed in renal oncocytomas but not in any renal cell carcinomas, including 5 chromophobe renal cell carcinomas, which morphologically resemble oncocytomas. To determine its diagnostic value, we studied Ron protein expression by immunohistochemistry in a larger number of renal cell neoplasms with emphasis on chromophobe renal cell carcinomas. Tissue microarrays containing 141 renal cell neoplasms, including 55 oncocytomas and 52 chromophobe renal cell carcinomas, were constructed. In addition, conventional sections from 15 cases of oncocytoma and 5 cases of chromophobe renal cell carcinoma were analyzed. Immunohistochemistry was carried out with a monoclonal mouse anti-human Ron-alpha antibody. Staining intensity was scored on a 0 to 3 scale. Ninety-nine percent of oncocytomas (69 of 70) and 96% of chromophobe renal cell carcinomas (55 of 57) showed moderate to strong, diffuse cytoplasmic Ron immunoreactivity with intensities > or =2, while only 17% of other renal cell carcinoma subtypes stained with intensities > or =2. Our study indicates that Ron immunostaining cannot be used to distinguish oncocytoma from chromophobe renal cell carcinoma.


Complexation of Am(III) and Eu(III) with DRAPA (N,N-dialkyl-6-amide-pyridine-2-carboxylic acid).
The similarity of the coordination chemistry of Am(III) and Eu(III) and two homologous tridentate ligands, N,N-di-2-ethylhexyl-6-amide-pyridine-2-carboxylic acid (DEHAPA, HL') in solvent extraction and N,N-dimethyl-6-amide-pyridine-2-carboxylic acid (DMAPA, HL) in aqueous solution and in the solid state, is revealed structurally and spectroscopically with complexes ML'3 (org), ML3 (aq) and ML3 (s), respectively.


The occurrence and clinical importance of infectious stage of Echinocephalus (Nematoda: Gnathostomidae) larvae in selected Australian edible fish.
Cases of gnathostomiasis, an infection caused by consuming infected seafood, have been reported in Australia. However, doubt exists over the validity of these diagnoses as there are no reports of Gnathostoma spp. in Australian teleost fish. Also, the diagnoses in human cases were based on a serological test developed in Thailand. The specificity and sensitivity of this test in non-endemic areas are uncertain. Interestingly, parasites belonging to the genus Echinocephalus, which morphologically are very similar to Gnathostomum, are commonly found in Australian fish and shellfish and can potentially infect humans. The aim of this study was to determine the occurrence of these zoonotic nematodes within commercial fish and to characterise nematode larvae in order to provide insights into the specific identity of the potential causative agents of gnathostomiasis in Australia. Six edible fish species (n = 163) were examined. Gnathostomid-type larvae were found only in Acanthopagrus australis and Rhabdosargus sarba. Detailed examination and sequence data suggested parasite larvae belonged to the genus Echinocephalus. Further investigation of the occurrence of zoonotic nematodes within marine environments and observation of their spatial and temporal patterns will help raise awareness of the significance of this food safety issue within global fishing industries and health sectors. The accurate identification of zoonotic nematodes is a key component of disease surveillance and control. This information can also be used to develop specific and sensitive diagnostic test.


Association of Stress Biomarkers With 30-Day Unplanned Readmission and Death.
The theory that posthospitalization stress might increase the risk of postdischarge complications has never been investigated. To assess whether serum levels of stress biomarkers at discharge are associated with readmission and death after an acute-care hospitalization. We prospectively included 346 patients aged ≥50 years admitted to the department of general internal medicine at a large community hospital between April 8, 2013 and September 23, 2013. We measured the serum levels of several biomarkers at discharge: midregional pro-adrenomedullin, copeptin, cortisol, and prolactin. All patients were followed for up to 90 days after discharge (none was lost to follow-up). The main outcome was first unplanned readmission or death within 30 days after hospital discharge. We assessed the additional value of biomarkers to 2 validated readmission prediction scores: the LACE index (Length of stay, Admission Acuity, Charlson Comorbidity Index, and number of Emergency department visits within preceding 6 months) and the HOSPITAL score (Hemoglobin level at discharge, discharge from Oncology service, Sodium level at discharge, any Procedure performed during index hospitalization, Index admission Type, number of Admissions within preceding 12 months, and Length of stay). Forty patients (11.6%) had a 30-day unplanned readmission or death. High serum copeptin and cortisol levels were associated with an increase in the odds of unplanned readmission or death (odds ratios [95% confidence interval] 2.69 [1.29-5.64] and 3.43 [1.36, 8.65], respectively). We found no significant association with midregional pro-adrenomedullin or prolactin. Furthermore, these stress biomarkers increased the performance of two readmission prediction scores (LACE index and HOSPITAL score). High serum levels of copeptin and cortisol at discharge were independently associated with 30-day unplanned readmission or death, supporting a possible negative effect of hospitalization stress during the postdischarge period. Stress biomarkers improved the performance of prediction models and therefore could help better identify high-risk patients.


[Analysis of factors associated with quality of life for patients with non-small lung cancer receiving outpatient vinorelbine therapy as alternative inpatient therapy].
An increasing number of patients with lung cancer are undergoing outpatient chemotherapy as an alternative inpatient therapy. To investigate the factors influencing the quality of life (QOL) for these patients,we used a QOL questionnaire, "The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs" (QOL-ACD) for 8 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories indicating "activity," "physical condition," "psychological condition," "social relationship" and "face scale" were analyzed. Significant improvements in the factors indicating "psychological condition" were observed in this study.


From transcriptome to biological function: environmental stress in an ectothermic vertebrate, the coral reef fish Pomacentrus moluccensis.
Our understanding of the importance of transcriptional regulation for biological function is continuously improving. We still know, however, comparatively little about how environmentally induced stress affects gene expression in vertebrates, and the consistency of transcriptional stress responses to different types of environmental stress. In this study, we used a multi-stressor approach to identify components of a common stress response as well as components unique to different types of environmental stress. We exposed individuals of the coral reef fish Pomacentrus moluccensis to hypoxic, hyposmotic, cold and heat shock and measured the responses of approximately 16,000 genes in liver. We also compared winter and summer responses to heat shock to examine the capacity for such responses to vary with acclimation to different ambient temperatures. We identified a series of gene functions that were involved in all stress responses examined here, suggesting some common effects of stress on biological function. These common responses were achieved by the regulation of largely independent sets of genes; the responses of individual genes varied greatly across different stress types. In response to heat exposure over five days, a total of 324 gene loci were differentially expressed. Many heat-responsive genes had functions associated with protein turnover, metabolism, and the response to oxidative stress. We were also able to identify groups of co-regulated genes, the genes within which shared similar functions. This is the first environmental genomic study to measure gene regulation in response to different environmental stressors in a natural population of a warm-adapted ectothermic vertebrate. We have shown that different types of environmental stress induce expression changes in genes with similar gene functions, but that the responses of individual genes vary between stress types. The functions of heat-responsive genes suggest that prolonged heat exposure leads to oxidative stress and protein damage, a challenge of the immune system, and the re-allocation of energy sources. This study hence offers insight into the effects of environmental stress on biological function and sheds light on the expected sensitivity of coral reef fishes to elevated temperatures in the future.


A regulatory node involving Gαq, PLCβ, and RGS proteins modulates platelet reactivity to critical agonists.
Most platelet agonists work through G protein-coupled receptors, activating pathways that involve members of the Gq, Gi, and G12/G13 families of heterotrimeric G proteins. Gq signaling has been shown to be critical for efficient platelet activation. Growing evidence suggests that regulatory mechanisms converge on G protein-coupled receptors and Gq to prevent overly robust platelet reactivity. To identify and characterize mechanisms by which Gq signaling is regulated in platelets. Based on our prior experience with a Gαi2 variant that escapes regulation by regulator of G protein signaling (RGS) proteins, a Gαq variant was designed with glycine 188 replaced with serine (G188S) and then incorporated into a mouse line so that its effects on platelet activation and thrombus formation could be studied in vitro and in vivo. As predicted, the G188S substitution in Gαq disrupted its interaction with RGS18. Unexpectedly, it also uncoupled PLCβ-3 from activation by platelet agonists as evidenced by a loss rather than a gain of platelet function in vitro and in vivo. Binding studies showed that in addition to preventing the binding of RGS18 to Gαq, the G188S substitution also prevented the binding of PLCβ-3 to Gαq. Structural analysis revealed that G188 resides in the region that is also important for Gαq binding to PLCβ-3 in platelets. We conclude that the Gαq signaling node is more complex than that has been previously understood, suggesting that there is cross-talk between RGS proteins and PLCβ-3 in the context of Gαq signaling.


Hormones and the stressed brain.
The stress system orchestrates brain and body responses to the environment. Cortisol (in humans) or corticosterone (in rodents) are important mediators of the stress system. Their action-in concert-is crucial for individual differences in coping with other individuals, which in turn depend on genetic- and experience-related factors. The actions exerted by cortisol and corticosterone have an enormous diversity. They include the regulation of rapid molecular aggregations, membrane processes, and gene transcription. In the latter transcriptional regulation, the corticosteroid hormones have two modes of operation. One mode is mediated by high-affinity mineralocorticoid receptors (MRs), which control gene networks underlying stabilization of neuronal activity as determinant for the sensitivity to trigger immediate responses to stress organized by corticotrophin-releasing hormone (CRH)-1 receptor. Whereas disturbance of homeostasis is prevented by MR-mediated processes, its recovery is facilitated via the low-affinity glucocorticoid receptors (GRs) that require stress levels of cortisol. GRs promote in coordination with CRH-2 receptors and the parasympathetic system behavioral adaptation and enhances storage of energy and information in preparation for future events. The balance in the two stress system modes is thought to be essential for cell homeostasis, mental performance, and health. Imbalance induced by genetic modification or stressors changes specific neural signaling pathways underlying cognition and emotion. This yin-yang concept in stress regulation is fundamental for genomic strategies to understand the mechanistic underpinning of corticosteroid-induced stress-related disorders such as severe forms of depression.


Crystal-Field and Covalency Effects in Uranates: An X-ray Spectroscopic Study.
The electronic structure of U(V) - and U(VI) -containing uranates NaUO3 and Pb3 UO6 was studied by using an advanced technique, namely X-ray absorption spectroscopy (XAS) in high-energy-resolution fluorescence-detection (HERFD) mode. Due to a significant reduction in core-hole lifetime broadening, the crystal-field splittings of the 5f shell were probed directly in HERFD-XAS spectra collected at the U 3d edge, which is not possible by using conventional XAS. In addition, the charge-transfer satellites that result from U 5f-O 2p hybridization were clearly resolved. The crystal-field parameters, 5f occupancy, and degree of covalency of the chemical bonding in these uranates were estimated by using the Anderson impurity model by calculating the U 3d HERFD-XAS, conventional XAS, core-to-core (U 4f-3d transitions) resonant inelastic X-ray scattering (RIXS), and U 4f X-ray photoelectron spectra. The crystal field was found to be strong in these systems and the 5f occupancy was determined to be 1.32 and 0.84 electrons in the ground state for NaUO3 and Pb3 UO6 , respectively, which indicates a significant covalent character for these compounds.


[The nurse interacting and relating: the context of nursing care in a semi-intensive unit].
This study aimed to understand the meaning of nursing care to nurses in the hospital. This is a qualitative research, based on theoretical and methodological assumptions of symbolic interaction. It was performed in a semi-intensive unit of a tertiary public hospital in Fortaleza-CE, Brazil. Eleven nurses participated on it. For data collection, it was used semi-structured interviews and field observation simple and, in data processing it was performed thematic category. The ethical aspects have been respected. It was observed that the nursing care means the establishment of the nurse's interpersonal relationships with other health professionals, patients and their accompanying persons. It was understood that, for nurses of the hospital, nursing care means social interaction with people.


Indel-II region deletion sizes in the white spot syndrome virus genome correlate with shrimp disease outbreaks in southern Vietnam.
Sequence comparisons of the genomes of white spot syndrome virus (WSSV) strains have identified regions containing variable-length insertions/deletions (i.e. indels). Indel-I and Indel-II, positioned between open reading frames (ORFs) 14/15 and 23/24, respectively, are the largest and the most variable. Here we examined the nature of these 2 indel regions in 313 WSSV-infected Penaeus monodon shrimp collected between 2006 and 2009 from 76 aquaculture ponds in the Mekong Delta region of Vietnam. In the Indel-I region, 2 WSSV genotypes with deletions of either 5950 or 6031 bp in length compared with that of a reference strain from Thailand (WSSV-TH-96-II) were detected. In the Indel-II region, 4 WSSV genotypes with deletions of 8539, 10970, 11049 or 11866 bp in length compared with that of a reference strain from Taiwan (WSSV-TW) were detected, and the 8539 and 10970 bp genotypes predominated. Indel-II variants with longer deletions were found to correlate statistically with WSSV-diseased shrimp originating from more intensive farming systems. Like Indel-I lengths, Indel-II lengths also varied based on the Mekong Delta province from which farmed shrimp were collected.


Cloning of a human epididymis-specific mRNA, HE6, encoding a novel member of the seven transmembrane-domain receptor superfamily.
A novel gene product, HE6, showing homology to the seven transmembrane-domain (Tm7) receptor superfamily, has been cloned by differential screening from a human epididymal cDNA library. The cDNA clone represented an abundant approximately 5-kb mRNA, comprising 0.01% of the cDNA library. Northern blot analysis including various human tissues revealed an epididymis-specific expression. In situ transcript hybridization localized the mRNA within the epithelial cells lining the epididymal duct. Southern blot analysis, employing a fragment encoding part of the amino-terminal extracellular domain as a probe, identified an autosomal single-copy gene in the human genome. Homologous cDNA products showing 90% sequence identity were observed in the epididymides of all mammalian species investigated. A cloning and sequencing strategy, combining approximately 3.7-kb cDNA fragments obtained by conventional cDNA library construction with overlapping 5' rapid amplification of cDNA ends (RACE) fragments, yielded total sequence information of 4.7 kb for the human mRNA. This sequence comprises a long open reading frame of 3.1 kb. A homology search for related sequences revealed highest similarity (25% amino acid identity) with the secretin/vasoactive intestinal peptide (VIP) superfamily of G-protein-coupled receptors. The predicted extracellular amino-terminal extension, however, was much longer than in the other members, and showed similarity to highly glycosylated mucin-like cell-surface molecules.


Effects of verapamil on electroconvulsive shock- and clonidine-induced amnesia.
The effect of the Ca2+ blocker verapamil on amnesia induced by electroconvulsive shock (ECS) or by the alpha-adrenoceptor agonist clonidine was studied in male Wistar rats trained in passive avoidance task ("step down"). Clonidine (0.1 mg/kg, i.p.) and ECS induced a pronounced amnesia, significantly reducing the percentage of rats that had acquired the task upon retention tests, given 3 h, 24 h and 7 days after training. Verapamil (10 mg/kg) administered orally for 12 days (5 days before and 7 days after training) completely abolished the ECS- or clonidine-induced amnesia. These data suggest that calcium channel blocker verapamil has a protective effect against experimentally provoked memory deficit and might be useful for the treatment of cognitive disorders.


Comparative evaluation of native top feeds of western Himalayas for utilization as goat's ration in mash and block form.
The current research was undertaken to scrutinize the effect of leaf meal mixture as concentrate mixture in the ration of goats. Leaf meal mixture (LMM) was prepared using equal quantities of ten top-foliages namely Acacia nilotica, Celtis australis, Ficus palmata, Ficus religiosa, Grewia optiva, Melia azadarach, Morus alba, Quercus incana, Salix alba and Zizyphus jujube obtained from district Poonch of Jammu region in western Himalayas. The LMM prepared was substituted for 15% in the concentrate mixture being fed to the goats. The study constituted of two trials. Concentrate mixture offered to the animals was in mash and multi-nutrient block in first and second trial respectively. A total of twelve non-descript, adult male goats were selected for each trial. Goats of 0-14 months age (27.71 ± 2.96 kg live body weight) of for first trial while goats of 12-16 months age (27.02 ± 2.93 kg live weight) for second trial were divided into control and treatment groups as per randomized block design and fed ad-lib wheat straw and concentrate mixture @ (20 g/kgW0.75). No significant variation was observed (p > 0.05) in body weight, feed and DM intake among all groups in both trials. Comparable intake as well as digestibility of various nutrients like DM, OM, CP, EE, CF, NFE, NDF, ADF and TDN were found between the two groups during individual trials. There was a positive nitrogen, calcium and phosphorus balance among all experimental animals in both the trials. Serum enzymes ALT, AST and haemato-biochemical parameters like total protein, albumin, globulin, albumin: globulin and blood urea nitrogen (BUN) showed no significant differences during both trials in all groups, being within normal physiological levels. However, haemoglobin concentration was significantly higher (P < 0.05) in treatment group with respect to the control group in first trial. On the basis of current results, it can be established that leaf meal mixture can successfully be used to replace concentrate mixture up to 15% in the ration of goats without expecting any adverse impacts on their growth and overall health.


Cystine-rich fish antifreeze is produced as an active proprotein precursor in fall armyworm cells.
Recombinant cystine-rich fish antifreeze protein (AFP) was produced by fall armyworm cells from a baculovirus expression vector containing sea raven AFP cDNA. The natural signal sequence encoded in the cDNA directed secretion of the antifreeze into the medium, from where it was recovered and purified to homogeneity. The M(r) of the exported protein (16k), as determined by SDS-PAGE, was larger than that (14k) of mature AFP isolated from sea raven serum. Sequencing of the recombinant AFP showed that it had a 17-amino-acid extension N-terminal to the 129-amino-acid mature AFP that began where signal peptide cleavage should occur according to current algorithms. Recombinant proAFP had antifreeze activity equivalent to that of the mature AFP, which indicates that the disulfide bonds were correctly formed and that the ice-binding site on the antifreeze is not sterically hindered by the 17-amino-acid N-terminal extension.


Psychological and social adjustment to mastectomy: a two-year follow-up study.
A consecutive series of 160 women admitted to hospital for breast tumor biopsy was assessed prior to, and at 3, 12, and 24 months following operation for marital, sexual, interpersonal and work adjustment, depression, and personality characteristics by means of rating scales based on structures interviews and standard tests. By 2 years there wery no significant differences in social adjustment between mastectomy patients and benign breast disease controls; 70% of cancer patients were no longer stressed by mastectomy at 1 year. Factors predicting poor adjustment to mastectomy were high preoperative scores on the Hamilton Rating Scale for Depression and the Neuroticism Scale of the Eysenck Personality Inventory; deterioration in sexual adjustment was associated with biological or chronological perimenopausal status. Significantly more cancer than benign disease patients were dissatisfied with the information they received about operation and diagnosis. Implications of these findings for the care of the mastectomy patient are discussed.


Euclidean distance can identify the mannitol level that produces the most remarkable integral effect on sugarcane micropropagation in temporary immersion bioreactors.
Plant scientists usually record several indicators in their abiotic factor experiments. The common statistical management involves univariate analyses. Such analyses generally create a split picture of the effects of experimental treatments since each indicator is addressed independently. The Euclidean distance combined with the information of the control treatment could have potential as an integrating indicator. The Euclidean distance has demonstrated its usefulness in many scientific fields but, as far as we know, it has not yet been employed for plant experimental analyses. To exemplify the use of the Euclidean distance in this field, we performed an experiment focused on the effects of mannitol on sugarcane micropropagation in temporary immersion bioreactors. Five mannitol concentrations were compared: 0, 50, 100, 150 and 200 mM. As dependent variables we recorded shoot multiplication rate, fresh weight, and levels of aldehydes, chlorophylls, carotenoids and phenolics. The statistical protocol which we then carried out integrated all dependent variables to easily identify the mannitol concentration that produced the most remarkable integral effect. Results provided by the Euclidean distance demonstrate a gradually increasing distance from the control in function of increasing mannitol concentrations. 200 mM mannitol caused the most significant alteration of sugarcane biochemistry and physiology under the experimental conditions described here. This treatment showed the longest statistically significant Euclidean distance to the control treatment (2.38). In contrast, 50 and 100 mM mannitol showed the lowest Euclidean distances (0.61 and 0.84, respectively) and thus poor integrated effects of mannitol. The analysis shown here indicates that the use of the Euclidean distance can contribute to establishing a more integrated evaluation of the contrasting mannitol treatments.


[Dynamics of peripheral blood B lymphocytes and natural killer cells in patients with severe acute respiratory syndrome].
To study the dynamics of peripheral blood B lymphocytes and natural killer (NK) cells in patients with severe acute respiratory syndrome (SARS). The absolute numbers of peripheral blood B lymphocytes and NK cells in 602 serial samples from 240 patients with SARS were counted, using flow cytometry, and compared with that of normal population. The absolute numbers of peripheral blood B lymphocytes and NK cells in SARS patients were significantly lower than that of the normal population (P < 0.001) and were much lower in SARS patients with severe or extremely severe types, as compared with that of moderate or mild type cases (P < 0.001). The amount of B lymphocytes in recovery SARS patients increased at the 2nd week after onset, and gradually becoming normal at the 5th week of the disease onset. The number of NK cells was in the low level at onset, and keep decreasing at the 2nd week. However, it was increasing with the recovery of the disease, but did not reach to normal level at the 5th week after onset. The absolute numbers of peripheral blood B lymphocytes and NK cells were associated with the severity of the disease, and detection of these two kinds of cells was useful for predicting the prognosis of SARS.


Cloning and sequencing of a species-specific nucleotide fragment of Borrelia burgdorferi sensu stricto, which is repeated in several plasmids of the species.
Among the etiological agents of Lyme disease, Borrelia burgdorferi sensu stricto strains carry a 16 kb plasmid, which did not hybridize to plasmids of B. garinii and B. afzelii strains. A 1271 bp DNA fragment of the 16 kb plasmid was cloned. It hybridized to several plasmids of this species (16, 27 and 55 kb). Sequencing of the cloned insert revealed a 327 bp ORF coding for a 14 kDa protein of unknown function, which could be expressed in E. coli. This ORF, conserved among B. burgdorferi sensu stricto strains, was carried by the same three plasmids.


In vivo detection of amyloid-β deposits using heavy chain antibody fragments in a transgenic mouse model for Alzheimer's disease.
This study investigated the in vivo properties of two heavy chain antibody fragments (V(H)H), ni3A and pa2H, to differentially detect vascular or parenchymal amyloid-β deposits characteristic for Alzheimer's disease and cerebral amyloid angiopathy. Blood clearance and biodistribution including brain uptake were assessed by bolus injection of radiolabeled V(H)H in APP/PS1 mice or wildtype littermates. In addition, in vivo specificity for Aβ was examined in more detail with fluorescently labeled V(H)H by circumventing the blood-brain barrier via direct application or intracarotid co-injection with mannitol. All V(H)H showed rapid renal clearance (10-20 min). Twenty-four hours post-injection (99m)Tc-pa2H resulted in a small yet significant higher cerebral uptake in the APP/PS1 animals. No difference in brain uptake were observed for (99m)Tc-ni3A or DTPA((111)In)-pa2H, which lacked additional peptide tags to investigate further clinical applicability. In vivo specificity for Aβ was confirmed for both fluorescently labeled V(H)H, where pa2H remained readily detectable for 24 hours or more after injection. Furthermore, both V(H)H showed affinity for parenchymal and vascular deposits, this in contrast to human tissue, where ni3A specifically targeted only vascular Aβ. Despite a brain uptake that is as yet too low for in vivo imaging, this study provides evidence that V(H)H detect Aβ deposits in vivo, with high selectivity and favorable in vivo characteristics, making them promising tools for further development as diagnostic agents for the distinctive detection of different Aβ deposits.


[Pharmacokinetics and pharmacodynamics of thiopental sodium in pregnant women during cesarean section].
Comparative study of thiopental pharmacokinetics and hemodynamics has been conducted in two groups of pregnant women subjected to planned cesarean section. Group I consisted of 6 women (thiopental dose 8.0 mg/kg was combined with components of neuroleptanalgesia), group II consisted of 7 women (the drug dose 4.68 mg/kg was combined with moradol analgesia). Dose-dependent differences in pharmacokinetic regularities of sodium thiopental in the groups compared have been revealed. Moradol did not cause the drug accumulation in the bodies of mother and fetus. The higher Apgar score was characteristic of the newborns from group II. Adequate anesthesia in pregnant women from group II was due to the potentiating effect of moradol. In both groups a correlation has been established between pharmacokinetic parameters and hemodynamic changes, as well as between sodium thiopental concentration in maternal and umbilical blood and pharmacokinetic parameters.


Hydatid renal cyst with characteristic sonographic pattern. A case report.
The kidney is a rare localisation of the hydatid cyst even in countries with a high rate of infestation. We report a case of renal hydatid cyst in a five-year-old girl. Conventional radiology did not yield any diagnosis, whereas in this case renal ultrasonography showed characteristic echographic signs pointing to the origin of the disease.


Acute pancreatitis and acute respiratory distress syndrome complicating dengue haemorrhagic fever.
Dengue infection is now known to present with wide spectrum of complications. Isolated cases of acute pancreatitis complicating dengue haemorrhagic fever have been reported in literature. Here the authors report a case of dengue haemorrhagic fever that develops acute pancreatitis and presented with acute onset of breathlessness, which then progressed to full-blown acute respiratory distress syndrome. To our knowledge, this is the first reported case of dengue haemorrhagic fever complicated with acute pancreatitis and acute respiratory distress syndrome.


The cardioprotective effects of statins.
Many large randomized clinical trials have demonstrated that statins are effective in terms of prevention of cardiovascular events. It has been presumed that these beneficial effects could be due to not only improved plasma lipid profiles but also to the direct actions on the vascular wall. In addition to the direct vascular protective effects, several lines of experimental evidence have been accumulated that statins have also cardioprotective effects against ischaemia/reperfusion injury. This effect appears to be a class-effect and activation and up-regulation of eNOS by statins play an important role.


Enhanced view totally extraperitoneal approach: A better alternative to transabdominal preperitoneal approach for irreducible inguinoscrotal and giant inguinal hernias!
The advantages of enhanced view totally extraperitoneal (eTEP) over TEP approach are well established in large inguinoscrotal, recurrent inguinal, patients with short pubis to umbilicus distance and in obese patients. Irreducible inguinoscrotal hernias (IISHs) and giant inguinal hernias (GIHs) pose a great challenge. GIHs are hernias which extend below the midpoint of the inner thigh with the patient in the standing position. Majority of these hernias are managed by open, hybrid or by transabdominal pre-peritoneal (TAPP) approach. TAPP was considered the optimal minimally invasive approach for these hernias as it provides a large working space and reduction of contents under vision. My practice of eTEP has been limited to IISH and GIH. I would like to share some technical tips to manage these cases by eTEP approach.


Effect of molecular weight and ratio of poly ethylene glycols' derivatives in combination with trehalose on stability of freeze-dried IgG.
The influence of poly ethylene glycol (PEG) at different molecular weights (MWs) and ratios was studied on the stability of freeze-dried immune globulin G (IgG). PEGs (600-4000 Dalton) at concentrations of 0.5 and 5% W/V were applied in the presence of 40 and 60% W/W of trehalose to prepare freeze-dried IgG formulations. Size-exclusion chromatography, infra-red spectroscopy, differential scanning calorimeter, and gel electrophoresis were performed to characterize lyophilized samples. Pure IgG demonstrated the highest aggregation of 5.77 ± 0.10% after process and 12.66 ± 0.50% as well as 44.69 ± 0.50% upon 1 and 2 months of storage at 45 °C, respectively. 5% W/V of PEGs 4000 in combination with 40% W/W trehalose, significantly suppressed aggregation, 0.05 ± 0.01%, with minimum aggregation rate constant of 0.32 (1/month). The integrity of IgG molecules and secondary conformation were properly preserved in all formulations comparing native IgG. It could be concluded that appropriate concentration and MW of PEGs, prominently augmented stabilizing effect of trehalose on freeze-dried antibody through inserting additional supportive mechanisms of actions.


Effectiveness and safety of belimumab in patients with systemic lupus erythematosus in a real-world setting.
Objective: To investigate the effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a real-life setting.Methods: All SLE patients treated with belimumab in the Department of Autoimmune Diseases of the Hospital Clinic of Barcelona were retrospectively analysed. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, clinical SLEDAI-2K, levels of anti-double-stranded DNA (anti-dsDNA) antibody, complement components C3 and C4, and 50% haemolytic complement activity (CH50) were recorded at baseline and at 6, 12, and 24 months. Adverse events were also collected.Results: Twenty-three patients (100% women) were enrolled in the study. The most frequent manifestations that led to belimumab use were arthritis (91%) and skin involvement (39%). Both SLEDAI-2K and clinical SLEDAI-2K improved over time at all time-points (p < 0.005). Complement levels increased and the values of anti-dsDNA antibody decreased during treatment. The mean dose of prednisone could be tapered at all time-points and achieved maximum and significant reduction at 24 months (10.4 ± 4.8 mg/day to 4.8 ± 2.1 mg/day; p < 0.0005). Belimumab was well tolerated and only six patients (26%) experienced adverse events, all of which were classified as infections (one urinary tract infection without bacterial detection in urine culture and five viral infections). No deaths, severe infusion reactions, or hypersensitivity reactions were noted.Conclusion: In our patients with SLE, belimumab decreased disease activity and allowed tapering of the daily glucocorticoid dose with a good safety profile.


Human YRNA 4 (HY4) plasma levels are a prognostic indicator of SARS-CoV-2 infection clinical severity.
SARS-CoV-2 infection can result in a range of outcomes from asymptomatic/mild disease to severe COVID-19/fatality. In this study, we investigated the differential expression of small noncoding RNAs (sncRNAs) between patient cohorts defined by disease severity. We collected plasma samples, stratified these based on clinical outcomes, and sequenced their circulating sncRNAs. Excitingly, we found YRNA HY4 displays significant differential expression (p=0.025) between patients experiencing mild and severe disease. In agreement with recent reports identifying plasma YRNAs as indicators of influenza infection severity, our results strongly suggest that circulating HY4 levels represent a powerful prognostic indicator of likely SARS-CoV-2 patient infection outcome.


Targeting the HGF/SF receptor c-met using a hammerhead ribozyme transgene reduces in vitro invasion and migration in prostate cancer cells.
Hepatocyte growth factor scatter factor (HGF/SF) elicits a number of biological activities including invasion and migration through activation of its tyrosine kinase receptor c-Met. Over expression of c-Met has been implicated in prostate cancer development and progression. This study examined the effect of a ribozyme transgene, designed to inhibit human c-Met expression, and its impact on in vitro invasion and migration in prostate cancer. A transgene (Met 560) consisting of U1 snRNA, hammerhead ribozyme, and antisense was cloned into a modified pZeoU1-EcoSpe vector and transfected into DU-145 cells. The effect of HGF/SF was tested on prostate cancer cells whose expression of c-Met had been blocked by way of a ribozyme transgene. Met 560 stable transfectants (DU-145(+/+)) manifested a complete loss of c-Met expression at mRNA and protein levels. In contrast, control plasmid (DU-145(+/-)) and wild-type DU-145 cells (DU-145(-/-)) had similar levels of c-Met expression. HGF/SF significantly increased the in vitro invasiveness (mean 47.71 +/- SE 7.75; P < 0.01 vs. control 24.14 +/- 1.34), and migration (mean 48.44 +/- SE 3.51; P < 0.01 vs. control 22.95 +/- 1.47) of DU-145(-/-) cells, respectively. Similarly, HGF/SF also increased the invasion (62.33 +/- 6.34; P < 0.001 vs. control 24.5 +/- 2.35) and migration (46.14 +/- 2.26; P < 0.01 vs. control 21.82 +/- 1.62) of DU-145(+/-) cells. In contrast, DU-145(+/+) cells had lost its response to HGF/SF induced invasion (22.33 +/- 2.08; P > 0.05 vs. control 23.5 +/- 2.11) and migration (24.12 +/- 0.86; P > 0.05 vs. control 23.27 +/- 0.81). Targeting the HGF/SF receptor by way of a hammerhead ribozyme encoding antisense to c-Met, is an effective method to reduce the invasive or migration potential in prostate cancer, and may have important therapeutic implications.


Performance improvement of Li-rich layer-structured Li(1.2)Mn(0.54)Ni(0.13)Co(0.13)O2 by integration with spinel LiNi(0.5)Mn(1.5)O4.
Li-rich layered Li1+xMnyM1-x-yO2 (or denoted xLi2MnO3·(1 -x)LiMO2, M = Ni, Co, Mn, etc.) are promising cathode materials for high energy-density Li-ion batteries. However, their commercial applications suffer from problems such as a drop in the capacity and discharge voltage during cycling. In this work, the cycling performance of a layered oxide Li1.2Ni0.13Co0.13Mn0.54O2 is improved by integration with spinel LiNi0.5Mn1.5O4 to obtain a layered-spinel composite. Characterization by powder X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM) as well as cyclic voltammetry (CV) indicates that delayed degradation of layered Li2MnO3 and the suppressed growth of LiMn2O4-like spinel are responsible for the performance improvement.


Interaction of BDNF and cytokines in executive dysfunction in patients with chronic schizophrenia.
Multiple lines of evidence indicate that patients with chronic schizophrenia (SCZ) display executive dysfunction across the illness course. However, the potential molecular pathophysiologic mechanisms remain poorly elucidated. Neurodevelopmental changes caused by alterations of inflammatory mediators and neurotrophins have been shown to occur in the earliest stages of SCZ, and be associated with executive dysfunction (ED) in SCZ. Therefore, the current study was to investigate whether the interplay between BDNF and inflammatory mediators was involved in the disruption of executive function of long-term hospitalized patients with chronic SCZ. Serum cytokines and BDNF levels were measured in 112 long-term hospitalized patients with chronic SCZ and 44 healthy normal controls. Executive functions were assessed by verbal fluency tests (VFT), the Stroop word-color test (Stroop), and the Wisconsin card sorting tests (WCST).The results showed that the patients had higher IL-2, IL-6, IL-8, but lower TNF-α and BDNF compared to control subjects. In the patient group, BDNF was positively associated with IL-2 and IL-8 levels, while lower BDNF levels were correlated with ED measured by VFT and WCST tests. Multiple stepwise regression analyses confirmed that BDNF × IL-8 and BDNF × TNF-α were factors influencing the total score of VFT, while BDNF × IL-8 and BDNF × TNF-α were recognized as influencing factors for WCST scores. Our results suggest complex interactions between BDNF and cytokines were involved in the pathophysiology of executive function impairments in patients with SCZ.


Pharmacology of 9-gamma-methylaminopropyl-9,10-dihydro-9,10-methanoanthracene-HCl (ID-9206-HCl), a new potent antidepressant.
The pharmacological properties of 9-gamma-methylaminopropyl-9,10-dihydro-9,10-methanoanthracene-HCl (ID-9206-HCl) were examined in comparison with those of imipramine, amitriptyline and maprotiline in animals. ID-9206 showed the characteristic pharmacological profile of an antidepressent: anti-reserpine and anti-tetrabenazine activities, potentiation of central and peripheral actions of norepinephrine, and potentiation of methamphetamine and yohimbine actions. ID-9206 had weak peripheral anticholinergic activities and sedative effects. ID-9206 was less toxic in mice and rats than the other three antidepressants.


Pathology Course Director Perspectives of a Recent LCME Experience: Preparation in an Integrated Curriculum With the Revised Standards.
Preparation for a Liaison Committee of Medical Education (LCME) accreditation site visit is a daunting task for any medical school, particularly for medical schools that have adopted integrated curricula. The LCME accreditation is the standard that all US and Canadian allopathic medical schools must meet in order for the school to award the degree of medical doctor. The Uniformed Services University of the Health Sciences (USU) recently underwent a full-scale LCME accreditation visit that was conducted under the newly revised LCME standards and elements. The site visit occurred just 5 years after our school began implementing a totally revised, organ system-based curriculum. Preparing for a critical, high-stakes site visit shortly after transitioning to a totally revised, integrated module-based preclerkship curriculum presented an array of new challenges that required a major modification to the type of preparation, communication, and collaboration that traditionally occurs between course directors and departmental chairs. These included the need to ensure accurate, timely communication of curricular details to different levels of the academic administration, particularly as it related to the execution of self-directed learning (SDL). Preparation for our site visit, did, however, provide a novel opportunity to highlight the unique educational experiences associated with the study of pathology, as pathology traverses both clinical and basic sciences. Sharing these experiences may be useful to other programs that are either undergoing or who are preparing to undergo an accreditation visit and may also aid in a broader communication of the highlights or initiatives of educational activities.


Conditional survival as a selection strategy to identify plant-inducible genes of Pseudomonas syringae.
A novel strategy termed habitat-inducible rescue of survival (HIRS) was developed to identify genes of Pseudomonas syringae that are induced during growth on bean leaves. This strategy is based on the complementation of metXW, two cotranscribed genes that are necessary for methionine biosynthesis and required for survival of P. syringae on bean leaves exposed to conditions of low humidity. We constructed a promoter trap vector, pTrap, containing a promoterless version of the wild-type P. syringae metXW genes. Only with an active promoter fused to metXW on pTrap did this plasmid restore methionine prototrophy to the P. syringae metXW mutant B7MX89 and survival of this strain on bean leaves. To test this method, a partial library of P. syringae genomic DNA was constructed in pTrap and a total of 1,400 B7MX89 pTrap clones were subjected to HIRS selection on bean leaves. This resulted in the enrichment of five clones, each with a unique RsaI restriction pattern of their DNA insert. Sequence analysis of these clones revealed those P. syringae genes for which putative plant-inducible activity could be assigned. Promoter activity experiments with a gfp reporter gene revealed that these plant-inducible gene promoters had very low levels of expression in minimal medium. Based on green fluorescent protein fluorescence levels, it appears that many P. syringae genes have relatively low expression levels and that the metXW HIRS strategy is a sensitive method to detect weakly expressed P. syringae genes that are active on plants. Furthermore, we found that protected sites on the leaf surface provided a higher level of enrichment for P. syringae expressing metXW than exposed sites. Thus, the metXW HIRS strategy should lead to the identification of P. syringae genes that are expressed primarily in these areas on the leaf.


Environmental/lifestyle factors in the pathogenesis and prevention of type 2 diabetes.
Environmental and lifestyle changes, in addition to the ageing of populations, are generally believed to account for the rapid global increase in type 2 diabetes prevalence and incidence in recent decades. In this review, we present a comprehensive overview of factors contributing to diabetes risk, including aspects of diet quality and quantity, little physical activity, increased monitor viewing time or sitting in general, exposure to noise or fine dust, short or disturbed sleep, smoking, stress and depression, and a low socioeconomic status. In general, these factors promote an increase in body mass index. Since loss of β-cell function is the ultimate cause of developing overt type 2 diabetes, environmental and lifestyle changes must have resulted in a higher risk of β-cell damage in those at genetic risk. Multiple mechanistic pathways may come into play. Strategies of diabetes prevention should aim at promoting a 'diabetes-protective lifestyle' whilst simultaneously enhancing the resistance of the human organism to pro-diabetic environmental and lifestyle factors. More research on diabetes-protective mechanisms seems warranted.


Surface-enhancement Raman scattering sensing strategy for discriminating trace mercuric ion (II) from real water samples in sensitive, specific, recyclable, and reproducible manners.
It is of essential importance to precisely probe mercury(II) (Hg(2+)) ions for environment-protection analysis and detection. To date, there still remain major challenges for accurate, specific, and reliable detection of Hg(2+) ions at subppt level. We herein employ gold nanoparticles (AuNPs) decorated silicon nanowire array (SiNWAr) as active surface-enhanced Raman scattering (SERS) substrates to construct a high-performance sensing platform assisted by DNA technology, enabling ultrasensitive detection of trace Hg(2+) in ∼64 min and with low sample consumption (∼30 μL). Typically, strong SERS signals could be detected when the single-stranded DNA structure converts to the hairpin structure in the presence of Hg(2+) ions, due to the formation of thymine (T)-Hg(2+)-T. As a result, Hg(2+) ions with a low concentration of 1 pM (0.2 ppt) can be readily discriminated, much lower than those (∼nM) reported for conventional analytical strategies. Water samples spiked with various Hg(2+) concentrations are further tested, exhibiting a good linear relationship between the normalized Raman intensities and the logarithmic concentrations of Hg(2+) ranging from 1 pM to 100 nM, with a correlation coefficient of R(2) = 0.998. In addition, such SERS sensor features excellent selectivity, facilely distinguishing Hg(2+) ions from various interfering substances. Moreover, this presented SERS sensor possesses good recyclability, preserving adaptable reproducibility during 5-time cyclic detection of Hg(2+). Furthermore, unknown Hg(2+) concentration in river water can be readily determined through our sensing strategy in accurate and reliable manners, with the RSD value of ∼9%.


The Manic Idea Creator? A Review and Meta-Analysis of the Relationship between Bipolar Disorder and Creative Cognitive Potential.
Even though a relationship between psychopathology and creativity has been postulated since the time of ancient Greece, systematic meta-analyses on this topic are still scarce. Thus, the meta-analysis described here can be considered the first to date that specifically focuses on the relationship between creative potential, as measured by divergent thinking, and bipolar disorder, as opposed to psychopathology in general. An extensive literature search of 4670 screened hits identified 13 suitable studies, including a total of 42 effect sizes and 1857 participants. The random-effects model showed an overall significant, positive, yet diminutively small effect (d = 0.11, 95% CI: [0.002, 0.209], p = 0.045) between divergent thinking and bipolar disorder. A handful of moderators were examined, which revealed a significant moderating effect for bipolar status, as either euthymic (d = 0.14, p = 0.043), subclinical (d = 0.17, p = 0.001), manic (d = 0.25, p = 0.097), or depressed (d = -0.51, p < 0.001). However, moderator analyses should be treated with caution because of the observed confounding of moderators. Finally, none of the employed methods for publication-bias detection revealed any evidence for publication bias. We discuss further results, especially regarding the differences between subclinical and clinical samples.


Development of a flow-injection fluorescence method for estimation of total polycyclic aromatic compounds in asphalt fumes.
Traditionally, measurements of specific polycyclic aromatic compounds (PACs) have been attempted as an estimate of asphalt fume exposure. However, asphalt fumes contain numerous alkyl substituted PACs, including PACs containing heteroatoms of nitrogen, oxygen, and sulfur. Many of these compounds coelute precluding the resolution of the individual compounds resulting in ambiguous data. Moreover, many researchers believe that some observed health hazards are associated with PACs overall and not just a few select PACs. Therefore, NIOSH method 5800 was developed to evaluate total PACs as a chemical class in asphalt fumes. Asphalt fume samples were collected on a poly(tetrafluoroethylene) filter backed by an XAD-2 sorbent tube. The samples were extracted with hexane; then, a cyano-solid-phase-extraction column was used to remove the polar compounds while the aliphatic and aromatic compounds were eluted with hexane. An equal volume of dimethyl sulfoxide (DMSO) was added to the hexane extract, causing the aromatic compounds to partition into the DMSO, thus isolating the PACs. The PACs were then analyzed for fluorescence using a flow-injection method with two fluorescence detectors. Wavelength settings for the first detector (254-nm excitation, 370-nm emission) emphasized the 2- to 4-ring PACs that may cause eye and respiratory tract irritation. Wavelength settings of the second detector (254-nm excitation, 400-nm emission) emphasized the 4- and higher-ring PACs that are often mutagenic and possibly carcinogenic.


Chemistry of acronycine IV. Minor constituents of acronine and the phytochemistry of the genus Acronychia.
In the course of isolating acronycine (1) from an alkaloid fraction of the bark of Acronychia baueri (Rutaceae), five alkaloids, 1,2,3-trimethoxy-10-methyl-acridone (9), 1,3,4-trimethoxy-10-methyl-acridone (10), des-N-methyl acronycine (14), normelicopine (5), and noracronycine (2), were isolated. Four of the isolates are new to the genus, and phytochemical analysis of the genus Acronychia is presented.


[Ancient mental healing and cognitive behavior therapy in comparison].
Although cognitive-behavior therapy (CBT) is a relatively new psychotherapeutic approach, the theoretical antecedents actually date back two thousand years, to the period of the hellenistic philosophers. The Stoic Epictetus is often acknowledged as the main philosophical father of CBT and especially of rational-emotive therapy (RET). Beck and Ellis frequently noted that they have drawn upon the writings of the ancient philosophers in developing their psychotherapeutic techniques. This paper reviews some implications of hellenistic philosophy for CBT. We like to show that the teachings of the ancient 'healer of souls' are remarkably consistent with the current theoretical framework and techniques of CBT.


Relationship competencies in child welfare services.
A series of nine focus groups were conducted to obtain worker and client views of key competencies in child welfare services. Both clients and workers cited the worker's ability to establish an effective working relationship as the primary prerequisite to effective assessment or intervention. A range of specific worker-client relationship competencies are identified and discussed, as are implications of the findings for social work practice, training, and education.


Improved myocardial function using cardiopulmonary support in resuscitation for hemorrhagic shock.
To clarify the pathophysiologic characteristics of hemorrhagic shock and to assess methods of resuscitation. An animal experiment using sheep subjected to hemorrhagic shock and fibrillation to compare various resuscitation techniques. An experimental laboratory setting meant to simulate hemorrhagic shock secondary to trauma. Group 1 animals (n = 6) were controls that were not subjected to shock and fibrillation. Group 2 animals (n = 6) were subjected to shock and fibrillation and were resuscitated with volume replacement. Group 3 animals (n = 6) were also subjected to shock and fibrillation but were resuscitated with epinephrine hydrochloride infusion. Group 4 animals (n = 6) were subjected to shock and fibrillation but were resuscitated with cardiopulmonary support. The shock was to a mean arterial pressure of 25 mm Hg for 1 hour followed by 5 minutes of fibrillation. Group 2 animals were resuscitated for 1 hour. Group 3 animals were supported for 6 hours on epinephrine after the shock period. Group 4 animals were supported for 1 hour on cardiopulmonary support, then were observed for another 5 hours. All animals were sedated and intubated, and a median sternotomy was performed. Survival, hemodynamic function, lactate production, myocardial blood flow, and water content. Group 1 sheep showed no detrimental effects in any of the measured variables. Group 2 sheep could not be resuscitated. Group 3 sheep could be supported with epinephrine but had a 60% depression in left ventricular function and an ultimately high mortality rate (67%) when the infusion of epinephrine was discontinued. Group 4 sheep had a 100% survival rate and only a 20% deterioration in left ventricular function. Cardiopulmonary support improves survival and preserves left ventricular function compared with volume resuscitation with or without inotropic support in this model of hemorrhagic shock.


Interrelationship between bone aging traits and basic anthropometric characteristics.
Using plain hand radiographs, the age dependence of various bone-aging traits (bone mineral density [BMD], cortical index [CI], osteoarthritis [OA], and osseographic [OSS] scores) was evaluated to test whether the correlation among these traits is an individual- or population-based phenomenon. In addition, the effect of anthropometric features on variation of bone-aging traits was estimated. The study included 1,295 individuals from Chuvasha, Russia, 18 to 89 years. BMD was measured from the compact compartment of the middle and distal phalanges of both 3(rd) fingers. The CI of the II-IV metacarpal bones and II-IV proximal phalanges was obtained. The development of OA was based on the standard Kellgren and Lawrence grading scheme for 28 hand joints. OSS score, a surrogate measure that takes into account different kinds of bone changes, was also obtained for each individual. Body weight and height, eight skinfold thicknesses on the trunk and extremities, and breadths of the long bones were measured. Sex-based univariate analyses and multivariate statistical analysis showed the following: 1) Age dependence was defined more strongly in "OA-linked" compared to "osteoporosis (OP)-linked" traits; 2) While "OP-linked" bone-aging traits correlated with age differently between sexes, "OA-linked" traits did not; 3) The strong interrelationship between OA-linked and OP-linked traits in both sexes became very weak and statistically insignificant (P > 0.10) after adjustment for age. Thus, OA and OP conditions in the same individual develop independently and probably reflect different underlying physiological mechanisms. 4) Anthropometric characteristics were significantly correlated with bone-aging traits, but correlations were low (r < 0.20). Thus, the contribution of anthropometric characteristics to the rate and pattern of bone aging of the hand was to relatively small.


Conformational structure of gaseous 3-chloropropanoyl chloride by electron diffraction, normal coordinate analysis, and ab initio molecular orbital, and density functional theory calculations.
The molecular and conformational structures of 3-chloropropanoyl chloride (CH(2)Cl-CH(2)-C(=O)Cl) have been studied by using gas-phase electron diffraction (GED) data obtained at 22 degrees C (295 K) and ab initio molecular orbital (MO) and density functional theory (DFT) calculations up to the levels of MP4(SDQ) and B3LYP using larger basis sets. Normal coordinate calculations (NCA) taking into account nonlinear vibrational effects were also used in the analyses. The title compound may have up to four low-energy conformers in the gas phase, labeled according to the position of each of the two chlorine atoms in relation to the CCC propanoyl backbone, labeling the carbonyl chlorine torsion angle first: AA, AG, GG, and GA; where A is anti (ideal C-C-C-Cl torsion angle of approximately 180 degrees) and G is gauche (ideal C-C-C-Cl torsion angle of approximately 60 degrees). It has been judged from the experimental GED data and the theoretical calculations, as well as from previously published infrared (IR) studies on the molecule in both the liquid phase and in argon-trapped matrices at 10 K, that the gas phase consists of a mixture of at least three conformers: AA (most stable), AG, and GG, with the possibility of a smaller contribution (<10%) from the higher-energy GA form. The GA conformer cannot be ruled out by the GED experimental data. Relevant structural parameter values obtained from the GED least-squares refinements, with calculated ab initio MO MP2/6-31+G(2d,p) values used as constraints, were as follows (AA values with estimated 2sigma uncertainties): Bond lengths (r(h1)): r(C-C(=O)) = 1.505(4) A, r(C-CH(2)Cl) = 1.520(4) A, r(C=O) = 1.197(4) A, r(C(=O)-Cl) = 1.789(3) A, and r(C-Cl) = 1.782(3) A. Bond angles (angle(h1)): angle CCC = 111.5(11) degrees , angle CCO = 127.0(5) degrees, angle CC(O)Cl = 112.5(3) degrees, and angle CCCl = 110.3(3) degrees. Torsion angles (phi(C-C) = phi(ClCCC)): for AA, phi(1)(C-C(O)) = phi(2)(C-CH(2)Cl) = 180 degrees (assumed for true C(s) symmetry); for AG, phi(1)(C-C(O)) = -140(5) degrees, phi(2)(C-CH(2)Cl) = 76(13) degrees; for GG, phi(1)(C-C(O)) = 46(8) degrees, phi(2)(C-CH(2)Cl) = 77(14) degrees; for GA, phi(1)(C-C(O)) = 67.9 degrees (assumed), phi(2)(C-CH(2)Cl) = 177.8 degrees (assumed). The non-AA conformers all have chiral C(1) symmetry with twice the statistical weight (multiplicity) of C(s). The MP2/6-31+G(2d,p) calculated composition (%) based on the zero-point energy (ZPE) corrected energy differences, and the statistical weights for conformers: AA/AG/GG/GA = 28/35/28/9 was assumed in the final GED refinement. The more recent literature concerning the title molecule, as well as for several related molecules, has been examined and a survey has been attempted in the present article. The new experimental results for 3-chloropropanoyl chloride are discussed and compared with the previously published findings.


[Effect of anterior cruciate ligament rupture on hamstring: quadriceps ratio during isokinetic knee extension and flexion at 30 degrees of flexion].
To evaluate the change in hamstring (H):quadriceps (Q) ratio following anterior cruciate ligament (ACL) rupture during isokinetic knee extension and flexion at 30 degrees of flexion which is important for knee dynamic function. A study was performed in 25 male complete unilateral ACL ruptures. Isokinetic concentric and eccentric quadriceps and hamstring muscle tests in both the deficient knees and intact knees were performed at 60°/s, respectively. At 30 degrees of flexion, the average torque of quadriceps and hamstring, Qe:Qc ratios (ratios of eccentric quadriceps to concentric quadriceps muscle torque), He:Hc ratios (eccentric hamstring to concentric hamstring), Hc:Qc ratios (concentric hamstring to concentric quadriceps), He:Qc ratios (eccentric hamstring to concentric quadriceps), and Hc:Qe ratios (concentric hamstring to eccentric quadriceps) were calculated. Wilcoxon matched-pairs signed-ranks test was used. At 30 degrees of knee flexion, a significant reduction (P<0.05) in the average torque of quadriceps was observed at concentric and eccentric 60°/s produced by the deficient-side compared with the intact side. In addition, Hc:Qc, He:Qc, and Qe:Qc significantly increased on the ACL-deficient side. The change in H :Q ratio in the mode of isokinetic 60°/s at 30 degrees of knee flexion might therefore be a new tool to objectively document muscle function in ACL-deficient knee.


How Advanced Is Our Understanding of the Role of Intestinal Barrier Dysfunction in the Pathogenesis of Recurrent Urinary Tract Infections.
A comprehensive understanding of urinary tract infections (UTIs), one of the most common human infections, is required as they are complex and poorly understood diseases. Periurethral and vaginal colonization by rectal flora, with the constant presence of pathogens in the urethra, is the initial step of the recurrent UTIs pathway. Current scientific data describe the genetic, etiological, biological, and behavioral risk factors for recurring UTIs, but they do not include the effect of intestinal barrier function on the disease. Although gut microbiota has been proposed as the main source for UTIs, the cross-talk between intestinal barrier dysfunction and the recurrence of UTIs has not yet been supported by scientific data. In this opinion review, based on published data and the results of our clinical studies, I aimed to outline the possible contribution of intestinal barrier dysfunction to the pathogenesis of recurrent UTIs. I believe that the unanswered questions raised by this review can guide further experimental and controlled studies to clarify the mechanisms underlying the role of intestinal barrier dysfunction in the pathogenesis of recurrent UTIs.


[Evaluability assessment of a health care campaign for improving the access to ophthalmologic care in a central region of Brazil, 2004].
In order to identify the areas of priority for a systematic evaluation of a campaign for improving the access to ophthalmologic care--"Keep an eye on your vision", occurred in the state of Goiás in 2004, an evaluability assessment was conducted by means of interviews with key-informants and document analysis. A logical model was developed for providing dimensions and criteria for evaluation. This framework was submitted to a panel of experts using the Delphi method. The results revealed that the campaign was sufficiently structured to allow for systematic evaluations. Differences in the interpretation of the objectives and of the target population of the campaign between the experts were verified. Problems related to accessibility and effectiveness indicated these components as priorities for evaluation. The authors discuss the relevance of evaluability assessment as a preliminary stage for the evaluation of programs.


Immediate functional loading of TiOblast dental implants in full-arch edentulous maxillae: a 3-year prospective study.
Immediate functional loading of dental implants for full-arch restoration is a patient-friendly approach, shown to be feasible with a good long-term prognosis in a completely edentulous mandible. For the complete restoration of the maxilla, acceptable long-term clinical follow-up is lacking or based on case reports rather than on prospective studies. This prospective mono-centre study reports the 3-year outcome of immediately functionally loaded Astra Tech Dental implants in completely edentulous maxillae based on clinical survival and success based on radiographical assessment of bone level. One hundred and ninety-five Astra Tech TiOblast surface fixtures were installed in 25 consecutively treated patients (age range: 42-76 years), of whom eight were smokers, 12 had a confirmed history of periodontitis and six had poor bone quality normally deemed for delayed loading. Fixtures and abutments were inserted in a one-stage procedure and functionally loaded within 24 h with a 10-unit provisional glass-fibre or metal-reinforced screw-retained restoration. After 6 months, each implant was checked for stability using a manual torque of 20 N cm and the provisional restoration was replaced by a 10-12-unit screw-retained metal-ceramic or metal-resin cantilever bridge. Bone level was assessed radiographically from the day of surgery up to 3 years and used to calculate mean bone loss at the patient level and individual implant success. No failures occurred in implants or prostheses, the total survival rate being 100%. Mean marginal bone loss was 0.58 mm (SD 0.58); 0.6 mm (SD 0.53); 0.63 (SD 0.61); and 0.72 (SD 0.63) after 6 and 12 months, and 2 and 3 years, respectively, yielding a 100% success at the patient level. Wilcoxon's signed ranks test showed only statistically significant bone loss between baseline and 6 months and a steady-state condition during all other intervals. At the individual fixture level, 82% lost <1 mm marginal bone between baseline and 1 year. After 3 years, 86% have <1.5 mm total bone loss and can be considered a success. The fixtures expressing more bone loss were all inserted in smokers. Immediate loading of a full-arch maxillary bridgework on 7-9 Astra Tech TiOblast implants is a predictable treatment option with 100% fixture survival and stable bone-to-implant contact up to 3 years. The steady state in bone remodelling is indicative of a good long-term prognosis in non-smokers but smokers seem to be more prone to bone loss.


De novo ceramide synthesis is responsible for the anti-tumor properties of camptothecin and doxorubicin in follicular thyroid carcinoma.
Doxorubicin and camptothecin are two cytotoxic chemotherapeutic agents triggering apoptosis in various cancer cells, including thyroid carcinoma cells. Recent studies revealed a critical role of ceramide in chemotherapy and suggested that anti-cancer drugs may kill tumor cells through sphingomyelinase activation. However, in comparison to sphingomyelin hydrolysis, the relative involvement of de novo ceramide synthesis remained poorly explored and highly controversial. Here, we evidenced that both doxorubicin and camptothecin triggered ceramide accumulation in thyroid carcinoma cells. We demonstrated that ceramide increase occurred via the de novo pathway without neither acidic nor neutral sphingomyelinase contribution. Interestingly, de novo ceramide generation was responsible for the drug-induced malignant cell apoptosis through a caspase-3-dependent pathway and a decrease of thrombospondin amount. Furthermore, blocking ceramide metabolism by inhibiting glucosylceramide synthase strengthened the camptothecin and doxorubicin-dependent effects. Altogether, we evidenced that de novo ceramide synthesis mediates the anti-tumor properties of doxorubicin and camptothecin in thyroid carcinoma and suggested that glucosylation of ceramide may contribute to the drug-resistance phenotype in thyroid malignancies.


Metabolic signatures of immune cells in chronic kidney disease.
Immune cells play a key role in maintaining renal dynamic balance and dealing with renal injury. The physiological and pathological functions of immune cells are intricately connected to their metabolic characteristics. However, immunometabolism in chronic kidney disease (CKD) is not fully understood. Pathophysiologically, disruption of kidney immune cells homeostasis causes inflammation and tissue damage via triggering metabolic reprogramming. The diverse metabolic characteristics of immune cells at different stages of CKD are strongly associated with their different pathological effect. In this work, we reviewed the metabolic characteristics of immune cells (macrophages, natural killer cells, T cells, natural killer T cells and B cells) and several non-immune cells, as well as potential treatments targeting immunometabolism in CKD. We attempt to elaborate on the metabolic signatures of immune cells and their intimate correlation with non-immune cells in CKD.


Additional CTA-Subtraction Technique in Detection of Pulmonary Embolism-a Benefit for Patients or Only an Increase in Dose?
Latest advantages in computed tomography (CT) come with enhanced diagnostic imaging and also sophisticated dose reduction techniques. However, overall exposure to ionizing radiation of patients in Germany rises slightly, which is mainly based on the growing number of performed CT scans. Furthermore, new possibilities in modern imaging, including 4D scans or perfusion protocols, offer new medical insights but require additional scans.In this study, we reevaluated data sets from patients undergoing CT examinations because of suspected pulmonary embolism and compared doses and diagnostic results of the standard protocol to the additional modern CT subtraction technique. Two groups of single-blinded radiologists were provided with CT data sets from 50 patients. One group (G1) had access to full datasets including CT subtraction with perfusion map. The other group (G2) only evaluated conventional CT angiography. Results were compared to final clinical diagnosis. Dose length product (DLP) of CT angiography was compared to CT subtraction technique, which consists of an additional non-contrast-enhanced scan and perfusion map. Effective dose was calculated using a Monte Carlo simulation-based software tool (ImpactDose). Inter-rater agreement of both groups was strong in G1 with κ = .896 and minimal in G2 (κ = .307). Agreement to final diagnosis was strong in both groups (G1, κ = .848; G2, κ = .767). Doses applied using the CT subtraction technique were 34.8% higher than for CT angiography alone (G1 DLP 337.6 ± 171.3 mGy x cm; G2 DLP 220.2 ± 192.8 mGy x cm; p < .001). Calculated effective dose was therefore significantly higher for G1 (G1 4.82 ± 2.20 mSv; G2 3.04 ± 1.33 mSv; p < .001). Our results indicate a benefit of the CT subtraction technique for the detection of pulmonary embolisms in clinical routine, accompanied by an increase in the dose administered. Although CT protocols should always be applied carefully to specific clinical indications in order to maximize the potential for dose reduction and keep the administered dose as low as reasonably achievable, one should never lose sight of the diagnostic benefit, especially in vital clinical indications.


The expression of chondrogenesis-related and arthritis-related genes in human ONFH cartilage with different Ficat stages.
It has been well known that the degeneration of hip articular cartilage with osteonecrosis of the femoral head (ONFH) increases the instability of hip and accelerates the development process of ONFH. A better understanding of the expression of chondrogenesis-related and arthritis-related genes of cartilage along with the progression of ONFH seems to be essential for further insight into the molecular mechanisms of ONFH pathogenesis. We analyzed the differentially expressed gene profile (GSE74089) of human hip articular cartilage with ONFH. The functions and pathway enrichments of differentially expressed genes (DEGs) were analyzed via GO and KEGG analysis. The expression of six selected critical chondrogenesis-related and four arthritis-related genes in eight human hip articular cartilage with femoral neck fracture (FNF) and 26 human hip articular cartilage with different stages ONFH (6 cases of Ficat stage II, 10 cases of Ficat stage III and 10 cases of Ficat stage IV) were detected. A total of 2,174 DEGs, including 1,482 up-regulated and 692 down-regulated ones, were obtained in the ONFH cartilage specimens compared to the control group. The GO and KEGG enrichment analysis indicated that the function of these DEGs mainly enriched in extracellular matrix, angiogenesis, antigen processing and presentation. The results showed a significant stepwise up-expression of chondrogenesis-related genes, including MMP13, ASPN, COL1A1, OGN, COL2A1 and BMP2, along with the progression of ONFH. The arthritis-related genes IL1β, IL6 and TNFα were only found up-expressed in Ficat IV stage which indicated that the arthritis-related molecular changes were not significant in the progression of ONFH before Ficat III stage. However, the arthritis-related gene PTGS2 was significant stepwise up-expression along with the progression of ONFH which makes it to be a sensitive arthritis-related biomarker of ONFH. Expression changes of six chondrogenesis-related and four arthritis-related genes were found in hip articular cartilage specimens with different ONFH Ficat stages. These findings are expected to a get a further insight into the molecular mechanisms of ONFH progression.


[Improved risk counselling possible for patients with unruptured intracranial aneurysms].
The 'International Study of Unruptured Intracranial Aneurysms' (ISUIA) investigators have recently published the results of a large prospective, observational study on risks of rupture and risks of treatment in patients with unruptured intracranial aneurysms. In patients with aneurysms smaller than 7 mm no rupture of the carotid, middle cerebral and anterior communicating arteries occurred during follow up (mean 4.1 years) if there was no history of subarachnoid haemorrhage from a separate aneurysm. Risks were higher in aneurysms of the posterior circulation (2.5% in 5 years), and in patients with a previous episode of subarachnoid haemorrhage from another aneurysm (1.5 to 3.4% in 5 years for aneurysms < 7 mm). Size was the most important risk factor for rupture, and aneurysms of the posterior circulation > 25 mm had a 50% cumulative risk of rupture over 5 years. The absence of rupture in some subgroups, such as small aneurysms of the anterior communicating artery, is probably explained by the small numbers in these subgroups. Similarly, the lack of identification of risk factors other than size is probably explained by insufficient power of the study. The overall risk (defined as death or dependence) of surgical treatment was 13%, with patient age and size and site of the aneurysm as the most important risk factors. Endovascular treatment carried a 7 to 10% risk in most subgroups; only patients with aneurysms > 25 mm had increased risks. Age was not a risk factor for endovascular treatment. By making use of these results, patients can now be given sound advice regarding the benefits of preventive treatment in each individual case.


Decreased 7,12-dimethylbenz[a]anthracene-induced carcinogenesis coincides with the induction of antitumor immunities in adult female B6C3F1 mice pretreated with genistein.
The objective of this study was to determine if genistein (GEN) modulation of the immune responses might contribute to the increased host resistances to tumors. A time-course study was performed in adult female B6C3F1 mice that had been exposed to GEN for 1-4 weeks at the dose level of 20 mg/kg by gavage. A significant increase in ex vivo cytotoxic T lymphocyte (CTL) activity was observed in the periods of 2 weeks and 4 weeks. Moreover, increased activities of CTLs were associated with a decrease in the percentage of CD4(+)CD25(+) T cells and an increase in the production of interferon-gamma and activation of STAT1 (signal transducer and activator of transcription 1) and STAT4. Additionally, exposure of mice to GEN increased the activities of in vivo CTLs. An increased activity of natural killer (NK) cells was also observed. Further study in the B16F10 tumor model suggested that GEN-mediated enhancement in host resistance to B16F10 tumor was partially related to its potentiating effect on NK cells. Finally, 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumor model was employed to determine the chemopreventive effect of oral GEN treatment. Mice pretreated with GEN for 2 weeks by gavage, the time when an enhanced CTL activity had been produced, had a decreased susceptibility toward DMBA-mediated carcinogenesis, while treatment with GEN after tumor induction conferred no protection. In conclusion, pretreatment with GEN by gavage could enhance host resistances to the B16F10 tumor and DMBA-induced carcinogenesis, suggesting that GEN modulation of immune response was, at least partially, responsible for the antitumor effect of this compound.


In Vivo Study of Dynamics and Stability of Dendritic Spines on Olfactory Bulb Interneurons in Xenopus laevis Tadpoles.
Dendritic spines undergo continuous remodeling during development of the nervous system. Their stability is essential for maintaining a functional neuronal circuit. Spine dynamics and stability of cortical excitatory pyramidal neurons have been explored extensively in mammalian animal models. However, little is known about spiny interneurons in non-mammalian vertebrate models. In the present study, neuronal morphology was visualized by single-cell electroporation. Spiny neurons were surveyed in the Xenopus tadpole brain and observed to be widely distributed in the olfactory bulb and telencephalon. DsRed- or PSD95-GFP-expressing spiny interneurons in the olfactory bulb were selected for in vivo time-lapse imaging. Dendritic protrusions were classified as filopodia, thin, stubby, or mushroom spines based on morphology. Dendritic spines on the interneurons were highly dynamic, especially the filopodia and thin spines. The stubby and mushroom spines were relatively more stable, although their stability significantly decreased with longer observation intervals. The 4 spine types exhibited diverse preferences during morphological transitions from one spine type to others. Sensory deprivation induced by severing the olfactory nerve to block the input of mitral/tufted cells had no significant effects on interneuron spine stability. Hence, a new model was established in Xenopus laevis tadpoles to explore dendritic spine dynamics in vivo.