Attitudes toward seeking professional psychological help among Chinese pregnant women: A cross-sectional study.
There exists a gap between the high prevalence of mental health problems and negative attitudes toward seeking professional psychological help among Chinese pregnant women. This study aimed to investigate the attitudes and factors toward seeking professional psychological help among Chinese pregnant women to provide some suggestions for improving pregnant women's psychological help-seeking behaviors. A total of 1024 pregnant women were recruited. The Chinese version of the Attitude Toward Seeking Professional Psychological Help Scale (ATSPPH) was used to assess the attitudes toward professional psychological help-seeking. Demographic and socio-psychological factors were collected by self-developed questionnaire, Perceived Social Support Scale, Simplified Coping Style Questionnaire, and Patient Health Questionnaire-9 Scale. 1006 pregnant women were included in the final analysis. Only 3.7 % of participants chose professionals as their first choice for psychological help-seeking. The attitudes toward seeking professional psychological help were relatively positive, with the highest score of stigma tolerance among four subscales in ATSPPH. Education level, perceived social support, and positive coping style had a positive predictive effect on the four subscales of ATSPPH. Women with prenatal depressive symptoms had a lower score in the subscales of recognition of need for psychotherapeutic help and confidence in mental health practitioner; women with higher scores of negative coping style had a lower score in the subscales of stigma tolerance and interpersonal openness. History of professional psychological help-seeking behaviors was only associated with the subscale of recognition of need for psychotherapeutic help; Maternal age was only associated with the subscale of interpersonal openness. The attitudes toward seeking professional psychological help were relatively positive among Chinese pregnant women, and stigma tolerance was the significant barrier to professional psychological help-seeking. More attention should be paid to those women with older age, negative coping style, and women with prenatal depressive symptoms.


Replacement of the ureter by an ileal loop. Quantitative aspects of long-term morphological alterations in minipigs.
In minipigs 1 ureter was replaced by a loop of the terminal ileum and the contralateral kidney removed. After 2.5 to 3 years the morphology of the replaced ureter was compared with the normal ileum. Independent of the 3 different operative techniques used, in about half of the pigs there was loss or flattening of the villi. In the other pigs the morphometrically determined number of intraepithelial lymphocytes, the cell density in the lamina propria and the length of the villi did not differ significantly compared with the normal ileum. There was no increase in goblet cells in the crypts. The transitional epithelium covered only a short distance at the anastomotic junctions. Peyer's patches of normal age-related size were found in the replaced ureter. Despite the long-term contact with urine instead of gut contents, in many pigs a normal amount of lymphocytes remained in the "ileal ureter".


Revealing the ultrastructure of the membrane pores of intact Serratia marcescens cells by atomic force microscopy.
This study aimed to characterize the surface ultrastructure of intact Serratia marcescens cells under physiological conditions. Topographic information of membrane pores of the cells was obtained by atomic force microscope (AFM). Three types of membrane pores (CH-1-Pore A, CH-1-Pore B and CH-1-Pore C) were observed and the spatial arrangements of membrane-spanning subunits in membranes were defined. High-resolution images revealed that the doughnut-shaped structures of CH-1-Pore A and CH-1-Pore B were composed of six-to-eight and four transmembrane subunits. The inverted teepee-shaped structure of CH-1-Pore C was segmented into two transmembrane subunits straddling a single funnel-like pore. This study, to the best of authors' knowledge, represents the first direct characterization of the surface ultrastructure of the membrane pores of Serratia marcescens CH-1 cells at the nanometer scale and offers new prospects of mapping membrane pores on intact prokaryotic cells.


Perception on the mind-nurse program among nursing students: A descriptive qualitative study.
Nursing undergraduates are susceptible to stress from academic and clinical matters. We developed the MIND-NURSE program for nursing students. This study aimed to explore students' perceptions towards the program. This was a descriptive qualitative study. A convenience sampling was used to recruit nursing undergraduates from a university in Singapore. Participants attended the eight-week MIND-NURSE program. Each session comprised two components: Education and mindfulness practice. Three focus group interviews were conducted after completion of the program, using a semi-structured interview guide. Thematic analysis was used to identify emerging themes and subthemes. Twenty students participated in the study. Overall, they reacted positively to the MIND-NURSE program, albeit some concerns raised regarding the mindfulness practice. Six themes were derived from the data including: a) enhanced awareness of the present moment; b) increased serenity through mindfulness practice; c) triad of thoughts, emotion and behaviors; d) working towards interpersonal mindfulness; e) adapting mindfulness into nursing practice; and f) overcoming the challenges for mindfulness practice. Mindfulness benefited the students in personal and professional ways. More research should be conducted to implement the program on nursing students in other universities.


Favorable long-term survival using consolidation chemotherapy without allogeneic hematopoietic cell transplantation for acute myeloid leukemia with wild-type NPM1 without FLT3-ITD.
The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (NPM1 wt/FLT3-ITDneg/low) has not yet been elucidated. In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including NPM1 and FLT3-ITD. According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1 wt/FLT3-ITDneg/low, complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1 wt/FLT3-ITDneg/low group (P=0.233). Among the intermediate-risk NPM1 wt/FLT3-ITDneg/low patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML. Among the AML patients, intermediate-risk NPM1 wt/FLT3-ITDneg/low patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1 wt/FLT3-ITDneg/low patients. Well controlled studies are needed to confirm the current results.


Neonatal and prospective follow-up study of infants delivered by vacuum extraction (VE).
Forty infants delivered by vacuum extraction have been studied in the neonatal period--neurological examination, neonatal CSF-examinations, skull X-ray examination, transillumination and sonoencephalography --and at 14 months of age--developmental and behavioural evaluation, neurological examination, skull X-ray examination, sonoencephalography and electroencephalography. Two infants died in the neonatal period but in both cases a life-threatening situation of the fetus required immediate delivery. CSF cytological signs of haemorrhage were observed in 42% of the 26 infants who had a successful lumbar tap, compared to 10% found in normal deliveries. The result of the neonatal neurological study did not differ from that in a control group. The result of the skull X-ray examination and sonoencephalography were also within normal limits. In the follow-up study behavioural problems were found in 25%, but otherwise very few abnormalities were found. The deviatiosn found do not for the present indicate any later signs of brain lesions. It is concluded that this prospective study has shown that VE-delivery in fullterm babies seem to imply no risk fo serious cerebral sequelae. Further follow-up studies at a later age in order to evaluate the incidence of so-called minimal brain damage in VE-delivered children are required.


Differential effect of isolated placental isoferritins on in vitro T-lymphocyte function.
The effect of isoferritins isolated from human term placenta on certain T-lymphocyte parameters was studied in vitro using normal human lymphocytes. These isoferritins differed in ion exchange affinity, isoelectric point, and subunit composition. Only the acidic isoferritins caused a marked suppression of phytohaemagglutinin (PHA) blastogenesis and the most acidic isoferritin ('Acid I') was suppressive at a concentration as low as 0.25 microgram/ml. All four isoferritins suppressed concanavalin A (Con A) blastogenesis in a similar concentration dependent manner, with maximum effect at an isoferritin concentration of 1 microgram/ml. Both basic and acidic isoferritins reduced the Con-A-capping phenomenon in normal lymphocytes at concentrations higher than 0.5 microgram/ml, but at 0.25 microgram/ml only the acidic isoferritin was effective. The above findings support our previous report concerning the suppressive effect of splenic ferritin on T-lymphocyte function in vitro and indicate that acidic isoferritins, which often predominate in malignancy, demonstrate a higher degree of immunosuppressive activity. Thus, acidic isoferritins may play a role in the development of abnormal lymphocyte function encountered in certain proliferative disorders.


The Effect of miR-145-5p, DANCR and NRAS Expression Levels on the Survival Rate of Colorectal Cancer Patients.
The prevalence of colorectal cancer (CRC) has been increasing in the world. There are different factors for colorectal cancer, and changes in the levels of gene expression such as miR-145-5p, DANCR and NRAS can be one of the factors. The case-control study was performed on 40 CRC specimens and 40 adjacent healthy tissues. Fresh tumor and tumor-free adjacent tissue samples were obtained from patients who underwent the surgical operation as a conventional treatment procedure. After tumor resection, the specimens were immediately frozen in liquid nitrogen and stored at -80°C until further investigation. Cox regression was used to get the hazard ratios. The mean ± SD age of the patients was 62.45± 12.89 years. Of these, 62.5% were males. The risk of death from CRC in patients with low miR-145-5p levels is about 10 times higher than the high expression levels (HR = 10.759, P = 0.009). High expression levels of NRAS can increase the risk of CRC death up to 4 times (HR = 4.12, P = 0.045). The study did not show a relationship between DANCR expression levels and death risk from CRC (HR = 1.582, P = 0.439). These expression levels revealed that miRNA-145-5p and NRAS can be utilized as diagnostic biomarkers in colorectal cancer death. This may also introduce the microRNAs as colorectal cancer therapeutic targets.


Antibacterial cleaning and hygiene products as an emerging risk factor for antibiotic resistance in the community.
Antibiotic resistance within the community setting is an emerging public-health concern. Infection with antibiotic-resistant organisms in the community among people lacking traditional risk factors has been reported. In addition, prevalence studies have identified individuals carrying antibiotic-resistant organisms in the absence of known risk factors. These studies strongly suggest the presence of contributing factors that have yet to be identified. In this paper we review the burden of antibiotic resistance and known risk factors within the community setting, assess the potential role of antibacterial cleaning and hygiene products containing triclosan in the emergence of resistance, and recommend future research on the assessment of household cleaning and hygiene products containing triclosan.


Stafne's bone defect with bicortical perforation: a need for modified classification system.
Stafne's bone defect (SBD) or salivary gland-related bone defects are asymptomatic bone cavities in the mandible caused by impingement by the salivary glandular tissue. The major salivary glands, particularly the submandibular gland, are in close relation with the mandible and their impingement can produce radiolucent defects on the lingual cortical surface of the mandible. Submandibular gland-related bone defects or depressions are referred as posterior lingual variant of SBD. These are asymptomatic and appear as well-defined radiolucent areas that are incidentally discovered on panoramic radiographs. Three-dimensional imaging may be required to evaluate the extent of cortical involvement and to determine the content of the cavity or defect. Usually, these defects are seen in the lingual cortices and are lined by cortex that causes a smooth radiopaque periphery. The involvement of both the buccal and lingual cortices by the defect is extremely uncommon. Literature has classified cases with buccal cortical expansion but buccal cortical perforation has not been described and classified. This case report describes this uncommon presentation of the salivary gland bone defect and through an in-depth literature review proposes a modification in the existing classification system.


Practical liquid diets for rats: effects on growth.
Liquid diets based on the AIN-76 formula are described. The diets employ xanthan gum as a stabilizer. Information is provided on how these diets may be modified to meet the requirements of a particular experiment (e.g., variations in water content, type of protein or carbohydrate or fat, etc.). These diets are superior to widely used diets with regard to nutritional adequacy, cost, ease of preparation, versatility, stability, osmolality, and use of natural ingredients. An experiment is described which compares the effects of feeding rats a solid diet or a liquid diet prepared three different ways. The results confirm that a properly prepared liquid diet can produce overweight and obesity.


Hepatobiliary elimination of bile acid-modified oligodeoxynucleotides in Wistar and TR- rats: evidence for mrp2 as carrier for oligodeoxynucleotides.
As therapeutic antisense tools, oligonucleotides (ODNs) must enter cells to bind to their target structures. ODNs distribute in nearly each tissue with relatively high concentrations in kidney and liver from where excretion into urine and bile occurs. To investigate mechanisms involved in hepatic ODN transport, normal mixed backbone phosphodiester/phosphorothioate ODNs (n-ODN) and two different bile acid-conjugated mixed backbone ODNs (1BA-ODN and 2BA-ODN) were applied to two different rat strains, normal Wistar rats and Wistar TR- rats. In normal Wistar rats, concentration-dependent hepatobiliary elimination of the ODNs was observed with a remarkable increase of excretion of the cholic acid BA-ODN conjugates. In contrast to normal Wistar rats, n-ODN excretion into bile by TR- rats, a mutant Wistar rat strain lacking a functional multidrug resistance-associated protein 2 (mrp2) at the canalicular membrane, was strongly diminished, whereas these rats excreted an ODN conjugated with two cholic acid molecules (2BA-ODN) into bile. Concomitant application of substrates transported by mrp2 such as bromosulfophthalein (BSP) or the synthetic chlorogenic acid derivative S 3025 significantly reduced the biliary appearance of normal ODN and 2BA-ODN in Wistar rats and also in TR- rats. To inhibit the expression of cRNA derived from the Na+ -dependent taurocholate cotransporting polypeptide (Ntcp), antisense ODNs were constructed which fully retained the antisense properties when coupled with two bile acid molecules. The results indicate that ODNs are secreted via the mrp2 into bile. In the absence of mrp2, further excretory transport systems with affinity for bile acids seem to be relevant for their excretion. The results further indicate that bile acid tagged ODNs are useful tools for liver specific antisense therapy.


[Expert Opinions in Court: Liability of the Expert].
Experts in criminal, civil and, increasingly, in social court cases have to present their expert opinions in court. This should be regarded not only as a burden, even if this may at times appear superfluous to the expert, perhaps because the discussion is mere repetition of the opinion he has already written, or because the questions appear to be biased against the expert. Nonetheless, the expert is always advised to appear calm and objective during the interrogation by judges and parties or participants and their legal representatives, and should not allow himself or herself to be provoked by questioning. Furthermore, it may be necessary to correct the written expert statement in the course of the interrogation, but this can be a sign of a truly competent medical expert. The expert consulted can be held liable for adverse health effects resulting from the interrogation and investigation, as well as for deliberate or grossly faulty reports.


Light microscopic study of degenerating cobalt-filled optic axons in goldfish: role of microglia and radial glia in debris removal.
Labeling severed axons with cobaltous-lysine ultimately leads to the degeneration of their distal segments. The present study was designed to determine whether microglia and radial glia have comparable roles in the elimination of degenerating axons. Another purpose was to determine whether the cobalt could escape from degenerating axons and enter intact neuronal cells. Optic axons were filled with cobaltous-lysine for 1 day and the retinal projections were examined from 1 to 106 days later. Optimal filling was obtained 1 day postlabeling. The number of filled axons in the optic tract was significantly reduced at the 2-day time point, indicating that many axons had disintegrated. Many axons contained large swellings that resembled cells. However, transneuronally labeled neuronal cells were never observed. Labeled, rounded microglia appeared among the degenerating axons at the 3-day time point, and the microglia changed shape at 5 days. They became elongated and manifested many processes. In addition, the microglia began to move toward, and entered, the ventricles and vasculature. Virtually all the labeled debris was removed between 17 and 28 days following the application of cobalt. The rapidity with which the axons were removed suggests that the cobalt accelerates the degenerative process either directly, or indirectly by accelerating the arrival of phagocytic cells. Radial glia appeared to play a smaller role in debris elimination. They took up labeled debris to a lesser degree than microglia and were briefly labeled. Interestingly, radial glia did not take up cobalt when it was injected intracranially and diffused through the brain. A previous claim of an axosomatic retinotectal projection to cells deep in the stratum periventriculare of a teleost fish is reinterpreted to represent cobalt within radial glia.


Induction of fos and sis proto-oncogenes and genes of the extracellular matrix proteins during butyrate induced glioma differentiation.
Sodium butyrate has been shown to inhibit the growth and induce the differentiation of F-98 rat glioma cells. In agreement with the morphological changes, we have found that mRNAs for fibronectin and collagen in these cells could be reversibly induced by butyrate. While Ki-ras mRNA levels remained relatively unchanged, mRNAs for fos and sis increased significantly during the course of butyrate induced differentiation. c-fos induction can be detected 30 min after butyrate addition, a peak level (greater than 20 fold) was reached at 2 h, with a subsequent gradual decline. c-sis induction was detectable 24 h after butyrate exposure, at which time the cells have assumed morphological transition. Interestingly, the sis mRNA induction was not reversible upon butyrate withdrawal. The sis mRNA half-life increased from 40 min in the untreated cells to 100 min in the butyrate induced cells indicating that the increase in the stability of sis mRNA contributed, at least in part, to the elevated levels of sis expression. These findings demonstrate a coordinated induction of fibronectin and collagen genes in the butyrate-treated F-98 cells. In addition, fos and sis transcripts were differentially induced; a rapid and transient induction of fos followed by an irreversible induction of sis at a later stage of differentiation.


Evaluation of immunologic crossreaction of antiasparaginase antibodies in acute lymphoblastic leukemia (ALL) and lymphoma patients.
To evaluate how well antibodies to one asparaginase preparation predict or correlate with antibodies to another preparation in acute lymphoblastic leukemia (ALL) and lymphoma patients who did and did not have hypersensitivity reactions during chemotherapy. In all, 24 children with newly diagnosed ALL or lymphoma, who received Escherichia coli asparaginase 10 000 IU/m(2) IM thrice weekly for nine doses as part of multiagent induction and reinduction chemotherapy, and seven monthly doses during the first 7 months of continuation treatment, were studied. Plasma samples were collected at postinduction and at postreinduction. Six of 24 patients had no overt clinical reactions (nonreacting) and received only the E. coli preparation. Of these, 18 patients who had allergic reactions were switched to Erwinia asparaginase. A total of 18 patients had an anaphylactoid reaction to Erwinia asparaginase and were switched to receive polyethylene glycol (PEG) asparaginase. Antibody levels were measured by enzyme-linked immunoadsorbent assay against all the three asparaginase preparations. At postinduction, antibodies against E. coli were higher in reacting patients (0.063+/-0.066) than in nonreacting patients (0.019+/-0.013) (P=0.03). At postreinduction, anti-Erwinia antibodies were significantly higher in reacting patients (0.431+/-0.727) than in nonreacting patients (0.018+/-0.009) (P=0.007). Anti-E. coli antibodies correlated with anti-PEG antibodies at postinduction (r=0.714, P<0.001) and at postreinduction (r=0.914, P<0.001), but did not correlate with anti-Erwinia antibodies at postinduction (r=0.119, P=0.580) and at postreinduction (r=0.078, P=0.716). The results indicate a crossreactivity between patient antibodies raised against natural E. coli and PEG asparaginase but not Erwinia asparaginase.


Diffusion MRI anisotropy in the cerebral cortex is determined by unmyelinated tissue features.
Diffusion magnetic resonance imaging (dMRI) is commonly used to assess the tissue and cellular substructure of the human brain. In the white matter, myelinated axons are the principal neural elements that shape dMRI through the restriction of water diffusion; however, in the gray matter the relative contributions of myelinated axons and other tissue features to dMRI are poorly understood. Here we investigate the determinants of diffusion in the cerebral cortex. Specifically, we ask whether myelinated axons significantly shape dMRI fractional anisotropy (dMRI-FA), a measure commonly used to characterize tissue properties in humans. We compared ultra-high resolution ex vivo dMRI data from the brain of a marmoset monkey with both myelin- and Nissl-stained histological sections obtained from the same brain after scanning. We found that the dMRI-FA did not match the spatial distribution of myelin in the gray matter. Instead dMRI-FA was more closely related to the anisotropy of stained tissue features, most prominently those revealed by Nissl staining and to a lesser extent those revealed by myelin staining. Our results suggest that unmyelinated neurites such as large caliber apical dendrites are the primary features shaping dMRI measures in the cerebral cortex.


The socio-behavioral development of children with symptoms of attachment disorder: An observational study of teacher sensitivity in special education.
Children with Reactive Attachment Disorder (RAD) have serious socio-behavioral problems and often rely on socially abnormal, aggressive, and manipulative forms of communication. Little is known, however, about the influence of teachers on the socio-behavioral development of children with symptoms of RAD. This longitudinal study examined the influence of teacher sensitivity on the socio-behavioral development of children with symptoms of RAD across one school year. The sample included 85 Belgian children and 70 teachers from special education schools. In the previous school year, teachers rated Inhibited and Disinhibited RAD symptoms. In the next school year, teacher Sensitivity was observed in interactions with individual children in the first trimester. Teacher-rated Overt aggression, Relational aggression, and Prosocial behavior was assessed in the first, second, and third trimester. We found no effects of Sensitivity on Prosocial behavior. Also, no effects were found for children with Disinhibited RAD symptoms. For children with Inhibited RAD symptoms, increases in Overt and Relational aggression were observed when Sensitivity was low, whereas decreases were observed when Sensitivity was high. The results suggest that teacher sensitivity is associated with the socio-behavioral development of children with Inhibited RAD symptoms but not with the socio-behavioral development of children with Disinhibited RAD symptoms. Children with Reactive Attachment Disorder (RAD) exhibit socio-behavioral problems that hinder their school adjustment. These socio-behavioral problems appear relatively stable and it is not known what influence special education teachers might have on the development of these problems across a school year. This study suggests that teacher sensitivity is associated with changes in the socio-behavioral development of children with Inhibited RAD symptoms. Whereas high sensitivity was associated with improvements, low sensitivity appeared to exaggerate the socio-behavioral problems of these children. As children with Inhibited RAD symptoms have difficulties communicating their needs and wishes in socially adaptive ways, it may not be easy for teachers to understand these children. Teachers may misinterpret a child's behavior and consequently will fail to respond to the child's underlying needs. This may reinforce the child's socio-behavioral problems and increase the child's reliance on egocentric and aggressive means in interactions with others. This study therefore highlights the need to support teachers in interactions with children with Inhibited RAD symptoms in order to help them understand how the children's observable behaviors in the classroom may convey their underlying socio-emotional needs and how they can respond to these needs. Importantly, teacher sensitivity was not associated with the socio-behavioral development of children with Disinhibited RAD symptoms (e.g., indiscriminate friendliness). Consistent with previous research, this study suggests that children with Inhibited RAD symptoms are more susceptible to the quality of the caregiving environment than children with Disinhibited RAD symptoms and extends this finding to the school context.


Molecular characterisation of five Sarcocystis species in domestic sheep (Ovis aries) from Spain.
The major aim of the present study was to determine by molecular methods whether the wide and narrow types of macroscopic sarcocysts in Spanish sheep belonged to different species, that is, Sarcocystis gigantea and Sarcocystis medusiformis, respectively. Additionally, we wanted to identify and characterize molecularly the species forming microscopic sarcocysts and determine the phylogenetic placement of all species found. Portions of the oesophagus, diaphragm and hind legs containing macroscopic sarcocysts were collected from slaughtered culled ewes at an abattoir in the Province of Madrid, Central Spain, but both macroscopic and microscopic sarcocysts were isolated for molecular examination. Genomic DNA from 63 sarcocysts (21 macroscopic, 42 microscopic) were examined at the cytochrome c oxidase subunit I gene (cox1), while selected isolates of each species found were further examined at the 18S and 28S ribosomal RNA (rRNA) genes. The 63 sarcocysts comprised five cox1 sequence types, each corresponding to a particular sarcocyst type, and thus represented five Sarcocystis spp. The slender fusiform and thick macrocysts belonged to S. medusiformis and S. gigantea, respectively. The microscopic sarcocysts belonged to Sarcocystis arieticanis, Sarcocystis tenella and a Sarcocystis mihoensis-like species with slanting thorn-like cyst wall protrusions, which was characterised molecularly for the first time. Based on its phylogenetic position, the S. mihoensis-like species probably uses corvids as definitive hosts.


Evaluation of the reproducibility of rest activity of the anterior temporal and masseter muscles in asymptomatic and symptomatic temporomandibular subjects.
There is a general assumption that temporomandibular disorders and the pain and tenderness of mastication muscles may be caused by hyperactivity. Five asymptomatic men, five asymptomatic women, and five women with temporomandibular disorders participated in this study. Multiple examinations were performed to provide information concerning the reproducibility of the rest electromyographic signals. No significant differences between groups were noted. This study supports the contention that the mean rest activity in women with pain and dysfunction is less than or equal to that of sex-matched controls.


Items and dimensions for the construction of a multidimensional computerized adaptive test to measure fatigue in patients with rheumatoid arthritis.
Development of an item pool to construct a future computerized adaptive test (CAT) for fatigue in rheumatoid arthritis (RA). The item pool was based on the patients' perspective and examined for face and content validity previously. This study assessed the fit of the items with seven predefined dimensions and examined the item pool's dimensionality structure in statistical terms. A total of 551 patients with RA participated in this study. Several steps were conducted to come from an explorative item pool to a psychometrically sound item bank. The item response theory (IRT) analysis using the generalized partial credit model was conducted for each of the seven predefined dimensions. Poorly fitting items were removed. Finally, the best possible multidimensional IRT (MIRT) model for the data was identified. In IRT analysis, 49 items showed insufficient item characteristics. Items with a discriminative ability below 0.60 and/or model misfit effect sizes greater than 0.10 were removed. Factor analysis on the 196 remaining items revealed three dimensions, namely severity, impact, and variability of fatigue. The dimensions were further confirmed in MIRT model analysis. This study provided an initially calibrated item bank and showed which dimensions and items can be used for the development of a multidimensional CAT for fatigue in RA.


Rational design, synthesis and biological evaluation of new 1,5-diarylpyrazole derivatives as CB1 receptor antagonists, structurally related to rimonabant.
Among cannabinoid type-1 (CB(1)) receptor antagonists, those developed around the 1,5-diarylpyrazole scaffold of rimonabant (Acomplia are the most extensively investigated. In recent years, many SAR and QSAR reports on this topic have been published, focusing on the substitution and orientation of the N1 and C5 aryl functionalities and on the substituents at the 3-carboxamide position. In this context, the purpose of our study was to design and synthesize a set of 1-(2,4-dichlorophenyl)-5-arylpyrazoles strictly related to rimonabant, but with the hydrazide/amide group shifted from position 3 to position 4 of the pyrazole scaffold. The synthesized compounds were evaluated in vitro for their affinity on human CB(1) and CB(2) (cannabinoid type-2) receptors. Computational studies, performed both in the design step and after biological assays, contributed to rationalize the obtained results in terms of specific molecular interactions between antagonists and the human CB(1) receptor.


FAT1 and PTPN14 Regulate the Malignant Progression and Chemotherapy Resistance of Esophageal Cancer through the Hippo Signaling Pathway.
Esophageal cancer (EC) is a common malignant tumor, which brings heavy economic burden to patients and society. Therefore, it is important to understand the molecular mechanism of recurrence, metastasis, and drug resistance of esophageal cancer. Human esophageal cancer cell line TE13 (poorly differentiated squamous cell carcinoma) and normal human esophageal epithelial cell line het-1a were selected for aseptic culture. At the same time, 6 bottles of TE13 cell line were inoculated in logarithmic phase. Cell apoptosis was analyzed by flow cytometry (FCM). Cell clone formation assay was used to analyze the proliferation. Fibronectin-coated dishes were used to detect the characteristics of cell adhesion to extracellular matrix. The Transwell method was used to detect the cell invasion ability. Western blot was used to analyze the expression of Yap1, PTPN14, FAT1, and Myc. Results showed that FAT1 and PTPN14 were downregulated, while Yap1 was upregulated in esophageal cancer tissues. FAT1 inhibited the proliferation, adhesion, and invasion of human esophageal cancer cell lines, which might be associated with the upregulation of PTPN14 and the inhibition of Yap1 and Myc. The results suggested that PTPN14 and FAT1 could regulate malignant progression and chemotherapy resistance of esophageal cancer based on the Hippo signaling pathway.


Affective neuroscience: tracing the trace of fear.
The trace of fear has been elusive and difficult to discern in the human brain. Researchers have come up with a clever new way to track it down.


Spatial-Cluster Signal Detection in Medical Devices Using Likelihood Ratio Test Method.
With more and more medical device databases being developed, there is an increasing interest in learning the geographical patterns of medical-device-related adverse events (AEs). For a specific medical device and an adverse event (AE) of interest, our aim is to detect a spatial-cluster signal that has a significantly higher AE rate than the AE rates for other regions, when the exposure information is available. We develop a likelihood ratio test (LRT) method incorporating exposure information, by geographical region, for spatial-cluster signal detection when the underlying observed health outcome associated with the medical device of interest is a Poisson-modeled count data (e.g., an outcome of AE count). An extensive simulation study shows that this method has good power, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The application of the method is demonstrated by two hypothetical case studies regarding a medical device that is used for patients who have reached end-stage heart failure. A methodological framework for exploring geographic patterns in device safety surveillance is discussed, including safety data collection, statistical tools, and display of the analysis results. The proposed statistical method can be used for spatial-cluster signal detection for an AE of interest from medical device registries or other databases that have patient-level geographical information.


Erratum: Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes [Corrigendum].
[This corrects the article DOI: 10.2147/JIR.S312963.].


A natural DNMT1 mutation elevates the fetal hemoglobin level via epigenetic derepression of the γ-globin gene in β-thalassemia.
DNA methyltransferase 1 (DNMT1) is a major epigenetic regulator of the formation of large macromolecular complexes that repress human γ-globin expression by maintaining DNA methylation. However, very little is known about the association of DNMT1 variants with β-thalassemia phenotypes. We systematically investigated associations between variants in DNMT1 and phenotypes in 1142 β-thalassemia subjects and identified a novel missense mutation (c.2633G>A, S878F) in the DNMT1 bromo-adjacent homology-1 (BAH1) domain. We functionally characterized this mutation in CD34+ cells from patients and engineered HuDEP-2 mutant cells. Our results demonstrate that DNMT1 phosphorylation is abrogated by substituting serine with phenylalanine at position 878, resulting in lower stability and catalytic activity loss. S878F mutation also attenuated DNMT1 interactions with BCL11A, GATA1, and HDAC1/2, and reduced recruitment of DNMT1 to the γ-globin (HBG) promoters, leading to epigenetic derepression of γ-globin expression. By analyzing the F-cell pattern, we demonstrated that the effect of DNMT1 mutation on increased fetal hemoglobin (HbF) is heterocellular. Furthermore, introduction of S878F mutation into erythroid cells by clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) recapitulated γ-globin reactivation. Thus, the natural S878F DNMT1 mutation is a novel modulator of HbF synthesis and represents a potential new therapeutic target for β-hemoglobinopathies.


Iron overload by transferrin receptor protein 1 regulation plays an important role in palmitate-induced insulin resistance in human skeletal muscle cells.
Free fatty acid is considered to be one of the major pathogenic factors of inducing insulin resistance. The association between iron disturbances and insulin resistance has recently begun to receive a lot of attention. Although skeletal muscles are a major tissue for iron utilization and storage, the role of iron in palmitate (PA)-induced insulin resistance is unknown. We investigated the molecular mechanism underlying iron dysregulation in PA-induced insulin resistance. Interestingly, we found that PA simultaneously increased intracellular iron and induced insulin resistance. The iron chelator deferoxamine dramatically inhibited PA-induced insulin resistance, and iron donors impaired insulin sensitivity by activating JNK. PA up-regulated transferrin receptor 1 (tfR1), an iron uptake protein, which was modulated by iron-responsive element-binding proteins 2. Knockdown of tfR1 and iron-responsive element-binding proteins 2 prevented PA-induced iron uptake and insulin resistance. PA also translocated the tfR1 by stimulating calcium influx, but the calcium chelator, BAPTA-AM, dramatically reduced iron overload by inhibiting tfR1 translocation and ultimately increased insulin sensitivity. Iron overload may play a critical role in PA-induced insulin resistance. Blocking iron overload may thus be a useful strategy for preventing insulin resistance and diabetes.-Cui, R., Choi, S.-E., Kim, T. H., Lee, H. J., Lee, S. J., Kang, Y., Jeon, J. Y., Kim, H. J., Lee, K.-W. Iron overload by transferrin receptor protein 1 regulation plays an important role in palmitate-induced insulin resistance in human skeletal muscle cells.


The inhibitory effects of horse anti-rat AFP antiserum on the uptake of 2-deoxy-D-glucose by AFP-producing rat hepatoma cells.
The inhibitory effects of horse antiserum against rat alpha-fetoprotein (AFP) on the uptake of 2-deoxy-D-glucose (2dG) by the AFP-producing rat ascites hepatoma AH66 cells was studied. AH66 cells cultured in medium containing 20% heat-inactivated antiserum had a 1.5-fold lower rate of sugar uptake than did AH66 cells which were cultured in medium containing 20% heat inactivated normal horse serum. The inhibition of 2dG uptake by antiserum was dependent on both the concentration and the exposure time of antiserum. Preincubation of AH66 tumor cells for 2 and 6 h with antiserum prior to the measurement of 2dG uptake resulted in a 70.1% and 58.2% decrease in 2dG uptake compared to control cells. Antiserum did not inhibit the rate of phosphorylation of 2dG by tumor cells. Kinetic constants for the uptake of 2dG in both AH66 cells treated with antiserum to AFP and in control cells were calculated from Lineweaver-Burk plots. The Km remained constant at approximately 1.2 mM, but the Vmax was twice as small for the cells treated with antiserum as for the control cells (571 vs 923 nanomoles/2 X 10(5) cells/min). These studies suggest that the inhibition of 2dG uptake by treatment with antiserum was the result of a decrease in the number of transport sites, or a decrease in the amount of carrier protein for the sugar which was present on the surface of the plasma membrane of the AH66 cells.


Activity of staphylococcal bacteriocins against Staphylococcus aureus and Streptococcus agalactiae involved in bovine mastitis.
The inhibitory activity of seven bacteriocins produced by Staphylococcus aureus (aureocins A70, A53, and 215FN) and Staphylococcus epidermidis (Pep5, epidermin, epilancin K7 and epicidin 280) was tested against strains of both S. aureus (165 strains) and Streptococcus agalactiae (74 strains) isolated from udders of cows suffering from bovine mastitis. Most strains of the two species were inhibited by epidermin (>85%), aureocin A53 (>67%) and by a combination of aureocins A70 and A53 (>91%), co-expressed in the genetic background of strain A70, the native producer of aureocin A70. Synergy between aureocins A70 and A53 was also demonstrated, which broadened the spectrum of strains inhibited. The remaining staphylococcins inhibited either none of, or a lower percentage (<48%) of, the mastitis-causing pathogens tested. Our results therefore show that the use of epidermin and/or a combination of aureocins A53 and A70 may represent a new non-antibiotic alternative for successfully inhibiting both mastitic staphylococci and streptococci.


Reproducibility over time of measurements of androgens, estrogens and hydroxy estrogens in urine samples from post-menopausal women.
Sex steroid concentrations in urine samples from post-menopausal women have been associated with risk of various chronic diseases. The basic requirement for the assessment of risk in such large-scale epidemiological studies is that subjects be ranked accurately by their average, long-term hormone levels. We examined the reproducibility over time of measurements of urinary testosterone (T), 5alpha-androstane-3alpha, 17beta-diol (ADIOL), estrone (E1), estradiol (E2), 2-hydroxy estrone and 2-hydroxy estradiol, (2(OH)-E), 16alpha-hydroxyestrone (16alpha(OH)-E1) and the ratio of 2(OH)-E and 16alpha(OH)-E1, in a representative sub-sample of post-menopausal women (n = 43) participating in an ongoing prospective cohort study. Women collected three first morning urine voids on different occasions, with average time difference between the first and the third urine sample of 5.1 years. T, ADIOL, E1 and E2 were measured by radio immunoassay after enzymatic hydrolysis, solid-phase extraction and HPLC purification of the samples, while 2(OH)-E and 16alpha(OH)-E1 were assayed by solid-phase enzyme immunoassay after enzymatic hydrolysis. Intra-class correlation co-efficients (ICCs) over time were very good for T (r = 0.85), acceptable for E2, E1 and ADIOL (r > 0.55), but low for 2(OH)-E, 16alpha(OH)-E1 and their ratio (r < 0.46). The adjustment for creatinine concentrations did not increase these correlations.


Time regularities of strontium concentration in drinking groundwater distant from the sea coast.
This paper confirms the regularities of the formation of increased concentrations of strontium (Sr) in fresh groundwater used for drinking water supply, depending on the time they are residen in the carbonate deposits of the aquifer. On average, every thousand years, the Sr concentration increases by 2.1-3.5 mg L-1. In addition, high strontium content is positively correlated with altitude and well depth and negatively correlated with redox conditions in the aquifer. Large relief elevations are associated with the development of marginal moraine deposits from the Last Glacial Period composed predominantly of clay, which contributes to a decrease in water exchange. The high Sr content is associated with the dissolution of significant formations of celestite and strontianite, up to their ore occurrences. For this reason, the saturation indices (SIs) for celestite and strontianite correlate with TDS and rise to - 1.42 and 2.05, respectively. Low Sr values do not correlate with the residence time of groundwater in the aquifer or the depth of wells and tend to depressions in the relief, with a virtual absence of overlying sediments and positive Eh values, which indicates an active water exchange. The low level of Sr is associated with the dissolution of gypsum, calcite, and dolomite containing strontium as an impurity. This causes the SIs for gypsum, calcite, and dolomite to correlate with TDS, while for celestite and strontianite, the SI drops to - 5.02 and - 0.92, respectively. The established patterns make it possible to more reasonably choose places for the construction of water wells to obtain drinking water of standard quality.


Nucleotide sequence of the putative regulatory gene and major promoter region of the Streptomyces griseus glycerol operon.
Nucleotide sequencing of the deduced major promoter region of the glycerol utilization operon and an upstream regulatory gene of Streptomyces griseus reveals extensive similarity to the previously sequenced homologous S. coelicolor region [Smith and Chater, J. Mol. Biol. 204 (1988) 569-580]. However, regions showing extensive divergence are found in the noncoding parts of the sequence. These may help to evaluate the significance of various sequence features in relation to promoter activity.


Identification of a serine protease as a major allergen (Per a 10) of Periplaneta americana.
Cockroach allergens are associated with the development of asthma, but none of these has been characterized for proteolytic activity. This study was undertaken to isolate and characterize a protease from Periplaneta americana and determine its allergenicity. A serine protease was isolated from P. americana extract using benzamidine sepharose column and characterized by immunobiochemical methods. Allergenicity of the protease was assessed by enzyme-linked immunosorbent assay, immunoblot, intradermal testing, histamine release and peripheral blood mononuclear cells (PBMCs) proliferation. Affinity purified protein of approximately 28 kDa (Per a 10) showed a single band of activity in gelatin zymogram and agarose plate assay. N-terminal sequence (IVGGRPAQI) revealed similarity with mite serine protease allergens and insect trypsins. It demonstrated proteolytic activity with azocollagen > gelatin > defatted-milk > casein including serine protease specific substrate, N-benzoyl-arginine-ethyl-ester-hydrochloride. It was inhibited by serine protease inhibitors, namely aprotinin > pefabloc > AEBSF > PMSF > benzamidine > antipain > leupeptin and trypsin-specific inhibitor (tosyl-lysyl-chloromethyl-ketone) suggesting it to be a trypsin-like serine protease. Per a 10 was recognized as a major allergen, showing IgE reactivity with >80% of cockroach sensitized patients by skin tests and immunoblot. It could induce significant histamine release (P < 0.05) in blood and secretion of interleukin-4 (IL-4) (P < 0.05) and IL-5 (P < 0.05) in culture supernatant of PBMCs from cockroach hypersensitive patients, suggesting a strong allergenic potency. A serine protease isolated from P. americana was demonstrated to be a major allergen (Per a 10). It has a potential for component-based diagnosis of allergy and will be useful in elucidating the mechanism of allergy.


Therapy with nitroglycerin increases coronary vasoconstriction in response to acetylcholine.
The purpose of this study was to investigate whether therapy with nitroglycerin (GTN) would lead to abnormal coronary artery responses to the endothelium-dependent vasodilator acetylcholine. Nitroglycerin therapy is associated with specific biochemical changes in the vasculature that may lead to increased vascular sensitivity to vasoconstrictors. Patients were randomized to continuous transdermal GTN, 0.6 mg/h (n = 8), or no therapy (n = 7), for 5 days prior to a diagnostic catheterization. Patients had similar risk factors for endothelial dysfunction. Quantitative angiography was performed in the morning to measure the mean luminal diameter of the left anterior descending coronary artery (LAD) in response to intracoronary acetylcholine (peak concentration, 10(-4) mol/liter). The transdermal preparation was removed from the GTN group, and 3 h later experimental procedures were repeated. In the morning, the GTN group experienced greater coronary constriction in response to acetylcholine infusion than those not receiving GTN (-19.6+/-4.2 vs. -3.8+/-3.0%; p = 0.01). Three hours later, the GTN group continued to display greater constriction to acetylcholine (-24.1+/-5.9%) as compared to the non-GTN group (-1.8+/-4.8%). When the morning and afternoon responses to acetylcholine were compared, the increase in coronary constriction in the GTN group was greater than the change observed in the non-GTN group (p < 0.05). This study demonstrates that therapy with GTN causes abnormal coronary vasomotor responses to the endothelium-dependent vasodilator acetylcholine, changes that were persistent for up to 3 hours after GTN discontinuation. This nitrate-associated vasomotor dysfunction has implications with respect to the development of nitrate tolerance and the potential for adverse events during nitrate withdrawal.


The epidemiology and clinical features of personality disorders in later life; a study of secondary care data.
Personality disorders (PDs) are often conceptualised as impacting individuals throughout their life. However, there has been limited study of the disorders in those over the age of 65. We have used the psychiatric secondary care medical records of 21,971 individuals over the age of 65 from Cambridgeshire, UK, who received care between 2014 and 2021 to characterise older patients with a PD diagnosis. The data from all patients >65 with a diagnosis of personality disorder (PD) was extracted (n = 217) along with two comparison groups (n = 2170); patients <65 with a diagnosis of PD and patients >65 with a psychiatric diagnosis other than PD or dementia. Compared to younger patients with PD, older patients were more likely to be male, married, suffering from a mixed PD and live in less deprived areas. Compared to patients >65 with diagnoses other than PD, older patients were more likely to be female, single or divorced and had a higher level of social deprivation. Our most striking finding was that older patients with PDs were more likely to experience polypharmacy. A mean of 18.48 different drugs had been prescribed over their lifetime, compared to 9.51 for patients >65 with other mental health diagnoses. Here we present the largest ever description of this group of patients and provide insights that could inform clinical practice and future research.


The role of intestinal stem cell within gut homeostasis: Focusing on its interplay with gut microbiota and the regulating pathways.
Intestinal stem cells (ISCs) play an important role in maintaining intestinal homeostasis via promoting a healthy gut barrier. Within the stem cell niche, gut microbiota linking the crosstalk of dietary influence and host response has been identified as a key regulator of ISCs. Emerging insights from recent research reveal that ISC and gut microbiota interplay regulates epithelial self-renewal. This article reviews the recent knowledge on the key role of ISC in their local environment (stem cell niche) associating with gut microbiota and their metabolites as well as the signaling pathways. The current progress of intestinal organoid culture is further summarized. Subsequently, the key challenges and future directions are discussed.


The diagnosis and treatment strategy of occipital skull mass in hemophilic patients: a rare case report and literature review.
Cranial hemophilic pseudotumor (cHPT) is a very rare disease, which is easy to misdiagnose. It is also difficult to manage such patients. We reported the first case of occipital cHPT. Here, we presented a rare case of an occipital bone mass in a 3-year-old boy who was diagnosed with hemophilia A. The mass was misdiagnosed as an aneurysmal bone cyst by pathological examination. After resection, the patient underwent one-stage cranioplasty. However, the patient was admitted again for hematoma caused by an invasive procedure. A second surgery and one-stage cranioplasty were performed at the same time. A follow-up 3 months after discharging showed the patient was uneventful, and the titanium mesh was well fixed. The diagnosis of cHPT requires the combining of history, radiological examination, and pathological examination. Resection is the best choice for symptomatic cHPT. Replacement treatment and less invasive treatment can make perioperative management safer. One-stage cranioplasty for resection of an occipital cHPT can improve the quality of life.


The regulatory interaction of EVI1 with the TCL1A oncogene impacts cell survival and clinical outcome in CLL.
Dysregulated T-cell leukemia/lymphoma-1A (TCL1A), a modulator in B-cell receptor (BCR) signaling, is causally implicated in chronic lymphocytic leukemia (CLL). However, the mechanisms of the perturbed TCL1A regulation are largely unknown. To characterize TCL1A-upstream networks, we functionally screened for TCL1A-repressive micro-RNAs (miRs) and their transcriptional regulators. We identified the novel miR-484 to target TCL1A's 3'-UTR and to be downregulated in CLL. In chromatin immunoprecipitations and reporter assays, the oncogenic transcription factor of myeloid cells, EVI1, bound and activated the miR-484 promoter. Most common in CLL was a pan-EVI1 transcript variant. EVI1 protein expression revealed distinct normal-tissue and leukemia-associated patterns of EVI1/TCL1A co-regulation. EVI1 levels were particularly low in TCL1A-high CLL or such cellular subsets. Global gene expression profiles from a 337-patient set linked EVI1 networks to BCR signaling and cell survival via TCL1A, BTK and other molecules of relevance in CLL. Enforced EVI1, as did miR-484, repressed TCL1A. Furthermore, it reduced phospho-kinase levels, impaired cell survival, mitigated BCR-induced Ca-flux and diminished the in vitro ibrutinib response. Moreover, TCL1A and EVI1 showed a strongly interactive hazard prediction in prospectively treated patients. Overall, we present regressive EVI1 as a novel regulatory signature in CLL. Through enhanced TCL1A and other EVI1-targeted hallmarks of CLL, this contributes to an aggressive cellular and clinical phenotype.


Molecular phylogeny and phylogeography of the Australian Diplodactylus stenodactylus (Gekkota; Reptilia) species-group based on mitochondrial and nuclear genes reveals an ancient split between Pilbara and non-Pilbara D. stenodactylus.
There is a paucity of research on intra-specific morphological and genetic diversity in Australian arid-zone reptiles, and a number of Australian reptile species have for many years been regarded as "species complexes" that classical morphological analyses could not resolve. We conducted a phylogenetic and phylogeographic study of a widespread species group of Australian geckonid lizards to address two main aims. First, based on a large mitochondrial and nuclear gene data set, we have generated the first molecular phylogeny for the Diplodactylus stenodactylus species group (D. alboguttatus, D. damaeus, D. maini, and D. squarrosus, D. stenodactylus) and multiple outgroups to examine the evolutionary relationships among these arid-zone species and phylogenetic patterns within some species. The edited alignment of 41 individuals comprises 2485 characters (1163 ND2+tRNAs; 490 16s; 832 RAG-1), and of these 717 (29%) were variable and parsimony informative (568 ND2+tRNAs; 89 16s; 60 RAG-1). This broad-scale, multi-gene phylogeny has supported previous conjectures on the higher-level phylogenetic relationships among members of the D. stenodactylus species-group based on morphology, but also has uncovered hidden diversity within the group with two new species identified. Analysis at this broad level has identified patterns associated with the distribution of the D. stenodactylus species group that appear to be influenced by environmental processes operating at large geographic scales. Two major clades within the species group were associated with broad differences in habitat types, with one group largely restricted to the temperate zone of the Southwest Province and another largely restricted to central and northern Western Australia north of Kalgoorlie, in line with the Eremaean Province of the Eremaean Zone and the Northern Province of the Tropical Zone. Second, we have assembled phylogeographic data based on a mitochondrial gene (ND2+tRNAs) for five species (Rhynchoedura ornata, Diplodactylus maini, D. pulcher, D. squarrosus, D. stenodactylus) where larger sampling is available, with particular focus on D. stenodactylus, which is distributed both in the iconic but little-known Pilbara area of endemism in north-western Australia as well as in other parts of the Australian arid zone. The edited alignment of 95 individuals comprises 1142 characters and of these 601 (53%) are variable and parsimony informative. We found significant intra-specific genetic variation in all five species, highlighting the need for large-scale screening of cryptic species, with sampling specifically targeted at determining the geographic limits of such taxa. In particular, within D. stenodactylus, a deep and ancient phylogenetic split distinguishes populations in the Pilbara region from non-Pilbara populations. This split may be the result of broad differences in underlying geological substrate, with the Pilbara clade generally preferring harder soils and the non-Pilbara clade adapted to sand.


[Sustainability and climate protection : Implications on patient-centered care in radiology].
Sustainability and patient-centered radiology (PCR) include a multivariant, complex network of synergic and opportunistic elements. PCR is a subfactor of the social element, climate protection is part of the ecological element, and sustainable economics are part of the financial element. We aimed to identify PCR-symbiotic and PCR-opposed elements of sustainability using literature research. This article will provide an overview of the core sustainability elements and innovative concepts for supporting PCR. A digital literature search was carried out to identify scientific publications about sustainability and PCR via Medline. Results are provided as a narrative summary. In particular, the social component and parts of the ecological element of sustainability support PCR. Climate protection and a natural environment show a positive correlation with health and patient satisfaction. Patient contact improves the quality of the diagnostic report and promotes satisfaction of patients and radiologists. However, increasing economization is often conditionally compatible with the social core element of sustainability and especially with PCR. Digital tools can ease communication and improve reports in times of increasing workload. Socially and environmentally sustainable radiology supports the well-being of both employees and patients. Innovative concepts are necessary to balance the ecological elements of sustainability with employees' and patients' interests.


Magnifying endoscopic observation of the gastric mucosa, particularly in patients with atrophic gastritis.
The gastric mucosal surface was observed using the magnifying fibergastroscope (FGS-ML), and the fine gastric mucosal patterns, which were even smaller than one unit of gastric area, were examined at a magnification of about 30. For simplicification, we classified these patterns by magnifying endoscopy in the following ways; FP, FIP, FSP, SP and MP, modifying Yoshii's classification under the dissecting microscope. The FIP, which was found to have round and long elliptical gastric pits, is a new addition to our endoscopic classification. The relationship between the FIP and the intermediate zone was evaluated by superficial and histological studies of surgical and biopsy specimens. The width of the band of FIP seems to be related to the severity of atrophic gastritis. Also, the transformation of FP to FIP was assessed by comparing specimens taken from the resected and residual parts of the stomach, respectively. Moreover, it appears that severe gastritis occurs in the gastric mucosa which shows a FIP. Therefore, we consider that the FIP indicates the position of the atrophic border.


Synthesis of purine N9-[2-hydroxy-3-O-(phosphonomethoxy)propyl] derivatives and their side-chain modified analogs as potential antimalarial agents.
6-Oxopurine acyclic nucleoside phosphonates (ANPs) have been shown to be potent inhibitors of hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT), a key enzyme of the purine salvage pathway in human malarial parasites. These compounds also exhibit antimalarial activity against parasites grown in culture. Here, a new series of ANPs, hypoxanthine and guanine 9-[2-hydroxy-3-(phosphonomethoxy)propyl] derivatives with different chemical substitutions in the 2'-position of the aliphatic chain were prepared and tested as inhibitors of Plasmodium falciparum (Pf) HGXPRT, Plasmodium vivax (Pv) HGPRT and human HGPRT. The attachment of an hydroxyl group to this position and the movement of the oxygen by one atom distal from N(9) in the purine ring compared with 2-(phosphonoethoxy)ethyl hypoxanthine (PEEHx) and 2-(phosphonoethoxy)ethyl guanine (PEEG) changes the affinity and selectivity for human HGPRT, PfHGXPRT and PvHGPRT. This is attributed to the differences in the three-dimensional structure of these inhibitors which affects their mode of binding. A novel observation is that these molecules are not always strictly competitive with 5-phospho-α-d-ribosyl-1-pyrophosphate. 9-[2-Hydroxy-3-(phosphonomethoxy)propyl]hypoxanthine (iso-HPMP-Hx) is a very weak inhibitor of human HGPRT but remains a good inhibitor of both the parasite enzymes with K(i) values of 2μM and 5μM for PfHGXPRT and PvHGPRT, respectively. The addition of pyrophosphate to the assay decreased the K(i) values for the parasite enzymes by sixfold. This suggests that the covalent attachment of a second group to the ANPs mimicking pyrophosphate and occupying its binding pocket could increase the affinity for these enzymes.


Prognostic role of Ca125 response criteria and RECIST criteria: analysis of results from the MITO-3 phase III trial of gemcitabine versus pegylated liposomal doxorubicin in recurrent ovarian cancer.
The aim of the study was to investigate i) the association between the Ca125 based and the RECIST assessed response in recurrent ovarian cancer patients enrolled in a Phase III randomized trial (MITO-3) comparing salvage treatment with pegylated liposomal doxorubicin (PLD) versus gemcitabine (GEM); ii) the correlation between the early modifications of Ca125 levels during treatment and the RECIST assessed response; iii) the prognostic value of response based on Ca125 and the RECIST criteria. Assessment of response was performed by the RECIST and the GCIG criteria. The prognostic impact of the response by the RECIST criteria and the GCIG criteria was analyzed by the landmark method. Overall, of 30 cases defined as responders on the basis of the GCIG criteria, 20 resulted as responders according to the RECIST criteria (NPV=66.7%); conversely, 93.7% of the cases considered not responders based on the GCIG criteria were defined as unresponsive at RECIST evaluation. Early modifications of Ca125 levels were not completely predictive of the ultimate RECIST defined response. Overall survival (OS) was longer in RECIST defined responders versus non responders, although the statistical significance was not reached (p value=0.092); conversely, median OS was significantly longer in GCIG defined responders than in non responding patients (p value=0.0059). In multivariate analysis, the GCIG assessed response maintained its independent association with OS. GCIG criteria for tumor response could replace the conventional assessment of response in the decision making process relative to the discontinuation or prolongation of the salvage treatment in ovarian cancer.


Quality-of-life, mood and executive functioning after childhood craniopharyngioma treated with surgery and proton beam therapy.
Childhood craniopharyngioma, a benign tumour with a good survival rate, is associated with important neurocognitive and psychological morbidity, reducing quality-of-life (QoL). This retrospective study analysed QoL, mood disorders, everyday executive functioning and disease's impact on family life in 29 patients (mean age at diagnosis 7 years 10 months (SD = 4.1); mean follow-up period 6 years 2 months (SD = 4.5)) treated for childhood craniopharyngioma by surgery combined with radiotherapy using proton beam. Assessment included a semi-structured interview and standardized scales evaluating self-report of QoL (Kidscreen 52) and depression (MDI-C) and proxy-reports of QoL (Kidscreen 52), executive functioning (BRIEF) and disease's impact (Hoare and Russel Questionnaire). Twenty-three families answered the questionnaires completely. Overall QoL self-report was within the normal range. QoL proxy-report was lower than self-report. Eleven patients reported depression; 24-38% had dysexecutive symptoms. A majority of families felt 'very concerned' by the disease. Depression and low parental educational level were associated with lower QoL and higher levels of executive dysfunction. Given the high morbidity of childhood craniopharyngioma, screening for psychosocial outcome, cognitive functioning, including executive functions, mood and QoL should be systematic and specific interventions should be developed and implemented.


Subcutaneous versus transvenous implantable defibrillator: An updated meta-analysis.
Implantable cardioverter-defibrillator (ICD) placement is a well-established therapy for prevention of sudden cardiac death. The subcutaneous implantable cardioverter-defibrillator (S-ICD) was specifically designed to overcome some of the complications related to the transvenous implantable cardioverter-defibrillator (TV-ICD), such as lead complications and systemic infections. Evidence on the comparison of S-ICD vs TV-ICD are limited. The purpose of this study was to conduct an updated meta-analysis comparing S-ICD vs TV-ICD. Electronic databases were searched for studies directly comparing clinical outcomes and complications between S-ICD and TV-ICD. The primary outcome was the composite of clinically relevant complications (lead, pocket, major procedural complications; device-related infections) and inappropriate shocks. Secondary outcomes included death and the individual components of the primary outcome. Thirteen studies comprising 9073 patients were included in the analysis. Mean left ventricular ejection fraction was 40% ± 10%; 30% of patients were female; and 73% had an ICD implanted for primary prevention. There was no statistically significant difference in the risk of the primary outcome between S-ICD and TV-ICD (odds ratio [OR] 0.80; 95% confidence interval [CI] 0.53-1.19). Patients with S-ICD had lower risk of lead complications (OR 0.14; 95% CI 0.06-0.29; P <.00001) and major procedural complications (OR 0.18; 95% CI 0.06-0.57; P = .003) but higher risk of pocket complications (OR 2.18; 95% CI 1.30-3.66; P = .003) compared to those with TV-ICD. No significant differences were found for the other outcomes. In patients with an indication for ICD without the need for pacing, TV-ICD and S-ICD are overall comparable in terms of the composite of clinically relevant device-related complications and inappropriate shock.


[Differential diagnosis of aortitis].
Aortitis are mainly described in inflammatory disorders such as Takayasu arteritis, giant cell arteritis or Behçet's disease. Aortitis is sometimes qualified as idiopathic. However, differential diagnoses must be searched since they need specific interventions. Infectious aortitis should be ruled out first as its rapid evolution and short-term poor prognosis makes it a therapeutic emergency. Furthermore, rarer differential diagnoses should be known as they require specific care that might sometimes differ from the treatment of inflammatory aortitis, such as retroperitoneal fibrosis mostly idiopathic but also secondary to neoplasia or malignant hemopathies. IgG4 related disease, Erdheim-Chester disease and inflammatory abdominal aortic aneurysm due to atherosclerosis are other differential diagnoses to mention in the presence of aortitis in order to adapt patients' care consequently.


Anticancer activity of N-heteroaryl acetic acid salts against breast cancer; in silico and in vitro investigation.
The present research was performed to assess N-heteroaryl acetic acid salts' anticancer activity against the breast cancer cell in order to introduce new inhibitory agents for histone deacetylase. A molecular docking simulation was performed to design the rational novel compounds. Afterward, the best compounds were selected for synthesis. The cytotoxic effects and mechanism of action have been studied via (Methyl Thiazol-Tetrazolium) MTT assay. Flow cytometry and gene expression analyses were performed to introduce an effective acetic acid derivative as an anticancer agent. Molecular docking simulations demonstrated that all compounds have the best interaction with histone deacetylase. The fold changes of Bcl-2, Bak, Bim, Caspase-3, and Caspase-8 gene expressions were investigated and compared with reference gene using real-time PCR. The cytotoxic studies showed the best anticancer activity of 4-benzyl-1-(carboxymethyl) pyridinium bromide (compound 2) with a low IC50 value (32 µM, p < 0.05). Also, the best anti HDAC activity was obtained for compound 2 with IC50 value of 1.1 µM. Furthermore, this compound showed a high percentage of apoptosis among all tested compounds after 72 h incubation which was associated with the significant increase in mRNA level of Bim, Bax, Bak, Caspase-3, and Caspase-8 and the considerable decrease in Bcl2 gene expression. These results suggest that compound 2 with the benzyl ring could be an effective anticancer compound for further investigation in breast cancer treatment.


An ISM approach to overcome the participation barriers in the waste source separation-a case study: Urmia University Campus.
A procedure developed to identify and facilitate the implementation of waste source separation strategies applicable in higher education centers, as a prerequisite for the expansion of recycling programs. The target materials proper to be separated were selected based on quantitative/qualitative analysis of waste produced on the Nazlou Campus of Urmia University, Iran (as a case study). The barriers to implementation of the program were identified using the interpretive structural modeling (ISM) methodology. Finally, regarding the main obstacles which could be broken down inside the campus complex, an analysis of factors affecting student participation were done. On average, 37.48% of 1.74 tons of waste daily produced on the campus could be recycled. Based on sieve analyses, the categories of non-ferrous metals, glass, and composite packaging have a wider size distribution (i.e., over 150 to under 80 mm) might lead to improper operation of further mechanical separations and be selected as target materials. The weakness of educational programs and persuading the students are considered the main obstacles. A significant relationship was observed between the three training options, namely "installation of announcements," "organizing waste management classes," and "training through holding the exhibition of recycled products" and the student participation in the program (with more emphasis on the last one). Women were estimated to be more likely than men to participate in the program (70 vs 49%). Also, there was a significant relationship between the knowledge and the student's participation. In other words, strengthening public awareness is essential to increase the participation level.


Translation of capped and uncapped vesicular stomatitis virus and reovirus mRNA'S. Sensitivity to m7GpppAm and ionic conditions.
In an attempt to elucidate the role of the 5'-terminal 7-methylguanosine residue in translation of mammalian mRNAs, vesicular stomatitis virus (VS virus), and reovirus mRNAs containing and lacking this residue, and also Qbeta RNA, were translated in cell-free extracts from reticulocytes and wheat germ under a variety of ionic conditions. Optimal translation of mRNAs lacking a 5' m7G occurred at concentrations of KOAc or KCl which were lower than those optimal for normal "capped" mRNAs. However, this salt dependence was much less marked in the mammalian reticulocyte extract and, at salt concentrations optimal for translation of normal capped mRNAs, reticulocyte lysates translated uncapped with mRNAs at 30 to 60% the normal efficiency. At low K+ concentrations, wheat germ ribosomes bound and translated appreciable amounts of uncapped VS virus mRNA; controls showed that no m7G residue is added to the 5' end of the bound RNA. Analogues of the 5' end, such as m7GpppAm, inhibited translation of both normal and uncapped VS virus RNAs in wheat germ extracts to about the same extent, but the efficiency of its action was reduced at low K+ concentrations. We conclude that there is a reduced importance of the 5' m7G residue in ribosome-mRNA recognition at low K+ concentrations, and that translation of mRNAs in reticulocyte extract is, under any reaction conditions, less dependent on the presence of a 5' "cap" than in wheat germ extracts.


[Not Available].
Due to nonspecific clinical symptoms and the influence of different factors the diagnosis of mycotoxicosis is difficult in many cases. Case descriptions in dairy herds with chronic and acute diseases suspected of having a mycotoxicosis show the necessity of a solid differential diagnosis. Screening methods (MTT-assay) for mycotoxin analysis are recommended in this case. Systematic investigations of fodder cereals before feeding allow a prophylactical assessment of mycotoxin risk. In Mecklenburg-Vorpommern such investigations of the 1999 and 2000 harvest revealed only a low contamination with Zearalenon and Deoxynivalenol. Zearalenon was not detected in 133 samples. 31 of 157 samples contained DON in low levels.


The effect of neuroendocrine secretion on brain morphology and EEG sleep in patients with eating disorders.
Neuroendocrine disturbances [low plasma levels of triiodothyronine (T3), high plasma concentrations of cortisol], morphological brain alterations [enlarged external cerebrospinal fluid (CSF) spaces, dilatation of the ventricles] and altered sleep patterns [fragmented sleep continuity, a reduction of slow wave sleep (SWS) or REM sleep] have been described in patients with anorexia nervosa and bulimia nervosa. The present study investigates to what degree these disturbances interact with each other. In ten anorexic and five bulimic patients cranial computed tomography (CT) to estimate the size of the CSF spaces, blood sampling to measure cortisol and T3 plasma concentrations, and all-night polysomnography were performed. In comparison with patients with normal CT scans, the patients displaying enlarged CSF spaces spent more time in SWS, and the duration of REM sleep was reduced. In the whole sample, a negative correlation was found between the amount of REM sleep and cortisol, whereas a positive association was found between the amount of REM sleep and the T3 level. In addition, the degree of brain shrinkage correlated positively with cortisol and negatively with T3. On the basis of these results, it can be assumed that in patients with eating disorders the disease process with its neuroendocrine alterations affects brain morphology as well as EEG sleep.


Effects of cyclophosphamide on pulmonary function in patients with scleroderma and interstitial lung disease: a systematic review and meta-analysis of randomized controlled trials and observational prospective cohort studies.
The purpose of the present study was to systematically review the effect of cyclophosphamide treatment on pulmonary function in patients with systemic sclerosis and interstitial lung disease. The primary outcomes were the mean change in forced vital capacity and in diffusing capacity for carbon monoxide after 12 months of therapy in patients treated with cyclophosphamide. Three randomized clinical trials and six prospective observational studies were included for analysis. In the pooled analysis, the forced vital capacity and the diffusing capacity for carbon monoxide predicted values after 12 months of therapy were essentially unchanged, with mean changes of 2.83% (95% confidence interval = 0.35 to 5.31) and 4.56% (95% confidence interval = -0.21 to 9.33), respectively. Cyclophosphamide treatment in patients with systemic sclerosis-related interstitial lung disease does not result in clinically significant improvement of pulmonary function.


The sensory-motor profile awake-A new tool for pre-, intra-, and postoperative assessment of sensory-motor function.
Awake craniotomy is a well-established procedure in surgery of intracranial tumors in eloquent areas. However, sufficiently standardized instruments for the assessment of sensory-motor function before, during and after the operation are currently lacking, despite their importance for evaluation of operative outcome. To address this issue, we designed a standardized assessment tool (the "sensory-motor profile awake scale"; SMP-a). The final scale consists of three motor sections (face, arm and leg) assessing both gross and fine motor skills and one sensory section. It differentiates between six grades of impairment and its tasks are applicable for intraoperative continuous monitoring of sensory-motor functions and supporting processes. We analyzed the data of 17 patients with intracranial tumors eligible for awake craniotomy who were preoperatively assessed with the SMP-a. In addition, we present an exemplary case. Our data support the assumption that the SMP-a is feasible in patients eligible for awake craniotomy, even in patients with symptoms of mild aphasia or more severe sensory-motor deficits caused by tumor recurrence. The exemplary case demonstrates the feasibility of repeated measures with the SMP-a in a tumor patient, including the adaption of tasks to the individual requirements of an intraoperative setting. This exploratory study suggests that the SMP-a might be a feasible rating scale in patients with intracranial tumors. The flexibility of the scale enables individual adaption, but preserves the standardized scoring system to allow comparison between assessment dates, patients and, hopefully in the future, institutions. However, future studies are mandatory to provide data on the instrument's diagnostic properties with respect to feasibility, objectivity, validity and reliability.


Unusual cone shaped epiphyses in spondyloepiphyseal dysplasia. Case report.
The radiological manifestations of an unusual spondyloepiphyseal dysplasia have been observed in a girl. A peculiar epi-metaphyseal involvement that is "cone shaped epiphyses" appears to be the major feature.


Exploring the therapeutic efficacy of Chlorella pyrenoidosa peptides in ameliorating Alzheimer's disease.
Alzheimer's disease (AD) is one of the neurodegenerative disorders, the hallmarks of which include deposits of extracellular beta-amyloid (Aβ) as well as intracellular tau neurofibrillary tangles (NFTs) tangles. With disease progression, neuronal apoptosis combined with cerebral atrophy occurs, leading to cognitive impairment and long-term memory loss. Recently, Chlorella species have been identified as a functional food and are being explored for the prevention of various diseases widely studied to prevent or treat many neurodegenerative diseases. Hence, we for the first time investigated the neuroprotective effects of Chlorella pyrenoidosa short-chain peptides (CPPs) i.e. <1 kDa, 1-3 kDa, 3-10 kDa, and >10 kDa on the in vitro and in vivo neuronal injury models. Our in vitro results showed that CPP with a molecular weight of 1-3 kDa and 3-10 kDa could elevate the survival rate of Aβ1-42 or l-Glutamic acid-injured N2A cells. These treatments also inhibited Aβ and tau NFTs in N2A cells and prevented progressive neuronal cellular damage by suppressing inflammatory cytokines such as PGE2, iNOS, IL-6, TNF-α, COX-2, IL-1β, TGF-β1, and NF-κB. Further, our in vivo Aβ1-42-induced AD mice model demonstrated that 1-3 kDa or 3-10 kDa CPP could improve spatial cognition and learning memory. We also observed a decreased cell loss ratio in CA1-CA3 hippocampal regions. Taken together, our findings imply that CPPs may exert their anti-AD impact through anti-inflammatory, and anti-amyloid activities via reducing APP and tau NFT.


Inhibition of lymphocyte proliferation in vitro by two lipid emulsions with different fatty acid compositions.
The effects of two lipid emulsions upon the proliferation of rat and human lymphocytes in vitro were investigated. The emulsions used were Intralipid, a soya bean oilbased emulsion in widespread clinical use, and Omegavenous, a newly-developed emulsion in which n-3 polyunsaturated fatty acids comprise approximately 40% of the total fatty acids. Both emulsions inhibited lymphocyte proliferation in a concentration- and time-dependent manner. Omegavenous was a much more potent inhibitor than Intralipid.


Mutation of the herpes simplex virus 1 KOS UL45 gene reveals dose dependent effects on central nervous system growth.
The herpes simplex virus type 1 (HSV-1) UL45 gene encodes an 18 kDa virion envelope protein whose function remains unknown. Previous studies using a UL45 null mutant, UL45A, demonstrated that deletion of the UL45 gene altered plaque size in Vero and HeLa cells, but was not essential for replication in these cell types. The goal of this study was to determine if mutation of the UL45 gene influenced virus growth in the CNS. Two UL45 mutants, as well as a repaired revertant virus, were constructed and tested for their ability to cause encephalitis and replicate in the CNS. The UL45 mutants were not lethal when 1 x 10(3) pfu were injected intracerebrally into Balb/c mice. In contrast, at inocula greater than 1 x 10(3), the UL45 mutants were lethal. In vivo growth curves derived from mice inoculated intracerebrally with 1 x 10(3) pfu of virus revealed that the mutants grew poorly compared to wild type or revertant viruses. These results suggest that the 18 kDa UL45 gene product is required for efficient growth in the central nervous system at low doses. We propose that the UL45 gene may play an important role under the conditions of a naturally acquired infection.


Potassium fluxes in contracting human skeletal muscle and red blood cells.
The present study examined K+ fluxes in red blood cells and muscle during muscle contractions. Seven subjects performed two-legged submaximal knee-extensor exercise for 30 min. After 10 min of leg exercise (L1), intense arm exercise was also performed for 10 min (L2+A). Plasma epinephrine and norepinephrine concentrations were higher (P < 0.05) in L2+A compared with L1. Arterial plasma K+ at the end of L2+A was higher than in L1 (5.6 vs. 4.4 mM, P < 0.05) and returned to the L1 level on cessation of arm exercise. A net K+ release of 0.16 mmol/min from the active legs during L1 was turned to a net K+ uptake of 0.79 mmol/min during L2+A. Both arterial and venous red blood cell K+-to-hemoglobin ratios were constant during exercise. The present data suggest that contracting muscle can take up K+ probably by a combination of K+ and hormone activation of the Na+-K+ pump. Furthermore, changes in red blood cell K+ concentrations during muscle activity appear to be due to water movements and not transmembrane fluxes of K+.


Generation and biological properties of a monoclonal antibody to galactocerebroside.
Galactocerebroside ( GalC ) is a major glycolipid of myelin and myelin-forming cells. We have generated a mouse IgM monoclonal antibody to GalC (M-anti- GalC ) which bound only to oligodendrocytes in rat and bovine central nervous system cultures as assessed by immunofluorescence. Double staining with rabbit anti-glial fibrillary acidic protein and anti-fibronectin antisera revealed no binding of M-anti- GalC to astrocytes or fibroblasts. Schwann cells, but not fibroblasts, were stained in short-term cultures of rat Schwann cells. M-anti- GalC exhibited in vitro cytotoxicity to rat and bovine oligodendrocytes in the presence of complement. This monoclonal antibody with its monospecificity, consistent titer, and capacity to induce cell lysis should be useful for in vitro and in vivo investigations concerning myelination and demyelination.


Effect of glucocorticoid receptor blockade on analgesic effect of corticotropin-releasing factor.
The role of glucocorticoid receptors in the analgesic effect of corticotropin-releasing factor in rats was studied after glucocorticoid receptor blockade with antagonist RU 38486. Glucocorticoid hormones can potentiate the analgesic effect of corticotropin-releasing factor or modulate the mechanisms of this effect, which depends on the type of painful stimulus.


Narrative as cultural attractor.
By structuring information in a systematic relational framework, narratives are cultural attractors that are particularly well-suited for transmission. The relational structure of narrative is partly what communicates causality, but this structure also complicates both transmission and selection on cultural elements by introducing correlations among narrative elements and between different narratives. These correlations have implications for adaptation, complexity, and robustness.


Mitochondrial reactive oxygen species are involved in chemoattractant-induced oxidative burst and degranulation of human neutrophils in vitro.
Activation of neutrophils is accompanied by the oxidative burst, exocytosis of various granule types (degranulation) and a delay in spontaneous apoptosis. The major source of reactive oxygen species (ROS) in human neutrophils is NADPH oxidase (NOX2), however, other sources of ROS also exist. Although the function of ROS is mainly defensive, they can also play a regulatory role in cell signaling. However, the contribution of various sources of ROS in these processes is not clear. We investigated a possible role of mitochondria-derived ROS (mtROS) in the regulation of neutrophil activation induced by chemoattractant fMLP in vitro. Using the mitochondria-targeted antioxidant SkQ1, we demonstrated that mtROS are implicated in the oxidative burst caused by NOX2 activation as well as in the exocytosis of primary (azurophil) and secondary (specific) granules. Scavenging of mtROS with SkQ1 slightly accelerated spontaneous apoptosis and significantly stimulated apoptosis of fMLP-activated neutrophils. These data indicate that mtROS play a critical role in signal transduction that mediates the major neutrophil functional responses in the process of activation.


Molecular Profiling Provides Clinical Insights Into Targeted and Immunotherapies as Well as Colorectal Cancer Prognosis.
Tumor genetic testing is indispensable in the management of primary and metastatic colorectal cancer (CRC), yet the indications for genomics-guided precision medicine and immunotherapy must be better understood and defined. We prospectively sequenced tumors from 869 Chinese patients with CRC by a large panel and evaluated the clinical significance of single-gene somatic mutations and co-occurring events in metastatic CRC, as well as their functional effects and tumorigenic mechanisms. We systematically assessed the heterogeneity of the tumor immune microenvironment in different genomic contexts through the combined analysis of Immunoscore, multiplex immunostaining, whole-exome sequencing, transcriptome, and single-cell sequencing. Single-gene somatic mutations in BRAF or RBM10 were associated with shorter progression-free survival in patients with metastatic CRC. Functional studies suggested RBM10 acts as a tumor suppressor in CRC development. Co-mutations of KRAS/AMER1 or KRAS/APC were enriched in the metastatic cohort, which had poor progression-free survival and did not benefit from bevacizumab due to accelerated drug metabolism. Forty patients (4.6%) carried pathogenic or likely pathogenic germline alterations in the DNA damage repair pathway and 37.5% of these tumors had secondary-hit events with loss of heterozygosity or biallelic alterations. A high tumor insertion or deletion burden with high microsatellite instability suggested immunogenicity with numerous activated tumor-infiltrating lymphocytes, whereas polymerase epsilon exonuclease mutation with ultrahigh tumor mutation burden indicated a relatively quiescent immunophenotype. The heterogeneous genomic-immunologic interactions were reflected in the divergent neoantigen presentation and depletion, immune checkpoint expression, PD-1/PD-L1 interaction, and T-cell responsiveness to pembrolizumab. Our integrated analysis provides insights into CRC prognostic stratification, drug response, and personalized genomics-guided targeted and immunotherapies.


Evaluation of articular cartilage with 3D-SPGR MRI after autologous chondrocyte implantation.
To assess the maturation process of the cartilage after autologous chondrocyte implantation (ACI), we performed a longitudinal study with three-dimensional spoiled gradient-recalled (3D-SPGR) magnetic resonance imaging (MRI). Five knees of five patients on which ACI of the femoral condyle was performed were studied. The signal intensity of reparative tissue approached that of normal articular cartilage with time. The volume of reparative tissue remained at an almost constant level after implantation. During second-look arthroscopy, the areas on which ACI was performed were covered with hyaline-like cartilage, and the reparative tissue removed by biopsy consisted of normal chondrocytes and extracellular matrix. The increased signal intensity of the reparative tissue represents maturation of implanted autologous chondrocytes. 3D-SPGR MRI is thought to be useful for evaluating reparative tissue after autologous chondrocyte implantation.


Synthesis and characterization of an aggrecan mimic.
Aggrecan (AGG) is a large, aggregating proteoglycan present throughout the body, but predominantly found in articular cartilage. The principle features of AGG, its hyaluronan (HA) binding domain and its abundance of covalently attached glycosaminoglycans (GAGs), make it an essential component of the functional ability of articular cartilage. Current tissue engineering constructs have attempted to stimulate AGG production, but have been unable to produce adequate amounts of mature AGG, and hence have suffered a mismatch in mechanical properties. To address these deficiencies, an AGG mimic was synthesized to match AGG functional properties and provide greater control within tissue engineering constructs. Chondroitin sulfate was functionalized with HA-specific binding peptides to replicate both the GAG presence and HA-binding ability of AGG, respectively. Upon characterization and testing, the mimic was able to effectively bind to HA, increase the compressive strength of cartilage extracellular matrix-based constructs, and protect the other extracellular matrix (ECM) components from degradation, replicating the important functions of AGG. In particular, the mimic produced a 78% increase in compressive strength of the ECM-based constructs, and was able to significantly reduce the degradation of both HA and collagen. The initial characterization of the newly synthesized AGG mimic demonstrates its potential in tissue engineering constructs, and provides an essential basis for more explorative studies of the AGG mimic's abilities as an AGG substitute and beyond.


Global information sampling in the honey bee.
Central to the question of task allocation in social insects is how workers acquire information. Patrolling is a curious behavior in which bees meander over the face of the comb inspecting cells. Several authors have suggested it allows bees to collect global information, but this has never been formally evaluated. This study explores this hypothesis by answering three questions. First, do bees gather information in a consistent manner as they patrol? Second, do they move far enough to get a sense of task demand in distant areas of the nest? And third, is patrolling a commonly performed task? Focal animal observations were used to address the first two predictions, while a scan sampling study was used to address the third. The results were affirmative for each question. While patrolling, workers collected information by performing periodic clusters of cell inspections. Patrolling bees not only traveled far enough to frequently change work zone; they often visited every part of the nest. Finally, the majority of the bees in the middle-age caste were shown to move throughout the nest over the course of a few hours in a manner suggestive of patrolling. Global information collection is contrary to much current theory, which assumes that workers respond to local information only. This study thus highlights the nonmutually exclusive nature of various information collection regimes in social insects.


Harp Seals Do Not Increase Their Call Frequencies When It Gets Noisier.
Some species avoid low-frequency masking by shifting their calls to higher frequencies. We addressed the hypothesis that Pagophilus groenlandicus (harp seals) will make more high-frequency underwater calls to avoid low-frequency conspecific masking as calling rates increase. The spectral shapes at high and low calling rates were compared (after equalizing the broadband amplitudes). There were no significant differences between the spectral shapes. Pagophilus groenlandicus do not alter the proportions of low- and high-frequency calls as it gets noisier. This suggests that they may not shift their calling frequencies when encountering low-frequency, broadband anthropogenic noise.


Hydrogen peroxide increases the activities of soxRS regulon enzymes and the levels of oxidized proteins and lipids in Escherichia coli.
The effects of hydrogen peroxide treatments on Escherichia coli KS400 and AB1157 cells were assessed by monitoring the accumulation of oxidative damage products, carbonyl proteins and thiobarbituric acid-reactive substances (TBARS), as well as the activities of selected antioxidant enzymes. H(2)O(2) treatment stimulated increases in both TBARS and carbonyl protein levels in dose- and time-dependent manners in KS400 cells. The accumulation of TBARS was much more variable with H(2)O(2) treatment; TBARS content was significantly increased in response to 5 microM H(2)O(2), whereas a significant increase in carbonyl protein content occurred at 100 microM H(2)O(2). Similarly, treatment with 20 microM hydrogen peroxide for different lengths of time resulted in peak TBARS accumulation by 20 min, whereas carbonyl protein levels were significantly elevated only after 60 min. In AB1157 cells, treatment with 20 microM hydrogen peroxide for 20 min led to strong increases in both carbonyl protein and TBARS levels. This treatment also triggered increased activities of enzymes of the oxyR regulon (catalase, peroxidase, and glutathione reductase) in both strains. In the AB1157 strain, H(2)O(2) exposure also increased the activities of two enzymes of the soxRS regulon (superoxide dismutase and glucose-6-phosphate dehydrogenase) by 50-60%. The data show differential variability of lipids versus proteins to oxidative damage induced by H(2)O(2,) as well as strain-specific differences in the accumulation of damage products and the responses by antioxidant enzymes to H(2)O(2) stress.


Biological soil crusts accelerate the nitrogen cycle through large NO and HONO emissions in drylands.
Reactive nitrogen species have a strong influence on atmospheric chemistry and climate, tightly coupling the Earth's nitrogen cycle with microbial activity in the biosphere. Their sources, however, are not well constrained, especially in dryland regions accounting for a major fraction of the global land surface. Here, we show that biological soil crusts (biocrusts) are emitters of nitric oxide (NO) and nitrous acid (HONO). Largest fluxes are obtained by dark cyanobacteria-dominated biocrusts, being ∼20 times higher than those of neighboring uncrusted soils. Based on laboratory, field, and satellite measurement data, we obtain a best estimate of ∼1.7 Tg per year for the global emission of reactive nitrogen from biocrusts (1.1 Tg a(-1) of NO-N and 0.6 Tg a(-1) of HONO-N), corresponding to ∼20% of global nitrogen oxide emissions from soils under natural vegetation. On continental scales, emissions are highest in Africa and South America and lowest in Europe. Our results suggest that dryland emissions of reactive nitrogen are largely driven by biocrusts rather than the underlying soil. They help to explain enigmatic discrepancies between measurement and modeling approaches of global reactive nitrogen emissions. As the emissions of biocrusts strongly depend on precipitation events, climate change affecting the distribution and frequency of precipitation may have a strong impact on terrestrial emissions of reactive nitrogen and related climate feedback effects. Because biocrusts also account for a large fraction of global terrestrial biological nitrogen fixation, their impacts should be further quantified and included in regional and global models of air chemistry, biogeochemistry, and climate.