Medicinal mushroom Phellinus igniarius induced cell apoptosis in gastric cancer SGC-7901 through a mitochondria-dependent pathway.
Gastric cancer (GC) is the fourth most common diagnosed cancer and the second leading cause of cancer death worldwide. Phellinus igniarius is a traditional medicinal mushroom used in China and other countries of East Asia for the treatment of various diseases including cancer. The aim of this study is to evaluate the antitumor activity of P. igniarius and elucidate the possible mechanism. MTT assay displayed that the total ethanol extract of P. igniarius (TPI) had antitumor activities against five human tumor cell lines of HepG-2, AGS, SGC-7901, Hela and A-549. TPI was found the most cytotoxity against gastric cancer SGC-7901 in vitro, and strongly inhibited the tumor growth in xenograft nude mice in vivo. Typical morphological changes due to cell apoptosis including chromatin condensation, and nuclear fragmentation with the formation of apoptotic bodies were observed in the SGC-7901 cells after TPI treatment. TPI blocked SGC-7901 cell cycle at G0/G1 phase and caused apoptosis by down-regulated the expression of cyclin D1. TPI caused a remarkable collapse of mitochondrial membrane potential (MMP, △ψm) in SGC-7901 cells and induced the mitochondrial-dependent apoptosis by triggered the caspase-9, -3 activation and PARP cleavage. Moreover, TPI increased the ratio of Bax/Bcl-2 in SGC-7901 both in vitro and in vivo. These findings suggested that P. igniarius could be a potential natural derived therapeutic agent for the prevention and treatment of gastric cancer, as it could induce the cancer cell apoptosis through a mitochondria-dependent pathway.


Inferring clonal structure in HTLV-1-infected individuals: towards bridging the gap between analysis and visualization.
Human T cell leukemia virus type 1 (HTLV-1) causes adult T cell leukemia (ATL) in a proportion of infected individuals after a long latency period. Development of ATL is a multistep clonal process that can be investigated by monitoring the clonal expansion of HTLV-1-infected cells by isolation of provirus integration sites. The clonal composition (size, number, and combinations of clones) during the latency period in a given infected individual has not been clearly elucidated. We used high-throughput sequencing technology coupled with a tag system for isolating integration sites and measuring clone sizes from 60 clinical samples. We assessed the role of clonality and clone size dynamics in ATL onset by modeling data from high-throughput monitoring of HTLV-1 integration sites using single- and multiple-time-point samples. From four size categories analyzed, we found that big clones (B; 513-2048 infected cells) and very big clones (VB; >2048 infected cells) had prognostic value. No sample harbored two or more VB clones or three or more B clones. We examined the role of clone size, clone combination, and the number of integration sites in the prognosis of infected individuals. We found a moderate reverse correlation between the total number of clones and the size of the largest clone. We devised a data-driven model that allows intuitive representation of clonal composition. This integration site-based clonality tree model represents the complexity of clonality and provides a global view of clonality data that facilitates the analysis, interpretation, understanding, and visualization of the behavior of clones on inter- and intra-individual scales. It is fully data-driven, intuitively depicts the clonality patterns of HTLV-1-infected individuals and can assist in early risk assessment of ATL onset by reflecting the prognosis of infected individuals. This model should assist in assimilating information on clonal composition and understanding clonal expansion in HTLV-1-infected individuals.


To Message or Browse? Exploring the Impact of Phone Use Patterns on Male Adolescents' Consumption of Palatable Snacks.
Surveys of mobile phone usage suggest that adolescents habitually use their phones while eating. In this study, we explored whether the manner in which one uses a mobile phone - to engage in a social or non-social activity - can affect appetite regulation. Participants were fifty male adolescents randomly assigned to engage in one of the following phone-based activities: (1) sending and receiving messages (social activity), or (2) reading a neutral article (non-social activity). When given the opportunity to snack, participants in the messaging group consumed more snacks that those who read the article. Our findings correspond to a large literature emphasizing social influences on food intake, and suggest that phone use patterns may predispose an individual to overeating.


The effects of continuous nurturance and nurturance withdrawal on children's behavior: a partial replication.
This research replicates and extends a study by Hartrup (1958) of the effects of continuous nurturance and nurturance withdrawal on children's behavior. Kindergarten and second-grade children interacted with either a continuously nurturant adult or an adult who was initially nurturant and then withdrew nurturance. A questionnaire was administered to assess children's perceptions of thier experiences and their perceptions of the reasons for the adult's withdrawal. Sessions ended after an assessment of the adult's social reinforcer effectiveness. The results indicated that the adult's social reinforcer effectiveness was an interaction of the effects of sex, children's frequency of verbalization, and nurturance condition. The results partially replicated Hartrup's (1958) and are discussed in terms of suggestions for future research on less complex contrasts between adult interaction patterns.


Use of human protein C concentrates in the treatment of patients with severe congenital protein C deficiency.
Protein C is one of the major inhibitors of the coagulation system that downregulate thrombin generation. Severe congenital protein C deficiency leads to a hypercoagulability state that usually presents at birth with purpura fulminans and/or severe venous and arterial thrombosis. Recurrent thrombotic events are commonly seen. From the 1990's, several virus-inactivated human protein C concentrates have been developed. These concentrates currently constitute the therapy of choice for the treatment and prevention of clinical manifestations of severe congenital protein C deficiency. This review summarizes the available information on the use of human protein C concentrates in patients with severe congenital protein C deficiency.


Urban-Rural Disparities in Energy Intake and Contribution of Fat and Animal Source Foods in Chinese Children Aged 4-17 Years.
Excessive energy intake and poor food choices are major health concerns associated with overweight and obesity risk. This study aims to explore disparities in energy intake and the contributions from fat and animal source foods among Chinese school-aged children and adolescents in different communities based on urbanization levels. Three consecutive 24 h recalls were used to assess dietary intake. Subjects' height and weight were measured using standard equipment. Standardized questionnaires were used to collect household demographic and socioeconomic characteristics by trained interviewers. The 2011 China Health and Nutrition Survey is part of an ongoing longitudinal household survey across 228 communities in nine provinces and three mega-cities in China. Subjects consisted of children aged 4-17 years (n = 1866; 968 boys and 898 girls). The estimated average energy intake was 1604 kcal/day (1706 kcal/day for boys and 1493 kcal/day for girls). Proportions of energy from fat and animal source foods were 36.8% and 19.8% respectively and did not differ by gender. Total energy intake showed no significant disparity, but the proportion of energy from fat and animal source foods increased with increasing urbanization levels and increasing household income level. The largest difference in consumption percentages between children in rural areas and those in highly urban areas was for milk and dairy products (14.8% versus 74.4%) and the smallest difference was seen in percent consuming meat and meat products (83.1% versus 97.1%). Results of this study highlight the need for developing and implementing community-specific strategies to improve Chinese children's diet quality.


Intelligent Assessment of Mental Health Based on Multisource Information Fusion.
Mental health problems will seriously damage social harmony and family happiness. This paper proposes a study on mental health intelligence assessment based on multisource information fusion. Combining the data description of UPI and SCL-90 and the corresponding task requirement analysis, the multisource information fusion visualization based on the Circos diagram is designed and realized, and the parallel coordinate visualization is established. The MDS algorithm is used to project multidimensional survey objects into low-dimensional visualization space, and the actual UPI and SCL-90 questionnaire data for 278 students of a certain major at a university provided by the cooperative unit are used. The results show that the mental health problems of student A are serious, and the symptoms of depression and schizophrenia are prominent, so it is necessary to seek psychological experts for corresponding treatment in time. By contrast, student B's mental health problems are also serious, and the user judges that student B still needs further diagnosis and treatment. The correlation analysis results of multisource information fusion are roughly the same as the actual situation, which is convincing. Therefore, the multisource mental health information fusion of college students has a certain correlation and complementarity.


[Aseptic femur head necrosis and therapeutic possibilities by using a bone graft with a vascular pedicle].
The review of the occurrence, etiopathology, classification and diagnosis of the aseptic necrosis of the femoral head is followed by the description of the method of transplantation of the vascular pedicled bone graft. During 5 years implantation of 12 vascular pedicled bone grafts in 10 young patients with severe and of major extension necrosis of the femoral head was carried out. The early result was in every case the quick and significant decrease of pains and that the necrosis did not progress. In the early stage the severe consequence of the necrosis the collapse can be prevented with core decompression. In a later stage the vascular pedicled revascularization of the femoral head may retain in young patients, beside adequate hip movements, the gait and the working capacity. This, though it is not a final solution, will give chance by gaining time to perform prosthesis operations later.


Isolation and genotyping of Toxoplasma gondii from Ugandan chickens reveals frequent multiple infections.
The genetic make-up of an infecting Toxoplasma gondii strain may be important for the outcome of infection and the risk of reactivation of chronic disease. In order to survey the distribution of different genotypes within an area, free-range chickens act as a good model species. In this study 85 chickens were used to investigate the prevalence, genotype and mouse virulence of T. gondii in Kampala, Uganda. Antibodies were detected in 40 chickens, of which 20 had MAT-titres of 1:20 or higher and were also positive by PCR. Genotyping of 5 loci (SAG1, SAG2, SAG3, BTUB and GRA6) showed that 6 strains belonged to genotype I, 8 to Type II and 1 to Type III. Five chickens had multiple infections; 3 individuals with Type I plus Type II and a further 2 harbouring Types I, II and III. Isolates were obtained from 9 chickens via bioassay in mice, 6 were Type II strains and 3 were from animals with mixed infection. This is the first set of African T. gondii strains to be genotyped at multiple loci and in addition to the 3 predominant lineages we found a small number of new polymorphisms and a high frequency of multiple infections.


Stylistic features of case reports as a genre of medical discourse.
The present paper discusses the lexical and grammatical peculiarities of English language medical case reports, taking into account their communicative purposes and intentions. The objective of the research is to clarify the principal mechanisms of producing an effective English language medical case report and thus to provide recommendations and guidelines for medical professionals who will deal with this genre. The analysis of medical case reports will largely focus on the most significant linguistic peculiarities, such as the use of active and passive voice, the choice of particular verb tenses, and pronouns. The selected medical case reports will be considered using methods of lexico-grammatical analysis, quantitative examination, and contextual, structural, narrative, and stylistic analyses. The research revealed a range of important stylistic features of medical case reports which markedly distinguish them from other genres of medical scientific writing: educational and instructive intentions, conciseness and brevity, direct and personal tone, and material presented in a narrative style. The present research has shown that the communicative strategies of the analyzed discourse, mentioned immediately above, are effectively implemented by means of specific lexical units and grammatical structures: the dominance of active voice sentences, past simple tense, personal pronouns, and modal verbs. The research has also detected the occasional use of the present perfect, present simple, and future simple tenses and passive voice which also serve particular communicative purposes of medical case reports. Medical case reports possess a range of unique characteristics which differ from those of research articles and other scientific genres within the framework of written medical discourse. It is to be emphasized that it is highly important for medical professionals to master the major stylistic principles and communicative intentions of medical case report as a genre in order to share their findings with fellow researchers from all over the world. Hence, in the process of training future medical researchers, the analysis of the basic mechanisms of writing a medical case report should be an integral part of the curricula in English for Specific Purposes at universities.


[Influencing factors and antenatal assessment of the vaginal birth after cesarean section].
Objective: To explore the influencing factors of the vaginal birth after cesarean section (VBAC), and establish a model for predicting the risk of trial of the trial of labor after cesarean section (TOLAC). Methods: From January 2016 to December 2018, total 694 pregnant women who underwent TOLAC in Northwest Women's and Children's Hospital were retrospectively analyzed. Those cases were divided into two groups according to the mode of delivery: the VBAC group and the failed TOLAC group. At the same time, 700 cases in the elective repeat cesarean section (ERCS) group were randomly selected as control group. The influencing factors of VBAC were analyzed by univariate and multivariate logistic regression, and the pregnancy outcomes between the three groups were compared. Results: (1) The VBAC rate was 76.1% (528/694) and 166 women underwent the failed TOLAC (23.9%, 166/694). (2) Univariate analysis found that, the pre-pregnancy body mass index (BMI) [(22.0±3.0), (23.3±2.7) kg/m(2)], the previous vaginal delivery history [10.4%(55/528), 3.6%(6/166)], the cervical score (5.2±1.9,4.3±1.6) and the neonatal birth weight [(3 315±468), (3 484±274) g] of the VBAC group were significantly different from the failed TOLAC group (P<0.05). (3) The comparison of pregnancy outcomes: the neonatal birth weight was (3 315±468) g, and the intrapartum hemorrhage volume was (255±121) ml in the VBAC group, which were significantly lower than those in the failed TOLAC group [intrapartum hemorrhage (325±173) ml] and the ERCS group [(3 572±344) g, (281±125) ml], there were statistically significant differences in the comparison among the three groups (all P<0.05). Two cases of bladder injury occurred during cesarean section in the TOLAC failure group (1.2%,2/166). The rates of the blood transfusion, puerperal infection, 5-minute Apgar score and neonatal ICU admission among the three groups were no statistically significantly different (all P>0.05). There was no maternal or perinatal death. (4) Multivariate logistic regression analysis showed that the delivery age of pregnant women (OR=0.92, 95%CI: 0.87-0.98), pre-pregnancy BMI (OR=0.92, 95%CI:0.86-0.98), vaginal delivery history (OR=3.31, 95%CI: 1.35-8.01), cervical score (OR=1.29, 95%CI: 1.13-1.42) and the birth weight of the neonates <3 300 g (OR=3.15, 95%CI: 2.02-4.90) were independent influencing factors for VBAC. The area under curve of the receiver operating characteristic curve was 0.74. Conclusions: The influencing factors of VBAC are delivery age, pre-pregnancy BMI, vaginal delivery history, cervical score and neonatal birth weight <3 300 g. The adequate individualized management and assessment of the TOLAC may be helpful to improve the VBAC rate.


How zebrafish turn: analysis of pressure force dynamics and mechanical work.
Whereas many fishes swim steadily, zebrafish regularly exhibit unsteady burst-and-coast swimming, which is characterized by repeated sequences of turns followed by gliding periods. Such a behavior offers the opportunity to investigate the hypothesis that negative mechanical work occurs in posterior regions of the body during early phases of the turn near the time of maximal body curvature. Here, we used a modified particle image velocimetry (PIV) technique to obtain high-resolution flow fields around the zebrafish body during turns. Using detailed swimming kinematics coupled with body surface pressure computations, we estimated fluid-structure interaction forces and the pattern of forces and torques along the body during turning. We then calculated the mechanical work done by each body segment. We used estimated patterns of positive and negative work along the body to evaluate the hypothesis (based on fish midline kinematics) that the posterior body region would experience predominantly negative work. Between 10% and 20% of the total mechanical work was done by the fluid on the body (negative work), and negative work was concentrated in the anterior and middle areas of the body, not along the caudal region. Energetic costs of turning were calculated by considering the sum of positive and negative work and were compared with previous metabolic estimates of turning energetics in fishes. The analytical workflow presented here provides a rigorous way to quantify hydrodynamic mechanisms of fish locomotion and facilitates the understanding of how body kinematics generate locomotor forces in freely swimming fishes.


Prevalence of Neospora spp. in donkeys in China.
This study was conducted to detect specific anti-Neospora antibodies using a commercial competitive-inhibition ELISA kit, and to evaluate the risk factors for Neospora spp. infection. Out of a total of 2,228 donkey sera collected in three provinces in China, 211 (9.5%) were found to be positive for anti-Neospora antibodies. Statistical analysis revealed that age (p = 0.019, OR = 1.62, 95%CI: 1.08-2.44), feeding status (p < 0.001, OR = 3.79, 95%CI: 2.65-5.43), miscarriage history (p = 0.006, OR = 2.56, 95%CI: 1.27-4.01), and contact with dogs (p < 0.001, OR = 2.69, 95%CI: 1.86-3.88) were significant risk factors for Neospora spp. infection. This is the first evidence of Neospora infection in donkeys in China.


Minimum competency: a comparison of reactions of southern black high school students, their parents and black teachers.
A questionnaire was administered to 300 black high school students, 77 parents and 79 black teachers to determine their reactions to minimum competency requirements being suggested for high school graduation. Black parents were strongest in their approval of such requirements, followed by black teachers and to a lesser degree by the students. In some areas all were essentially in agreement. Being able to communicate, handle money matters, stay healthy, recognize dishonest merchandising and make simple home repairs were agreed upon as necessary for survival as adults in our society. Minimal and necessary competencies were thus equated.


Case Report: Short-Term Spinal Cord Stimulation and Peripheral Nerve Stimulation for the Treatment of Trigeminal Postherpetic Neuralgia in Elderly Patients.
Objective: We aimed to report on the use of short-term high cervical spinal cord stimulation (SCS) combined with peripheral nerve stimulation (PNS) to successfully treat trigeminal postherpetic neuralgia (TPHN) affecting the V2 and V3 divisions. We also sought to use a novel PNS approach to the maxillary nerve next to the external opening of the foramen rotundum (FR) to treat TPHN at the V2 division. Method: Two elderly patients successfully treated with different neuromodulation methods for TPHN are presented in this case series. Results: The first case referred to an 83-year-old Chinese female patient with V2 and V3 TPHN who experienced a significant pain relief using a combination of short-term high cervical SCS at the C1-C2 level and PNS on the infraorbital nerve (ION). Case 2 was a 68-year-old Chinese male patient with V1 and V2 TPHN that obtained an excellent pain relief after having received short-term PNS on the supraorbital nerve (SON), the supratrochlear nerve (STN), and the maxillary nerve. Both reported improvements in their quality of life and ability to perform daily tasks during a 3-month follow-up period. Conclusions: Short-term high cervical SCS at the C1-C2 spinal segments may be a feasible method to treat recent-onset V3 TPHN in elderly patients. Additionally, by placing the stimulation lead next to the external FR opening, we demonstrated a novel PNS approach to the maxillary nerve not previously reported for TPHN therapy.


The utility of simple mathematical models in understanding gene regulatory dynamics.
In this review, we survey work that has been carried out in the attempts of biomathematicians to understand the dynamic behaviour of simple bacterial operons starting with the initial work of the 1960's. We concentrate on the simplest of situations, discussing both repressible and inducible systems and then turning to concrete examples related to the biology of the lactose and tryptophan operons. We conclude with a brief discussion of the role of both extrinsic noise and so-called intrinsic noise in the form of translational and/or transcriptional bursting.


Phytochemical and toxicological investigations of crude methanolic extracts, subsequent fractions and crude saponins of Isodon rugosus.
Isodon rugosus is used traditionally in the management of hypertension, rheumatism, tooth-ache and pyrexia. Present study was arranged to investigate I. rugosus for phytoconstituents, phytotoxic and cytotoxic activities to explore its toxicological, pharmacological potentials and to rationalize its ethnomedicinal uses. Briefly, qualitative phytochemical analysis of the plant extracts were carried out for the existence of alkaloids, flavonoids, saponins, oils, glycosides, anthraquinones, terpenoids, sterols and tannins. Plant crude methanolic extract (Ir.Cr), its subsequent fractions; n-hexane (Ir.Hex), chloroform (Ir.Chf), ethyl acetate (Ir.EtAc), aqueous (Ir.Aq) and saponins (Ir.Sp) in different concentrations were tested for phytotoxic and cytotoxic activities using radish seeds and brine shrimps (Artemia salina) respectively. The phytotoxic activity was determined by percent root length inhibition (RLI) and percent seeds germination inhibition (SGI) while the cytotoxicity was obtained with percent lethality of the brine shrimps. Ir.Cr was tested positive for the presence of alkaloids, glycosides, flavonoids, oils, terpenoids, saponins, tannins and anthraquinones. Among different fractions Ir.Sp, Ir.Chf, Ir.EtAc, and Ir.Cr were most effective causing 93.55, 89.32, 81.32 and 58.68% inhibition of seeds in phytotoxicity assay, with IC50 values of 0.1, 0.1, 0.1 and 52 μg/ml respectively. Similarly, among all the tested samples, Ir.Sp exhibited the highest phytotoxic effect causing 91.33% root length inhibition with IC50 of 0.1 μg/ml. Ir.Sp and Ir.Chf were most effective against brine shrimps showing 92.23 and 76.67% lethality with LC50 values of 10 and 12 μg/ml respectively. It may be inferred from the current investigations that I. rugosus contains different secondary metabolites and is a potential source for the isolation of natural anticancer and herbicidal drug molecules. Different fractions exhibited phytotoxic and cytotoxic activities, thus providing pharmacological basis for ethnomedicinal uses of this plant.


Bis(tetra-ethyl-ammonium) bis-(dimethyl-formamide)-tetra-kis-(μ-N,2-dioxido-benzene-1-carboximidato)penta-copper(II).
The title compound, (C(8)H(20)N)(2)[Cu(5)(C(7)H(4)NO(3))(4)(C(3)H(7)NO)(2)], abbreviated as (TEA)(2)[Cu(II)(12-MC(Cu(II) ) (N(shi))-4](DMF)(2) [where TEA is tetra-ethyl-ammonium, shi(3-) is salicyl-hydroximate (or N,2-dioxidobenzene-1-carboximidate) and DMF is N,N-dimethyl-formamide], contains five Cu(II) ions. Four of the Cu(II) ions are members of a metallacrown ring (MC), while the fifth Cu(II) is bound in a central cavity. Two of the ring Cu(II) ions are five-coordinate with distorted square-pyramidal geometry. The coordination sphere is composed of two shi(3-) ligands and one DMF mol-ecule. The other two ring Cu(II) ions and the central Cu(II) ion are four-coordinate with square-planar geometry. The coordination spheres of these ions are only composed of shi(3-) ligands. The charge of the [Cu(II)(12-MC(Cu(II) ) (N(shi))-4](2-) unit is balanced by two uncoordinated TEA(+) countercations. The structure shows severe static disorder with the metallacrown, the tetra-ethyl-ammonium cations and the DMF solvent mol-ecule all disordered over each of two mutually exclusive sites, with occupancy rates for the major moieties of 0.6215 (6) for the metallacrown, 0.759 (3) for the tetra-ethyl-ammonium ion and 0.537 (6) for the DMF mol-ecules. The metallacrown unit is located on a crystallographic inversion center and disordered about a non-crystallographic twofold axis. The DMF mol-ecule and the tetra-ethyl-ammonium ion are disordered about a non-crystallographic twofold axis and pseudo-inversion center, respectively.


Cerebral blood flow thresholds for mRNA synthesis after focal ischemia and the effect of MK-801.
MK-801 is a noncompetitive antagonist of N-methyl-d-aspartate subtype glutamate receptors with protective efficacy in experimental stroke. This study examined the impact of MK-801 on cerebral blood flow (CBF) and its relationship to gene expression changes during focal ischemia. Spontaneously hypertensive rats were subjected to surgical occlusion of the middle cerebral artery and ipsilateral common carotid artery after 30 minutes pretreatment with 5 mg/kg MK-801 or saline vehicle. After 2.5 hours of ischemia, regional CBF was evaluated by [14C]iodoantipyrine autoradiography and compared with distributions of gene expression changes evaluated by in situ hybridization detection of mRNAs encoding several immediate-early genes and the stress protein, hsp72. MK-801 increased CBF in contralateral cortex from 93+/-15 to 187+/-37 mL/100 g per minute and produced a significant 25% reduction in the volume of ischemic cortex ipsilateral to occlusion. The extent of cortex failing to express inducible mRNAs correspondingly decreased, but the CBF threshold for mRNA synthesis remained unchanged (25 to 30 mL/100 g per minute). Widespread immediate-early gene expression in the neocortex became restricted to periinfarct regions after MK-801 treatment, and hybridization patterns in the striatum and hippocampus reflected the altered topography of cortical activation after drug treatment. MK-801 alters ischemia-induced gene expression by 2 distinct mechanisms. Generalized increases in CBF reduce the volume of cortex falling below ischemic injury thresholds, protecting tissue and facilitating transcription of inducible genes proximal to the ischemic focus. In addition, MK-801 attenuates the signals that induce expression of immediate-early genes in cortical and subcortical regions remote from the middle cerebral artery territory.


Pedicled fasciocutaneous flap of multi-island design for large sacral defects.
We designed a new pedicled fasciocutaneous flap for large sacral defects that combined a classic superior gluteal artery perforator flap and an acentric axis perforator pedicled propeller flap. We asked whether this technique would be simple and result in few complications. Six patients with large sacral defects had reconstruction using this technique in one stage. The size of the defect and postoperative complications in each patient were assessed. The minimum followup was 6 months (mean, 20.1 months; range, 6-38 months). All wounds healed with no recurrence during followup. Five patients achieved healing primarily, and another with minimal drainage achieved healing by secondary intention after a dressing change. No patients had deep infection, wound dehiscence, necrosis, or partial loss or shrinkage of the flap at final followup. The buttocks were symmetric. We consider this a good alternative for reconstructing large sacral defects because it is a relatively simple procedure and results in few complications. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.


NCTD Prevents Renal Interstitial Fibrosis via Targeting Sp1/lncRNA Gm26669 Axis.
In our previous study, we demonstrated that norcantharidin (NCTD) is a potential therapeutic agent for renal interstitial fibrosis (RIF). Recently, we found that lncRNA Gm26669 (Gm26669) contributed to the development of RIF and could be regulated by NCTD. However, the upstream mechanisms of Gm26669 and whether the anti-RIF effects of NCTD are related to its regulatory action on Gm26669 remain unclear. Our bioinformatics analysis indicated that special protein1 (Sp1), a transcription factor, may bind to the promoter of Gm26669. In the present study, we observed a significant increase in the nuclear translocation of Sp1 using both in vivo and in vitro models of RIF. Furthermore, the knockdown of Sp1 inhibited the expression of collagen type I (CoL-I) and fibronectin (Fn). Mechanistically, Sp1 promoted the expression levels of CoL-I and Fn by directly binding to the promoter of Gm26669 to elevate its expression level. Moreover, we found that NCTD alleviated RIF by inhibiting Gm26669 and the nuclear translocation of Sp1. Collectively, above results suggested that NCTD might prevent RIF via targeting the Sp1/Gm26669 axis, thus providing a new theoretical basis for the clinical application of NCTD in the treatment of RIF.


Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics.
Antipsychotic treatment-related alterations of cortical thickness (CT) and clinical symptoms have been previously corroborated, but less is known about whether the changes are driven by gene expression and epigenetic modifications. Utilizing a prospective design, we recruited 42 treatment-naive first-episode schizophrenia patients (FESP) and 38 healthy controls. Patients were scanned by TI weighted imaging before and after 8-week risperidone monotherapy. CT estimation was automatically performed with the FreeSurfer software package. Participants' peripheral blood genomic DNA methylation (DNAm) status, quantified by using Infinium® Human Methylation 450K BeadChip, was examined in parallel with T1 scanning. In total, CT measures from 118 subjects and genomic DNAm status from 114 subjects were finally collected. Partial least squares (PLS) regression was used to detect the spatial associations between longitudinal CT variations after treatment and cortical transcriptomic data acquired from the Allen Human Brain Atlas. Canonical correlation analysis (CCA) was then performed to identify multivariate associations between DNAm of PLS1 genes and patients' clinical improvement. We detected the significant PLS1 component (2,098 genes) related to longitudinal alterations of CT, and the PLS1 genes were significantly enriched in neurobiological processes, and dopaminergic- and cancer-related pathways. Combining Laplacian score and CCA analysis, we further linked DNAm of 33 representative genes from the 2,098 PLS1 genes with patients' reduction rate of clinical symptoms. This study firstly revealed that changes of CT and clinical behaviors after treatment may be transcriptionally and epigenetically underlied. We define a "three-step" roadmap which represents a vital step toward the exploration of treatment- and treatment response-related biomarkers on the basis of multiple omics rather than a single omics type as a strategy for advancing precise care.


Distinct sonographic features of acute appendicitis in sickle cell disease.
The purpose of this study was to report sonographic findings of appendicitis in patients with positive screening tests for sickle cell compared to normal control patients. A retrospective study of the medical records of 396 patients who underwent appendectomy during a 3-year period from March 2005-2008. The study included 216 males and 180 females, whose ages ranged from 7 to 55 years. Four patients (0.9%) had sickle cell disease (SCD), 101 had sickle cell trait (SCT) (25%) and 291 (74%) patients were without sickle cell anemia (control group). Positive sonographic findings of appendicitis were identified in 95 (90%) SCT patients and in 253 (87%) control patients. The mean maximal mural thickness was higher in sickle cell patients (4.5 [1.4] mm) in comparison with the control group (3.0 [2.2] mm) (P < .0001). Appendicolith was significantly detected in 53% of the control group and in 8.5% of the sickle cell group (P < .0001). Color Doppler showed hypervascularity in 72% of patients with appendicitis in the control group with a significant difference compared to only 12 cases (11%) of SC patients (P < .05). Ultrasonography findings suggesting perforation were found in 35 sickle cell patients and in 75% (3 of the 4 patients) with SCD. Findings suggesting perforation were found only in 49 patients (17%) of the control group. Perforated appendix was significantly higher in sickle cell patients in preoperative US and intraoperatively (P < .05) Positive sonographic findings of appendicitis in sickle cell patients are different from the general population. These findings include mural thickening with a low incidence of appendicolith and wall hypervascularity. Also sonographic features of perforation in sickle cell patients are more common suggesting a need for more urgent operative intervention.


Ca2+-binding protein S100A11: a novel diagnostic marker for breast carcinoma.
To evaluate whether S100A11 could be considered to be a novel diagnostic marker in breast carcinoma, the method of differential proteomics, Western blotting, and immunohistochemistry were used to detect the expression pattern and subcellular localization of S100A11. Statistical analyses indicated that specific up-regulated of A100A11 did not correlate with other prognostic factors such as age, tumor size, grade and stage, ER, PR, HER-2 and nodal status. Our data support that S100A11 is a novel diagnostic marker in breast carcinoma. Analysis of S100A11 expression in breast cancer may be an effective tool help in detection of early-stage breast cancer.


Neurocognitive profile analysis in obsessive-compulsive disorder.
Although neurocognitive deficits have been identified in obsessive-compulsive disorder (OCD), little research has focused on whether these deficits are generalized or specific to a given cognitive domain. We assessed the relative strengths and weaknesses of 26 adult patients with OCD compared to 38 age- and sex-matched healthy volunteers in domains of motor, verbal memory, visual memory, reasoning/problem solving, processing speed processing, and language. Profile analysis revealed an overall neurocognitive deficit of 1/2 standard deviation in OCD patients versus healthy volunteers, with relative weaknesses in motor and processing speed domains. In contrast, relative strengths were observed in language, verbal memory, and reasoning/problem solving. Our findings demonstrate neurocognitive impairment in OCD that may relate to functional outcome in this population. Findings of specific abnormalities on tasks of motor and processing speed are consistent with a hypothesized role of thalamocortical and basal ganglia regions in the pathogenesis of OCD.


Trends in Racial-Ethnic Disparities in Access to Mental Health Care, 2004-2012.
This study compared trends in racial-ethnic disparities in mental health care access among whites, blacks, Hispanics, and Asians by using the Institute of Medicine definition of disparities as all differences except those due to clinical appropriateness, clinical need, and patient preferences. Racial-ethnic disparities in mental health care access were examined by using data from a nationally representative sample of 214,597 adults from the 2004-2012 Medical Expenditure Panel Surveys. The main outcome measures included three mental health care access measures (use of any mental health care, any outpatient care, and any psychotropic medication in the past year). Significant disparities were found in 2004-2005 and in 2011-2012 for all three racial-ethnic minority groups compared with whites in all three measures of access. Between 2004 and 2012, black-white disparities in any mental health care and any psychotropic medication use increased, respectively, from 8.2% to 10.8% and from 7.6% to 10.0%. Similarly, Hispanic-white disparities in any mental health care and any psychotropic medication use increased, respectively, from 8.4% to 10.9% and 7.3% to 10.3%. No reductions in racial-ethnic disparities in access to mental health care were identified between 2004 and 2012. For blacks and Hispanics, disparities were exacerbated over this period. Clinical interventions that improve identification of symptoms of mental illness, expansion of health insurance, and other policy interventions that remove financial barriers to access may help to reduce these disparities.


Strengthening systematic reviews in public health: guidance in the Cochrane Handbook for Systematic Reviews of Interventions, 2nd edition.
Decision makers in public health practice and policy rely on access to trustworthy, relevant, synthesized evidence. The second edition of the Cochrane Handbook for Systematic Reviews of Interventions ('the Handbook') reflects a major revision in guidance for authors of systematic reviews, incorporating a decade of methodological development and a number of significant changes to previous recommendations. This paper aims to highlight new guidance that addresses a number of key methodological challenges for authors of systematic reviews in public health. The revised Handbook includes guidance on framing public health research questions for synthesis, considering equity, intervention complexity, risk of bias assessment and synthesis methods other than meta-analysis. Reviews of public health interventions frequently encounter the types of methodological complexity addressed in this new guidance. We hope that readers will find that the Cochrane Handbook includes detailed and thoughtful guidance on both conceptualizing and executing systematic reviews relevant to public health questions. Considering the available methods guidance will, we hope, provide support for authors of public health reviews to tackle the challenges they encounter, strengthen their analysis and provide useful answers to the important questions asked by stakeholders and users of public health evidence.


Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis.
To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). Stool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with (n = 32) or without (n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low taxonomic levels. Data were further processed in QIIME employing MaAsLin and LEfSe tools for analysis of the output data. Microbial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease (IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales. PSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes (PSC-IBD and UC).


Influence of rural background and rural medical training on postgraduate medical training and location in New Zealand.
To evaluate the influence of the Otago Medical Programme's rural entry pathway and rural immersion programme on postgraduate medical training and location. Retrospective cohort study of 2008-2011 medical school graduates. Rural background/training included students gaining preferential entry to medical training based on rural residence or schooling, and/or those who spent a year training in a rural setting. Postgraduate medical training and location were obtained from the NZ Medical Register in December 2013. 112/733 students (15.3%) had rural background/training. Significantly more students with rural background/training were training in rural hospital medicine or general practice after graduation. Multiple logistic regression identified both variables (rural background and rural training) as independently statistically significant (Odds Ratios (95%CI); rural background OR 2.1, 95%CI 1.2-3.6; rural training OR 2.5, 95%CI 1.4-4.5; p=0.002). Almost twice as many students with rural background/training were working in non-Major Urban Centres. These findings are similar to international reports on the influence of medical schools' rural initiatives on postgraduate training choices and practice location. University policies aimed at increasing the proportion of medical graduates practising in rural areas appear to be working as intended.


On the sources of forgetting in working memory: The test of competing hypotheses.
Whether forgetting from working memory (WM) is only due to interference or is also caused by temporal decay is still a matter of debate. In the present study, this question was examined using complex span tasks in which each memory item was followed by a series of processing episodes, the duration and number of which were varied. It is known that recall performance in these tasks depends on the cognitive load ( CL) of concurrent processing conceived as the ratio between processing time and free time, higher CL resulting in lower spans. The decay-and-refresh hypothesis accounts for this effect by assuming that memory traces decay during processing but are refreshed during free time. This hypothesis predicts lower recall performance with longer processing episodes, but no effect of their number as long as CL remains constant. The interference-only hypothesis supposes that free time is used to alleviate the interference created by processing distractors. This hypothesis is potentially compatible with an effect of the duration of processing episodes through increased interference, but predicts a detrimental effect of their number. In three experiments, the recall pattern fitted the predictions of the decay-and-refresh hypothesis for verbal WM, but that of the interference-only hypothesis for visuospatial WM. Although the entire pattern of data is more easily accommodated by the decay-and-refresh hypothesis than by its interference-only contender, our results suggest that it is unwise to aim at identifying a unique source to a complex phenomenon like WM forgetting.


Ramelteon attenuates hippocampal neuronal loss and memory impairment following kainate-induced seizures.
Evidence suggests that the neuroprotective effects of melatonin involve both receptor-dependent and -independent actions. However, little is known about the effects of melatonin receptor activation on the kainate (KA) neurotoxicity. This study examined the effects of repeated post-KA treatment with ramelteon, a selective agonist of melatonin receptors, on neuronal loss, cognitive impairment, and depression-like behaviors following KA-induced seizures. The expression of melatonin receptors decreased in neurons, whereas it was induced in astrocytes 3 and 7 days after seizures elicited by KA (0.12 μg/μL) in the hippocampus of mice. Ramelteon (3 or 10 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) mitigated KA-induced oxidative stress and impairment of glutathione homeostasis and promoted the nuclear translocation and DNA binding activity of Nrf2 in the hippocampus after KA treatment. Ramelteon and melatonin also attenuated microglial activation but did not significantly affect astroglial activation induced by KA, despite the astroglial induction of melatonin receptors after KA treatment. However, ramelteon attenuated KA-induced proinflammatory phenotypic changes in astrocytes. Considering the reciprocal regulation of astroglial and microglial activation, these results suggest ramelteon inhibits microglial activation by regulating astrocyte phenotypic changes. These effects were accompanied by the attenuation of the nuclear translocation and DNA binding activity of nuclear factor κB (NFκB) induced by KA. Consequently, ramelteon attenuated the KA-induced hippocampal neuronal loss, memory impairment, and depression-like behaviors; the effects were comparable to those of melatonin. These results suggest that ramelteon-mediated activation of melatonin receptors provides neuroprotection against KA-induced neurotoxicity in the mouse hippocampus by activating Nrf2 signaling to attenuate oxidative stress and restore glutathione homeostasis and by inhibiting NFκB signaling to attenuate neuroinflammatory changes.


Separation and Complexation of Trivalent Actinides and Lanthanides by Two Novel Asymmetric N,O-Hybrid Pyridyl Ligands: A Combination of Phosphoryl and Triazinyl Groups.
Two novel asymmetric hard-soft combined ligands, diphenyl(6-(5,9,9-trimethyl-5,6,7,8-tetrahydro-5,8-methanobenzo-[1,2,4]triazin-3-yl)pyridin-2-yl)phosphine oxide (Ph2-MTP) and butylphenyl(6-(5,9,9-trimethyl-5,6,7,8-tetrahydro-5,8-methanobenzo-[1,2,4]triazin-3-yl)pyridin-2-yl)phosphine oxide (BuPh-MTP), were designed based on the combination of the nature of phosphoryl and triazinyl groups for the selective extraction of trivalent minor actinides from lanthanides. The synthesis of these two ligands and their solvent extraction and complexation behaviors with Am(III) and typical lanthanides were investigated using UV-vis and time-resolved fluorescence spectrophotometry, 1H/31P NMR spectrometry, single-crystal X-ray diffraction, and DFT calculation methods. Solvent extraction experiments showed that both the ligands had strong extraction ability and high selectivity toward Am(III) over Eu(III) from the highly acidic HNO3 solution. The separation factors (SFAm/Eu) of these two ligands ranged from 17 to 26, with the concentrations of HNO3 increasing from 1.0 to 4.0 M. Slope analysis showed that the 3:1 ligand/metal complex was the prevailing species formed during extraction. The formation of the 3:1 ratio of the species of these two ligands with lanthanides was also identified by UV-vis spectrophotometry and single crystallography methods. The stability constants for the formation of the 1:3 complexes of Ph2-MTP and BuPh-MTP with Nd(III) were determined as 7.06 ± 0.015 and 6.67 ± 0.007, respectively. The geometric structures of the 1:3 complexes were clearly illustrated using the single-crystal X-ray diffraction technique and DFT theoretical calculation. This work provides an effective strategy to design new asymmetric hard-soft mixed actinide extractants by combining two different functional groups in one ligand, and the interaction mechanism between the functional groups and metal ions needs to be further investigated.


Body pushing, prescription drugs and hospital admission.
A 39-year-old man died of multi-organ failure complicating mixed drug toxicity that included methadone, oxazepam, oxycodone and nitrazepam. His past medical history involved alcohol and poly-substance abuse with chronic self-harm and suicidal ideation. There had been multiple hospital admissions for drug overdoses. At autopsy the most unusual finding was of two packages of 10 tablets each, wrapped in thin plastic film within the rectum. The insertion of drugs into body orifices and cavities has been termed body pushing to distinguish it from body packing where illicit drugs are wrapped and swallowed for transport and smuggling, and body stuffing where small amounts of loosely wrapped or unwrapped drugs are swallowed to conceal evidence from police. This case demonstrates that body pushing may not always involve illicit drugs or attempted concealment from police or customs officials. It appears that the drugs had been hidden to ensure an additional supply during the time of residence in hospital. The extent to which body pushing is currently being used by patients to smuggle drugs into secure medical facilities is yet to be determined.


Color Doppler imaging of orbital venous flow in dysthyroid optic neuropathy.
Color Doppler imaging was performed to evaluate the venous stasis in 39 orbits, including 9 optic neuropathy orbits, of 20 patients with dysthyroid ophthalmopathy and 22 orbits of 11 healthy subjects. The superior ophthalmic vein (SOV) was detected in 26 dysthyroid ophthalmopathy orbits and in 13 control orbits. The blood flow in the SOV was in the anteroposterior direction in 20 dysthyroid ophthalmopathy orbits and in 13 control orbits. Reversed flow, ie, the flow in the posteroanterior direction, was seen in 6 dysthyroid ophthalmopathy orbits and in none of the control orbits. In dysthyroid ophthalmopathy orbits, the blood flow in the SOV was reversed in 5 (36%) of the 14 orbits with apical orbital crowding observed on computed tomography, which means there was compression of the optic nerve by enlarged extraocular muscles, as compared to in 1 (4%) of the 25 orbits without apical orbital crowding (P < 0.05). The percentage of the orbits having reversed flow in SOV was 44% of dysthyroid ophthalmopathy orbits with optic neuropathy as opposed to 7% of those without optic neuropathy (P < 0.05). Reversed blood flow in the SOV strongly supported the existence of severe venous stasis in the orbits, which may be related to the development of dysthyroid optic neuropathy.


Perioperative low molecular weight heparin for infrageniculate bypass.
Recent studies suggest that subcutaneous low molecular weight heparin (LMWH) is a safe, effective alternative to intravenous heparin (IVH) for deep venous thrombosis. LMWH may also be a safe, effective alternative to IVH when necessary for lower extremity bypass procedures performed with polytetrafluoroethylene (PTFE) grafts. The purpose of this study was to compare subcutaneous LMWH with IVH for perioperative anticoagulation in patients who underwent infrageniculate bypass procedures with PTFE grafts. Of 361 lower extremity bypass operations performed at a single center over a 32-month period, 76 were to the tibial or below-knee levels using PTFE grafts for limb salvage. Seven patients were excluded because of absolute indications for perioperative IVH (ventricular thrombus in 1 patient, prosthetic valve in 2, cardiac dysrhythmia in 2, and documented hypercoagulable syndrome in 2), leaving 68 patients (35 women; mean age, 69.8 years) with 69 bypass procedures for study. Grafts completed in the past 16 months were treated with LMWH (28 grafts; Oct. 1994 to Jan. 1996) and were compared with 41 consecutive control grafts from the previous 16-month interval (Apr. 1993 to Oct. 1994) who received IVH. There were similar percentages of composite bypasses (IVH, 50%; LMWH, 46%), patients with tissue loss or gangrene (IVH, 56%; LMWH, 61%), and patients with prior ipsilateral bypass (IVH, 57%; LMWH, 56%) in each group. Age, sex, and atherosclerotic risk factors were also similar between the two groups. Morbidity rates (IVH, 19%; LMWH, 11%) and mortality rates (IVH, 2.5%; LMWH, 4%) were not significantly different. There were no significant differences in the number of grafts that failed before discharge (IVH, 1; LMWH, 0) or percentage of hemorrhagic complications (IVH, 15%; LMWH, 7%). The mean number of postoperative hospital days (IVH, 9.5; LMWH, 7.2; p < 0.009) and coagulation monitoring studies (IVH, 22; LMWH, 8.4; p < 0.0001) were significantly decreased in patients who were anticoagulated with LMWH. The mean number of days before conversion to oral anticoagulation (IVH, 7.3; LMWH, 8.0) did not differ significantly. When perioperative anticoagulation is deemed necessary, LMWH provides a safe, effective alternative to IVH for infrageniculate PTFE bypass grafting procedures. LMWH may reduce the number of postoperative hospital days and coagulation studies by allowing discharge before therapeutic anticoagulation with warfarin.


EGF stimulates both cyclooxygenase activity and cell proliferation of cultured guinea pig gastric mucous cells.
Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and insulin all dose-dependently stimulated [3H]-thymidine incorporation into guinea pig gastric mucous cells cultured in vitro. On the other hand, other growth factors, e.g., platelet-derived growth factor (PDGF) and gastrointestinal hormones, such as gastrin, had no effect on DNA synthesis in these cells. Exposure of the cells to EGF at concentrations which stimulated DNA synthesis caused increases in both prostaglandin (PG) E2 release and cyclooxygenase (COX) enzyme protein synthesis, as evaluated by Western blot analysis. These results suggest that such increases in DNA synthesis and PGE2 release may be involved, at least in part, in the mechanism of EGF-induced local regulation of gastric mucosal integrity.


Crossreactive autoantibodies directed against cutaneous and joint antigens are present in psoriatic arthritis.
Psoriatic arthritis (PsA) is a chronic inflammatory disease of unknown origin, characterized by erosions and new bone formation. Diagnosis of PsA is mainly clinical and there are no biomarkers available. Moreover in PsA autoantibodies have not been described so far. Indeed an autoimmune origin has been suggested but never proven. Aim of the study was to investigate the possible presence of autoantibodies typically associated with PsA. We used pooled IgG immunoglobulins derived from 30 patients with PsA to screen a random peptide library in order to identify disease relevant autoantigen peptides. Among the selected peptides, one was recognised by nearly all the patients' sera. The identified peptide (PsA peptide: TNRRGRGSPGAL) shows sequence similarities with skin autoantigens, such as fibrillin 3, a constituent of actin microfibrils, desmocollin 3, a constituent of the desmosomes and keratin 78, a component of epithelial cytoskeleton. Interestingly the PsA peptide shares homology with the nebulin-related anchoring protein (N-RAP), a protein localized in the enthesis (point of insertion of a tendon or ligament to the bone), which represents the first affected site during early PsA. Antibodies affinity purified against the PsA peptide recognize fibrillin, desmocollin, keratin and N-RAP. Moreover antibodies directed against the PsA peptide are detectable in 85% of PsA patients. Such antibodies are not present in healthy donors and are present in 13/100 patients with seroposive rheumatoid arthritis (RA). In seronegative RA these antibodies are detectable only in 3/100 patients. Our results indicate that PsA is characterized by the presence of serum autoantibodies crossreacting with an epitope shared by skin and joint antigens.


New Insights into the N2O formation mechanism over Pt-BaO/Al2O3 model catalysts using H2 as a reductant.
The N2O formation mechanism was investigated over a Pt-BaO/Al2O3 catalyst applied on light-duty diesel vehicles using H2 as a reductant in the absence and presence of H2O. In the absence of H2O, N2O forms mainly at the initial phase of lean NOx trapping; while in the presence of H2O, N2O appears mainly at the beginning of the rich reduction phase. In the lean period, N2O is formed via the gaseous NO/O2 reacting with the adsorbed H and NH3 that are formed during the previous rich period. The N2O formation in the rich period is insignificant in the absence of H2O but is greatly enhanced by the presence of H2O. The amount of N2O formed is proportional to the H2O level in the feed, and its formation is favored at low temperatures. Our FTIR data show that H2O enhances the rate of nitrite/nitrate reduction during the rich regeneration, which increases the amount of released NOx, an oxygen source for N2O formation. Our temperature-programmed experiments indicate that H2O competes with NH3 for adsorption sites on Pt surface. This competitive adsorption may increase the NH3 desorption rate at low temperatures in the rich phase and make Pt surface more accessible to NO.


Trait similarity patterns within grass and grasshopper communities: multitrophic community assembly at work.
Trait-based community assembly theory suggests that trait variation among co-occurring species is shaped by two main processes: abiotic filtering, important in stressful environments and promoting similarity, and competition, more important in productive environments and promoting dissimilarity. Previous studies have indeed found trait similarity to decline along productivity gradients. However, these studies have always been done on single trophic levels. Here, we investigated how interactions between trophic levels affect trait similarity patterns along environmental gradients. We propose three hypotheses for the main drivers of trait similarity patterns of plants and herbivores along environmental gradients: (1) environmental control of both, (2) bottom-up control of herbivore trait variation, and (3) top-down control of grass trait variation. To test this, we collected data on the community composition and trait variation of grasses (41 species) and grasshoppers (53 species) in 50 plots in a South African savanna. Structural equation models were used to investigate how the range and spacing of within-community functional trait values of both grasses and their insect herbivores (grasshoppers; Acrididae) respond to (1) rainfall and fire frequency gradients and (2) the trait similarity patterns of the other trophic level. The analyses revealed that traits of co-occurring grasses became more similar toward lower rainfall and higher fire frequency (environmental control), while showing little evidence for top-down control. Grasshopper trait range patterns, on the other hand, were mostly directly driven by vegetation structure and grass trait range patterns (bottom-up control), while environmental factors had mostly indirect effects via plant traits. Our study shows the potential to expand trait-based community assembly theory to include trophic interactions.


Integration of MFC reduces CH4, N2O and NH3 emissions in batch-fed wetland systems.
The combination of microbial fuel cells (MFCs) with constructed wetlands (CWs) for enhancing water purification efficiency and generating bioelectricity has attracted extensive attention. However, the other benefits of MFC-CWs are seldom reported, especially the potential for controlling gaseous emissions. In this study, we have quantitatively compared the pollutant removal efficiency and the emission of multiple gases between MFC-CWs and batch-fed wetland systems (BF CWs). MFC-CWs exhibited significantly (p < 0.01) higher COD, NH4+-N, TN, and TP removal efficiencies and significantly (p < 0.01) lower global warming potential (GWP) than BF CWs. The integration of MFC decreased GWP by 23.88% due to the reduction of CH4 and N2O fluxes, whereas the CO2 fluxes were slightly promoted. The quantitative PCR results indicate that the reduced N2O fluxes in MFC-CWs were driven by the reduced transcription of the nosZ gene and enhanced the ratio of nosZ/(nirS + nirK); the reduced CH4 fluxes were related to pomA and mcrA. Additionally, the NH3 fluxes were reduced by 52.20% in MFC-CWs compared to BF CWs. The integration of MFC promoted the diversity of microbial community, especially Anaerolineaceae, Saprospiraceae and Clostridiacea. This study highlights a further benefit of MFC-CWs and provides a new strategy for simultaneously removing pollutants and abating multiple gas emissions in BF CWs.


Neuroprotection by scorpion venom heat resistant peptide in 6-hydroxydopamine rat model of early-stage Parkinson's disease.
Neuroprotective effect of scorpion venom on Parkinson's disease (PD) has already been reported. The present study was aimed to investigate whether scorpion venom heat resistant peptide (SVHRP) could attenuate ultrastructural abnormalities in mitochondria and oxidative stress in midbrain neurons of early-stage PD model. The early-stage PD model was established by injecting 6-hydroxydopamine (6-OHDA) (20 μg/3 μL normal saline with 0.1% ascorbic acid) into the striatum of Sprague Dawley (SD) rats unilaterally. The rats were intraperitoneally administered with SVHRP (0.05 mg/kg per day) or vehicle (saline) for 1 week. Two weeks after 6-OHDA treatment, the rats received behavior tests for validation of model. Three weeks after 6-OHDA injection, the immunoreactivity of dopaminergic neurons were detected by immunohistochemistry staining, and the ultrastructure of neuronal mitochondria in midbrain was observed by electron microscope. In the meantime, the activities of monoamine oxidase-B (MAO-B), superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the mitochondria of the midbrain neurons, as well as the inhibitory ability of hydroxyl free radical and the antioxidant ability in the serum, were measured by corresponding kits. The results showed that 6-OHDA reduced the optical density of dopaminergic neurons, induced damage of mitochondrial ultrastructure of midbrain neurons, decreased SOD activity, increased MAO-B activity and MDA content, and reduced the antioxidant ability of the serum. SVHRP significantly reversed the previous harmful effects of 6-OHDA in early-stage PD model. These findings indicate that SVHRP may contribute to neuroprotection by preventing biochemical and ultrastructure damage changes which occur during early-stage PD.


GENETIC CONSEQUENCES OF PASSIVE DISPERSAL IN POND-DWELLING COPEPODS.
Pond-dwelling copepods have colonized habitats throughout North America after glaciers have receded. Most species are passively transported via resting eggs into new habitats. Colonists originating in a glacial refugium could lose some of the ancestral genetic diversity when they establish new populations and the attenuation may be substantial in populations far removed from the refugium due to multiple founder events. Genetic variation was measured in Heterocope septentrionalis from 27 populations at arctic sites near potential refugia and those more recently deglaciated to determine the effects of postglacial dispersal on patterns of genetic relatedness and diversity. Some populations were more distant, genetically, from others within the same site than those from other more distant sites. Eleven polymorphic enzyme loci were significantly more variable (F [1,294 df] = 5.94, P < 0.025) among individuals from populations near the Alaskan refuge than those at the eastern limit of their distribution. Because populations are typically extremely large and stable this loss of genetic diversity is attributed primarily to repeated founder events during colonization. This result suggests profound genetic changes may occur on a continental scale in passively dispersed copepods due to founder events alone. Their potential for divergence and speciation is greater than currently recognized.


p27Kip1 represses the Pitx2-mediated expression of p21Cip1 and regulates DNA replication during cell cycle progression.
The tumor suppressor p21 regulates cell cycle progression and peaks at mid/late G1. However, the mechanisms regulating its expression during cell cycle are poorly understood. We found that embryonic fibroblasts from p27 null mice at early passages progress slowly through the cell cycle. These cells present an elevated basal expression of p21 suggesting that p27 participates to its repression. Mechanistically, we found that p27 represses the expression of Pitx2 (an activator of p21 expression) by associating with the ASE-regulatory region of this gene together with an E2F4 repressive complex. Furthermore, we found that Pitx2 binds to the p21 promoter and induces its transcription. Finally, silencing Pitx2 or p21 in proliferating cells accelerates DNA replication and cell cycle progression. Collectively, these results demonstrate an unprecedented connection between p27, Pitx2 and p21 relevant for the regulation of cell cycle progression and cancer and for understanding human pathologies associated with p27 germline mutations.


Diminished responsibility: the difference it makes.
Should there be a defence of diminished responsibility after the mandatory life sentence for murder has been abolished? This is the main question posed in this article, on the basis of a review of the central features of the defence and its surrounding forensic context. The views of the defence taken by the Law Reform Commissions of New South Wales and New Zealand are then compared. In conclusion, it is argued that opinions about the continuing validity of the defence of diminished responsibility are bound to be influenced by wider positions taken on the value of rules, as opposed to discretion, in the criminal law.


Prediction of dispositional dialectical thinking from resting-state electroencephalography.
This study aims to explore the possibility of predicting the dispositional level of dialectical thinking using resting-state electroencephalography signals. Thirty-four participants completed a self-reported measure of dialectical thinking, and their resting-state electroencephalography was recorded. After wave filtration and eye movement removal, time-frequency electroencephalography signals were converted into four frequency domains: delta (1-4 Hz), theta (4-7 Hz), alpha (7-13 Hz), and beta (13-30 Hz). Functional principal component analysis with B-spline approximation was then applied for feature reduction. Five machine learning methods (support vector regression, least absolute shrinkage and selection operator, K-nearest neighbors, random forest, and gradient boosting decision tree) were applied to the reduced features for prediction. The model ensemble technique was used to create the best performing final model. The results showed that the alpha wave of the electroencephalography signal in the early period (12-15 s) contributed most to the prediction of dialectical thinking. With data-driven electrode selection (FC1, FCz, Fz, FC3, Cz, AFz), the prediction model achieved an average coefficient of determination of 0.45 on 200 random test sets. Furthermore, a significant positive correlation was found between the alpha value of standardized low-resolution electromagnetic tomography activity in the right dorsal anterior cingulate cortex and dialectical self-scale score. The prefrontal and midline alpha oscillations of resting electroencephalography are good predictors of the dispositional level of dialectical thinking, possibly reflecting these brain structures' involvement in dialectical thinking.


The antioncogenic effect of Beclin-1 and FOXP3 is associated with SKP2 expression in gastric adenocarcinoma.
An overexpression of S-phase kinase-associated protein 2 (SKP2) is frequently observed in human cancer progression and metastasis, and evidence suggests that SKP2 plays a proto-oncogenic role both in vitro and in vivo. However, the function of SKP2 in gastric adenocarcinoma remains largely obscure. We investigated SKP2 expression in human gastric carcinomas.Tissue samples were acquired from 182 cases of gastric adenocarcinoma that were surgically resected from 2006 to 2012. Immunohistochemical staining for SKP2, Beclin-1, and forkhead box protein P3 (FOXP3) was performed. Pearson chi-square test was used to evaluate the associations among clinicopathological variables. The Kaplan-Meier method, the log-rank test, and the Cox proportional-hazards model were used in the analysis of the overall survival (OS) and disease-free survival (DFS).As a result, SKP2 overexpression in gastric adenocarcinomas showed a significant correlation with several favorable clinical factors, including the tumor size, T category, N category, lymphatic invasion, vascular invasion, OS, and DFS. SKP2 expression was positively correlated with the tumoral FOXP3, Beclin-1 expression, and regulatory T cell (Treg) infiltration. The difference in DFS between the SKP2 positive and negative group was attenuated by FOXP3 high expression, Beclin-1 high expression, and Tregs infiltration. Attenuation of the difference in OS by FOXP3 high expression, Beclin-1 high expression, and Tregs infiltration was not significant. In multivariable analysis, SKP2 expression was not correlated with OS and DFS.Our study showed a complex interrelationship between SKP2 and Beclin-1 and FOXP3 expression in gastric adenocarcinoma. The antioncogenic effect of Beclin-1 and FOXP3 expression in gastric adenocarcinoma is related to SKP2 expression.


Current Application of Quantum Dots (QD) in Cancer Therapy: A Review.
Semiconductor quantum dots proved themselves as efficient fluorescent probes in cancer detection and treatment. Their size, high stability, non-photobleaching and water solubility made them a unique fluorophore in place of conventional organic dyes. Newly emerged theranostic drug delivery system using quantum dots helped us in better understanding of the drug delivery mechanism inside the cells. Surface modified Quantum dots and their applications became wide in bioimaging, immunohistochemistry, tracking intracellular drug and intracellular molecules target. We have highlighted various applications of quantum dots in cancer treatment, drug delivery, flow cytometry, and theranostics.


High Cycling Stability and Extreme Rate Performance in Nanoscaled LiMn2O4 Thin Films.
Ultrathin LiMn2O4 electrode layers with average crystal size of ∼15 nm were fabricated by means of radio frequency sputtering. Cycling behavior and rate performance was evaluated by galvanostatic charge and discharge measurements. The thinnest films show the highest volumetric capacity and best cycling stability, retaining the initial capacity over 70 (dis)charging cycles when manganese dissolution is prevented. The increased stability for film thicknesses below 50 nm allows cycling in both the 4 and 3 V potential regions, resulting in a high volumetric capacity of 1.2 Ah/cm3. It is shown that the thinnest films can be charged to 75% of their full capacity within 18 s (200 C), the best rate performance reported for LiMn2O4. This is explained by the short diffusion lengths inherent to thin films and the absence of phase transformation.


Novel crown ether-capped cationic gold nanoclusters in an aqueous medium and their single-electron charging features.
On the basis of the formation of a noncovalent inclusion complex through crown ether-ammonium ion interaction, a new ligand, 18-crown-6-aminoethanethiol (18C6-AET), was predesigned and synthesized with a formation constant of 4.26 x 10(2) M(-1)s(-1) for the 1:1 noncovalent complex. Consequently, stable crown ether-protected gold nanoclusters were synthesized with 18C6-AET in an aqueous medium with a rate of formation of 3.688 x 10(-4) min(-1). The newly formed 18C6-AET-capped gold nanoclusters showed quantized double-layer charging, revealing their concentric capacitor structure, and effective cluster capacitance, C(CLU) was calculated to be 0.93 aF from the single-electron events. A larger C(CLU) in comparison to that of monolayer-protected gold clusters with longer chain lengths was attributed to a smaller ligand shell thickness as well as the cationic nature of the nanoclusters formed in an aqueous electrolyte medium.


[Lipoma, multiple lipomas and lipomatosis].
Lipomatous tumors are very frequent; simple lipoma is the most common variety. According to Enzinger, lipomatous tumors are classified into five different groups: simple lipomas, variant lipomas forms, heterotopic lipomas, infiltrating lipomas and lipomatosis, and finally hibernomas. Usually, lipomatous tumors are characterized by a slow, unpainful, growth. Classical treatment includes surgical resection. The clinical diagnosis is confirmed by histology. Liposucion can be a therapeutic option in certain cases.


Rb and p53 Execute Distinct Roles in the Development of Pancreatic Neuroendocrine Tumors.
Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1 to 3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of the Rb gene (Pdx1-Cre;Rbf/f ) in mice did not affect pancreatic exocrine cells, the α-cell/β-cell ratio of islet cells was decreased at 8 months of age. During long-term observation (18-20 months), mice formed well-differentiated PanNET with a Ki67-labeling index of 2.7%. In contrast, pancreas-specific induction of a p53 mutation (Pdx1-Cre;Trp53R172H ) had no effect on pancreatic exocrine and endocrine tissues, but simultaneous induction of a p53 mutation with Rb gene deletion (Pdx1-Cre;Trp53R172H;Rb f/f ) resulted in the formation of aggressive PanNET with a Ki67-labeling index of 24.7% over the short-term (4 months). In Pdx1-Cre;Trp53R172H;Rbf/f mice, mRNA expression of Pten and Tsc2, negative regulators of the mTOR pathway, significantly decreased in the islet cells, and activation of the mTOR pathway was confirmed in subsequently formed PanNET. Thus, by manipulating Rb and p53 genes, we established a multistep progression model from dysplastic islet to indolent PanNET and aggressive metastatic PanNET in mice. These observations suggest that Rb and p53 have distinct roles in the development of PanNET. SIGNIFICANCE: Pancreas-specific manipulation of Rb and p53 genes induced malignant transformation of islet cells, reproducing stepwise progression from microadenomas to indolent (grade 1) and subsequent aggressive PanNETs (grade 2-3).


Immunoglobulin isotype response to the group-A streptococcal carbohydrate in humans.
We used an ELISA to determine the levels of specific anti-GAS carbohydrate IgG, IgM and IgA in 34 patients with acute rheumatic fever (ARF) with or without carditis, in 15 patients with acute glomerulonephritis (AGN) and in 18 control patients with noncomplicated GAS pharyngitis. Patients with ARF and AGN showed a significantly higher geometric mean titer as well as a higher frequency of elevated Ig of the IgG, IgM and IgA A-CHO class antibodies during the acute stage of this disease, when compared to controls. The IgM and IgA geometric means of the antibody were higher in ARF with carditis patients as compared to the non-carditis or AGN patients; however, the differences were not significant. In addition a lower frequency of antibody decline was observed in ARF with carditis patients who were seen in follow-up after a 1-year period, supporting previous observations of the persistence of this antibody in patients with rheumatic heart disease.


[Single chain antibody against β-site of amyloid precursor protein inhibits the generation of β-amyloid peptide].
To construct and express a single chain fragment of variety region (scFv) against β-site of amyloid precursor protein (APP), and evaluate the effect of scFv on α- and β-processing of APP. The β-site specific scFv 2H10 was amplified and fused with signal sequence Igκ and myc tag by PCR to create the expression cassette, which was then subcloned into expression vector pcDNA3.1hyg⁺. The plasmid was transferred into CHO cells over-expressing Swedish mutation type human APP695 (APP695sw/CHO). The positive clones were identified by hygromycin B. The concentrations of Aβ40 and soluble APPα (sAPPα) in the conditioned media supernatant were measured by sandwich ELISA. The recombinant eukaryotic expression plasmids were identified by PCR, restriction endonuclease digestion and DNA sequencing. The expression of scFv was confirmed by Western blotting. When scFv 2H10 was stably expressed in APP695sw/CHO, the extracellular level of Aβ40 decreased by 30.4%, while sAPPα increased by 23.1%. The APP β-site scFv 2H10 could inhibit the secretion of Aβ. Meanwhile, it might be favorable for the α-processing of APP. Hence it can be explored as an inhibitor of β-site APP-cleaving enzyme (BACE).


3D printing with 2D colloids: designing rheology protocols to predict 'printability' of soft-materials.
Additive manufacturing (AM) techniques and so-called 2D materials have undergone an explosive growth in the past decade. The former opens multiple possibilities in the manufacturing of multifunctional complex structures, and the latter on a wide range of applications from energy to water purification. Extrusion-based 3D printing, also known as Direct Ink Writing (DIW), robocasting, and often simply 3D printing, provides a unique approach to introduce advanced and high-added-value materials with limited availability into lab-scale manufacturing. On the other hand, 2D colloids of graphene oxide (GO) exhibit a fascinating rheology and can aid the processing of different materials to develop 'printable' formulations. This work provides an in-depth rheological study of GO suspensions with a wide range of behaviours from Newtonian-like to viscoelastic 'printable' soft solids. The combination of extensional and shear rheology reveals the network formation process as GO concentration increases from <0.1 vol% to 3 vol%. Our results also demonstrate that the quantification of 'printability' can be based on three rheology parameters: the stiffness of the network via the storage modulus (G'), the solid-to-liquid transition or flow stress (σf), and the flow transition index, which relates the flow and yield stresses (FTI = σf/σy).


Watertight Dural Closure in Pediatric Craniotomies-Is It Really Necessary?
Dural closure after intracranial procedures is considered crucial to reduce postoperative complications such as pseudomeningocele (PM), cerebrospinal fluid (CSF) leaks, hydrocephalus, and infections. However, watertight dural closure (WTDC) is often difficult to achieve, and dural substitutes often are used. We describe our experience with non-WTDC in children. Data were collected retrospectively. Redo and craniectomy cases were excluded. Collected data included demographics, surgical etiology, various radiologic parameters, ventricular opening, usage of drains and shunts, dural closure technique, and complications. In total, 163 cases aged 3 months to 18.5 years (90 ± 56 months) were included. Main surgical indications were tumors (120, 74%) and epilepsy (29, 18%). In total, 122 (74%) cases were supratentorial. The ventricular system was opened in 69 (42%) cases. In 145 (89%) cases, a non-WTDC was performed. Fibrin glue was used in 22 (13%) cases. In 156 cases (96%), a dural substitute was used. One patient (0.6%) had a CSF leak. At 3 months, 20% had a radiologic PM but only 8.4% were noticed clinically. At 1 year, 7.7% had a radiologic PM but only 3% were noticed clinically. Overall, 3% needed a PM tap, and 15 patients (9%) underwent CSF diversion procedures. There were no infections. The only factor significantly associated with PM or a need for CSF surgery was an infratentorial location. Non-WTDC after cranial surgery in children was associated with a low rate of clinically significant PM, infections, leaks, and hydrocephalus. Non-WTDC is fast and reduces the need to harvest additional tissue, thus minimizing the surgical incision.


Schwannian crystalline-like inclusions bodies (Fardeau-Engel bodies) revisited in peripheral neuropathies.
In 1969, Fardeau and Engel described polygonal organelles containing crystalline-like structures located in the Schwann cell cytoplasm of unmyelinated fibers. Such inclusions were reported in various conditions, mainly with axonal lesions. They were also reported in a few cases of peripheral neuropathy associated with primary mitochondriopathy. Although they are surrounded by a double membrane, their mitochondrial origin is not definitely proven. Their significance remains obscure but they deserve to be better known as Fardeau-Engel bodies, so as not to be mistaken with mitochondrial crystalline inclusions, which are frequently observed in patients with ragged-red fibers in muscle.


Receptor binding sites of hypoglycemic sulfonylureas and related [(acylamino)alkyl]benzoic acids.
The blood glucose level lowering activity of [(acylamino)ethyl]benzoic acids, such as p-[2-(5-chloro-2-methoxy-benzamido)ethyl]benzoic acid (HB699, 2), is discussed in terms of binding at putative insulin-releasing receptor sites of pancreatic beta cells. The hypoglycemic potencies found for synthetic analogues of 2 indicate that high hypoglycemic activity is only found when a carboxyl group or a group that is readily oxidized to carboxyl in vivo, such as methyl, is attached to the aromatic ring of the phenethyl group. It is proposed that this carboxyl group is able to bind at the same receptor site as the SO2NHCONH group of the sulfonylurea drugs, such as tolbutamide (3). The role of the benzamide group in 2 was attributed to protein binding.


Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis.
Previous studies have shown that common human coronavirus might be neurotropic, although it was first isolated as a pathogen of the respiratory tract. We noticed that a few patients with severe acute respiratory syndrome (SARS) experienced central nervous symptoms during the course of illness. In the present study, we isolated a SARS coronavirus strain from a brain tissue specimen obtained from a patient with SARS with significant central nervous symptoms. Using transmission electronic microscopy and nested reverse transcription-polymerase chain reaction, the causative pathogen was identified in cultures of a brain tissue specimen obtained from the patient with SARS. Histopathologic examination of the brain tissue was performed using the methods of immunohistochemistry analysis and double immunofluorescence staining. Fifteen cytokines and chemokines were detected in the blood of the patient with SARS by means of a bead-based multiassay system. A fragment specific for SARS human coronavirus was amplified from cultures of the brain suspension, and transmission electronic microscopy revealed the presence of an enveloped virus morphologically compatible with a coronavirus isolated in the cultures. Pathologic examination of the brain tissue revealed necrosis of neuron cells and broad hyperplasia of gliocytes. Immunostaining demonstrated that monokine induced by interferon- gamma (Mig) was expressed in gliocytes with the infiltration of CD68+ monocytes/macrophages and CD3+ T lymphocytes in the brain mesenchyme. Cytokine/chemokine assay revealed that levels of interferon- gamma -inducible protein 10 and Mig in the blood were highly elevated, although the levels of other cytokines and chemokines were close to normal. This study provides direct evidence that SARS human coronavirus is capable of infecting the central nervous system, and that Mig might be involved in the brain immunopathology of SARS.


Lessons learned from the whole child and coordinated school health approaches.
The new Whole School, Whole Community, Whole Child (WSCC) model, designed to depict links between health and learning, is founded on concepts of coordinated school health (CSH) and a whole child approach to education. The existing literature, including scientific articles and key publications from national agencies and organizations, was reviewed and synthesized to describe (1) the historical context for CSH and a whole child approach, and (2) lessons learned from the implementation and evaluation of these approaches. The literature revealed that interventions conducted in the context of CSH can improve health-related and academic outcomes, as well as policies, programs, or partnerships. Several structural elements and processes have proved useful for implementing CSH and a whole child approach in schools, including use of school health coordinators, school-level and district-level councils or teams; systematic assessment and planning; strong leadership and administrative support, particularly from school principals; integration of health-related goals into school improvement plans; and strong community collaborations. Lessons learned from years of experience with CSH and the whole child approaches have applicability for developing a better understanding of the WSCC model as well as maximizing and documenting its potential for impacting both health and education outcomes.


Improvement of hypertension, endothelial function and systemic inflammation following short-term supplementation with red beet (Beta vulgaris L.) juice: a randomized crossover pilot study.
Hypertension is a major risk factor for cardiovascular disease and has a prevalence of about one billion people worldwide. It has been shown that adherence to a diet rich in fruits and vegetables helps in decreasing blood pressure (BP). This study aimed to investigate the effect of raw beet juice (RBJ) and cooked beet (CB) on BP of hypertensive subjects. In this randomized crossover study, 24 hypertensive subjects aged 25-68 years old were divided into two groups. One group took RBJ for 2 weeks and the other group took CB. After 2 weeks of treatment, both groups had a washout for 2 weeks then switched to the alternate treatment. Each participant consumed 250 ml day(-1) of RBJ or 250 g day(-1) of CB each for a period of 2 weeks. Body weight, BP, flow-mediated dilation (FMD), lipid profile and inflammatory parameters were measured at baseline and after each period. According to the results, high-sensitivity C-reactive protein (hs-CRP) and tumour necrosis factor alpha (TNF-α) were significantly lower and FMD was significantly higher after treatment with RBJ compared with CB (P<0.05). FMD was significantly (P<0.05) increased, but systolic and diastolic BP, intracellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1), hs-CRP, interleukin-6, E-selectin and TNF-α were significantly (P<0.05) decreased with RBJ or CB. Total antioxidant capacity was increased and non-high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC) were decreased with RBJ but not with CB. Although both forms of beetroot were effective in improving BP, endothelial function and systemic inflammation, the raw beetroot juice had greater antihypertensive effects. Also more improvement was observed in endothelial function and systemic inflammation with RBJ compared with CB.


[Patterns of injuries and preventive measures for motorcycle accidents].
Retrospective analysis of a series of 32 motorcyclists admitted after road accidents was performed. 62% were injured on scooters with 50 cc engine capacity and most of the combined injuries occurred in this group. Most crashes occurred at road junctions. Riders of scooters with larger engine capacities tended to wear protective garments as opposed to riders with smaller engines. There was no correlation between engine capacity and severity of injury. We conclude that motorcyclists should receive special education, especially as to behavior on entering road junctions. We recommend that taxes on protective garments should be lowered in order to encourage motorcyclists to use them.


Kimchi, a fermented vegetable, improves serum lipid profiles in healthy young adults: randomized clinical trial.
Vegetable-based diets have generally focused on their health benefits including negative associations with the serum cholesterol concentrations. The aim of this study was to investigate whether serum lipid concentrations are influenced by the amount of kimchi intake. For the study, 100 volunteers were assigned to 2 dietary groups, low (15 g/day, n=50) and high (210 g/day, n=50) kimchi intake, and were housed together in a dormitory for 7 days. Identical meals except with different amount of kimchi were provided and subjects were instructed to maintain their normal physical activity. Concentrations of fasting blood glucose (FBG), total glucose, total cholesterol and low density lipoprotein (LDL)-C significantly decreased in both groups after 7 days of kimchi intake, but the effects were dose dependent. Lipid lowering effects of kimchi were more profound in the subjects with total cholesterol and LDL-C level over 190 and 130 mg/dL, respectively, in both groups. FBG was significantly decreased in the high kimchi intake as compared to the low intake group (P=.003). In conclusion, greater consumption of kimchi improved FBG and serum total cholesterol in young healthy adults.


Enhanced angiogenesis and reduced contraction in thrombospondin-2-null wounds is associated with increased levels of matrix metalloproteinases-2 and -9, and soluble VEGF.
Thrombospondin-2 (TSP2) is an inhibitor of angiogenesis with pro-apoptotic and anti-proliferative effects on endothelial cells. Mice deficient in this matricellular protein display improved recovery from ischemia and accelerated wound healing associated with alterations in angiogenesis and extracellular matrix remodeling. In this study, we probed the function of TSP2 by performing a detailed analysis of dermal wounds and wound-derived fibroblasts. Specifically, we analyzed incisional wounds by tensiometry and found no differences in strength recovery between wild-type and TSP2-null mice. In addition, analysis of full-thickness excisional wounds by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling stain and MIB-5 immunohistochemistry revealed similar numbers of apoptotic and proliferating cells, respectively. In contrast, the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2, and soluble vascular endothelial growth factor were increased in wounds of TSP2-null mice. Evaluation of the ability of TSP2-null wound fibroblasts to contract collagen gels revealed that it was compromised, even though TSP2-null wounds displayed normal myofibroblast content. Therefore, we conclude that the lack of TSP2 leads to aberrant extracellular matrix remodeling, increased neovascularization, and reduced contraction due in part to elevated levels of MMP-2 and MMP-9. These observations provide in vivo supporting evidence for a newly proposed function of TSP2 as a modulator of extracellular matrix remodeling.


[Analysis of surgical procedures on the vena saphena magna in the Czech Republic and an effect of Detralex during its stripping].
The aim of this clinical study was to compare the degree of postoperative pain (VAS--10 cm, quality of life questionnaire CIVIQ and patient diary) between two groups of patients: patients treated with Detralex 14 days before and 14 days after the stripping of greater saphenous vein (GSV) and patients not treated with Detralex. In addition, the two groups were also compared for the incidence of symptoms associated with chronic venous insufficiency (CVI) (using the VAS scale: edema, tired and heavy legs, cramps, itching sensation), size of hematoma, use of analgesics and overall efficacy of the treatment. Clinical study included 181 patients from 15 medical centers throughout the Czech Republic. High ligation and partial stripping of greater saphenous vein on one lower extremity was performed in all patients (short stripping from groin to knee). Patients were randomly assigned in two groups: patients treated with Detralex (92) and patients not treated with Detralex (89). Patients in the first group were treated with Detralex for the period of 1 month. Degree of pain and patient's health condition were evaluated by the physician during D-14 (14 days prior to the surgery), D7 and D14 (7 and 14 days after the surgery) visits using the 10-cm visual analog scale VAS. The results indicate that Detralex reduced the intensity of postoperative pain, which resulted in decreased consumption of analgesics. Hematoma was smaller in patients already using Detralex 14 days prior to the scheduled stripping procedure. These patients also showed significant improvement of CVI symptoms and the quality of life of patients with CVI. High quality venoactive drugs administered 14 days prior to the surgery improve postoperative course in patients indicated for surgical treatment of varices.


Four-Step Total Synthesis of (+)-Euphococcinine and (±)-Adaline.
A four-step enantiospecific total synthesis of bicyclic homotropinone alkaloid euphococcinine and a racemic synthesis of adaline were reported. Key reactions in the synthesis are the diastereoselective addition of a Wittig phosphorene to the ketimines derived from Davis-Ellman sulfinamides, ring-closing metathesis, and intramolecular Michael reactions.


Establishment of a new human immortalized chondrocyte cell line.
Chondrocytes from human adult articular healthy cartilage were transfected in primary culture with a plasmid containing two human papilloma virus type 16 early function genes: E6 and E7, using the highly efficient cationic liposome-mediated (lipofection) procedure. The transfection was verified by reverse transcriptase-polymerase chain reaction analysis of E7 mRNA and by immunofluorescence localization of the E7 protein in the cell cytoplasm. The established chondrocyte cell line was examined in monolayer and in two culture conditions that were described to re-induce differentiated characteristics: culturing in a serum-free defined medium and seeding on a hyaluronan-based three-dimensional biomaterial. Immortalized cells were able to re-express the main markers of chondrocyte phenotype, both at mRNA and protein levels, under the two defined cultured conditions used. The cell line that we obtained may be a useful tool for increasing our knowledge of the genetic and biochemical events involved in the processes of cartilage growth and differentiation, and of the etiopathogenesis of many rheumatic diseases.


Dedifferentiated chondrosarcoma: an ultrastructural study of two cases, with immunocytochemical correlations.
The clinicopathologic features of two cases of dedifferentiated chondrosarcoma (DCS) are presented, in which anaplastic components showed the electron microscopic features of malignant fibrous histiocytoma, as well as immunoreactivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Rare cells also displayed S100 protein in high-grade areas of the primary tumors, but a pulmonary metastasis lacked this determinant. These findings could be interpreted as reflecting a retained potential for primitive chondrogenesis in primary DCS, which may be lost in its metastases. In all other respects, this tumor appears to assume the morphological and immunocytochemical attributes of a fibrohistiocytic neoplasm.


Optimal vitamin D levels in Crohn's disease: a review.
Vitamin D deficiency is common among patients with Crohn's disease. Serum 25-hydroxyvitamin D (25(OH)D) is the best measure of an individual's vitamin D status and current cut-off ranges for sufficiency are debatable. Several factors contribute to vitamin D deficiency in Crohn's disease. These include inadequate exposure to sunlight, inadequate dietary intake, impaired conversion of vitamin D to its active metabolite, increased catabolism, increased excretion and genetic variants in vitamin D hydroxylation and transport. The effects of low 25(OH)D on outcomes other than bone health are understudied in Crohn's disease. The aim of the present review is to discuss the potential roles of vitamin D and the possible levels required to achieve them. Emerging evidence suggests that vitamin D may have roles in innate and adaptive immunity, in the immune-pathogenesis of Crohn's disease, prevention of Crohn's disease-related hospitalisations and surgery, in reducing disease severity and in colon cancer prevention. The present literature appears to suggest that 25(OH)D concentrations of ≥75 nmol/l may be required for non-skeletal effects; however, further research on optimal levels is required.


FDG-Avid Granulomatous Lymphocytic Interstitial Lung Disease With Common Variable Immunodeficiency.
A 26-year-old woman with known common variable immunodeficiency was referred for FDG PET/CT because of interstitial pulmonary abnormalities and enlarged mediastinal and hilar lymph nodes. FDG PET showed a combination of ground-glass abnormalities and pulmonary nodules, both displaying increased FDG uptake. In addition, multiple FDG-avid axillary, mediastinal, hilar, and inguinal lymph nodes were found. The abnormalities were diagnosed as granulomatous-lymphocytic interstitial lung disease. Cytology of mediastinal lymph nodes yielded only benign disease, without further specification, whereas histology of an excised axillary lymph node showed reactive changes, but no malignancy.