Principal components for morphometric traits in Campolina horses.
Principal component analysis (PCA) was applied to evaluate the genetic variability and relationship between 15 morphometric traits in 91,483 Campolina horses, as well as to propose an index based on an aggregate genotype that promotes a particular selection objective. PCA was applied to the genetic (co)variance matrix among variables. After calculation of the principal components, the breeding values were estimated to obtain an index related to the component that explained most of the variation. The first principal component (PC1) accounted for 97.8% of the total additive genetic variance of the traits. PC1 contrasted animals in terms of body size (wither, back and croup heights, body length, and thoracic girth). PC1 traits showed higher heritabilities and positive and high genetic correlations. An index was obtained (HPC1) with the combination of the breeding values of different traits from PC1 which permitted the use of this index as an aggregate genotype to identify the best animals for selection. The second principal component (PC2) was much smaller and grouped traits related to head and neck morphometry, among others. These traits are commonly used for breed qualification, a fact explaining the small variation in this component. An evaluation of the effect of HPC1 on withers height in two-trait analysis was also made which provided positive genetic correlations of moderate to high magnitude (0.73-0.86), indicating that selection for this trait (important in Campolina horses) is accounted for in the index. The use of HCP1 could be considered as an important alternative to selection since it does not consider a single trait but rather a set of variables that capture body proportions.


Fluorescent 'two-faced' polymer wafers with embedded pyrene-functionalised gelator nanofibres.
Pyrene-functionalised gelators self-assemble into nano-fibrillar organogels in DMSO/styrene/divinylbenzene mixtures, which when polymerised yield polymer wafers with two distinct faces, only one of which is fluorescent and has embedded gelator nanofibres.


Ictal EEG-fMRI in localization of epileptogenic area in patients with refractory neocortical focal epilepsy.
To evaluate the usefulness of ictal electroencephalography (EEG)-combined functional magnetic resonance imaging ( MRI) (EEG-fMRI) in localizing epileptogenic zone in refractory neocortical focal epilepsy. From the EEG-fMRI database of our institution including 62 adult patients, 14 (age 18-46 years) experienced some ictal event during the test. Data were segmented into 10-s blocks, and the results were analyzed by contrasting each block to the contiguous 10-s block from the onset of seizure onward, in all cases. In seizures lasting >10 s (five cases), a supplementary analysis was performed, contrasting each block to a baseline condition, in the framework of the general linear model (GLM) of analysis. Regions of activations were compared to results from the different techniques performed during presurgical evaluation, such as SISCOM, positron emission tomography (PET), and invasive subdural EEG monitoring. Regarding the structural MRI findings, nine cases presented some lesion, with blood oxygen level- dependent (BOLD) signal activation placed in the same location in eight of them (89%). SISCOM studies were performed in 11 patients; 5 were concordant with the increase in BOLD signal in a sublobar level, whereas in 3 cases the concordance was in a lobar level. Eleven patients underwent PET studies, being also concordant in a sublobar level in four of them and in a lobar level in four additional cases. Finally, invasive EEG evaluation was performed in three patients and all of them had the seizure-onset zone in the initial area of BOLD activation. This study adds relevant information to support the integration of EEG-fMRI in the multidisciplinary presurgical workup in patients with refractory epilepsy.


Diseases associated with thyroid autoimmunity: explanations for the expanding spectrum.
Anyone who has been in an endocrine clinic will appreciate that associations exist between autoimmune thyroid disease (AITD) and other autoimmune disorders. However, the full extent of these associations is still not fully appreciated, and new associations are being uncovered which may shed new light on the pathogenic basis for these connections, and the underlying reasons for them are only now becoming understood. This review is based on the British Thyroid Association Pitt-Rivers Lecture 2010. The first section provides an update on studies which have detailed the strength of various autoimmune disease associations, the second section discusses the environmental and genetic factors which underlie these associations and the final section describes some recently identified, unexpected AITD associations. Unravelling these associations further will illuminate the pathogenesis of autoimmune diseases and offers the prospect of new therapeutic approaches.


Antigenic profiles of individual-matched pairs of primary and melanoma metastases.
A unique collection of individual-matched pairs of primary and melanoma metastases were studied immunohistochemically with a panel of 6 monoclonal antibodies directed to gp-100, pigmentation-associated antigen, tyrosinase-related protein, human leukocyte antigen DR, MAA-1, and MAA-2 (high molecular weight melanoma-associated antigens). The antigenic profile of immunoreactive pigment cells was compared with the stage of tumor progression. Our data show consistent antigenic profiles of primary melanomas and their metastases within the same patient. Expression of tyrosinase-related protein and pigmentation-associated antigen was observed in the radial growth phase of primary melanomas but showed diminished or complete loss of expression in the vertical growth phase and in metastatic melanomas. HLA-DR was negative in the most primary lesions, but melanoma cells and a larger proportion of immunoreactive cells were observed at the metastatic site. The melanoma-associated antigens MAA-1 and MAA-2 were expressed throughout tumor progression. Although no clear distinction could be made between primary and secondary melanoma lesions for both melanoma-associated antigens, there was a profound variability in the topographical antigen distribution when compared with HLA-DR. The loss of expression of pigmentation-associated antigen and tyrosinase-related protein in the vertical growth phase of the primary lesions and metastatic melanomas did not reach statistical significance but still may be related to tumor progression. This indicates that primary melanomas can be distinguished from their metastases by evaluation of the antigenic profile and in this respect facilitate the recognition of tumor progression stages.


Splicing of mRNA precursors: the role of RNAs and proteins in catalysis.
Splicing of mRNA precursors was discovered over 30 years ago. It is one of the most complex steps in gene expression and therefore must be tightly controlled to ensure that splicing occurs efficiently and accurately. Splicing takes place in a large complex, the spliceosome, which contains approximately 200 proteins and five small RNAs (U snRNAs). Since its discovery, much work has been done to elucidate the pathway of the chemical reaction as well as the proteins and RNAs involved in catalysis. A variety of studies have established the potential for U2 and U6 snRNAs to play a role in splicing catalysis, raising the possibility that the spliceosome is a ribozyme. If correct, this would point to the spliceosomal proteins playing a supporting role during splicing. On the other hand, it may be that proteins contribute more directly to the spliceosomal active site, with the highly evolutionarily conserved Prp8 protein being an excellent candidate. This review will concentrate on recent work on splicing catalysis, and on elucidating the possible roles proteins play in this process.


Suitable Dose of Long-Term Tolvaptan to Reduce Heart Failure Rehospitalizations.
The short-term effectiveness of tolvaptan (TLV) for heart failure (HF) has been established, but the long-term effects are controversial. We investigated HF patients who could not discontinue both loop diuretics and TLV at discharge from AURORA (Acute Heart Failure Registry in Osaka Rosai Hospital). We compared the following factors at discharge between the RH group, consisting of patients with rehospitalizations due to worsening HF within 1 year after discharge (RH group), and non-RH group: age, gender, blood pressure, history of HF admission, electrocardiogram and echocardiographic parameters, atherosclerotic risk factors, laboratory data, and medications. Furthermore, we compared the effects of long-term low-dose TLV (≤ 7.5 mg/day) and high-dose TLV on HF rehospitalizations. The RH group consisted of 81 patients (58.7%). A multivariate analysis revealed that a history of HF admission and the TLV dose were independently and significantly associated with 1-year HF rehospitalizations. A receiver operating characteristic curve revealed that 7.5 mg of TLV was a suitable cutoff value for 1-year HF rehospitalizations. The Kaplan-Meier curves demonstrated that the HF rehospitalization free ratio was significantly higher in the low-dose TLV group (≤ 7.5 mg/day) than in high-dose TLV group over 1 year.In conclusion, the TLV dose, in addition to a history of HF admission, was associated with 1-year HF rehospitalizations in diuretic-dependent HF patients. In these patients, long-term low-dose TLV (≤ 7.5 mg/day) may be favorable for reducing HF rehospitalizations.


Inflammatory regulatory T cells in the microenvironments of ulcerative colitis and colon carcinoma.
Foxp3(+)CD4(+) regulatory T (Treg) cells are thought to express negligible levels of effector cytokines, and inhibit immune responses and inflammation. Here, we have identified a population of IL-8(+)Foxp3(+)CD4(+) T cells in human peripheral blood, which is selectively increased in the microenvironments of ulcerative colitis and colon carcinoma. Phenotypically, this population is minimally overlapping with IL-17(+)Foxp3(+)CD4(+) T cells, and is different from IL-8(-)Foxp3(+)CD4(+) T cells in the same microenvironment. 40-60% of IL-8(+)Foxp3(+)CD4(+) T cells exhibit naive phenotype and express CD127, whereas IL-8(-)Foxp3(+)CD4(+) cells are basically memory T cells and express minimal CD127. The levels of CXCR5 expression are higher in IL-8(+)Foxp3(+) cells than in IL-8(-)Foxp3(+) cells. IL-2 and TGFβ induce IL-8(+)Foxp3(+) T cells. Exogenous Foxp3 expression promotes IL-8(+)Foxp3(+) T cells and inhibits effector cytokine IFNγ and IL-2 expression. Furthermore, Foxp3 binds to IL-8 proximal promoter and increases its activity. Functionally, IL-8(+)Foxp3(+) T cells inhibit T cell proliferation and effector cytokine production, but stimulate inflammatory cytokine production in the colon tissues, and promote neutrophil trafficking through IL-8. Thus, IL-8(+)Foxp3(+) cells may be an "inflammatory" Treg subset, and possess inflammatory and immunosuppressive dual biological activities. Given their dual roles and localization, these cells may be in a unique position to support tumor initiation and development in human chronic inflammatory environment.


Random Fourier Features-Based Deep Learning Improvement with Class Activation Interpretability for Nerve Structure Segmentation.
Peripheral nerve blocking (PNB) is a standard procedure to support regional anesthesia. Still, correct localization of the nerve's structure is needed to avoid adverse effects; thereby, ultrasound images are used as an aid approach. In addition, image-based automatic nerve segmentation from deep learning methods has been proposed to mitigate attenuation and speckle noise ultrasonography issues. Notwithstanding, complex architectures highlight the region of interest lacking suitable data interpretability concerning the learned features from raw instances. Here, a kernel-based deep learning enhancement is introduced for nerve structure segmentation. In a nutshell, a random Fourier features-based approach was utilized to complement three well-known semantic segmentation architectures, e.g., fully convolutional network, U-net, and ResUnet. Moreover, two ultrasound image datasets for PNB were tested. Obtained results show that our kernel-based approach provides a better generalization capability from image segmentation-based assessments on different nerve structures. Further, for data interpretability, a semantic segmentation extension of the GradCam++ for class-activation mapping was used to reveal relevant learned features separating between nerve and background. Thus, our proposal favors both straightforward (shallow) and complex architectures (deeper neural networks).


[Control of graft-versus-host disease and infection associated with immunosuppression].
Graft-versus-host disease (GVHD) in leukemia patients following allogeneic bone marrow transplantation (BMT) has a lot of demerits but it also has a merit, namely graft-versus-leukemia effect. We reported the results of our recent trials on prevention, treatment and induction of GVHD, and prevention of viral infection after BMT. The results were as follows: 1) Twenty-four percent of patients who received prophylactic administration of cyclosporine and short term methotrexate still developed II degree-IV degree acute GVHD. 2) Patients with I degree or II degree acute GVHD showed good clinical courses. But, most patients with III degree GVHD gradually developed chronic GVHD. All patients with IV degree GVHD died of GVHD or infection. 3) Mizoribine and deoxyspergualin were effective for steroid-resistant GVHD. 4) Bestatin was administered to recipients who did not develop GVHD until day 30 after BMT. An interim report suggests that bestatin may induce chronic GVHD and suppress the relapse of leukemia. 5) Oral administration of gamma-globulin may prevent viral enteritis. Intravenous administration of anti-cytomegalovirus monoclonal antibody may prevent cytomegalovirus pneumonia.


An evaluation of cellulose saccharification and fermentation with an engineered Saccharomyces cerevisiae capable of cellobiose and xylose utilization.
Commercial-scale cellulosic ethanol production has been hindered by high costs associated with cellulose-to-glucose conversion and hexose and pentose co-fermentation. Simultaneous saccharification and fermentation (SSF) with a yeast strain capable of xylose and cellobiose co-utilization has been proposed as a possible avenue to reduce these costs. The recently developed DA24-16 strain of Saccharomyces cerevisiae incorporates a xylose assimilation pathway and a cellodextrin transporter (CDT) that permit rapid growth on xylose and cellobiose. In the current work, a mechanistic kinetic model of cellulase-catalyzed hydrolysis of cellulose was combined with a multi-substrate model of microbial growth to investigate the ability of DA24-16 and improved cellobiose-consuming strains to obviate the need for exogenously added β-glucosidase and to assess the impact of cellobiose utilization on SSF and separate hydrolysis and fermentation (SHF). Results indicate that improved CDT-containing strains capable of growing on cellobiose as rapidly as on glucose produced ethanol nearly as rapidly as non-CDT-containing yeast supplemented with β-glucosidase. In producing 75 g/L ethanol, SSF with any strain did not result in shorter residence times than SHF with a 12 h saccharification step. Strains with improved cellobiose utilization are therefore unlikely to allow higher titers to be reached more quickly in SSF than in SHF.


Technique to derive discrete population models with delayed growth.
We provide a procedure for deriving discrete population models for the size of the adult population at the beginning of each breeding cycle and assume only adult individuals reproduce. This derivation technique includes delay to account for the number of breeding cycles that a newborn individual remains immature and does not contribute to reproduction. These models include a survival probability (during the delay period) for the immature individuals, since these individuals have to survive to reach maturity and become members of, what we consider, the adult population. We discuss properties of this class of discrete delay population models and show that there is a critical delay threshold. The population goes extinct if the delay exceeds this threshold. We apply this derivation procedure to obtain two models, a Beverton-Holt adult model and a Ricker adult model and discuss the global dynamics of both models.


Clinical Review of Cochlear Implantation Performed at Sapporo Medical University Hospital.
More than 20 years have passed since cochlear implantation (CI) was first introduced in Japan. We began CI at the Sapporo Medical University Hospital in 1988; since then, up to the first half of 2015, we have performed CI on 280 ears. In patients aged less than and those aged over 18 years, 121 and 159 ears, respectively, have undergone surgery. This report presents typical cases of CI, such as an adult case, a bilateral case, a case where both hearing and vision were impaired, a pediatric case, a case with multiple handicaps, a case with a genetic mutation leading to severe hearing loss, and a complicated case. In addition, complications with CI cases experienced during extended follow-up periods are also summarized.


Intraoperative motor and somatosensory evoked potential monitoring during surgical clipping of ruptured and unruptured intracranial aneurysms: a comparative study.
The current study investigated the correlation between intraoperative motor evoked potential (MEP) and somatosensory evoked potential (SSEP) monitoring and both short-term and long-term motor outcomes in aneurysm patients treated with surgical clipping. Moreover, the authors provide a relatively optimal neurophysiological predictor of postoperative motor deficits (PMDs) in patients with ruptured and unruptured aneurysms. A total of 1017 patients (216 with ruptured aneurysms and 801 with unruptured aneurysms) were included. Patient demographic characteristics, clinical features, intraoperative monitoring data, and follow-up data were retrospectively reviewed. The efficacy of using changes in MEP/SSEP to predict PMDs was assessed using binary logistic regression analysis. Subsequently, receiver operating characteristic curve analysis was performed to determine the optimal critical value for duration of MEP/SSEP deterioration. Both intraoperative MEP and SSEP monitoring were significantly effective for predicting short-term (p < 0.001 for both) and long-term (p < 0.001 for both) PMDs in aneurysm patients. The critical values for predicting short-term PMDs were amplitude decrease rates of 57.30% for MEP (p < 0.001 and area under the curve [AUC] 0.732) and 64.10% for SSEP (p < 0.001 and AUC 0.653). In patients with an unruptured aneurysm, the optimal critical values for predicting short-term PMDs were durations of deterioration of 17 minutes for MEP (p < 0.001 and AUC 0.768) and 21 minutes for SSEP (p < 0.001 and AUC 0.843). In patients with a ruptured aneurysm, the optimal critical values for predicting short-term PMDs were durations of deterioration of 12.5 minutes for MEP (p = 0.028 and AUC 0.706) and 11 minutes for SSEP (p = 0.043 and AUC 0.813). The authors found that both intraoperative MEP and SSEP monitoring are useful for predicting short-term and long-term PMDs in patients with unruptured and ruptured aneurysms. The optimal intraoperative neuromonitoring method for predicting PMDs varies depending on whether the aneurysm has ruptured or not.


Brain nitric oxide inactivation is governed by the vasculature.
The mechanisms underlying nitric oxide ((•)NO) synthesis and inactivation in the brain are essential determinants of (•)NO neuroactivity. Although (•)NO production is well characterized, the pathways of inactivation in vivo remain largely unknown. Here, we characterize the kinetics and the major mechanism of (•)NO inactivation in the rat brain cortex and hippocampus in vivo by measuring locally applied (•)NO with carbon-fiber microelectrodes (CFMs) and ceramic-based microelectrode arrays (MEAs). An apparent first-order clearance was observed in both brain regions, with decay rate constants (k) of (•)NO signals of 0.67 to 0.84 per second, significantly higher than the k obtained in agarose gel (0.099 per second), used as a (•)NO diffusion-control medium. (•)NO half-life in vivo, estimated by mathematical modeling, was 0.42 to 0.75 s. Experiments using MEAs support that the (•)NO diffusion radius is heterogeneous and related to local metabolic activity and vascular density. After global ischemia, k decreased to control values of diffusion in gel, but during anoxia, k decreased only 21%. Additionally, k in brain slices was threefold to fivefold lower than that in vivo, and hemorrhagic shock induced a 53% decrease in k. Overall, the results support that (•)NO scavenging by circulating erythrocytes constitutes the major (•)NO-inactivation pathway in the brain.


Impact of graphic format on perception of change in biological data: implications for health monitoring in conditions such as asthma.
Variation in graphic format can substantially influence interpretation of data. Despite a large body of literature on the optimal design of graphs, little attention has been paid to the format of charts for health monitoring. This study assessed the effect of aspect ratio (x:y ratio) and interconnecting lines on visual identification of change in biological data, such as during asthma exacerbations. Eighty volunteers viewed 72 sets of six consecutive blocks of unidentified biological data, recording if each block of data was increasing, decreasing, or the same as the previous block. Three chart aspect ratios were examined (A, 5.2:1; B, 3.0:1; C, 1.1:1), with or without lines between data points. Datasets from lung function monitoring by asthma patients included a mild/moderate/severe fall ('exacerbation') or no exacerbation. False negative (missing true exacerbations) and false positive (identifying non-existent exacerbations) responses were calculated. 84% of exacerbation blocks were correctly identified. There was a significant interaction between exacerbation severity and aspect ratio (p=0.0048). The most compressed chart (C) had the fewest false negative responses. Moderate falls were missed in 24%, 12%, and 5% of trials on charts A, B, and C, respectively (C vs A: adjusted relative risk 0.19 (95% CI 0.12 to 0.30)). False positive responses were infrequent (A, 2.5%; B, 3.8%; C, 8.3%), increasing slightly if data points were joined with lines (4.3% vs 5.1%, p=0.004) . Compressed charts can improve the visual detection of change in biological data by up to 80%. The aspect ratio of charts should be standardised to facilitate clinical pattern recognition.


Grammatical constructions in Cri du chat syndrome--findings from a case study.
The literature on grammatical skills in persons with Cri du chat syndrome (CCS) is very limited, and the need for more knowledge in this area is thus evident, in particular for speech and language therapists working with individuals with this syndrome. This case study report describes the syntactic skills of a 14-year-old Norwegian girl with CCS. The theoretical framework is construction grammar. Data for the study were collected in a diary by the author over a period of 4 months and make up a corpus of 552 utterances. These utterances are described in terms of MLU, diversity of argument structure constructions, proportion and types of complex utterances, use of auxiliaries, as well as deviant word order patterns, types of omissions, and use of prefabricated units. The primary aim of the study is to identify strengths and weaknesses in syntactic skills, which provide the basis for future research on grammatical skills in persons with CCS.


Triple Starr valve replacement.
Of nine patients who have had triple valve replacements for organic rheumatic triple valve disease two died in the postoperative period from inadequate myocardial reserve, and a third died four months later from cerebral embolism originating from clot on the left atrial wall. The remainder are well and, except for one, leading normal lives. Though cardiac transplantation has been recommended and used successfully for triple valve disease by Cooley, it is suggested that the long-term outlook today of triple valve replacement is likely to be better than that of transplantation.


L-Glutamine inhibits beta-aminobutyric acid-induced stress resistance and priming in Arabidopsis.
The non-protein amino acid beta-aminobutyric acid (BABA) enhances Arabidopsis resistance to microbial pathogens and abiotic stresses through potentiation of the Arabidopsis defence responses. In this study, it is shown that BABA induces the stress-induced morphogenic response (SIMR). SIMR is observed in plants exposed to sub-lethal stress conditions. Anthocyanin, a known modulator of stress signalling, was also found to accumulate in BABA-treated Arabidopsis. These data and a previous microarray study indicate that BABA induces a stress response in Arabidopsis. High concentrations of amino acids, except for L-glutamine, cause a general amino acid stress inhibition. General amino acid inhibition is prevented by the addition of L-glutamine. L-Glutamine was found to inhibit the BABA-mediated SIMR and anthocyanin accumulation, suggesting that the non-protein amino acid BABA causes a general amino acid stress inhibition in Arabidopsis. L-Glutamine also blocked BABA-induced resistance to heat stress and to the virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000. During bacterial infection, priming of the salicylic acid-dependent defence marker PR1 was abolished by L-glutamine treatment. These results indicate that L-glutamine removal of the BABA-mediated stress response is concomitant with L-glutamine inhibition of BABA priming and BABA-induced resistance.


Actinomycosis as a rare complication of orthognathic surgery.
Modern orthognathic surgery is said to be clean contaminated due to the intraoral means of access. Complications after orthognathic surgery, a common operation, occur about 10% of the time. Actinomycosis, a rare specific infection, plays a negligible role. Diagnostically, it should be differentiated from other infections that occur a long time after the operation. Three cases of actinomycosis that occurred after orthognathic surgery were observed, and therapeutic measurements are described case by case.


Desmoplastic small round cell tumors: cytologic, histologic, and immunohistochemical features.
Desmoplastic small round cell tumor (DSRCT) is a recently recognized clinicopathologic entity that has a predilection for adolescent males and usually affects the abdominal cavity. Due to its uncommon nature, many pathologists lack experience with this tumor. The literature regarding DSRCT is reviewed with special attention to its histologic and cytologic diagnosis. Morphologic features of DSRCT and its immunohistochemical and cytogenetic profile are summarized and differential diagnosis with other small round cell tumors is discussed. As observed by both histologic and cytologic examinations, small round blue cells and fibrosclerotic stroma are the striking morphologic features of DSRCT. The typical immunohistochemical profile is characterized by coexpression of epithelial, mesenchymal, myogenic, and neural markers. Cytogenetically, this tumor harbors a specific karyotypic abnormality, namely t(11;22)(p13;q12). These features distinguish DSRCT from other members of the family of small round cell tumors.


Volatile Organic Compounds From Lysobacter capsici AZ78 as Potential Candidates for Biological Control of Soilborne Plant Pathogens.
The genus Lysobacter includes several bacterial species which show potential for being used in biological control of plant diseases. It was shown recently that several Lysobacter type strains produce volatile organic compounds (VOCs) which controlled the growth of Phytophthora infestans in vitro when the bacteria were grown on a protein rich medium. In the present study, Lysobacter capsici AZ78 (AZ78) has been tested for its potential to produce VOCs that may contribute to the bioactivity against soilborne plant pathogens. To this end, split Petri dish assays of bacterial cultures have been combined with GC-MS measurements with the aim to reveal the identity of the VOCs which inhibit the growth of Pythium ultimum Rhizoctonia solani, and Sclerotinia minor. While AZ78 completely suppressed the growth of P. ultimum and S. minor, the growth of R. solani was still reduced significantly. The GC-MS analysis revealed 22 VOCs to be produced by AZ78, the majority of which were (putatively) identified as mono- and dialkylated methoxypyrazines. Based on additional cultivation and GC-MS experiments, 2,5-dimethylpyrazine, 2-ethyl-3-methoxypyrazine and 2-isopropyl-3-methoxypyrazine were selected as presumable bioactive compounds. Further bioassays employing indirect exposure to standard solutions (1-10 mg per Petri dish) of the synthetic compounds via the gas phase, revealed that each of these pyrazines was able to suppress the growth of the pathogens under investigation. The results of this study highlight the possible future implementation of pyrazine derivatives in the control of soilborne plant diseases and further support the biocontrol potential of L. capsici AZ78.


How can a Theory of Change framework be applied to short-term international volunteering?
Short-term international volunteering has become enormously popular among individuals from high-income countries who travel to low-income countries to offer support on initiatives often related to health and development. However, their impact on global development is questionable, particularly when volunteer skills are not matched to local needs, or when teams operate outside the local health system. Furthermore, the impact of these volunteer programs is rarely evaluated. Theory of Change is a framework for program design meant to facilitate measurable social change. We propose that a Theory of Change framework, appropriately deployed in the design and conduct of short-term international volunteerism, could help improve volunteer efforts by identifying problems and clearly defining goals, designing and implementing effective strategies, and evaluating the real impacts these have on identified concerns.


A preliminary analysis of divorce in China.
"With data from the 1982 and 1990 censuses and data of divorce from civil administration departments, it is possible to make a preliminary analysis on changes in the number of divorces and the population of divorcees in China since the 1980s." Aspects considered include regional differentials, sex differences, age patterns, and remarriage.


[Electrophysiological characteristics of neurons in rat substantia nigra by visual patch clamp technique].
To establish the brain slices of substantia nigra and striatum in rats and study the properties and functional significance of substantia nigra neurons. The technique of infrared differential interference contrast (IR-DIC) and CCD-Camera system with visual patch clamp whole-cell recording were combined. One hundred healthy substantia nigra neurons were located and the measurements of active potential and Ih current recorded and analyzed. Visual patch clamp technique could be used to make a direct localization of substantia nigra and to identify the active neurons. Spontaneous active potential was shown in 94/100 neurons. Among them, 85 (Group A) had a frequency less than 10 Hz and 9 more than 10Hz (Group B). The means were (5.0 +/- 2.7) Hz and (14.0 +/- 2.6) Hz. respectively. As compared with the former, the latter had no obvious hyperpolarization during active potential period. Apparent hyperpolarizing current could be induced in 92.9% (79/85) of Group A neurons (-120 mV, 47.5 pA +/- 5.8 pA). They were classified as dopaminergic neurons. However, the Group B neurons had no or little Ih current and were classified as GABA neurons (P < 0.001). The types of nigra neurons can be distinguished by observing the fundamental electrical characteristic of dopaminergic neurons in nigrostriatal brain slices under visual inspections. And it may provide rationales for an in-depth knowledge of the occurrence and transmission of signal pathways between substantia nigra and


UDP-Glucose: (1-->3)-beta-Glucan Synthases from Mung Bean and Cotton: Differential Effects of Ca and Mg on Enzyme Properties and on Macromolecular Structure of the Glucan Product.
A re-examination of the kinetic properties of UDP-glucose: (1-->3)-beta-glucan (callose) synthases from mung bean seedlings (Vigna radiata) and cotton fibers (Gossypium hirsutum) shows that these enzymes have a complex interaction with UDP-glucose and various effectors. Stimulation of activity by micromolar concentrations of Ca(2+) and millimolar concentrations of beta-glucosides or other polyols is highest at low (<100 micromolar) UDP-glucose concentrations. These effectors act both by raising the V(max) of the enzyme, and by lowering the apparent K(m) for UDP-glucose from >1 millimolar to 0.2 to 0.3 millimolar. Mg(2+) markedly enhances the affinity of the mung bean enzyme for Ca(2+) but not for beta-glucoside; with saturating Ca(2+), Mg(2+) only slightly stimulates further production of glucan. However, the presence of Mg(2+) during synthesis, or NaBH(4) treatment after synthesis, changes the nature of the product from dispersed, alkali-soluble fibrils to highly aggregated, alkali-insoluble fibrils. Callose synthesized in vitro by the Ca(2+), beta-glucoside-activated cotton fiber enzyme, with or without Mg(2+), is very similar in size to callose isolated from cotton fibers, but is a linear (1-->3)-beta-glucan lacking the small amount of branches at C-0-6 found in vivo. We conclude that the high degree of aggregation of the fibrils synthesized with Mg(2+)in vitro is caused either by an alteration of the glucan at the reducing end or, indirectly, by an effect of Mg(2+) on the conformation of the enzyme. Rate-zonal centrifugation of the solubilized mung bean callose synthase confirms that divalent cations can affect the size or conformation of this enzyme.


Fallopian bridge technique in surgery for chronic ear disease.
Disease that lies in the posterior mesotympanum, including inflammatory polyps, cholesterol granuloma, and cholesteatoma, is often difficult to extirpate. The literature reflects a divided and often controversial opinion regarding the removal of the bony posterior canal wall to reach this disease. Recently, endoscopic visualization has been advocated to enhance exposure. Employing a fallopian bridge technique wherein the bone medial to the facial nerve is opened into the posterior mesotympanum the authors have used this approach in selective circumstances to optimize the eradication of disease. Three hundred patients undergoing tympanomastoidectomy were included in this analysis. The fallopian bridge technique was attempted in 58 cases and was successfully employed in 42 patients. Indications as well as limitations for this procedure are discussed.


State of heat shock factor 1 expression as a putative diagnostic marker for oral squamous cell carcinoma.
Heat shock factor 1 (HSF1) is responsible for expres-- sion of a large class of heat shock proteins that have been implicated in the malignant phenotype of human cancers. Little is known about the effect of a high level of HSF1 on the behavior of oral squamous cell carcinoma (OSCC). In this study, we assessed the value of HSF1 for predicting clinical outcomes in OSCC. Quantitative reverse transcriptase-polymerase chain reaction and Western blotting showed that the expressions of HSF1 mRNA and protein in OSCC-derived cell lines (HSC-2, HSC-3, HSC-4, Sa3, Ca9-22, KON and Ho-1-u-1) were elevated compared with those in human normal oral keratinocytes (P<0.05). Similar to in vitro data, HSF1 mRNA expression in primary OSCCs (n=50) was significantly greater than in normal counterparts (P<0.05). Since HSF1 was observed in the nucleus and cytoplasm by immu-- nohistochemistry, we investigated the correlation between the HSF1 expression status at each subcellular location and the clinical behavior of OSCCs. Among the clinical classifications, higher nuclear HSF1 expression was closely related to tumor size and histopathologic types (P<0.05). These results showed for the first time that nuclear HSF1 expression may contribute to cancer progression and that HSF1 might be a potential diagnostic biomarker and a therapeutic target for OSCCs.


The efficacy of duct tape vs cryotherapy in the treatment of verruca vulgaris (the common wart).
To determine if application of duct tape is as effective as cryotherapy in the treatment of common warts. A prospective, randomized controlled trial with 2 treatment arms for warts in children. The general pediatric and adolescent clinics at a military medical center. A total of 61 patients (age range, 3-22 years) were enrolled in the study from October 31, 2000, to July 25, 2001; 51 patients completed the study and were available for analysis. Patients were randomized using computer-generated codes to receive either cryotherapy (liquid nitrogen applied to each wart for 10 seconds every 2-3 weeks) for a maximum of 6 treatments or duct tape occlusion (applied directly to the wart) for a maximum of 2 months. Patients had their warts measured at baseline and with return visits. Complete resolution of the wart being studied. Of the 51 patients completing the study, 26 (51%) were treated with duct tape, and 25 (49%) were treated with cryotherapy. Twenty-two patients (85%) in the duct tape arm vs 15 patients (60%) enrolled in the cryotherapy arm had complete resolution of their warts (P =.05 by chi(2) analysis). The majority of warts that responded to either therapy did so within the first month of treatment. Duct tape occlusion therapy was significantly more effective than cryotherapy for treatment of the common wart.


Efficient synthesis of 2'-C-beta-methylguanosine.
2'-beta-Methyl nucleosides have potential value as therapeutic agents and as nucleoside analogues for exploring RNA biology. Here we develop a strategy for efficient synthesis for 2'-C-beta-methylguanosine (3). Starting from 1,2,3,5-tetra-O-benzoyl-2-C-beta-methyl-d-ribofuranose (1) and N2-acetylguanine, we obtained the title compound in two steps (78% overall yield) with high stereoselectivity (beta/alpha > 99:1) and high regioselectivity (N9/N7 > 99:1). Extension of this strategy to the classic synthesis of guanosine also resulted in high stereoselectivity (beta/alpha = 99:1) and improved regioselectivity (N9/N7 = 97:3).


Loneliness, Sociodemographic and Mental Health Variables in Spanish Adults over 65 Years Old.
Loneliness is a risk factor for morbidity as well as mortality. Older people are more vulnerable to feeling alone due to age-associated changes and losses they might experience. This study aimed to analyze sociodemographic, psychosocial, and mental health variables related to loneliness in the elderly. A random sample of 419 people over 65 years old from the Community of Madrid was used. The UCLA Loneliness Scale, the CIDI65+ Diagnostic Interview, and the WHOQOL-BREF Quality of Life Measure were administered. A regression p model was estimated to identify the variables that best predict loneliness associated with old age. Loneliness-associated variables included living alone t(161.41) = 2.07; p < .040, marital status F(5, 404) = 4.52; p < .001, frequency of economic problems F(1, 408 ) = 4.86; p < .028, quality of life F(4, 405) = 7.36; p < .001, satisfaction with life F(4, 405) = 3.80; p < .005, satisfaction with social relationships F(4, 405) = 19.50; p < .001, presence of a mental disorder (t(98.70) = 2.92; p < .004), and having an anxiety disorder (t(51.11) = 2.19; p < .033). The results presented in this paper highlight some predictors of loneliness in older people that could be useful in intervention, to minimize harmful conditions that can lead to loneliness in people over 65.


Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein.
The MDM2 oncoprotein has transforming potential that can be activated by overexpression, and it represents a critical regulator of the p53 tumor suppressor protein. To identify other factors with a potential role in influencing the expression and/or function of MDM2, we utilized a yeast two-hybrid screening protocol. Here we report that MDM2 physically interacts with a structurally related protein termed MDMX. The results obtained in these studies provide evidence that C-terminal RING finger domains, contained within both of these proteins, play an important role in mediating the association between MDM2 and MDMX. The interaction of these proteins interferes with MDM2 degradation, leading to an increase in the steady-state levels of MDM2. MDMX also inhibits MDM2-mediated p53 degradation, with subsequent accumulation of p53. Taken together, these data indicate that MDMX has the potential to regulate the expression and function of the MDM2 oncoprotein.


With Fearful Eyes: Exploring Relatives' Experiences With Out-of-Hospital Cardiac Arrest: A Qualitative Study.
Out-of-hospital cardiac arrest (OHCA) imposes significant consequences for a family, but little is known about relatives' experiences. Our aim was to explore relatives' experiences with the OHCA and the following months after. A qualitative approach using phenomenological-hermeneutic methodology was applied. Data consisted of semistructured interviews with 12 relatives of OHCA survivors. We analyzed data based on Paul Ricoeur's theory of interpretation. Relatives experienced OHCA as an abrupt and stressful event filled with imposing concerns for the cardiac arrest survivor. Relatives were fellow sufferers confronted with the possibility of bereavement, watching from the sideline with fearful eyes. After the OHCA, relatives experienced a troubled time with anxiety and edginess, monitoring the survivor for signs of a new cardiac arrest and trying to adapt to a new normality. Relatives' previous identities and positions within their families were disrupted. Relatives were challenged with the OHCA and the trajectory after it, experiencing a high level of distress and anxiety. Relatives took on an immense responsibility, always watching the survivor for potential symptoms of a new cardiac arrest. The cardiac arrest and the survivor's possible cognitive impairments gave rise to assuming a new authority as a relative. We advocate for a new family approach to relatives, acknowledging relatives' stress and central role in supporting cardiac arrest survivors.


Jaccoud's-type arthropathy: an association with sarcoidosis.
We describe a patient with sarcoidosis involving the lungs, muscles and tendons of the forearms who developed Jaccoud's-type arthropathy of the hands. This is the first reported case to the best of our knowledge of sarcoidosis associated with this type of arthropathy.


[Historical aspects of the problem of work capacity evaluation].
This article addresses one of the as yet unresolved issues pertaining to forensic medical examination of certain health problems, namely the absence of an accurate universally accepted approach to the interpretation of the term "working capacity". Historical prerequisites for the evolvement of such notions as "economic criterion" and "disability percentage tables" are discussed with special reference to the estimation of the degree of harm to human health. Analysis of the literature data is used to compare different points of view of the problem and ascertain their validity.


The Thirty-First Year Journey, the Journal of the Korean Academy of Child and Adolescent Psychiatry.
The Journal of the Korean Academy of Child and Adolescent Psychiatry (JKACAP) has had a 31 year-long history, sharing research and reviews of children and adolescents' mental health to promote voluntary participation and communication of the members of this society. Here, we have reviewed the detailed history of the journal from the perspective of developmental progression of JKACAP and discussed the direction of further development. We reviewed the journey of the journal by focusing on the effort it took to take the journal to a global standard, and discussed the future direction of progress of JKACAP, based on the opinions raised at the Editor-in-Chiefs' reunion. JKACAP has just stepped on the path to globalization by being indexed in Emerging Sources Citation Index, PubMed Central, and Scopus. It is time to progress to another dimension, by acknowledging and overcoming more complicated issues, such as augmenting impact of the journal, expanding domains of interdisciplinary collaboration, and more global cooperation.


1H NMR studies of human lysozyme: spectral assignment and comparison with hen lysozyme.
Complete main-chain (NH and alpha CH) 1H NMR assignments are reported for the 130 residues of human lysozyme, along with extensive assignments for side-chain protons. Analysis of 2-D NOESY experiments shows that the regions of secondary structure for human lysozyme in solution are essentially identical with those found previously in a similar study of hen lysozyme and are in close accord with the structure of the protein reported previously from X-ray diffraction studies in the crystalline state. Comparison of the chemical shifts, spin-spin coupling constants, and hydrogen exchange behavior are also consistent with closely similar structures for the two proteins in solution. In a number of cases specific differences in the NMR parameters between hen and human lysozymes can be correlated with specific differences observed in the crystal structures.


Actinomyces meyeri causing disseminated actinomycosis in the presence of concurrent bronchogenic carcinoma.
We describe the presentation of a 72-year-old woman with concurrent diagnoses of lung adenocarcinoma in conjunction with disseminated Actinomyces meyeri infection; a rare pathogen which can mimic lung cancer both symptomatically and radiologically. The patient was found to have a pelvic mass initially presumed to be cervical metastases-later confirmed to be of xanthogranulomatous inflammatory origin following transvaginal ultrasound-guided biopsy. The pathogenic cause, identified following pleural aspirate, being a fully sensitive A. meyeri infection; treated with prolonged course amoxicillin.


Critical role of PI3K/Akt/GSK3β in motoneuron specification from human neural stem cells in response to FGF2 and EGF.
Fibroblast growth factor (FGF) and epidermal growth factor (EGF) are critical for the development of the nervous system. We previously discovered that FGF2 and EGF had opposite effects on motor neuron differentiation from human fetal neural stem cells (hNSCs), but the underlying mechanisms remain unclear. Here, we show that FGF2 and EGF differentially affect the temporal patterns of Akt and glycogen synthase kinase 3 beta (GSK3β) activation. High levels of phosphatidylinositol 3-kinase (PI3K)/Akt activation accompanied with GSK3β inactivation result in reduction of the motor neuron transcription factor HB9. Inhibition of PI3K/Akt by chemical inhibitors or RNA interference or overexpression of a constitutively active form of GSK3β enhances HB9 expression. Consequently, PI3K inhibition increases hNSCs differentiation into HB9(+)/microtubule-associated protein 2 (MAP2)(+) motor neurons in vitro. More importantly, blocking PI3K not only enhances motor neuron differentiation from hNSCs grafted into the ventral horn of adult rat spinal cords, but also permits ectopic generation of motor neurons in the dorsal horn by overriding environmental influences. Our data suggest that FGF2 and EGF affect the motor neuron fate decision in hNSCs differently through a fine tuning of the PI3K/AKT/GSK3β pathway, and that manipulation of this pathway can enhance motor neuron generation.


Terbinafine-induced subacute cutaneous lupus erythematosus.
Nearly 10% of lupus erythematosus (LE) are drug induced. More than 60 different drugs are involved in iatrogenic LE. We report herein 3 cases of terbinafine-induced LE. Three patients receiving terbinafine for a suspected dermatophytic infection developed a subacute cutaneous LE, within 7 weeks following terbinafine introduction. The patients' medical history included sicca syndrome, lung carcinoma and Kikuchi disease, respectively. Clinical remission occurred within 15 weeks following terbinafine withdrawal. Sixteen cases of terbinafine-induced LE have been previously reported, including 13 women. The median age was 54 years. Prior autoimmunity was reported in 10 cases, including 5 pre-existing LE. The median delay between terbinafine introduction and LE onset was 5 weeks. The median time until clinical recovery following terbinafine withdrawal was 8 weeks. Terbinafine should be prescribed only in patients with proven dermatophytosis. We recommend cautious monitoring in patients with pre-existing autoimmunity. The diagnosis of terbinafine-induced LE should lead to the immediate and definitive withdrawal of the drug.


Use of immunocytochemical techniques in canine melanoma.
The staining patterns of the monoclonal antibodies S-100 and Melan-A in canine melanoma were assessed based on cytological specimens of six canine melanomas (four benign, two malignant). In addition, eight regional lymph nodes of the two dogs with malignant melanomas were stained using these markers. For reference, all specimens were also evaluated immunohistochemically using S-100 and Melan-A. To assess the immunocytochemical specificity of both antibodies, various canine tumours and normal tissues were stained. The immunocytochemical staining results of the canine melanomas and the regional lymph nodes showed high conformity with the immunohistochemical reactivity patterns for S-100 and Melan-A. The specificity of Melan-A was higher compared with S-100. Melan-A, in particular, may be helpful for the cytological diagnosis of canine melanoma.


Colorectal adenocarcinoma in children and adolescents: a report of 8 patients from Zaria, Nigeria.
Colorectal adenocarcinoma is predominantly a disease of the old and less than 1% of patients are below 20 years in most reports. Though increasingly younger patients are seen in Africa, most reports indicate that the disease is extremely rare in children and adolescents. This is a report of 8 patients below 20 years managed for colorectal adenocarcinoma in a 10-year period in Zaria, Nigeria. They represented 16.3% of all cases of colorectal adenocarcinoma seen at the institution, an incidence higher than that in other parts of Africa and developed countries. All the tumours were in the rectosigmoid region and are accessible to digital rectal examination and proctosigmoidoscopy. The histology was mucinous adenocarcinomas in 6 patients, 5 of who had a Duke's stage C or D disease and well-differentiated in 2 (Duke's stage B and C respectively). Haemorrhoids was found in association in 2 patients and schistosoma mansoni in one and were responsible for delay in referral and diagnosis. Only palliative treatment could be offered in most patients due to advanced disease. Three patients died within 7 months and one after 2 years from their disease. One patient died from sepsis following surgery. The outcome in 3 patients could not be ascertained. It is emphasized that children and adolescents with rectal bleeding must have digital rectal examination and proctosigmoiscopy as this is the only hope of making an early diagnosis.


Ocular injuries caused by airsoft guns - ten-year experience.
The study describes ocular injuries caused by airsoft guns pellets, type of these injuries and their incidence in different age groups. This is a retrospective review of medical charts of patients who were hospitalized due to airsoft guns ocular injuries in ten-year period (from 2000 to 2009). Patient's age, gender, duration of hospitalization, type of treatment and initial and final visual acuity were analyzed. Overall 92 patients with ocular injuries caused by airsoft gun pellets were hospitalized in ten-year period. In all patients only one eye was injured and there were 72 (78.3%) male patients. Injuries involved ocular adnexa, anterior and posterior segment of the eye. On initial examination 41 (44.6%) patients were presented with subconjunctival hemorrhages, 42 (45.6%) with corneal abrasion, 42 (45.6%) patients had corneal edema, 6 (6.5%) had traumatic mydriasis, 90 (97.8%) patients exhibited hyphema, 10 (10.9%) iridodialysis, in 27 (29.3%) patients high intraocular pressure (IOP) was measured, one patient had subluxation of intraocular lens (IOL) and one patient had traumatic cataract. Posterior segment findings included vitreous hemorrhage in 3 (3.3%) patients, retinal hemorrhage in 15 (16.3%) patients, retinal edema in 35 (38.0%) patients and one patient had globe rupture. Average duration of hospitalization was 5.7 days (range from 1 to 18 days). Three patients (3.3%) required eye surgery, eight patients (8.7%) had anterior chamber washout while rest of the patients were conservatively managed. Visual acuity at hospital release was significantly improved comparing to initial visual acuity, ranging from counting fingers at 1 meter to 20/60 in 7 (8.6%) patients, from 20/50 to 20/30 in 13 (16.0%) patients and from 20/25 to 20/20 in 61 (75.3%) patients. In 11 patients testing the visual acuity was not possible because of their young age. Injuries attributed to airsoft guns were confined mostly to anterior segment. There was also high percentage of severe posterior segment trauma requiring hospital admission. The most important factors in preventing such injuries are restricting access to airsoft guns, especially to minors, as well as mandatory use of protective equipment such as protective eyeglasses.


Proof of principle for inversion of vector sensor array data.
Acoustic data collected from a 22 m long horizontal line array with elements comprised of omni-directional hydrophone sensors co-located with acceleration vector sensor triplets are analyzed for seabed geo-acoustic information. Broadband and continuous wave tone data were recorded from the passage of a surface vessel source, the R/V Montague, in an August 2006 experiment conducted in Monterey Bay. The water depth at the array and along the source track was approximately 85 m. Simultaneous inversions for source track and geo-acoustic parameters were performed with 18 tones from the 62-415 Hz tone data for source ranges 0.5-2.0 km. The efficacy of inversions with vector sensor data is demonstrated by the fact that data from vector sensor acceleration components parallel to the array line of bearing produced inversion solutions approximately identical to the solutions obtained from the inversion of data for the same tones from the hydrophone array components. In addition the source spectra derived from these inversions are in nominal agreement with the source spectra obtained from an independent measurement.


[Immunohematologic study and transfusion approach to patients with public antibodies].
To analyze the different immunohematologic studies required to identify anti-red cell antibodies directed against high incidence antigens and comment the best tranfusion management. Five patients with suspected anti-red cell alloantibodies directed against high frequency antigens are reported. After a positive antibody screening test (AST), an agglutination test with a commercial panel of 24 red cells was performed. Red cells were treated with proteolytic enzymes and AET to try to identify the circulating antibody. However, it was necessary to send the samples to reference laboratories for definitive identification. In order to evaluate the haemolytic potential of the antibody serum samples were treated with DTT and immunoglobulin subtype was studied with the capillary agglutination test. Finally, we analyze the half life of Cr51 labelled red cells. To obtain compatible blood for transfusion, autologous transfusion and cross-match with blood from direct relatives were performed. AST was positive in every case. A decrease in the agglutination test was observed after ficin treatment in two patients, and an increase in the remaining. The treatment of red cells with ZZAP and AET resulted in a decrease of agglutination in three cases and an increase in the remaining two. Specificity of the antibodies was as follows: anti-Cellano (two cases), anti-Ku (one case) and anti-Yta (two cases). Anti-Kell antibodies were IgG1 and anti-Cartwright antibodies were IgG4. One patient was transfused with autologous blood alone, another patient received compatible blood from direct relatives. A third patient was transfused both with autologous and allogeneic compatible blood. The fourth patient did not need red cell transfusion and, finally the last patient had to be transfused with incompatible blood but no postransfusion haemolysis was observed. In patients with anti-red cell antibodies against high-frequency antigens, red blood cells treatment with proteolytic enzymes (ZZAP, ficin) and AET are useful techniques to approach to their identification. Beside this, the study of type and subtype of Ig are necessary to know the haemolytic activity of the antibody. Regarding the transfusional management, autologous transfusion, crossmatch with blood from direct relatives and cryopreservation of compatible blood are the most adequate attitudes to cover future needs.


[Treatment of life-threatening arrhythmias in patients with chronic heart failure].
Several proven medical therapies such as beta-blockers and angiotensin converting enzyme inhibitors play important roles in preventing sudden death of patients with heart failure. Therapy with amiodarone and therapy with implantable cardioverter defibrillator (ICD) have developed specifically to prevent sudden death by life-threatening arrhythmias. But recently many large-scale clinical trials have proved that ICD therapy improves prognosis of patients with heart failure better than amiodarone therapy. Because ICD is not a treatment to prevent the occurrence of ventricular arrhythmias, it may not necessarily improve quality of life of patients. In that respect catheter ablation may play a role in preventing life-threatening arrhythmias.


B(E2) values in 150Nd and the critical point symmetry X(5).
Lifetimes of states in 150Nd were measured using the recoil distance method following Coulomb excitation of 150Nd by a 132 MeV 32S beam. The experiment was performed at the Yale Tandem accelerator, employing the SPEEDY gamma-ray detector array and the New Yale Plunger Device. Reduced transition probabilities in 150Nd are compared to the predictions of the critical point symmetry X(5) of the phase/shape transition that occurs for the N = 90 rare earth isotones. Very good agreement was observed between the parameter-free (apart from scale) X(5) predictions and the low-spin level scheme of 150Nd, revealing this as the best case thus far for the realization of the X(5) symmetry.


Increased expression of interleukin-8 and aminopeptidase N by cell-cell contact: interleukin-8 is resistant to degradation by aminopeptidase N/CD13.
In rheumatic joints, high concentrations of interleukin-8 (IL-8) have been measured in synovial fluid and in pannus tissue. In both locations aminopeptidase N (APN)/CD13, an exopeptidase with reported activity towards IL-8 is also present. The surprising stability of IL-8 in the presence of an alleged IL-8-degrading peptidase prompted us to undertake the present study. Cocultivation of fibroblast-like synoviocytes (SFC) with T cells or with T lymphocytic cell membranes, or of T cells with SFC cell membranes, all resulted in increased IL-8 mRNA expression and IL-8 secretion into the medium, and an increase of APN expression on lymphocytes. IL-8 degradation was monitored by Western blots and HPLC. IL-8(72), as a partially processed form, was used throughout this study since it is abundant in tissues and has increased biological activity in comparison to IL-8(77). Thus its degradation/inactivation is considered of high biological significance. Whereas trypsin as a positive control rapidly degraded IL-8, we did not see any IL-8 degradation, either by a variety of soluble APNs, by leucine aminopeptidase or by APN expressed on the surface of SFC, or on ECV304 cells transfected with an APN expression vector. The much more sensitive HPLC technique resulted in negative results as well.


Non operative management of renal gunshot wounds.
To analyze the experience of nonoperative management (NOM) of renal injuries caused by a firearm projectiles (FAP) in the right thoraco-abdominal region in patients with hemodynamic stability and no signs of peritoneal irritation, highlighting the assessment of the safety of this approach. This was a prospective study with patients sustaining injuries by FAP in the right thoraco-abdominal region and kidney lesions, treated at the João XXIII Hospital (FHEMIG) in Belo Horizonte, from January 2005 to December 2012. Inclusion criteria were: hemodynamic stability, renal morphofunctional study by CT and no signs of peritoneal irritation. A total of 128 patients met the inclusion criteria of the protocol and underwent NOM for right thoraco-abdominal injury by FAP. Of these, 37 (28.9%) had renal injuries. Trauma indexes: RTS 7.8, ISS16, and TRISS 99%. Lesions grade II and grade III were the most frequent. The most commonly associated intra-abdominal injury was of the liver, present in 81.1% of cases. Two patients (5.4%) had failed nonoperative treatment. The nonoperative treatment of such renal lesions, when properly indicated, has a high success rate, low complication rate and increases the chance of renal preservation. It is safe for well-selected patients in trauma centers with adequate infrastructure, experienced professionals and use of a specific protocol.


Total regioselective control of tartaric acid.
An efficient strategy to synthesize tartaric acid building blocks for totally regioselective transformations or derivatizations was disclosed. Starting from l-tartaric acid or l-dimethyl tartrate, respectively, we obtained type I and II building blocks with orthogonal sets of protecing groups (4-8 steps, 38-56% overall yield).


Effect of arterial carbon dioxide tension on the duration of action of atracurium.
The duration of action of atracurium was studied in two groups of patients. In group I (n = 15), patients' lungs were hyperventilated to a mean PaCO2 of 3.3 kPa and in group II (n = 15) lungs were ventilated to maintain a mean PaCO2 of 5.3 kPa. Anaesthesia was maintained using an infusion of propofol. The time taken to return to a T1 twitch height of 10% of control was measured following each incremental dose of atracurium 0.15 mg kg-1. It was found that the duration of action of atracurium was significantly (P less than 0.0005) shorter in the hypocapnic group.


Single-staged vs. two-staged implant placement in vertically deficient alveolar ridges using bone ring technique - Part 2: implant osseointegration.
The aim of this study was to evaluate the osseointegration of implants placed in a single-staged compared to two-staged procedure using bone ring technique. In this study were used standardized, vertical alveolar bone defects in dogs. In the test group, dental implants (Straumann BL® , Basel, Switzerland) were inserted simultaneously with bone ring technique. As control group served implants inserted 6 months following grafting. Implants of both groups were left for an osseointegration period of 3 and 6 months. The peri-implant bone loss and bone-to-implant contact within the bone ring and native bone were analyzed morphometrically. An explorative statistical analysis was performed. The peri-implant bone level remained relatively stable within groups and between groups per given time period. Most of bone apposite on the implant surface in two groups was composed of newly formed bone. A nonparametric analysis of variance (ANOVA) revealed no significant advantage for two-staged implant placement for new and total bone, except for residual bone (P = .0084). Furthermore, two groups of implants performed similarly in bone ring and in native bone throughout the observation period. In terms of osseointegration, both techniques are likely equally efficient in the present defect model. The single-staged implant placement with cortical bone grafts warrants further documentation in clinical studies.


Lipid peroxidation may predict restenosis after coronary balloon angioplasty.
The present study assessed whether lipid peroxidation in plasma might predict restenosis after coronary balloon angioplasty. A total of 87 patients, who had undergone successful coronary balloon angioplasty using standard techniques, were enrolled. Fasting blood samples before the intervention were measured for plasma levels of thiobarbituric acid reactive substances (TBARS, an indicator of lipid peroxidation). Angiography was carried out before and 15 min after angioplasty, and at follow-up (4 months after angioplasty), and evaluated using a quantitative approach. There were 23 patients with restenosis (group R) and 64 patients without restenosis (group N) after coronary balloon angioplasty. The plasma TBARS level (mean+/-SEM) of 4.3+/-0.1 micromol/L in group R was significantly higher than that of 3.2+/-0.1 micromol/L in group N (p<0.01). There were no significant differences in other parameters, including plasma lipid levels, between the 2 groups. The plasma level of TBARS positively correlated with lumen loss of the coronary artery at the time of follow-up angiography (r=0.57, p<0.01). Our results suggest that oxidative stress contributes to restenosis and indicate that an elevated plasma level of TBARS may be a reliable predictor of restenosis.


Evolution of fibrosis during HCV recurrence after liver transplantation--influence of IL-28B SNP and response to peg-IFN and ribavirin treatment.
The IL-28 gene is associated with sustained viral response (SVR) after treatment with peg-IFN and ribavirin in liver transplant recipients with chronic hepatitis C genotype 1 infection. We analysed the importance of recipient and donor IL-28B genotype for response to treatment and fibrosis progression in 54 liver transplant recipients. Fibrosis stage (F) was defined as mild when F≤2 and severe when F≥3 in a liver biopsy or according to liver elasticity analysis. We found a significantly lower prevalence of IL-28B SNP CC in the recipients (22%) than in the donors (67%), P<0.0001. SVR was seen in 61% of the recipients with mild and 27% with severe fibrosis pretreatment, P=0.01. Recipients with IL-28 CC and non-CC had mild fibrosis in 64% and 38% prior to treatment, P=0.13. At follow-up, after treatment, significantly more recipients with CC had mild fibrosis than non-CC recipients (75% versus 32%, P=0.0072), and all with CC and SVR had mild fibrosis. The strongest baseline factor predicting SVR was genotype. Hence, 13/19 (68%) genotype non-1 patients reached SVR versus only 9/35 (26%) genotype 1 patients, P=0.0022. In summary, we found that liver transplant recipients with IL-28B CC tended to have less advanced fibrosis prior to and significantly less after SOC treatment and that all recipients with IL-28B CC who achieved SVR had mild fibrosis at follow-up. A significantly higher SVR rate was achieved in recipients with mild than severe fibrosis pretreatment and with genotype non-1 than 1 infection. Our findings indicate that treatment for post-transplant HCV recurrence should be offered before advanced fibrosis is seen in the recipient.


Heteromerization Modulates mu Opioid Receptor Functional Properties in vivo.
Mu opioid receptors modulate a large number of physiological functions. They are in particular involved in the control of pain perception and reward properties. They are also the primary molecular target of opioid drugs and mediate their beneficial analgesic effects, euphoric properties as well as negative side effects such as tolerance and physical dependence. Importantly, mu opioid receptors can physically associate with another receptor to form a novel entity called heteromer that exhibits specific ligand binding, signaling, and trafficking properties. As reviewed here, in vivo physical proximity has now been evidenced for several receptor pairs, subsequent impact of heteromerization on native mu opioid receptor signaling and trafficking identified and a link to behavioral changes established. Selective targeting of heteromers as a tool to modulate mu opioid receptor activity is therefore attracting growing interest and raises hopes for innovative therapeutic strategies.


In vitro activity of S-(3,4-dichlorobenzyl)isothiourea hydrochloride and novel structurally related compounds against multidrug-resistant bacteria, including Pseudomonas aeruginosa and Burkholderia cepacia complex.
The aim of this study was to establish the antimicrobial activities of S-(3,4-dichlorobenzyl)isothiourea hydrochloride (A22) and a series of structurally related compounds against multidrug-resistant (MDR) bacteria. The minimum inhibitory concentrations (MICs) of 21 compounds were determined against 18 strains of pathogenic bacteria in addition to Pseudomonas aeruginosa (n=19) and Burkholderia cepacia complex (BCC) (n=20) isolated from the sputa of cystic fibrosis patients. Selected compounds were tested against further isolates, including P. aeruginosa (n=100), BCC (n=12) and Stenotrophomonas maltophilia (n=19). The interaction of S-(4-chlorobenzyl)isothiourea hydrochloride (C2) in combination with conventional antimicrobials was examined against 10 P. aeruginosa strains. Selected compounds were also tested against Enterobacteriaceae producing NDM-1 carbapenemase (n=64) and meticillin-resistant Staphylococcus aureus (MRSA) (n=37). Of the 21 compounds, 14 showed antimicrobial activity that was generally more pronounced against Gram-negative bacteria. Against P. aeruginosa, the most active compound was C2 [MIC for 50% of the organisms (MIC(50))=32μg/mL]. This compound was also the most active against BCC, with all isolates inhibited by 64μg/mL. For all ten strains of P. aeruginosa subjected to combination testing with C2 and conventional antimicrobials, a bactericidal effect was achieved with at least one combination. C2 and A22 both showed strong activity [MIC for 90% of the organisms (MIC(90))=4μg/mL] against Enterobacteriaceae that produced NDM-1 carbapenemase. Finally, S-(4-chlorobenzyl)-N-(2,4-dichlorophenyl)isothiourea hydrochloride showed good activity (MIC(90)=8μg/mL) against MRSA. This work establishes the activity of isothiourea derivatives against a broad range of clinically important MDR bacteria.


Association of bioelectric impedance analysis body composition and disease severity in COVID-19 hospital ward and ICU patients: The BIAC-19 study.
The current severe acute respiratory syndrome coronavirus 2 pandemic is unprecedented in its impact. It is essential to shed light on patient characteristics that predispose to a more severe disease course. Obesity, defined as a BMI>30 kg/m2, is suggested to be one of these characteristics. However, BMI does not differentiate between fat mass and lean body mass, or the distribution of fat tissue. The aim of the present study was to assess the body composition of COVID-19 patients admitted to the ward or the ICU and identify any associations with severity of disease. We performed an observational cross-sectional cohort study. Bioelectric impedance analysis was conducted amongst all confirmed COVID-19 patients admitted to the ward or ICU of our hospital in the Netherlands, between April 10 and 17, 2020. Body water measurements and derived values were recalculated to dry weight, using a standard ratio of extracellular water to total body water of 0.38. Data were compared between the ward and ICU patients, and regression models were used to assess the associations between baseline characteristics, body composition, and several indicators of disease severity, including a composite score composed of mortality, morbidity, and ICU admission. Fifty-four patients were included, of which 30 in the ward and 24 in the ICU. The mean age was 67 years (95%-CI 64-71), and 34 (63%) were male. Mean BMI was 29.7 (95%-CI 28.2-31.1) kg/m2 and did not differ between groups. Body composition values were not independently associated with disease severity. In multiple logistic regression analyses, a low phase angle was associated with COVID-19 severity in the composite score (OR 0.299, p = 0.046). We found no significant associations between body composition, including fat mass, visceral fat area, and fat-free mass, and disease severity in our population of generally overweight COVID-19 patients. A lower phase angle did increase the odds of severe COVID-19. We believe that factors other than body composition play a more critical role in the development of severe COVID-19.


Function of dynein in budding yeast: mitotic spindle positioning in a polarized cell.
Cytoplasmic dynein is a microtubule motor that powers minus-end-directed motility in a variety of biological settings. The budding yeast, Saccharomyces cerevisiae, has been a useful system for the study of dynein, due to its molecular genetics and cell biology capabilities, coupled with the conservation of dynein-pathway proteins. In this review we discuss how budding yeast use dynein to manipulate the position of the mitotic spindle and the nucleus during cell division, using cytoplasmic microtubules, and we describe our current understanding of the genes required for dynein function. Cell Motil. Cytoskeleton 2009. (c) 2009 Wiley-Liss, Inc.


Psychogenic vomiting complicated by marijuana abuse and spontaneous pneumomediastinum.
This case illustrates an unusual physical sequel of psychogenic vomiting. A 22-year-old man with a picture of psychogenic vomiting and marijuana use developed the complications of a pneumomediastinum and subcutaneous emphysema. Therapy included gradual exposure to anxiety provoking stimuli, psychotropics to reduce vomiting and psychotherapeutic exploration of family relationships. The patient's vomiting and physical state resolved without complication. Follow-up at 12 months revealed continued improvement with occasional less severe vomiting. Psychogenic vomiting as a manifestation of anxiety can result in serious physical and psychological sequelae. This patient's desperate attempts to control such vomiting complicated the picture. Successful short term intervention included the use of several treatment modalities.


Impact of advanced maternal age on maternal and neonatal outcomes in preterm birth.
The aim of this study was to investigate the influence of advanced maternal age on the maternal and neonatal outcomes of preterm pregnancies. The characteristics of patients admitted to the Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University between January 2015 and March, 2019 were retrospectively reviewed. The maternal and neonatal outcomes were compared between advanced maternal age group (≥ 35 years) and younger age group (18-34 years). Statistical analysis was performed by applying the SPSS software. The study population consisted of 986 pregnancies with preterm delivery and 1094 liveborn preterm infants. Multivariate analyses demonstrated that mothers of advanced age were more likely to suffer iatrogenic preterm birth, placenta previa, preeclampsia, gestational diabetes mellitus and postpartum hemorrhage, but less likely to suffer multiple gestation. In terms of neonatal outcomes, advanced maternal age was associated with a decreased rate of low birthweight in an adjusted model without multiple gestation. However, with multiple gestation included in the adjusted model, advanced maternal age was only associated with an increased rate of hyperbilirubinemia. Advanced maternal age was a risk factor for adverse pregnancy outcomes including iatrogenic preterm birth, placenta previa, preeclampsia, gestational diabetes mellitus, postpartum hemorrhage, and a protective factor for multiple gestation. Regarding neonatal outcomes, advanced maternal age was related to a decreased rate of low birthweight or an increased rate of hyperbilirubinemia depending on the adjustment for multiple gestation.


Conjunctival Blue Naevus in an Anophthalmic Socket.
To describe an unusual brown pigmented lesion of the conjunctiva in an anophthalmic socket in a 16-year-old male. A 16-year-old male patient presented with socket irritation whilst wearing an artificial eye due to meibomian gland dysfunction. An area of flat, subepithelial, dark brown pigmentation with irregular and indistinct borders on the bulbar conjunctiva of the anophthalmic socket was seen. The patient believed it had been present for at least 2 years. His past ocular history was of childhood trauma to the right eye at the age of 9 years, and he underwent primary enucleation and hydroxyapatite orbital implant insertion at that time. Unfortunately, the implant extruded and was removed a year later. An incisional biopsy of the pigmented lesion showed a conjunctival, subepithelial bland spindle cell melanocytic lesion, with uniform-sized and -shaped melanosomes. Immunohistochemistry showed the cells to express Melan A and HMB45 and they were negative for CD68 and pan-cytokeratins. The features were of a common blue naevus. This is the first documentation of a post-enucleation conjunctival naevus in an anophthalmic socket. We propose a pathogenesis and suggest surveillance as there is a risk of transformation to melanoma.


Esophageal stricture induced by an ultraslim upper endoscope in a novel rabbit model of corrosive injury.
Benign esophageal strictures are regularly encountered problems in clinical practice. The management of refractory benign esophageal stricture, which fails to establish adequate food passage despite multiple dilatation sessions, has been considered challenging. Experimental animal models are essential for the development of effective treatment methods. The aim of this study was to establish a new animal model of benign esophageal stricture using rabbits. Corrosive injury of the esophagus was induced by administration of 1 ml of 1.5% sodium hydroxide in eight rabbits using an ultraslim upper endoscope equipped with a 5-Fr polytetrafluoroethylene tube and 5-Fr balloon catheter. Two weeks after corrosive injury, endoscopic examination was performed to confirm the state of the injury site. Four weeks after corrosive injury, the esophageal stricture was assessed by endoscopy and esophagography. All animals were then euthanized. Two weeks after corrosive injury, endoscopic examination showed that ulceration had been induced. Four weeks after corrosive injury, endoscopic, radiologic and gross examinations showed that esophageal stricture had been induced without complications in all animals. The esophageal lumen diameter was reduced by an average of 51.8% (range, 48.3%-57.2%), and the mean stricture length was 25.7 mm (range, 20.1-29.3 mm). Microscopic examination revealed focal ulceration and submucosal thickening secondary to fibrosis. Rabbit esophageal stricture induced by endoscopic delivery of a small amount of low-concentration sodium hydroxide is a relatively simple, safe, and reproducible animal model. This model may be useful in the development of new treatment methods for esophageal stricture.


Unique tauopathy in Fukuyama-type congenital muscular dystrophy.
Fukuyama-type congenital muscular dystrophy (FCMD) is characterized by muscular dystrophy and cortical dysgenesis of the cerebrum and cerebellum. We investigated the extent and nature of tauopathy in the brains of 7 postfetal (14-34 years of age) and 2 fetal (18- and 20-week gestational age) FCMD cases. In all postfetal cases, tauopathy was found in the areas of cortical dysgenesis in the cerebrum, in addition to predictable sites such as the hippocampus. In fetal cases, the neuropil of malformed cerebral cortex was diffusely immunostained with anti-aberrantly phosphorylated tau antibodies. By immunoelectron microscopy, the epitope of the antibodies was associated with microtubule-like bundles within cellular processes protruding through disrupted glia limitans. In Western blot analysis, a unique 50-kDa band of tau was detected in a fetal and a postfetal case. In addition, 3 to 4 tau bands of 60 to 68 kD, similar to tau in Alzheimer disease, were also detected in the latter. After dephosphorylation, the insoluble tau from the fetal and the postfetal cases showed highly similar immunoblotting patterns. This anomalous phosphorylation of tau may be related to the development of the cortical dysgenesis in FCMD and may shed light on the biologic function of tau in the development of the central nervous system.


[Sex behavior of women seeking hormonal contraception and women seeking induced abortion].
Using an anonymous questionnaire, the authors assessed the sexual and contraceptive behaviour of 130 applicants for induced abortions and 330 applicants for hormonal contraception. Between the two groups these main differences were found: applicants for abortion used less frequently effective contraception and used more frequently unreliable contraceptive methods. This difference was obvious during the first intercourse as well as during later life. The use of contraception in this group is more limited also as compared with the nationwide average. In the case-history of applicants for abortion previous abortions were more frequent, as well as prostitute behaviour and the prevalence of venereal diseases. As regards heterosexual behaviour the applicants for abortion and applicants for hormonal contraception did not differ substantially. According to the authors the differences between the examined groups depend more on personality traits than sexuological characteristics.


[Application research on dextran-based hydrogel and its drug controlled release].
To introduce the development of dextran-based hydrogel and its drug delivery system in drug sustained and/or controlled release, and to investigate their application in tissue engineering. Related literature was extensively reviewed and comprehensively analyzed. In recent years, great progress was made in the studies of dextran-based hydrogels and study on dextran-based intelligent materials became an investigative hotspot especially in tissue engineering. Dextran-based hydrogel is considered to be a good potential material in field of drug delivery and tissue engineering. Endowed with new characteristics, a series of intelligent biomaterials can be derived from dextran-based hydrogels, which can be widely used in biomedicine. Further study should be done on the industrialization of its interrelated production.


Serotonin and platelet activation during treatment with isradipine.
The effect of the calcium antagonist isradipine on serotonin metabolism and platelet aggregation was studied in 17 patients with essential hypertension. Platelet serotonin content, plasma serotonin, 5-hydroxyindoleacetic acid levels, and platelet aggregation [induced ex vivo by serotonin and low-density lipoprotein (LDL)] were measured after a 4-week placebo period and after 12 weeks of oral treatment with isradipine. Isradipine treatment significantly inhibited platelet aggregation induced by LDL and serotonin; the amplifying effect of LDL on serotonin-induced aggregation seen with placebo was not observed after 12 weeks of treatment with isradipine. Platelet serotonin content increased significantly during isradipine treatment; this increase was inversely related to the pretreatment content of serotonin in platelets. The results indicate that treatment with isradipine restores the impaired handling of platelet serotonin as well as the platelet response to serotonin and LDL in hypertensive patients. This effect of isradipine may be regarded as one of the cellular mechanisms of thrombovascular protection and may be of clinical significance in terms of platelet and vessel wall interaction.


Ovarian carcinomas in endometriosis: an immunohistochemical and comparative genomic hybridization study.
Malignant transformation of endometriosis, an uncommon phenomenon, can occur in gonadal and extragonadal sites and results in a wide histological range of tumors. Published series reporting malignant transformation of endometriosis have largely been confined to clinical and histopathological discussions with no studies reporting oncoprotein expression and genetic alterations. We report three cases of carcinomas arising in ovarian endometriosis: a serous cystadenocarcinoma, an endometrioid carcinoma with squamous differentiation, and a pure squamous cell carcinoma. Each tumor was analyzed immunohistochemically to compare oncoprotein expression (p53, bcl2, cyclin D1, and c-erb B2) between the tumors and the endometriotic tissue as well as with comparative genomic hybridization (CGH) to compare genetic alterations. All three tumors expressed nuclear p53, in contrast to the endometriotic tissue in which no p53 expression was found. Both endometrial and tumor tissue expressed bcl-2. No expression of cyclin D1 or c-erb B2 was detected in endometriotic or tumoral tissues. The CGH analysis revealed one or two chromosomal aberrations in each of the three tumors with gains on chromosomes 1q, 8q, and 13q, and losses on chromosome 10p. The endometriotic tissue, as expected, showed a normal genetic profile. These results suggest that p53 protein abnormalities and chromosomal aberrations may be involved in malignant transformation of endometriosis in the ovary. However, our results are limited by the number of cases examined and a definite conclusion on the pathogenesis of this process should be followed by future studies with a larger number of cases.


The Impact of Occupational Noise on Hypertension Risk: A Case-Control Study in Automobile Factory Personnel.
Many epidemiological studies have investigated the relationship between occupational noise and hypertension, but with conflicting findings. This study aimed to assess the relationship between occupational noise exposure and the risk of hypertension. A case-control study was conducted to explore hypertension predictors, and then sensitivity analysis was performed based on propensity score matching (PSM). Data were collected from participants' annual physical examinations and occupational noise exposure measurements. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analysis. A restricted cubic spline (RCS) function was used to fit the dose-effect relationship. 500 cases and 4,356 controls were included in the study. Multivariate logistic regression showed that an increase in the level of occupational noise [range 68-102 dB(A)] of 1 dB(A), corresponded to an increase in hypertension risk of 8.3% (OR: 1.083, 95% CI: 1.058-1.109). Compared to the first quartile, the risk of hypertension in the fourth quartile was 1.742 (95% CI: 1.313-2.310). After applying PSM to minimize bias, we obtained a population of 500 cases and 1,000 controls. Noise level was significantly associated with the risk of hypertension. In addition, the RCS curve showed the risk of hypertension was relatively stable until a predicted noise level of around 80 dB(A) and then started to increase rapidly afterward (P nonlinear = 0.002). Occupational noise exposure was significantly associated with hypertension risk and there was a positively correlated dose-response relationship.


The formation of egg granulomas in the spleens of mice with late Schistosoma japonicum infection alters splenic morphology.
Splenomegaly is a characteristic symptom of schistosome infection. Unlike the well known hepatic pathology of schistosomiasis, splenomegaly has received little scientific research and is generally considered to be a non-specific congestion caused by increased blood pressure within the venous sinuses. Moreover, to date, few studies have reported the deposition of schistosome eggs in the spleen. In a previous study, however, we observed that prolonged S. japonicum infections destroyed the structure of the lymphoid follicles in the spleen of mice at 8 weeks post-infection and found that eggs were frequently deposited in the spleen. These prior observations suggested a relationship between granulomas and splenic morphology which we investigate further in this study. C57BL/6 mice were infected percutaneously with twenty cercariae of S. japonicum and sacrificed at different times post-infection. The number of eggs present in the homogenates of spleens and livers was quantified by light microscopy. Splenic pathology was observed by immunohistochemistry staining of paraffin-embedded sections. At 18 weeks post-infection the infected mice were divided into two groups (granulomatous spleens and non-granulomatous spleens). Serum antibodies and cytokines in the antigen- or mitogen-stimulated lymphocyte cultures were then determined by ELISA. We found that eggs deposition in the spleens of infected mice occurred frequently but only occasionally led to granulomas formation. The lymphoid follicles within the granulomatous spleens maintained their structural integrity until 20 weeks post-infection, unlike the lymphoid follicles in spleens without egg granulomas. Mice with granulomatous spleens accompanied by lymphoid follicles exhibited a germinal center (GC)-like structure and had enhanced humoral immune responses. Splenocytes from granulomatous spleens also showed significantly elevated levels of Th2 cytokines during late infection stages. Our results highlight that lymphoid follicles, which are not completely destroyed or are re-established in the spleen, can change the local immune environment and lead to changes in the splenic morphology of mice with chronic schistosomiasis.


"Hairiness" is a Facsimile of Reorganized Cytoskeletons: A Cytopathic Effect of Coxiella burnetii.
In 1993, I reported that Coxiella burnetii transforms human B cells into hairy cells (cbHCs), the first hairy cell reported outside of hairy cell leukemia (HCL). Over last few decades, advances in molecular biology have provided evidence supporting that C. burnetii induces hairiness and inhibits the apoptosis of host cells. The present review summarizes new information in support of cbHC. C. burnetii was shown to induce reorganization of the cytoskeleton and to inhibit apoptosis in host cells. Peritoneal B1a cells were found to be permissive for virulent C. burnetii Nine Mile phase I (NMI) strains in mice. C. burnetii severely impaired E-cad expression in circulating cells of Q fever patients. B-cell non-Hodgkin lymphoma was linked to C. burnetii. Mutation of BRAF V600E was pronounced in HCL, but "hairiness" was not linked to the mutation. Risk factors shared among coxiellosis and HCL in humans and animals were reported in patients with Q-fever. Accordingly, I propose that C. burnetii induces reorganization of the cytoskeleton and inhibits apoptosis as cytopathic effects that are not target cell specific. The observed hairiness in cbHC appears to be a fixed image of dynamic nature, and hairy cells in HCL are distinct among lymphoid cells in circulation. As the cytoskeleton plays key roles in maintaining cell structural integrity in health and disease, the pathophysiology of similar cytopathic effects should be addressed in other diseases, such as myopathies, B-cell dyscrasias, and autoimmune syndromes.


Validation of the Chinese version of Addenbrooke's cognitive examination III for detecting mild cognitive impairment.
To evaluate the reliability and validity of Chinese version of Addenbrooke's Cognitive Examination III (ACE-III-CV) in the identification of mild cognitive impairment (MCI), and further investigate the optimal cutoff scores according to different age and education level. A total of 716 individuals aged from 50 to 90 years old were recruited through internet-based and print advertisements, including 431 cognitively normal controls (NC) and 285 individuals with MCI according to an actuarial neuropsychological method put forward by Jak and Bondi. Besides the cognitive screening tests of ACE-III-CV, Mini-Mental State Examination (MMSE) and Chinese version of Montreal Cognitive Assessment-Basic (MoCA-BC), all the participants underwent a battery of standardized neuropsychological tests. Validations of the ACE-III-CV, MMSE, and MoCA-BC for detecting MCI from NC were determined by Receiver operating characteristic (ROC) curves. ACE-III-CV had a good reliability (Cronbach's coefficient α = 0.807, intraclass correlation coefficients for interrater and test-retest reliability were 0.95 and 0.93). According to the area under ROC curve (AUC), ACE-III-CV and MoCA-BC showed better ability than MMSE in detecting MCI. No significant difference was found between ACE-III-CV and MoCA-BC. The optimal cutoff scores of ACE-III-CV for screening MCI were 72 for individuals with 1-9 years of education, 78 for individuals with 10-15 years of education, and 80 for individuals with more than 16 years of education. The Chinese version of ACE-III-CV is a reliable and valid screening tool for detecting MCI. The optimal cutoff scores are closely related with education level.


Paracrine factors from fibroblast aggregates in a fibrin-matrix carrier enhance keratinocyte viability and migration.
Efficient re-epithelialization of skin lesions is dependent on paracrine support from connective tissue fibroblasts. In deep skin defects, the supporting growth factor incentive is lacking. Current methods of keratinocyte transplantation with compromised attachment, spread, and cell proliferation warrant improvement and refinement. We describe here how human keratinocytes can be stimulated by matrix-embedded factors from a novel process of fibroblast activation: nemosis. Interestingly, the unique set of mediators released in this process also plays a key role in normal wound healing. To develop a system for targeted delivery of nemosis-derived paracrine effectors, herein designated as Finectra, we combined them with fibrin to establish a controlled-release gel. Keratinocytes seeded to cover this active matrix showed better adherence, outgrowth, and viability than did cells on control matrix. The matrix incorporating Finectra supported viability of both primary keratinocytes and green fluorescent protein (GFP)-labeled HaCaT cells, as evaluated by MTT assay and persistence of GFP-fluorescence. The fibrin-Finectra matrix promoted migration of keratinocytes to cover a larger area on the matrix, suggesting better wound coverage on transplantation. An inhibitor of EGFR/c-Met receptor tyrosine kinases abolished keratinocyte responses to fibrin-Finectra matrix. This matrix can thus deliver biologically relevant synergistic stimuli to keratinocytes and hasten re-epithelialization.


Mechanics of Corrugated and Composite Materials.
The main aim of this Special Issue in Materials was to collect interesting and innovative works on the mechanics of corrugated and composite materials [...].


[Spectrophotometric determination of protein content in THP-1 monocytes/macrophages - description of the method].
Proteins are the basic building block of tissue, and are part of enzymes and hormones regulating many important life processes. Changes in their concentration control the metabolic processes of the cell. Quantitative determination of the protein content is divided into indirect methods (e.g. Kjeldahl method) and direct methods (buret method, Lowry, immunoenzymatic, formol method, based on incorporation of dye in the range of ultraviolet spectrophotometry, and based on the phenomenon of selective absorption of radiation in the infrared range). One of the methods for the determination of protein content is the spectrophotometric method described by Bradford. The protein concentration assay procedure utilizes the phenomenon of formation of the dye (Coomassie Brillant Blue G-250)-protein and colour intensity is proportional to the protein content in the solution. The aim of this study was to verify the usefulness of this method for determining the protein content in THP-1 cells cultured with extracts of nettle fruit stalks (Urtica dioica L.). Aqueous and alcohol extracts at two concentrations were used. It has been shown that the spectrophotometric determination of protein content by the Bradford method is an effective and accurate method for determining the concentration of protein in THP-1 macrophages. The results indicate that this method can be recommended for the determination of the protein content in other cell cultures.


The biological basis of a universal constraint on color naming: cone contrasts and the two-way categorization of colors.
Many studies have provided evidence for the existence of universal constraints on color categorization or naming in various languages, but the biological basis of these constraints is unknown. A recent study of the pattern of color categorization across numerous languages has suggested that these patterns tend to avoid straddling a region in color space at or near the border between the English composite categories of "warm" and "cool". This fault line in color space represents a fundamental constraint on color naming. Here we report that the two-way categorization along the fault line is correlated with the sign of the L- versus M-cone contrast of a stimulus color. Moreover, we found that the sign of the L-M cone contrast also accounted for the two-way clustering of the spatially distributed neural responses in small regions of the macaque primary visual cortex, visualized with optical imaging. These small regions correspond to the hue maps, where our previous study found a spatially organized representation of stimulus hue. Altogether, these results establish a direct link between a universal constraint on color naming and the cone-specific information that is represented in the primate early visual system.