Comparison of scleral buckling and vitrectomy using wide angle viewing system for rhegmatogenous retinal detachment in patients older than 35 years.
To compare scleral buckling (SB) and pars plana vitrectomy (PPV) using a wide angle viewing system (WAVS) for uncomplicated phakic rhegmatogenous retinal detachment (RRD). The medical records of patients with uncomplicated phakic RRD were retrospectively reviewed. Eyes with pseudophakic or attached fovea were excluded. Patients treated with SB were classified as group B, and PPV using WAVS as group V. Primary success rate, visual acuity (VA), macular complications, and sustained subretinal fluid (SRF) were compared between groups. Seventy-two eyes were included in group B and 57 eyes in group V. Group B had better preoperative VA (1.38 ± 0.87 vs 1.84 ± 0.97 in LogMAR, P = 0.010), but worse final VA (0.51 ± 0.48 vs 0.30 ± 0.23, P = 0.012) than group V. The primary success rate of 94.7 % in group V was higher than 77.8 % in group B (P = 0.010). Final success rate was 100 % in both groups. There was no significant difference in macular complications between groups (P = 0.087). Sustained SRF was found in 22 eyes in group B (38.6 %), while only two eyes in group V exhibited sustained SRF (2.8 %, P < 0.001). Pars plana vitrectomy using WAVS was more efficacious than SB for treating uncomplicated phakic RRD.


Identification without manipulation: a study of the relations between object use and semantic memory.
The role of semantic knowledge in object utilisation is a matter of debate. It is usually presumed that access to semantic knowledge is a necessary condition for manipulation, but a few reports challenged this view. The existence of a direct, pre-semantic route from vision to action has been proposed. We report the case of a patient with a disorder of object use in everyday life, in the context of probable Alzheimer's disease. This patient was also impaired when manipulating single objects. He showed a striking dissociation between impairment in object use and preserved capacity to perform symbolic and meaningless gestures. To elucidate the nature of the disorder, and to clarify the relations between semantic knowledge and object use, we systematically assessed his capacity to recognise, name, access semantic knowledge, and use 15 common objects. We found no general semantic impairment for the objects that were not correctly manipulated, and, more importantly, no difference between the semantic knowledge of objects correctly manipulated and objects incorrectly manipulated. These data, although not incompatible with the hypothesis of a direct route for action, are better accommodated by the idea of a distributed semantic memory, where different types of knowledge are represented, as proposed by Allport (Allport, D. A. Current perspectives in dysphasia, pp. 32-60. Churchill Livingstone, Edinburgh, 1985).


Contribution to problems of pseudohypoaldosteronism type I in children.
Pseudohypoaldosteronism Type I may occur due to several different causes. The authors recommend distinguishing between effector and receptor disorders with regard to the diverse mode of inheritance and prognosis.


A novel PSEN1 H163P mutation in a patient with early-onset Alzheimer's disease: clinical, neuroimaging, and neuropathological findings.
We report a novel presenilin 1 gene (PSEN1) mutation (H163P) in a patient with sporadic early-onset Alzheimer's disease. Clinical, molecular, and neuropathological examinations were performed on an index patient, who presented at the age of 34 years with depression and memory disturbances. At the age of 36 years, she exhibited seizures and myoclonus, cerebellar ataxia, and Parkinsonism. A novel mutation at codon 163 was found in PSEN1, which was changed from histidine to proline. Severe atrophy was noted in the frontal and temporal lobes of the brain. A histopathological examination of the frontal cortex revealed senile plaques and severe neurofibrillary tangles. PSEN1 codon 163 could be a mutational hot spot in early-onset Alzheimer's disease, and may result in a homogeneous phenotype similar to that of other patients with codon-163 mutations; thus, widening the spectrum of PSEN1 codon-163-linked phenotypes.


Associated factors for tuberculosis recurrence in Taiwan: a nationwide nested case-control study from 1998 to 2010.
The contribution of human immunodeficiency virus (HIV) co-infection to tuberculosis (TB) recurrence is well established worldwide. We conducted this study to investigate associated factors for recurrent TB in Taiwan, which has a relatively low prevalence of HIV. A case-control study nested within a nationwide population-based cohort was performed using the Taiwan National Health Insurance (NHI) database from 1998 to 2010. Patients with notified TB were identified according to diagnosis codes and prescriptions of anti-TB drugs for more than 60 days. Recurrent TB was defined as cases being retreated for more than 60 days and 6 months after the end of previous TB episode. Four controls were randomly selected from cohort and matched to each case by observational period within a calendar year. Socio-demographic variables and comorbidities were evaluated as factors associated with TB recurrence. There were totally 760 patients being investigated (608 controls and 152 cases). During an average 5.12 years of follow-up, 3.76% of all developed recurrent TB and the incidence of TB recurrence was 734 per 100,000 person-years. About half of recurrence (55%) was notified within three years of follow-up, and most (86%) recurrences were intrapulmonary. Independent associated factors for TB recurrence included: male (odds ratio, OR: 2.23, 95% confidence interval, CI: 1.40-3.53), diabetes mellitus (DM) (OR: 1.51, 95% CI: 1.02-2.13), chronic obstructive pulmonary disease (COPD) (OR: 1.59, 95% CI: 1.08-2.36) and lower socio-economic status (p=0.001 between groups). Despite low prevalence of HIV in the Taiwanese population, the incidence of recurrent TB among Taiwanese was not less than that of other countries. Identification of subgroups such as male gender, low economic status, DM and COPD should be a high priority in TB control programs.


Effect of raloxifene on stroke and venous thromboembolism according to subgroups in postmenopausal women at increased risk of coronary heart disease.
Raloxifene, a selective estrogen receptor modulator, reduces risk of invasive breast cancer and osteoporosis, but the effect on risk for stroke and venous thromboembolism in different patient subgroups is not established. The purpose of this analysis was to evaluate the effect of raloxifene on the incidence of all strokes, stroke deaths, and venous thromboembolic events according to participant subgroups. This was a secondary end point analysis of an international, randomized, placebo-controlled clinical trial of 10 101 postmenopausal women with or at increased risk of coronary heart disease followed a median of 5.6 years. Strokes, venous thromboembolic events, and deaths were adjudicated by expert centralized committees. Strokes were categorized as ischemic, hemorrhagic, or undetermined and venous thromboembolic events were subclassified. The incidences of all strokes did not differ between raloxifene (incidence rate per 100 woman-years=0.95) and placebo (incidence rate=0.86) treatment groups (P=0.30). In women assigned raloxifene versus placebo, there was a higher incidence of fatal strokes (incidence rates=0.22 and 0.15, respectively, P=0.0499) and venous thromboembolic events (incidence rates=0.39 and 0.27, respectively, P=0.02). No significant subgroup interactions were found except that there was a higher incidence of stroke associated with raloxifene use among current smokers. In postmenopausal women at increased risk for coronary events, the incidences of venous thromboembolism and fatal stroke but not all strokes were higher in those assigned raloxifene versus placebo. Raloxifene's effect did not differ across subgroups, except that the risk of stroke differed by smoking status. Treatment decisions about raloxifene should be based on a balance of projected absolute risks and benefits.


Cytogenetics of melanoma and nonmelanoma skin cancer.
Cytogenetic analysis of melanoma and nonmelanoma skin cancers has revealed recurrent aberrations, the frequency of which is reflective of malignant potential. Highly aberrant karyotypes are seen in melanoma, squamous cell carcinoma, solar keratosis and Merkel cell carcinoma with more stable karyotypes seen in basal cell carcinoma, keratoacanthoma, Bowen's disease, dermatofibrosarcoma protuberans and cutaneous lymphomas. Some aberrations were common amongst a number of skin cancer types including rearrangements and numerical abnormalities of chromosome 1, -3p, +3q, partial or entire trisomy 6, trisomy 7, +8q, -9p, +9q, partial or entire loss of chromosome 10, -17p, +17q and partial or entire gain of chromosome 20. Combination of cytogenetic analysis with other molecular genetic techniques has enabled the identification of not only aberrant chromosomal regions, but also the genes that contribute to a malignant phenotype. This review provides a comprehensive summary of the pertinent cytogenetic aberrations associated with a variety of melanoma and nonmelanoma skin cancers.


Mental Health and Postpartum Care in California: Implications from California's Provisional Postpartum Care Extension.
California's Provisional Postpartum Care Extension (PPCE) extended Medicaid eligibility through 1 year postpartum for women enrolled in Medi-Cal with annual household incomes of 138%-322% of the federal poverty level and maternal mental health diagnoses. For this cross-sectional descriptive study, we used the 2017 Listening to Mothers in California survey of postpartum women to identify those potentially eligible for PPCE. We then sought to describe their demographic characteristics, self-reported mental health, and utilization of postpartum care and mental health services compared with those with Medi-Cal during pregnancy who did not meet PPCE eligibility criteria. Overall, potentially PPCE-eligible women comprised 6.8% of respondents. Among those who did not qualify for PPCE, the primary reason was the absence of self-reported maternal mental health symptoms. Potentially PPCE-eligible women were approximately two-thirds Hispanic/Latina and more than one-third were ages 25 to 29. The most common self-reported mental health symptom was anxiety during pregnancy (78.9%). Among potentially PPCE-eligible women, 8.4% were taking medicine for anxiety/depression postpartum and 16.0% were receiving postpartum counseling/treatment for emotional or mental well-being. Our analyses suggest that PPCE could have extended postpartum coverage eligibility for approximately 30,360 women statewide. However, our findings demonstrate how narrowly defined PPCE eligibility criteria likely excluded many postpartum women in Medi-Cal who would have been left with limited benefits or more cost-sharing under alternative coverage options. This research could inform state and federal policymakers considering other proposals to extend postpartum Medicaid eligibility.


Hemodynamic Characterization of Peripheral Arterio-venous Malformations.
Peripheral arterio-venous malformations (pAVMs) are congenital vascular anomalies that require treatment, due to their severe clinical consequences. The complexity of lesions often leads to misdiagnosis and ill-planned treatments. To improve disease management, we developed a computational model to quantify the hemodynamic effects of key angioarchitectural features of pAVMs. Hemodynamic results were used to predict the transport of contrast agent (CA), which allowed us to compare our findings to digital subtraction angiography (DSA) recordings of patients. The model is based on typical pAVM morphologies and a generic vessel network that represents realistic vascular feeding and draining components related to lesions. A lumped-parameter description of the vessel network was employed to compute blood pressure and flow rates. CA-transport was determined by coupling the model to a 1D advection-diffusion equation. Results show that the extent of hemodynamic effects of pAVMs, such as arterial steal and venous hypertension, strongly depends on the lesion type and its vascular architecture. Dimensions of shunting vessels strongly influence hemodynamic parameters. Our results underline the importance of the dynamics of CA-transport in diagnostic DSA images. In this context, we identified a set of temporal CA-transport parameters, which are indicative of the presence and specific morphology of pAVMs.


Caregivers' psychological suffering and posttraumatic growth after patient death.
This study aimed to identify the association between caregivers' psychological suffering and posttraumatic growth (PTG) after patient death. Participants were a total of 254 caregivers, including nurses, nursing assistants, social workers, and care workers. Higher psychological suffering, in terms of expanding self-consciousness, change of values, and spiritual sublimation, had a positive correlation with PTG. For nurses and nursing assistants, the change of values and spiritual sublimation had a positive correlation with PTG. For social workers, the higher self-consciousness was associated with greater PTG. For care workers, the expanded self-consciousness and lower helplessness had a positive correlation with PTG. These findings will serve as a basis for the development of supportive programs to assist caregivers in improving PTG after patient death.


Radiographic evaluation of immature traumatized incisors following different endodontic treatments.
Indirect pulp capping, pulpotomy, and apexification are three common endodontic treatments for immature traumatized incisors. They all affect tooth root development to some extent. The aim of this retrospective study was to compare the influence of these treatments on root development of immature permanent incisors following dental trauma. Twenty-one indirect pulp capping, 48 pulpotomy, and 58 apexification cases with a mean age of 8.4 ± 1.0 years and median follow up of 12 months were included. NIH ImageJ with TurboReg plug-in was used to correct angular differences between the pre-operative and recall periapical radiographs, and to calculate variations of root length, dentin wall thickness, and apical closure. Kruskal-Wallis ANOVA followed by pairwise comparisons was applied to compare the radiographic variations. The type of apical closure was assessed qualitatively and analyzed using Fisher's exact test. The apexification group had a lower trend toward apical closure than the other two groups (P < .05). It also showed thinner dentin wall thickness compared with the pulpotomy group (P = .001). There was no significant difference between pulpotomy and indirect pulp capping in the trend to apical closure (P > .05) or dentin wall thickness (P = .775). There was no significant difference in the variation of root length among the three groups (P = .06). There was a moderate correlation between the treatment and the type of apical closure (Cramer's V Coefficient = .375). Pulpotomy tended to form a normal apical constriction rather than a calcific barrier while apexification showed the opposite inclination. Indirect pulp capping had no specific inclination toward any type of apical closure. Apexification resulted in an abnormal root development mostly by affecting the dentin wall thickness and apical closure. Pulpotomy was beneficial for normal root development of immature traumatized teeth.


[Clinical and experimental study on improving cellular immunological function of uterine myoma patients by xiaoliu tablet].
To explore the effect of Xiaoliu Tablet (XLT) in treating uterine myoma (UM) and the relationship between effect and the cellular immunological function of the UM patients. Seventy-one UM patients by treatment with XLT was observed. The activities of natural killer (NK) cells of 50 patients and 30 normal women were determined. There were good effect in reducing the volume of myoma and improving the menses by XLT, especially in patients whose myoma were singly and small. The activity of NK cells of these patients (24.61 +/- 6.04%, n = 50) was significantly different from that of normal women (45.42 +/- 9.05%, n = 30), P < 0.01. There was a notable rise of NK cells of the patients (37.54 +/- 5.01%, n = 39), after the treatment of six months by XLT (P < 0.01). Improving the immunological function might be one of the mechanisms of the effect of XLT.


Temporal oscillations in neuronal nets.
A model for the interactions of cortical neurons is derived and analyzed. It is shown that small amplitude spatially inhomogeneous standing oscillations can bifurcate from the rest state. In a periodic domain, traveling wave trains exist. Stability of these patterns is discussed in terms of biological parameters. Homoclinic and heteroclinic orbits are demonstrated for the space-clamped system.


Ranitidine versus ranitidine and prazepam in the short-term treatment of duodenal ulcer--a double-blind controlled trial.
Fifty out-patients with an active, endoscopically proven duodenal ulcer were entered a double-blind trial of ranitidine + prazepam or ranitidine + placebo. Two drop-outs occurred in the prazepam group and 1 in the placebo group. After 28 days of treatment, the ulcer had healed in 95.6% of the patients on ranitidine + prazepam and 75% of the patients on ranitidine + placebo (p = 0.03). Sleepiness was the most frequent side effect, reported by 8 subjects in the prazepam group and by 1 subject in the placebo group. It is concluded that prazepam can be usefully combined with ranitidine in the short-term treatment of duodenal ulcer.


PI3Kγ controls IL-17A expression and attenuates alveolar bone loss in an experimental periodontitis model.
In this study, we investigated the modulatory effects of PI3Kγ on IL-17A expression and the progression of experimental periodontitis in vivo. Ligature-induced periodontitis was developed around the first molar of mice. Animals were treated with anti-mouse IL-17A or IPI-549 (PI3Kγ inhibitor). In addition, PI3Kγ-deficient mice (PI3Kγ-/-) were used in the study. Alveolar bone loss was measured and real-time PCR of Il17a and Rankl genes was performed. A bioinformatics analysis was carried out using the Gene Set Enrichment Analysis computational tool. Nine days after ligature placement, alveolar bone loss scores were significantly increased, with upregulation of Il17a and Rankl genes in the gingival tissues. Treatment with anti-mouse IL-17A (100 µg/mice) significantly attenuated alveolar bone loss. Mice with ligature-induced periodontitis treated with IPI-549 (3 mg/kg) or PI3Kγ-/- mice showed reduced alveolar bone loss and downregulation of Il17a and Rankl gene expression in the gingival tissues. Consistent with this, the bioinformatics analysis showed upregulation of IL17F, IL17A, IL17D, and STAT3 genes, as well as greater activation of IL-17 and PI3KCI pathways (upregulation of PIK3CG gene) in the gingival tissue of patients with periodontitis. PI3Kγ plays an important role in modulating IL-17A expression and alveolar bone loss in vivo and can be considered a promising pathway for the management of periodontal disease and the development of new therapies.


5-Aminosalicylic acid enemas: effective agent in maintaining remission in left-sided ulcerative colitis.
The efficacy of 5-aminosalicylic acid enemas in maintaining remission in left-sided ulcerative colitis was studied. Twenty-five patients in remission for at least 2 mo were randomized to receive either 1-g 5-aminosalicylic acid or placebo enemas daily and were followed up for 1 yr. Eleven of 13 patients randomized to placebo relapsed after a mean of 16 wk. Nine of 12 patients randomized to 5-aminosalicylic acid remained in remission for 1 yr, 2 others in remission withdrew by request, and 1 relapsed at 10 wk. The difference between relapse rate on 1-g 5-aminosalicylic acid versus placebo was significant (p less than 0.005). Seven patients entered the blinded trial a second time. Three of 4 patients randomized to 5-aminosalicylic acid remained in remission and 1 relapsed. Three randomized to placebo relapsed at a mean of 14 wk. One-gram 5-aminosalicylic acid enemas are safe and effective in maintaining remission in patients with left-sided ulcerative colitis.


Identification of upstream miRNAs of SNAI2 and their influence on the metastasis of gastrointestinal stromal tumors.
SNAI2, a member of the snail zinc finger protein family, plays an important role in the metastasis of several types of carcinoma. This study aims to investigate the upstream miRNAs of SNAI2 and their influence on the metastasis of gastrointestinal stromal tumors (GISTs). The expression levels of SNAI2, CDH1, and CDH2 in GISTs were determined by immunohistochemistry, and the correlations with their clinicopathologic characteristics were analyzed. Subsequently, the miRNAs involved in regulating SNAI2 expression were predicted by bioinformatics technique, screened by miRNA microarray tests, and verified by real-time PCR, dual luciferase reporter assay, and invasion assay. The influence of SNAI2 and miRNAs on the invasive ability of the GIST cells and the related mechanism were detected. SNAI2 expression significantly increased and CDH1 expression markedly decreased in the cases of GISTs with distant metastasis. Silencing of the SNAI2 gene impaired the invasiveness of GIST cells in vitro. MiR-200b-3p, miR-30c-1-3P, and miR-363-3P were verified as the upstream metastasis-associated miRNAs of SNAI2 in GISTs by miRNA microarray, real-time PCR, dual luciferase reporter assay, and invasion assay. They bound to the 3'-UTR of SNAI2, downregulated SNAI2 expression, and inhibited the invasiveness of GIST cells. SNAI2 targetedly bound to the promoter of the CDH1 gene, downregulated the expression of CDH1, and contributed to the metastasis of GISTs. SNAI2 and CDH1 correlated with the metastasis of GISTs, and silencing of the SNAI2 gene impaired the invasiveness of GIST cells. MiR-200b-3p, miR-30c-1-3P, and miR-363-3P contribute to the metastasis of GISTs in vitro by mediating the SNAI2/CDH1 axis. SNAI2 may be a potential target for the treatment of GISTs in the future.


The assessment of red cell survival in normal subjects and in patients with haemolytic disorders and ineffective erythropoiesis using the radioiron occupancy method.
A direct method for measuring red cell lifespan in vivo using the radioiron occupancy method (Dagg et al, 1972) has been applied to eight normal subjects. The mean red cell lifespan was 116 d with a range of 104-124 d. To establish the method clinically in the presence of haemolysis and ineffective erythropoiesis, 22 patients with haemolytic disease and six patients with megaloblastic and sideroblastic anaemia were studied. All 22 patients with haemolytic anaemia had shortening of the red cell lifespan, with a range from 62 to 10 d; the results were compared with red cell lifespan derived from simultaneous radiochromium studies (Bentley et al, 1974). A close agreement between the two methods was obtained (r = 0.87; P less than 0.001). To assess the validity of the method in the presence of ineffective erythropoiesis, double isotope studies were also carried out in three patients with megaloblastic anaemia and three with sideroblastic anaemia. Close agreement was again obtained between lifespan measurements obtained from radioiron occupancy data and those derived from radiochromium studies, suggesting that the presence of significant ineffective erythropoiesis does not invalidate the method. The theoretical considerations involved in the application of the radioiron occupancy method to haemolytic states are discussed.


Improving the quality of life of parents of patients with congenital abnormalities using psychoeducational interventions: a systematic review.
To identify psychoeducational interventions that target parents of children with congenital abnormalities (CA) and evaluate their impact on quality of life (QoL). The search was conducted in six electronic databases, complemented by references of the studies found, studies of evidence synthesis, a manual search of relevant scientific meetings' abstracts and contact with experts. We included primary studies on parents of children with CA that studied psychoeducational interventions versus standard care. We assessed the risk of bias using Cochrane Collaboration's tool. We included six studies focusing on congenital heart defects (CHD). They described four different psychoeducational strategies. In four studies, statistically significant differences were found. For clinical practice, we considered three interventions as more feasible: the Educational program for mothers, with a group format of four sessions weekly; CHIP-Family intervention, which includes a parental group workshop followed by an individual follow-up booster session; and WeChat educational health program with an online format. This review is the first that assesses the impact of psychoeducational interventions targeted at parents of children with CA on their QoL. The best approach to intervention is multiple group sessions. Two essential strategies were to give support material, enabling parents to review, and the possibility of an online program application, increasing accessibility. However, because all included studies focus on CHD, generalizations should be made carefully. These findings are crucial to guide future research to promote and improve comprehensive and structured support for families and integrate them into daily practice.


Experimental gynogenesis in the newt species Pleurodeles waltlii and P. poireti.
Eggs of diploid females of Pleurodeles waltlii, inseminated by genetically inactivated sperm of Salamandra salamandra, have been treated by heat-shock or increased hydrostatic pressure during the first hour of their development. The resulting viable gynogenetic individuals show different degrees of ploidy although they mostly are diploid. The use of females with a pericentric inversion as a marker chromosome allow the chromosomal constitution to be clarified. Eggs of females heterozygous for a recessive semilethal mutation (ascite caudale, ac) subjected to the same experimental treatment gave 50% ac/ac embryos. Experiments with Pleurodeles poireti gave the same results as those with P. waltlii. These observations prove that gynogenetic Urodeles can be produced in large numbers. In their offspring the detection of inherent or spontaneous recessive mutations is greatly facilitated.


Reactions of peroxynitrite with globin proteins and their possible physiological role.
It is now widely accepted that, besides their well-established function in O(2) transport, hemoglobin and myoglobin also undergo several redox reactions aimed to scavenge toxic free radicals and reactive oxygen and nitrogen species. At least some of these reactions are believed to play an important physiological role in the defense against oxidative stress. This aspect is exemplified by the recently discovered neuroglobin, a globin expressed in the brain. Rather than being considerably involved in reversible O(2) binding, neuroglobin is likely to undergo redox reactions to protect neurons against oxidative and potentially pathogenic pathways, as those operating after episodes of tissue hypoxia or ischemia. A major part of the cellular damage occurring under such conditions has been ascribed to formation of peroxynitrite, that originates from the reaction between two biologically important free radicals, nitric oxide (NO ) and superoxide. Here we review the current knowledge of the reactions of different forms of hemoglobin, myoglobin, and neuroglobin with peroxynitrite and discuss their physiological role on the basis of measured rate constants and on the probability of occurrence of these reactions in vivo.


High Thermoelectric Performance of AgSb1-xPbxSe2 Prepared by Fast Nonequilibrium Synthesis.
AgSbSe2 is a typical member of cubic I-V-VI2 semiconductors, which are known for their extremely low lattice thermal conductivity (κl). However, the low electrical conductivity of AgSbSe2, below ∼10 S cm-1 at room temperature, has hindered its thermoelectric performance. In this work, single-phase AgSbSe2 bulk samples with much higher electrical conductivity were synthesized via self-propagating high-temperature synthesis (SHS) combined with spark plasma sintering (SPS) for the first time. Pb doping through the nonequilibrium process further increases the electrical conductivity to >100 S cm-1. Furthermore, continuously increased effective mass md* can be achieved upon Pb doping because of the multiple degenerate valence bands of AgSbSe2 and the energy-filtering effect induced by in situ-formed nanodots. The simultaneous enhancement of both the electrical conductivity and Seebeck coefficient contributes to an unprecedentedly high average power factor of 6.75 μW cm-1 K-2. Meanwhile, the introduced dense grain boundaries and point defects enhance the phonon scattering and consequently suppress κl, yielding a high ZT value of 1.2 at 723 K in AgSb0.94Pb0.06Se2. This study opens a new avenue for rapid, low-cost, large-scale production of AgSbSe2-based materials and demonstrates that Pb-doped AgSbSe2 prepared via the SHS-SPS method is a promising candidate for thermoelectric applications.


α-Synuclein oligomers mediate the aberrant form of spike-induced calcium release from IP3 receptor.
Emerging evidence implicates α-synuclein oligomers as potential culprits in the pathogenesis of Lewy body disease (LBD). Soluble oligomeric α-synuclein accumulation in cytoplasm is believed to modify neuronal activities and intraneural Ca2+ dynamics, which augment the metabolic burden in central neurons vulnerable to LBD, although this hypothesis remains to be fully tested. We evaluated how intracellular α-synuclein oligomers affect the neuronal excitabilities and Ca2+ dynamics of pyramidal neurons in neocortical slices from mice. Intracellular application of α-synuclein containing stable higher-order oligomers (αSNo) significantly reduced spike frequency during current injection, elongated the duration of spike afterhyperpolarization (AHP), and enlarged AHP current charge in comparison with that of α-synuclein without higher-order oligomers. This αSNo-mediated alteration was triggered by spike-induced Ca2+ release from inositol trisphosphate receptors (IP3R) functionally coupled with L-type Ca2+ channels and SK-type K+ channels. Further electrophysiological and immunochemical observations revealed that α-synuclein oligomers greater than 100 kDa were directly associated with calcium-binding protein 1, which is responsible for regulating IP3R gating. They also block Ca2+-dependent inactivation of IP3R, and trigger Ca2+-induced Ca2+ release from IP3R during multiple spikes. This aberrant machinery may result in intraneural Ca2+ dyshomeostasis and may be the molecular basis for the vulnerability of neurons in LBD brains.


The Phys-Can observational study: adjuvant chemotherapy is associated with a reduction whereas physical activity level before start of treatment is associated with maintenance of maximal oxygen uptake in patients with cancer.
Adjuvant therapy may cause multiple sideeffects on long term health, including reduced cardiorespiratory fitness (CRF) in patients with breast cancer (1, 2). However, there is currently limited knowledge regarding the effect of different types of adjuvant cancer treatment on CRF in other cancer populations. The primary objective of the present study was to assess whether previously known correlates (age, diagnosis, initial CRF, physical activity level), type of adjuvant treatment and cancer-related fatigue were associated with changes in V ˙ O 2 max in patients with breast, prostate or colorectal cancer. Prospective study with two time points of assessment, 85 patients scheduled for adjuvant cancer treatment were included. Cardiorespiratory fitness was assessed by V ˙ O 2 max during a maximal incremental exercise test on a treadmill before start of adjuvant therapy and again six months later. Physical activity level was recorded with a physical activity monitor (Sense Wear™ Mini) at baseline as average minutes of moderate-to-vigorous intensity physical activity (MVPA) per day. Physical fatigue at baseline was reported using the Multidimensional Fatigue Inventory-20 questionaire. In multivariate linear regression analysis, 30 min higher daily MVPA at baseline was associated with a 5% higher V ˙ O 2 max at six months follow up when adjusted for adjuvant treatment (P = 0.010). Patients receiving adjuvant chemotherapy had a mean decline in V ˙ O 2 max of 10% (- 19, - 1; 95% confidence interval) compared to patients receiving adjuvant endocrine treatment (P = 0.028). Adjuvant radiotherapy, fatigue, age and diagnosis were not significantly associated with changes in V ˙ O 2 max . The results of the present study indicate that adjuvant chemotherapy is associated with a subsequent reduction in V ˙ O 2 max in patients with cancer whereas MVPA before start of adjuvant treatment is positively associated with a higher V ˙ O 2 max after end of adjuvant treatment.


Juvenile idiopathic arthritis presenting as diffuse alveolar hemorrhage at onset: A case series.
The etiology of diffuse alveolar hemorrhage (DAH) in childhood is often unknown, and it may be an early manifestation of rheumatic disease. Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in children, but DAH as an onset manifestation of JIA is rare. This study summarizes the clinical characteristics of patients with JIA presenting as DAH. We retrospectively analyzed the age of onset, clinical manifestations, imaging features, treatments, and prognosis of five cases of JIA presenting as DAH. Themedian age at DAH onset was 6 months (range, 2 months-3 years). Pallor was the most common manifestation of onset (5/5). Other symptoms included cough (2/5), tachypnea (2/5), hemoptysis (1/5), cyanosis (1/5), and fatigue (1/5). Imaging showed ground-glass opacity (GGO) (5/5), subpleural or intrapulmonary honeycombing (4/5), consolidation (3/5), interlobular septal thickening (2/5), and nodules (1/5). Anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) were positive in five children (5/5), and antinuclear antibody (ANA) was positive in four children (4/5). ANA in three children and ACPA/RF in one child were positive before the onset of joint symptoms. The median age at the onset of joint symptoms was 3 years and 9 months (2 years and 6 months-8 years). Joint symptoms were mainly characterized by joint swelling, pain, and difficulty walking, and the most commonly affected joints were the knees, ankles, and wrists. After the diagnosis of DAH, the five patients were treated with glucocorticoids. Alveolar hemorrhage was effectively controlled in three cases, but the other two patients still had anemia and poor improvements in chest imaging. After joint symptoms, the patients were treated with glucocorticoids combined with diclofenac, disease-modifying antirheumatic drugs, and biological agents. Alveolar hemorrhage was in remission, and joint symptoms were relieved in the five cases. DAH can be the first clinical manifestation of JIA, and joint involvement occurs 1-5 years later. Children with DAH who are positive for RF, ACPA, and/or ANA and have GGO accompanied by honeycombing on imaging should be concerned about their joint involvement in future.


Levetiracetam versus phenytoin in children with status epilepticus.
To compare the efficacy and safety of intravenous levetiracetam and phenytoin in status epilepticus. A prospective, randomized controlled, nonblinded study was conducted in children 1 month to 12 years of age with active seizure and with status epilepticus. A total of 104 children were randomly allocated to either group 1 (levetiracetam) or group 2 (phenytoin) on the basis of computer-generated random number table. Children already on antiepileptic drugs, very sick children with shock, impending respiratory failure, or head injury, and children hypersensitive to phenytoin or levetiracetam were excluded. Data analysis was done by IBM SPSS statistics. The mean age was 4.09 years with a male preponderance with the most common type of seizure being generalized type (74%). The seizures were controlled in all 104 patients initially within 40 min. Seizure control for 24 h was significantly better in group 1 (96%) when compared with group 2 (59.6%) (P = 0.0001). Minibolus of drug was given in 28.8% in group 1 and 46.2% in group 2 (P = 0.068). The seizure recurrence in groups 1 and 2 in the first hour was 1.9% and 5.8%, respectively (P = 0.61), whereas the recurrence between 1 and 24 h was significantly more in group 1 (34.6%) when compared with group 2 (3.8%) (P = 0.0001). The mean time to control seizure was comparable between both the groups (P = 0.71). There was no significant adverse effect in both the groups. Levetiracetam is more effective than phenytoin for seizure control for 24 h in children with status epilepticus, and it is safe and effective as a second-line therapy.


Resistance training programs on bone related variables and functional independence of postmenopausal women in pharmacological treatment: A randomized controlled trial.
Osteoporosis is a chronic disease that leads to bone fragility and is associated with fracture risks and serious consequences for mobility. To verify the effects of two linear programs of resistance training (RT) on bone mineral density (BMD), functional autonomy (FA), muscular strength and quality of life (QoL) of postmenopausal women in pharmacological treatment. Randomized controlled trial, code: RBR-6bqsw8. 52 volunteers were distributed into three groups, according to randomly parallel form: RT3times-per-week (RT3, n=20); RT2times-per-week (RT2, n=16) and control group (CG, n=16). The following assessment tools were used: bone mineral density (BMD) by dual X-ray absorptiometry, 'Latin America Group for maturity' (GDLAM) protocol for FA, 10RM test for leg exercises and the 'Osteoporosis Assessment Questionnaire' (OPAQ) for QoL. The physical activities were planned for 13 months in cycles with different intensities. A two-way ANOVA with Bonferroni post-hoc test were used. The results showed that the RT3/week was significantly more efficient (p<0.05) compared with RT2/week, including: All BMD variables, FA (Δ%=29.3%), leg press at 45° (Δ%=24.97%) and OPAQ (Δ%=20.23%). In addition, both RT3 and RT2 groups were more efficient (p<0.05) compared with CG, including: total BMD (Δ%=0.09%) and (Δ%=0.06%); FA (Δ%=7.1%) and RT2 (Δ%=3.78%); Leg press at 45° (Δ%=84.1%) and (Δ%=59.1%); keen extension (Δ%=15.28%) and (Δ%=20.37%); OPAQ (Δ%=57.61%) and (Δ%=37.37%), respectively. The study showed that both experimental groups presented favorable results for BMD, strength, FA and QoL. However, the RT3 showed the best results compared to other groups after 13 months of intervention.


An experimental study of population regulation in the salamander, Notophthalmus viridescens dorsalis (Urodela: Salamandridae).
The roles of density-dependent larval survival and cannibalism of larvae as potential mechanisms of population regulation in the newt (Notophthalmus viridescens dorsalis) were evaluated in laboratory and field experiments. In laboratory containers, adults cannibalized larvae and large larvae cannibalized smaller larvae. In artificial ponds, larval survival did not depend on initial larval density. No cannibalism could be demonstrated in the complex environment, although the experiment was powerful enough to detect an ecologically relevant difference in survival. Adult growth was negatively correlated with the final biomass of larval newts, suggesting that the two life stages competed for resources. Larval growth rates were negatively correlated with final larval density, suggesting that larvae competed with each other. The proportion of larvae that became sexually mature at age 7 months (paedomorphs and adults that skipped the eft stage) varied inversely with larval density. Therefore, the potential regulatory mechanisms identified in this study are competition within and between life stages.


Presence and timing of cat ownership by age 18 and the effect on atopy and asthma at age 28.
Asthma and allergic sensitization to cats frequently coexist, although recent studies show less atopic disease among people who had pets in infancy. However, no longterm evaluations have been performed thus far. We sought to evaluate the relationship between cat ownership at different age periods (< 18, > 18, and both periods and atopic disease at age 28. Australian school children aged 8 to 10 years were recruited in 1982 and participated in follow-up surveys until 2002. Cat ownership was defined by surveys in 1992 and 2002 as having a cat before age 18 only, after age 18 only, or in both periods of life. Health outcomes were defined at a mean age of 28.5 years. Complete data were available for 224 subjects, 50 of whom had a cat before 18 years of age only, 14 after age 18 only, and 70 in both periods. Compared with 90 subjects that never had a cat, having a cat before age 18 protected against atopy to outdoor allergens, airway hyperresponsiveness (AHR) to histamine, current wheeze, and current asthma (P < .05). In contrast, subjects who acquired their first cat after age 18 showed a trend toward higher prevalence rates for asthma symptoms and AHR (P > .10). Having had a cat before 18 years of age protects against adult asthma and atopy.


Properties of ornithine decarboxylase-antizyme from mammary gland of lactating rats.
Ornithine decarboxylase-antizyme was induced in mammary gland of fasted lactating rats by administration of 1,3-diaminopropan-2-ol. Antizyme from mammary gland showed similar chemical and kinetic behavior to that previously reported by Canellakis and co-workers for antizyme from liver [J. S. Heller, W. F. Fong, and E. S. Canellakis (1976) Proc. Natl. Acad. Sci. USA 72, 1858-1862]; specifically the inhibitor was nondialyzable, heat labile, and ribonuclease insensitive, and the inhibition was time independent, proportional to the concentration of antizyme present, and noncompetitive with respect to the substrate, ornithine. However, ornithine decarboxylase-antizyme from mammary gland eluted from Sephadex G-75 with an apparent molecular mass of 55 kDa, compared with 27 kDa, for antizyme from liver under identical conditions. The elution pattern was unaffected by the presence of high salt concentrations, indicating that the larger size was not due to macromolecular complexes. The presence of antizyme-ornithine decarboxylase complex was detected in mammary gland of untreated lactating rats fasted for 6 or 24 h, thus indicating that antizyme plays a role in the regulation of ornithine decarboxylase in mammary gland under physiological conditions.


Lessons from SARS-CoV-2 screening in a Brazilian organ transplant unit.
Protecting immunosuppressed patients during infectious disease outbreaks is crucial. During this novel coronavirus disease 2019 pandemic, preserving "clean areas" in hospitals assisting organ transplant recipients is key to protect them and to preserve transplantation activity. Evidence suggests that asymptomatic carriers might transmit the SARS-CoV-2, challenging the implementation of transmission preventive strategies. We report a single-center experience using universal SARS-CoV-2 screening for all inpatients and newly admitted patients to an Organ Transplant Unit located in a region with significantly high community-based transmission.


Quantitative Flow Cytometry-Based Assays for Measuring Constitutive Secretion.
Constitutive secretion is predominantly measured by collecting the media from cells and performing plate-based assays. This approach is particularly sensitive to changes in cell number, and a significant amount of effort has to be spent to overcome this. We have developed a panel of quantitative flow cytometry-based assays and reporter cell lines that can be used to measure constitutive secretion. These assays are insensitive to changes in cell number making them very robust and well suited to functional genomic and chemical screens. Here, we outline the key steps involved in generating and using these assays for studying constitutive secretion.


Regulon analysis identifies protective FXR and CREB5 in proximal tubules in early diabetic kidney disease.
Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus and a leading cause of kidney failure worldwide. Despite its prevalence, the mechanisms underlying early kidney damage in DKD remain poorly understood. In this study, we used single nucleus RNA-seq to construct gene regulatory networks (GRNs) in the kidney cortex of patients with early DKD. By comparing these networks with those of healthy controls, we identify cell type-specific changes in genetic regulation associated with diabetic status. The regulon activities of FXR (NR1H4) and CREB5 were found to be upregulated in kidney proximal convoluted tubule epithelial cells (PCTs), which were validated using immunofluorescence staining in kidney biopsies from DKD patients. In vitro experiments using cultured HK2 cells showed that FXR and CREB5 protected cells from apoptosis and epithelial-mesenchymal transition. Our findings suggest that FXR and CREB5 may be promising targets for early intervention in patients with DKD.


[An experimental study on the occurrence of brain edema after retrograde cerebral perfusion].
To assess the safety of retrograde cerebral perfusion, the occurrence of brain edema after this procedure was investigated. Twenty-eight adult mongrel dogs were divided into three groups that underwent the following treatments: antegrade perfusion (group 1, n = 9); retrograde perfusion alone (group 2, n = 11); or tetrograde perfusion with drugs (manuitol, thiopental sodium, and methylprednisolone; group 3, n = 8). After 90 minutes of cerebral perfusion at 20 degrees C of the pharyngeal temperature, evans blue (EB) was administered to check for disruptions of the blood-brain-barrier (BBB) and brain tissue water content was measured. Intracranial pressure after cerebral perfusion was markedly higher in group 2 than in group 1 (26.4 +/- 9.4 vs. 11.2 +/- 3.6 mmHg), and brain tissue water content was also significantly higher in group 2 than in group 1 (80.7 +/- 2.0 vs. 77.8 +/- 0.9%). These data suggested that brain edema was more prominent after retrograde perfusion than after antegrade perfusion. The extent of EB to brain tissue was greater in group 2 than in group 1 (169.8 +/- 97.7 vs. 54.7 +/- 31.5 micrograms/dl). The BBB was highly disrupted in group 2 and vasogenic edema appeared after retrograde cerebral perfusion. Maximum intracranial pressure, brain tissue water content and EB concentration were significantly lower in group 3 than in group 2, and did not differ significantly between group 3 and 1. Administration of pharmacologic agents suppressed edema formation and extravasation of EB. We conclude that 90 minutes of retrograde cerebral perfusion at 20 degrees C of the pharyngeal temperature causes brain edema and disrupts the BBB in a manner different from that associated with antegrade perfusion. Mannitol, thiopental sodium, and methylprednisolone prevent these phenomena, indicating that pharmacologic intervention may improve the safety of retrograde cerebral perfusion.


Are close contacts between astrocytes and endothelial cells a prerequisite condition of a blood-brain barrier? The rat subfornical organ as an example.
The microvessels of the rat subfornical organ (SFO) are heterogeneous: those of the caudal part lack a blood-brain barrier (BBB) unlike those of the rostral part. The astroglial environment of these microvessels has been studied by combining an immunocytochemical technique employing an anti-GFAP (glial fibrillary acidic protein) antiserum with the morphological detection of a barrier to the protein-silver complex. All the SFO microvessels are surrounded by astrocytes characterized by a tumescent aspect; however, the relative proximity between the astrocytic feet and the endothelial cells varies considerably. The capillaries provided with a barrier (rostral SFO) are contiguous with the astrocytes from which they are only separated by a basement membrane. The capillaries devoid of BBB (caudal SFO) are surrounded by a pericapillary space that keeps the astrocytes at a short distance (capillaries with a very rich vesicular endothelium) or at a long distance (capillaries with a fenestrated endothelium). The astrocytes are absent in the choroid plexus where all microvessels are fenestrated and lack a barrier. These data suggest that the astrocytes release one or more signals which in their vicinity inhibit the expression of endothelial morphological characteristics (fenestrations, vesicles) responsible for the leakage of plasmatic proteins from the blood to the cerebral parenchyma of the circumventricular organs.


Gustatory innervation and bax-dependent caspase-2: participants in the life and death pathways of mouse taste receptor cells.
In the adult mouse tongue, an average of 11% of the gustatory receptor cells are replaced each day. In investigating homeostatic cell death mechanisms in gustatory renewing epithelium, we observed that taste receptor cells were selectively immunopositive for the bcl-2 family death factor, Bax, and for the protease Caspase-2 (Nedd2/Ich1). We determined that 8-10% of the taste receptor cells of the vallate papilla were Bax positive and that 11% were Caspase-2 positive. Some of these immunopositive taste cells had apoptotic morphological defects. Within the subset of vallate taste cells immunopositive for either Caspase-2 or Bax, up to 79% coexpressed both death factors. Bax and Caspase-2 first appeared in occasional vallate taste receptor cells on the same postnatal day-the day after birth. bax null mutation markedly reduced gustatory Caspase-2 immunoexpression. These observations suggest that taste cell death pathways utilize p53, Bax, and Caspase-2 to dispose of aged receptor cells. Apart from reducing Caspase-2 expression, Bax deficiency also altered taste organ development. bax(-/-) mice had a more profusely innervated vallate papilla, which grew to be 25% longer and taller, with the mean taste bud containing more than twice the normal number of taste cells. This augmentation of taste organ development with increased innervation is complementary to the well-documented reduction in taste organ development with sparse innervation. We propose that additional taste neurons survived programmed cell death in Bax-deficient mice, thereby providing an inductive boost to vallate gustatory development.


Isolation of natural products by ion-exchange methods.
The primary goal of many natural products chemists is to extract, isolate, and characterize specific analytes from complex plant, animal, microbial, and food matrices. To achieve this goal, they rely considerably on highly sophisticated and highly hyphenated modern instrumentation. Yet, the vast majority of modern instrumentation typically found in the laboratories of natural products chemists is founded on the simple principles of intermolecular forces to achieve separation. Ion-exchange chromatography (IEC) is, at heart, the most fundamental, and strongest, of these interactions and is considered a relatively inexpensive and effective medium in which to "clean-up" a sample. Additionally, IEC offers high recoveries of key analytes and offers the ability to modify the stationary and mobile phases in order to selectively "catch and release" compounds of interest.


Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo.
Patterning of the mouse embryo along the anteroposterior axis during body plan development requires migration of the distal visceral endoderm (DVE) towards the future anterior side by a mechanism that has remained unknown. Here we show that Nodal signalling and the regionalization of its antagonists are required for normal migration of the DVE. Whereas Nodal signalling provides the driving force for DVE migration by stimulating the proliferation of visceral endoderm cells, the antagonists Lefty1 and Cerl determine the direction of migration by asymmetrically inhibiting Nodal activity on the future anterior side.


Dosage effects of Waxy gene on the structures and properties of corn starch.
The objective of this study was to understand dosage effects of the Waxy gene on the structures of amylose and amylopectin and on the properties of corn starch. Reciprocal crossing of isogenic normal and waxy corn lines was conducted to develop hybrids with different dosages (0, 1, 2, 3) of Waxy gene in the endosperm. The amylose content of starch and proportions of branch chains of DP 17-30 and extra-long branch chains (DP>100) of amylopectin were positively correlated with the Waxy-gene dosage. Proportions of short (DP<17) and long branch-chains (DP 30-80), however, were negatively correlated with the Waxy-gene dosage. The gelatinization conclusion-temperature and temperature-range of the starch were negatively correlated with the Waxy-gene dosage, indicating that amylose facilitated dissociation of the surrounding crystalline regions. These results helped us understand the function of granule-bound starch synthase I in the biosynthesis of amylose and amylopectin and impacts of Waxy-gene dosages on the properties of corn starch.


Associations of drug burden index with falls, general practitioner visits, and mortality in older people.
On a population level in people aged ≥65 years old living in New Zealand, the aim of this study is to quantify each individual's cumulative exposure to anticholinergic and sedative medicines using the Drug Burden Index (DBI) and examine the impact of DBI on fall-related hospitalisations, general practitioner (GP) visits, and all-cause mortality. The study used data extracted from Pharmaceutical Claims Data Mart (2011), National Minimum Data set (2012), Births, Death and Marriages (2012) and GP Visits (2012) for patient demographics, hospitalisations and mortality. Cumulative anticholinergic and sedative exposure was measured using the DBI. Polypharmacy was defined as greater than or equal to five medicines dispensed concurrently at any time during the study period. Amongst the study population (n = 537,387; 45% male), 43.22% were exposed to DBI drugs (95% confidence intervals (CIs) = 43.09-43.35). The odds of DBI exposure for individuals with polypharmacy are 4.92 (95%CI = 4.86-4.98) times greater than that for individuals without polypharmacy. DBI drugs were associated with fall-related hospitalisations (incidence rate ratio (IRR) 1.56, 95%CI = 1.47-1.65) and greater number of GP visits (IRR 1.13, 95%CI = 1.12-1.13). Individuals with DBI > 0 had a 1.29 times higher mortality risk (95%CI = 1.25-1.33). Polypharmacy is also associated with a higher mortality risk with a hazard ratio (HR) of 1.66 (95%CI = 1.59-1.73). Polypharmacy and exposure to DBI drugs were independently associated with fall-related hospitalisations, frequency of GP visits, and risk of mortality. On a population level, DBI may be useful as a quality indicator to guide policy to improve prescribing and optimize clinical outcomes in older people.


Mirizzi syndrome with an unusual type of biliobiliary fistula-a case report.
Gallstone obstruction of the cystic duct, resulting in chronic cholecystitis and pressure necrosis leads to the formation of biliobiliary fistula (BBF). We herein reported a case of Mirizzi syndrome (MS) with an unusual type of BBF (Corlette type I) that was successfully managed by a staged treatment strategy. The patient was diagnosed with a solitary gallstone, marked atrophy of the gallbladder, and BBF and underwent mucosal incineration of the atrophic gallbladder and simple closure, followed by extirpation of gallbladder. Although an optimal treatment strategy has not yet been established for MS with BBF because of its rarity and anatomical variations in fistulas, the current treatment strategy may be applicable. In conclusion, clinicians need to carefully diagnose and evaluate chronic cholecystitis in MS with BBF and adopt an optimal treatment strategy to avoid the complication associated with this disease.


Multilocus sequence typing analysis of Leishmania clinical isolates from cutaneous leishmaniasis patients of Iran.
Cutaneous leishmaniasis (CL) is mainly caused by L. major and L. tropica in Old World and might be represented as typical skin lesion(s) or sometimes as a spectrum of atypical manifestations. We applied multilocus sequence typing (MLST) to explore genetic variations of Leishmania strains isolated from atypical vs. typical CL patients from Iran. A PCR-sequencing was performed for seven housekeeping genes (g6pd, mpi, asat, icd, 6pgd, fh, and trys) and genetic diversity indices and phylogenetic relationships were analyzed. A total of 41 isolates of L. major (28/41) and L. tropica (13/41) from 21 (51.2%) atypical CL and 20 (48.8%) typical CL cases were included. A set of additional sequences of 41 strains of 17 species of Leishmania were retrieved from databases. Different SNP variations were detected and the highest rate of heterozygous sites was found in g6pd and 6pgd genes (6 sites) for L. tropica and in asat and 6pgd genes (7 sites) for L. major strains. All strains were clustered into 58 unique sequence types (STs) including 17 STs related to 41 strains of Leishmania of this study. Concatenated tree clustered all strains in 6 main clades (A to F) including L. major (clade D) and L. tropica (clade B) strains. Two strains of L. major (codes 28 and 42) with highest nucleotide variations were more close to L. tropica and were grouped in Clade B. All of the STs were related in clonal complexes by using eBURST with the prediction of founder genotypes. A high rate of genetic variations and heterozygocity was evident in L. tropica and L. major strains; nevertheless, there was no significant difference in the diversity of Leishmania strains between typical CL and atypical CL groups. This study represents the first successful application of MLST approach to L. tropica and L. major strains in Iran.


Cytotoxicity of silicone oil on cultivated human corneal endothelium.
To investigate the cytotoxic effects of silicone oil on the cultivated human corneal endothelial cells (CEs). We cultured human CE and passed them in insert wells that allowed the apical side of CE monolayer in contact with the silicone oil. The tested silicone oils were of two different viscosities, 1,000 and 5,000 centistoke (CS). MTS proliferation bioassay and calcein-acetoxymethyl ester (CAM)-ethidium homodimer staining were performed to evaluate cell viability after CEs were co-cultured with silicone oils for 48 h. Apoptosis of CEs was evaluated by TdT-mediated dUTP nick-end labelling (TUNEL) stain. The MTS bioassay showed that contact of silicone oil inhibited CE proliferation. The higher viscosity (5,000 CS) silicone oil suppressed cell cycling significantly more than the lower viscosity (1,000 CS) silicone oil. CAM-ethidium homodimer staining revealed CE death, 9.1+/-0.1% (1,000 CS silicone oil) and 41.6+/-0.4% (5,000 CS), but apoptosis played only minor role in silicone oil toxicity, 1.7+/-0.1% (1,000 CS silicone oil) and 9.4+/-0.1% (5,000 CS). Silicone oil is cytotoxic to cultivated human CEs. Avoiding the forward migration of silicone oil to the anterior chamber and corneal CE contact is critical in preventing silicone oil-associated keratopathy. Silicone oil should be removed as early as possible once the goal of tamponade has been achieved.


Treatment of adult acute lymphoblastic leukaemia using an intensive chemotherapy protocol.
A total of 25 evaluable adult patients with acute lymphoblastic leukaemia (ALL) were treated with an intensive chemotherapy regime modified from the L17/L17M protocol of the Sloan-Kettering Hospital. There were 18 men and 7 women; their median age was 36 years (range, 13-78). Seven cases had L1 morphology and 18, L2. The immunophenotype was common-ALL in 10, null-ALL in 9, T-ALL in 4 and B-ALL in 1. Of the 25 patients, 14 (56%) achieved a complete remission (CR). The causes of induction failure were partial remission (PR) only in 7 (28%) and hypoplastic death in 4 (16%). Of the 14 CR patients, 11 (78.6%) relapsed. Five patients developed CNS disease. The median disease-free survival and overall survival were only 9 and 13 months, respectively. As the follow-up periods of the surviving patients were short, late relapses may still occur and the overall treatment result is likely to be worse on longer follow-up. The possible causes of this disappointing result are discussed.


CRISPR Assays for Disease Diagnosis: Progress to and Barriers Remaining for Clinical Applications.
Numerous groups have employed the special properties of CRISPR/Cas systems to develop platforms that have broad potential applications for sensitive and specific detection of nucleic acid (NA) targets. However, few of these approaches have progressed to commercial or clinical applications. This review summarizes the properties of known CRISPR/Cas systems and their applications, challenges associated with the development of such assays, and opportunities to improve their performance or address unmet assay needs using nano-/micro-technology platforms. These include rapid and efficient sample preparation, integrated single-tube, amplification-free, quantifiable, multiplex, and non-NA assays. Finally, this review discusses the current outlook for such assays, including remaining barriers for clinical or point-of-care applications and their commercial development.


Friendship and dating relationships among French adolescents.
The focus of this study is to analyse, within the same population, the specificity of friendship in comparison with dating relationships among French adolescents. The subjects interviewed (63 boys and 82 girls, aged 15 to 19 years), all volunteers, were recruited from three "classic and modern" senior high schools and three vocational high schools. The data were collected by using a semi-directive interview (recorded) dealing with subjects' friendships and dating relationships. All hypotheses were confirmed: (1) Friendship between partners of the same sex constitutes the main form of privileged interpersonal relationship in early and middle adolescence. (2) The specificity of interactions between partners lies in their mode of relationship: psycho-social exchanges are more intimate between friends than between dating partners. (3) Exchanges between friends are more intimate than between dating partners even when these partners have complete sexual intimacy.


Metabolomics identifying biomarkers of PM2.5 exposure for vulnerable population: based on a prospective cohort study.
Long-term exposure to particular matter (PM), especially fine PM (< 2.5 μm in the aerodynamic diameter, PM2.5), is associated with increased risk of cardiovascular disorders. This study aimed to evaluate the association between long-term exposure to PM2.5/PM10 and the metabolic change in the plasma. Specifically, using metabolomics, we sought to identify the biomarkers for the vulnerable subgroup to PM2.5 exposure. A total of 78 college student volunteers were recruited into this prospective cohort study. All participants received 8 rounds of physical examinations at twice quarterly. Air purifiers were placed in 40 of 78 participants' dormitories for 14 days. Before and after intervention, physical examinations were performed and the peripheral blood was collected. Plasma metabolomics was determined by ultra-performance liquid chromatography-mass spectrometry. During the follow-up, the average concentrations of PM2.5 and PM10 were 53 μg/m3 and 93 μg/m3, respectively. Totally, 42 and 120 differential metabolic features were detected for PM10 and PM2.5 exposure, respectively. In total, 25 differential metabolites were identified for PM2.5 exposure, most of which were phospholipids. No distinctive metabolites were found for PM10 exposure. A total of 6 differential metabolites (lysoPC (P-20:0), lysoPC (P-18:1(9z)), lysoPC (20:1), lysoPC (O-16:0), choline, and found 1,3-diphenylprop-2-en-1-one) were characterized and confirmed for sensitive individuals. Importantly, we found LysoPC (P-20:0) and LysoPC (P-18:1(9z)) changed significantly before and after air purifier intervention. Our results indicated that the phospholipid catabolism was involved in long-term PM2.5 exposure. LysoPC (P-20:0) and LysoPC (P-18:1(9z)) may be the biomarkers of PM2.5 exposure.


Proteinivorax hydrogeniformans sp. nov., an anaerobic, haloalkaliphilic bacterium fermenting proteinaceous compounds with high hydrogen production.
A search for the organisms responsible for the degradation of biomass of primary producers in Tanatar lakes resulted in the isolation of a novel anaerobic, haloalkaliphilic microorganism, strain Z-710T. The strain grows on proteinaceous substrates (peptides) but not on proteins. A rather limited range of substances of other classes can be utilised together with tryptone but not individually. An interesting physiological feature of the novel strain is a high capacity for hydrogen production (up to 30% v/v) during proteolytic fermentation. Phylogenetic analysis based on the 16S rRNA gene sequence similarity revealed that the organism can be assigned to the previously described genus Proteinivorax. According to its physiological features and the low DNA-DNA hybridisation level of the strain with the type strain of the only previously described Proteinivorax species-Proteinivorax tanatarense Z-910T-strain Z-710T is described here as representing a novel species with the name Proteinivorax hydrogeniformans sp. nov. The type strain is Z-710T (= DSM 102085T = VKM B-3042T).


Mitochondrial ribosomes in a trypanosome.
The nature, and even the existence, of trypanosome mitochondrial ribosomes has been the subject of some debate. We investigated this further in the insect trypanosome, Crithidia fasciculata. In sucrose gradients of parasite lysates, mitochondrial ribosomal RNA co-sediments at approximately 35S with nascent peptides synthesized in the presence of the cytosolic translational inhibitor, cycloheximide. Co-sedimenting peptides in this peak are much reduced when the parasites are treated with the bacterial translational inhibitor, chloramphenicol. In CsCl gradients this peak resolves at a buoyant density of 1.42 g/cm(3), a value typical for mito-ribosomes. Electron microscopy of peak material shows particles smaller than cytosolic ribosomes, but with characteristic ribosomal shapes. We propose that these particles represent the parasite's mitochondrial ribosomes.


Efficient catalytic activity and bromate minimization over lattice oxygen-rich MnOOH nanorods in catalytic ozonation of bromide-containing organic pollutants: Lattice oxygen-directed redox cycle and bromate reduction.
The inhibition of bromate formation is a challenge for the application of ozonation in water treatment due to the carcinogenicity and nephrotoxicity of bromate. In this study, the high-mobility lattice oxygen-rich MnOOH nanorods were synthesized successfully and applied for the bromate inhibition during catalytic ozonation in bromide and organic pollutants-containing wastewater treatment. The catalytic ozonation system using lattice oxygen-rich MnOOH nanorods exhibited an excellent performance in bromate control with an inhibition efficiency of 54.1% compared with the sole ozonation process. Furthermore, with the coexistence of 4-nitrophenol, the catalytic ozonation process using lattice oxygen-rich MnOOH nanorods could inhibit the bromate formation and boost the degradation of 4-nitrophenol simultaneously. Based on the experiments of ozone decomposition, surface manganese inactivation and reactive oxygen species detection, the inhibition of bromate could be attributed to the effective decomposition of ozone with generating more ·O2- and the reduction of bromate into bromide by lattice oxygen-rich MnOOH. The existed surface Mn(IV) on lattice oxygen-rich MnOOH can accept electrons from lattice oxygen and ·O2- to generate surface transient Mn(II)/Mn(III), in which Mn(II)/Mn(III) can promote the reduction of bromate into bromide during catalytic ozonation. This study provides a promising strategy for the development of bromate-controlling technologies in water treatment.


Platelet-leucocyte aggregates form in the mesenteric vasculature in patients with ulcerative colitis.
Inflammation and thrombosis are closely related processes, which may play a role in the pathogenesis, as well as complications, of inflammatory bowel disease (IBD). Platelet activation and platelet-leucocyte aggregation are increased and platelet aggregation is known to occur in the mesenteric vasculature in IBD. The aims of this study were to test the hypotheses that platelet-leucocyte aggregation, platelet activation and neutrophil activation occur in the mesenteric vessels of patients with ulcerative colitis (UC). Platelet-leucocyte aggregates (PLAs), platelet activation (P-selectin expression) and neutrophil activation (L-selectin expression, which decreases on neutrophil activation) were assessed flow cytometrically in mesenteric arterial, and venous blood sampled in eight patients with UC and eight controls with colonic carcinoma undergoing intestinal resections. In the patients with UC, the number of PLAs in the mesenteric vein exceeded that in the artery, the median rise being 38% (P=0.02). In UC, arterial PLA numbers were 0.17 (0.02-0.32) (median, range) x 10(9)/l versus venous 0.26 (0.09-1.6) x 10(9)/l (P=0.02). The median percentage increase was 45%. Mesenteric PLA formation did not occur in patients with colonic carcinoma [arterial 0.06 (0.03-0.49) x 10(9)/l vs. venous 0.05 (0.02-0.35) x 10(9)/l; P=0.55]. The median percentage change was +45% for UC patients and -5% for controls. No arteriovenous gradient was observed in P-selectin expression, but L-selectin expression (arbitrary units), increased in the mesenteric vasculature of the UC patients [arterial 839 (503-995), venous 879 (477-1035); P=0.03] and fell in those with colonic carcinoma [arterial 900 (660-959), venous 850 (546-957); P=0.04]. The median percentage change was +4% for UC and -7% for controls. The finding of increased numbers of PLAs in the venous mesenteric circulation supports the hypothesis that activated vascular endothelium stimulates PLA formation in UC.


Molecular aspects of glucose homeostasis in skeletal muscle--A focus on the molecular mechanisms of insulin resistance.
Among all the varied actions of insulin, regulation of glucose homeostasis is the most critical and intensively studied. With the availability of glucose from nutrient metabolism, insulin action in muscle results in increased glucose disposal via uptake from the circulation and storage of excess, thereby maintaining euglycemia. This major action of insulin is executed by redistribution of the glucose transporter protein, GLUT4 from intracellular storage sites to the plasma membrane and storage of glucose in the form of glycogen which also involves modulation of actin dynamics that govern trafficking of all the signal proteins of insulin signal transduction. The cellular mechanisms responsible for these trafficking events and the defects associated with insulin resistance are largely enigmatic, and this review provides a consolidated overview of the various molecular mechanisms involved in insulin-dependent glucose homeostasis in skeletal muscle, as insulin resistance at this major peripheral site impacts whole body glucose homeostasis.


Pharmacological stimulation of sperm motility in frozen and thawed testicular sperm using the dimethylxanthine theophylline.
To evaluate whether the use of theophylline improves sperm motility and treatment outcome in frozen-thawed testicular sperm extraction (TESE). Artificial sperm activation was offered to azoospermic patients between January and October 2010 in two different centers (identical lab conditions). IVF units of public hospitals. Sixty-five patients participated and gave informed consent. Sibling oocytes were split into a study (intracytoplasmic sperm injection [ICSI] with thawed testicular sperm treated with theophylline) and a control group (ICSI with thawed untreated sperm). Sperm motility, time for sperm selection, rates of fertilization, implantation, clinical pregnancy, and live birth. All patients but one (98.5%) showed a significant improvement in testicular sperm motility when theophylline was used. In addition, sperm selection took significantly less time in the study as compared with in the untreated control group. Corresponding rates of fertilization (79.9% vs. 63.3%) and blastulation (63.9% vs. 46.8%) were significantly increased. Significantly more patients achieved clinical pregnancy if embryos/blastocysts derived from oocytes that had been injected with pharmacologically stimulated testicular spermatozoa were transferred (53.9% vs. 23.8%). This also holds true for the implantation rate. Theophylline turned out to be a reliable tool in stimulating testicular spermatozoa after thawing. Its immediate effect allows for faster and more accurate selection of viable sperm, which in turn improved fertilization and pregnancy outcome in this prospective study.


Prevalence of snoring and facial profile type, malocclusion class and dental arch morphology among snorer and nonsnorer university population.
The objectives of this study were to determine the prevalence of snoring in an adult male university population, and to test the null hypothesis that there is no difference in facial profile shape, malocclusion type, or palatal morphology among snorer and nonsnorer. Berlin questionnaire was given to 840 students and employees aged 18-45 years (24 ± 40). Both snorers and nonsnorers were assessed for the facial profile type, malocclusion type, and palatal morphology. Chi-square and Student's t-test were used to compare the difference between the two groups. The prevalence of snoring was 16.28%. The most frequent findings among snorer were straight profiles (52.0%), Class I malocclusion (74.7%), and V palatal shape (16.0%), respectively. The Chi-square test revealed a significant difference in terms of V-shaped palatal morphology (P < 0.05); higher neck circumference (NC) (P < 0.007); upper arch length was significantly shorter (P < 0.038); and the inter- first upper premolar distance was significantly narrower (P < 0.013). The null hypothesis is rejected. Snoring in our university population is associated with V-shape palatal morphology, increased NC and decrease in the upper arch length, and inter- first upper premolar distance.


The Abnormal Ovary: Evolving Concepts in Diagnosis and Management.
Ovarian lesions are common and require a consistent approach to diagnosis and management for best patient outcomes. In the past 20 years, there has been an evolution in the approach to abnormal ovarian lesions, with increasing emphasis on reducing surgery for benign disease, standardizing terminology, assessing risk of malignancy through use of evidence-based scoring systems, and triaging suspicious abnormalities to dedicated oncology centers. This article provides an evidence-based review of how these changes in diagnosis and management of ultrasound-detected abnormal ovarian lesions have occurred. Current recommended practices are summarized. The current literature on transvaginal screening for ovarian cancer also is reviewed and summarized.


Prostaglandins in human semen during fish oil ingestion: evidence for in vivo cyclooxygenase inhibition and appearance of novel trienoic compounds.
Marine oils may offer cardiovascular benefits, but inhibition of prostaglandin E and prostaglandin F synthesis by fish oil has been found in animal studies, and such effects could alter physiological responses in man to a clinically significant degree. Since greater amounts of E and F-type prostaglandins are made in human seminal vesicles than in the rest of the body combined, the influence of n-3 supplements upon semen prostaglandins was assessed in 10 subjects before and after one month of taking 50 ml menhaden oil daily. Prostaglandins E1, E2 and their 19-hydroxy derivatives were measured by HPLC-UV as PGB's, and prostaglandin E3, 19-OH PGE3, and analogous PGF's by gas chromatography/mass spectrometry. Fish oil ingestion reduced concentrations of one- and two series prostaglandins (mean reduction in PGE's = 37%, in PGF's = 20%, p less than 0.05), while more than doubling the low amounts of PGE3 and PGF3 alpha, and their previously undescribed 19-hydroxy derivatives. Semen phospholipids were enriched in eicosapentaenoic acid after dietary fish oil, but sperm counts and motility were not altered during the study. Since dietary fish oil reduces prostaglandin concentration in semen, clinical trials of n-3 fatty acids should also evaluate other possible results of in vivo cyclooxygenase inhibition.


Low TLR and PSMA-TV predict biochemical response to abiraterone acetate in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage.
To explore whether 68Ga-PSMA-11 PET/CT-derived parameters could predict biochemical response to abiraterone acetate (AA) treatment and prognosis in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage. The clinicopathologic data of 106 mCRPC cases receiving AA treatment were retrospectively analyzed. Logistic regression analysis was used to determine the independent predictors of biochemical response to AA treatment. Cox analyses were applied to investigate the independent prognostic factors for time to biochemical progression (TTBP) and radiological progression-free survival (rPFS). Survival analysis and ROC curve were also used. Multivariable Logistic analysis demonstrated that prior ADT duration ≥ 12 months, low prostate specific membrane antigen receptor-expressing tumor volume (PSMA-TV), low tumor to liver ratio (TLR) were independent predictors of biochemical response to AA treatment. Multivariate Cox analysis demonstrated that low PSMA-TV and low TLR were independent prognostic factors of longer TTBP and rPFS. The TTBP and rPFS of patients with higher PSMA-TV or TLR were significantly decreased compared with that of patients with lower PSMA-TV and TLR. The area under ROC curve (AUC) of combining ADT duration, PSMA-TV and TLR was 0.82 for predicting biochemical response to AA, which was significantly increased compared with that of other 68Ga-PSMA-11 PET/CT-derived parameters alone. Low PSMA-TV, low TLR were vital independent predictors of biochemical response to AA treatment and were associated with preferable prognosis in mCRPC patients. Combining ADT duration, PSMA-TV and TLR performed well in distinguishing AA responders from non-responders in mCRPC patients.


Patient-centered care coordination, education and counseling of patients treated with oral anticancer drugs: An importance-performance analysis.
To analyse the importance and performance of key elements in patient-centered care coordination, education and counseling of patients treated with oral anticancer drugs. In four Belgian non-academic hospitals, the importance and performance of a set of 82 key elements was cross-sectionally evaluated by primary and secondary healthcare professionals and by patients. These key elements were divided in 6 themes: coordination of care, style and content of patient contacts, medication counseling at treatment initiation, follow-up of treatment, psychosocial support, and involvement of family and friends. Participants were asked to indicate for each key element if it was implemented in the current care process for patients on oral anticancer drugs ('yes', 'no', 'I don't know') and if they considered it important that the component was implemented or would be in the future ('yes' or 'no'). Three levels of performance were defined, based on the number of participants who had answered 'yes' or 'no': 'systematically performed' (≥90% of participants), 'not systematically performed' (≥75% and <90%) and 'not performed' (<75%). Importance-rates were based on the number of 'yes' or 'no'. In total, 85 participants evaluated the key elements. More than half of key elements, 13/82 (15.9%) and 35/82 (42.6%) respectively, were considered as 'not' or 'not systematically performed'. The majority of these elements concerned coordination of care, medication counseling at treatment initiation and follow-up of treatment. Especially key elements on involving primary care and on discussing adherence had low performance rates. Nearly all key elements were assigned an importance score of ≥90%. Performance of key elements of patient-centered care coordination, education and counseling of patients treated with oral anticancer drugs proved moderate. Our findings suggest that strategies are needed to prioritize and operationalize key elements to coordinate transmural care and to provide effective education and counseling.


Preservation of ischaemically injured canine kidneys with hypertonic citrate solution: the importance of mannitol.
The ability of hypertonic citrate solution to preserve ischaemically injured canine kidneys was investigated. It was found that if mannitol was given i.v. before ischaemia and again after graft revascularization, kidneys subjected to 30 min of warm ischaemia could be preserved for 24 hr, maintaining immediate life-sustaining function.


In vitro expansion of cord blood does not prevent engraftment of severe combined immunodeficient repopulating cells.
This study aimed to assess the potential of human cord blood (CB) cells to engraft in the xenogenic non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse model after in vitro expansion culture. We also studied the quality of human haemopoiesis arising from the transplantation of fresh or expanded cells in this model. Cord blood CD34(+) cells were cultured for 3, 7 or 10 d with stem cell factor, Flt3, thrombopoietin, interleukin 3 (IL-3), IL-6 and granulocyte colony-stimulating factor, all at 10 ng/ml in serum-replete conditions. Transplantation of mice with fresh CB containing 3 x 10(4) CD34(+) cells and 1-2 SCID repopulating cells (SRC) resulted in a median of 7.4% (0.4%-76.8%) human engraftment. When mice received the expanded product of 1-2 SRC, the ability to repopulate NOD/SCID mice was maintained even after 10 d of in vitro culture. Serial dilution of the expanded cells suggested that in vitro expansion had increased SRC numbers two- to fourfold. Expanded SRC produced long-term culture-initiating cells, clonogenic cells and CD34(+) cells in the same proportions as fresh cells after successful engraftment. Therefore, expanded SRC were able to differentiate in the same way as fresh SRC. There was a trend towards lower levels of engraftment when d 7 cultured cells were transplanted (median engraftment 0.8%, range 0.0-24.0%) compared with 1-2 fresh SRC. Our data suggest that this is owing to reduced proliferation of cultured cells in vivo. By utilizing limiting numbers of CB SRC, we confirmed that the engraftment potential of SRC in the NOD/SCID model was preserved after in vitro expansion. Furthermore, dilution experiments strongly suggest two- to fourfold expansion of SRC in vitro. These studies are relevant for developing clinical stem cell expansion strategies.


Floral biology of the saguaro (Cereus giganteus) : I. Pollen harvest by Apis mellifera.
A saguaro cactus (Cereus giganteus) produces an average of 295 flowers per season, each of which produces 286 mg fresh weight of pollen and 543 mg of nectar containing 24% sugar. At 7600 pollen grains/mg pollen, the yearly output per saguaro plant is 6.4×108 grains. Based on the measured saguaro density of 6.56 plants/ha, 553 g/ha of pollen is produced yearly. The enormous variation among individual plants in terms of flower numbers and floral bloom patterns is documented.Honey bees (Apis mellifera L.), the main collectors of saguaro pollen, collect an average of 12.2 mg pollen per foraging trip and can thus harvest 23.5 pollen loads from one flower. An average honey bee colony collects 290 g of saguaro pollen over the season, which is 24.4% of their total intake. Individual colonies exhibit wide variation in pollen collecting activities with some closely tracking the pollen resource and others almost totally ignoring it. The average for seven colonies indicates that even though variation is great the overall trend is toward closely tracking and exploiting the saguaro pollen resource. Based on the pollen productivity of saguaro and a hypothetical 90% pollen harvesting efficiency of bees, the pollen harvest potential of the saguaro environment is 1.72 colony equivalents of pollen/ha and 0.5/ha for saguaro alone. This is the first quantitative reporting of the total pollen productivity and pollen resource utilization for any plant and an opportunistic pollinator.


Atypical neurocytoma of the spinal cord in a young child.
Extraventricular neurocytoma is a well-established entity, and non-classical sites like the cerebellum and spinal cord have occasionally been reported. We report a rare case of intramedullary neurocytoma in an 8-year-old boy who presented with paraparesis and urinary incontinence. This tumour was isointense on T1-weighted image and hyperintense on T2-weighted image, and showed heterogenous contrast enhancement. Pathological examination showed atypical histology in the form of vascular endothelial proliferation, increased proliferation index, mitosis and necrosis. Atypical location, younger age and histopathological features are some of the interesting findings in this case, which need to be documented. To the best of our knowledge, this is the youngest patient of spinal cord neurocytoma.


Coronary artery spasm and ventricular fibrillation after off-pump coronary surgery.
Native coronary artery or bypass graft spasm is a rare cause of acute myocardial infarction after coronary artery bypass grafting. This report presents angiographic documentation of native coronary artery spasm following successful multivessel off-pump coronary revascularization, which caused myocardial ischemia leading to inferior wall myocardial infarction and ventricular fibrillatory arrest.


On Testing and Developing Cognitive Models.
The target article, "Robust Modeling in Cognitive Science", proposes a number of recommended practices in computational modeling in response to the growing "crisis of confidence" facing many scientific disciplines, including psychology and neuroscience. Those of us who do modeling, write about modeling, teach modeling, and mentor modelers worry deeply about best practices and any new suggestions for making modeling more transparent, trusted, and robust is welcome. Many of the recommendations seem uncontroversial. My commentary focuses on forms of preregistration and postregistration, which constitute three of the four key ideas highlighted as take-home recommendations at the conclusion of the target article. I have chosen to consider these recommendations by reflecting on my own past experiences developing new models and modeling approaches.


Mechanistic basis of infertility of mouse intersubspecific hybrids.
According to the Dobzhansky-Muller model, hybrid sterility is a consequence of the independent evolution of related taxa resulting in incompatible genomic interactions of their hybrids. The model implies that the incompatibilities evolve randomly, unless a particular gene or nongenic sequence diverges much faster than the rest of the genome. Here we propose that asynapsis of heterospecific chromosomes in meiotic prophase provides a recurrently evolving trigger for the meiotic arrest of interspecific F1 hybrids. We observed extensive asynapsis of chromosomes and disturbance of the sex body in >95% of pachynemas of Mus m. musculus × Mus m. domesticus sterile F1 males. Asynapsis was not preceded by a failure of double-strand break induction, and the rate of meiotic crossing over was not affected in synapsed chromosomes. DNA double-strand break repair was delayed or failed in unsynapsed autosomes, and misexpression of chromosome X and chromosome Y genes was detected in single pachynemas and by genome-wide expression profiling. Oocytes of F1 hybrid females showed the same kind of synaptic problems but with the incidence reduced to half. Most of the oocytes with pachytene asynapsis were eliminated before birth. We propose the heterospecific pairing of homologous chromosomes as a preexisting condition of asynapsis in interspecific hybrids. The asynapsis may represent a universal mechanistic basis of F1 hybrid sterility manifested by pachytene arrest. It is tempting to speculate that a fast-evolving subset of the noncoding genomic sequence important for chromosome pairing and synapsis may be the culprit.


A histochemical study of the microvasculature in the left and right cardiac ventricles of the dog.
Subepicardial and subendocardial arteries and arterioles in both the left and right normal canine ventricle were examined histochemically to determine their metabolic profiles. Aerobic metabolic capacity was assessed by determining the reactivities of the enzymes cytochrome oxidase, succinate dehydrogenase and NAD-isocitrate dehydrogenase. Glucose-6-phosphate dehydrogenase was examined to assess activity of the hexose-monophosphate-shunt. The substrate glycogen was determined as an evaluation of anaerobic metabolic capacity, while the amounts of deoxyribonucleic and ribonucleic acid were assessed as an indication of protein synthesis. Results of the present investigation indicate that despite known hemodynamic differences, the metabolic profile of the coronary vasculature is similar in all regions of ventricular myocardium. Reactivities of the enzymes succinate and NAD-isocitrate dehydrogenase and cytochrome oxidase are greater in smooth muscle of arterioles than in arteries. This suggests that arteriolar smooth muscle has a higher capacity for aerobic metabolism than does arterial smooth muscle. The greater reactivity of glycogen in arterial, than in arteriolar smooth muscle, suggests that arterial muscle is more adapted for anaerobic metabolism. Deoxyribonucleic and ribonucleic acids demonstrate a low reactivity in both arteries and arterioles from all regions of ventricular myocardium which conforms to the opinion that under normal conditions, coronary vasculature is quite stable with little cell proliferation. Glucose-6-phosphate dehydrogenase shows little reactivity in all myocardial vessels with implies a low capacity for nucleic acid and protein synthesis.


Dopaminergic and adrenergic receptors synergistically stimulate browning in 3T3-L1 white adipocytes.
The browning of white adipose tissue (WAT) has attracted considerable attention in the scientific community as a popular strategy for enhancing energy expenditure to combat obesity. As a part of this strategy, β3-adrenergic receptor (β3-AR) is the most widely studied receptor that mediates thermogenesis. Parenthetically, further studies in search for additional receptors expressed in adipocytes that can mediate thermogenesis has been appearing, and this paper reports that dopaminergic receptor 1 (DRD1) and β3-AR synergistically stimulate browning in 3T3-L1 white adipocytes. qRT-PCR and immunoblot analysis methods were applied to evaluate the effects of DRD1 on the target proteins downstream of β3-AR and other markers involved in lipid metabolism, mitochondrial biogenesis, and browning events. These results show that DRD1 is expressed in epididymal WAT (eWAT), brown adipose tissue (BAT), and inguinal WAT (iWAT) of normal and high-fat-fed mice, and a deficiency of DRD1 downregulates the expression of brown adipocyte-specific proteins. Silencing of DRD1 affected lipid metabolic activity in 3T3-L1 adipocytes by reducing mitochondrial biogenesis as well as levels of lipolytic and fat oxidative marker proteins in a similar pattern to β3-AR. Moreover, mechanistic studies showed that the depletion of DRD1 downregulates β3-AR and its downstream molecules, suggesting both receptors might synergistically stimulate browning. Parallel to the UCP1-dependent thermogenesis, the depletion of DRD1 also downregulates the expression of core proteins responsible for UCP1-independent thermogenesis. Overall, DRD1 mediates β3-AR-dependent 3T3-L1 browning and UCP1-independent thermogenesis.


Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice.
We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4-10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤ 2-week-old C57BL/6 mice following RSV infection. Mice (5-14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1-10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1-10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O2 consumption) and ATP following RSV infection is independent of either age or genetic background of the host.


Human insulin: much ado about hypoglycaemia (un)awareness.
The biological effects, hypoglycaemic symptoms, endocrine counterregulatory responses and glucose recovery following the injection of purified porcine and human insulin preparations were compared in a number of controlled clinical investigations and prospective clinical trials. In these studies involving healthy volunteers, Type 1 (insulin-dependent) diabetic patients on continuous subcutaneous insulin infusion or intensified conventional insulin therapy and insulin treated Type 2 (non-insulin-dependent) diabetic patients, no differences with regard to biological effects, counterregulatory responses, hypoglycaemic awareness or the long-term incidence of severe hypoglycaemia between porcine and human insulin preparations were identified. These data fail to confirm any specific risk of severe hypoglycaemia attributable to the use of human insulin preparations in the treatment of patients with diabetes mellitus.


Poly-N-acryloyl-Tris gels as anticonvection media for electrophoresis and isoelectric focusing.
We describe in detail the synthesis of an acrylic monomer, N-acryloyl-tris(hydroxy-methyl)aminomethane (NAT), which was successfully used for the preparation of gels for electrophoresis and isoelectric focusing. The polymerization kinetics and transparency of the poly(NAT) gels crosslinked by N,N'-methylenebisacrylamide (Bis) are also shown. Poly(NAT)-Bis gradient (4-24%) gel resolves proteins according to their size. The exclusion limit of this gel is slightly over 3 X 10(6), which is more than threefold higher than the exclusion limit of the polyacrylamide gradient gel of the same concentration. The gel made of 6% NAT and 3% Bis represents a suitable matrix for isoelectric focusing. These results demonstrate that poly(NAT)-Bis gels could be advantageously used in those applications where the extensive sieving by the polyacrylamide matrix is not desir desirable.


An Extra Benefit of Allogeneic Peripheral Blood Stem Cell Transplantation in a Patient with Lymphoblastic Lymphoma: Cure of Thalassemia Minor.
b thalassemia minor is frequent in mediterranean countries. It is a benign disorder and does not warrant any therapeutical intervention. We transplanted a 25-year-old Turkish male who was diagnosed as lymphoblastic lymphoma and had b thalassemia minor as well. He received peripheral blood stem cells transplantation from his HLA-identical sibling who was not a carrier of b thalassemia. After the allogeneic transplantation we did not only observe remission of the lymphoblastic lymphoma but also the disappearance of b thalassemia minor.


Mycoplasmas, a review of surveys examining human genital infections and experimental infection in mice with special reference to in vitro fertilization.
Patients attending an "In Vitro Fertilization" clinic were shown to be commonly infected in the semen with Ureaplasma urealyticum (29%) and Mycoplasma hominis (12%). Other mycoplasmas were rarely recovered. M. hominis was not eradicated from sperm by washing, although washing removed 71% of the ureaplasmas from infected semen. There was a significantly higher incidence of U. urealyticum and M. hominis in patients with cervical intraepithelial neoplasia (P = less than 0.05 and P = less than 0.01 respectively) than in controls. The results showed a possible association of U. urealyticum and M. hominis with CIN type 3. Mouse experiments showed that M. pulmonis has an affinity for genital tissue, adhered to the surface of eggs and could penetrate the zona pellucida, but did not affect fertilization except where pus was present in the oviduct.


The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme.
The RNA moieties of ribonuclease P purified from both E. coli (M1 RNA) and B. subtilis (P-RNA) can cleave tRNA precursor molecules in buffers containing either 60 mM Mg2+ or 10 mM Mg2+ plus 1 mM spermidine. The RNA acts as a true catalyst under these conditions whereas the protein moieties of the enzymes alone show no catalytic activity. However, in buffers containing 5-10 mM Mg2+ (in the absence of spermidine) both kinds of subunits are required for enzymatic activity, as shown previously. In the presence of low concentrations of Mg2+, in vitro, the RNA and protein subunits from one species can complement subunits from the other species in reconstitution experiments. When the precursor to E. coli 4.5S RNA is used as a substrate, only the enzyme complexes formed with M1 RNA from E. coli and the protein moieties from either bacterial species are active.