Annual testicular activity in the gray partridge (Perdix perdix L.).
Seasonal changes in plasma androgens, testicular total protein content, gonosomatic index, and spermatogenic activity were studied in the grey partridge, Perdix perdix. Moreover, testicular androgen output after stimulation with ovine LH (oLH) was tested in vitro during different periods of the sexual cycle. Androgens and the gonosomatic index peaked in April, during which all the spermatogenic stages were observed. Total protein content in the testes was highest in January and March. Gonadal responsiveness to oLH was found to increase in the period April-May in coincidence with the hormone peak in the plasma, while February testes were irresponsive.


Prevention of nosocomial infection in a pediatric intensive care unit (PICU) through the use of selective digestive decontamination.
To assess the effectiveness of selective digestive decontamination (SDD) on the control of nosocomial infection (NI) in critically ill pediatric patients. A prospective, randomized, non-blinded and controlled clinical microbiology study. The pediatric intensive care unit (PICU) of a tertiary level pediatric university hospital. CRITERIA FOR INCLUSION: Patients 1 month to 14 years old, who underwent some kind of manipulation or instrumentation (mechanical ventilation, vascular cannulation, monitoring of intracranial pressure, thoracic or abdominal drainage, bladder catheterization, peritoneal dialysis, etc.) and/or presented a neurological coma requiring a stay in the PICU of 3 or more days. Over a period of 2 years, 244 patients met the inclusion criteria; 18 patients were withdrawn because of protocol violation. The treatment group comprised 116 patients and the control group, 110 patients. The treatment group received a triple therapy of colimycin, tobramycin and nystatin administered orally or via nasogastric tube every 6 hours. All patients with mechanical ventilation or immune-depression received decontamination treatment of the oropharyngeal cavity with hexitidine (Oraldine 0.5 mg/ml) every 6-8 hours in accordance with the PICU's conventional protocol. Up to 10 types of nosocomial infection were diagnosed following criteria of the Centers for Disease Control (CDC). The severity and manipulation of the patients on admission was assessed using the therapeutic intervention scoring system (TISS) and multi-organ system failure scores (MOSF). UNIVARIANT ANALYSIS: SDD did not significantly reduce the incidence of NI, antibiotic use, the length of stay, or mortality; although a small percentage of respiratory and urinary tract infections was detected, catheter-related bacteremia was the most common infection. MULTIVARIANT ANALYSIS: Controlling the risk factors for each child through log regression showed that SDD acted as a protective factor for more than 90% of the sample with respect to the appearance of respiratory and urinary tract infections, reducing the risk of such infections to 1/5 and 1/3, respectively. SDD was effective in controlling respiratory and urinary tract infections in children admitted to the PICU, but it did not reduce the incidence of other types of nosocomial infection.


Diffusion tensor imaging (DTI) of desmoid tumours in familial adenomatous polyposis: initial experience.
To assess the feasibility of diffusion tensor imaging (DTI) of desmoid tumours in familial adenomatous polyposis (FAP). Following ethical approval and informed consent, FAP patients with desmoids underwent DTI. Fractional anisotropy (FA), relative anisotropy (RA) and apparent diffusion coefficient (ADC) were compared to control muscle using Mann-Whitney test; and to tumour site and signal intensity using one way analysis of variance (ANOVA). Imaging was repeated after 1 year. 15 desmoids (6 intra-abdominal; 6 abdominal wall, 3 extra-abdominal; size range: 1.6-22.9 cm) were evaluated in 9 patients. DTI was successful in 12/15 desmoid tumours. Median (range) of RA, FA and ADC were 0.23×10(-3) mm2/s (0.17-0.26); 0.27×10(-3) mm2/s (0.21-0.31); and 1.65×10(-3) mm2/s (1.39-1.91) for desmoids, significantly different from muscle: 0.27×10(-3) mm2/s (0.23-0.40), 0.32×10(-3) mm2/s (0.28-0.46), and 1.45×10(-3) mm2/s (0.92-1.63) (p=0.0001, p=0.0001, p=0.0016, respectively). There was no difference in RA, FA or ADC between tumour sites, or signal intensity (p>0.05). One year later, 2 patients had died. Tumour increased in size in 1 patient (+61%). DTI quantification was possible in only 8/13 tumours. FA, RA and ADC were not significantly different from baseline (p=0.77, 0.71 and 0.34, respectively). Assessment of water diffusion has the potential to provide insight into tumour microstructure and is feasible in desmoids. Desmoid tumours demonstrate anisotropy but diffusion is less restricted and less directional than in muscle.


Public health and preventive healthcare in children: current practices of Victorian GPs and barriers to participation.
To assess general practitioners' attitudes to and involvement in child public health activities and identify barriers affecting their participation. Cross-sectional written questionnaire survey of a representative sample of actively practising GPs. General practices in the State of Victoria. 840 GPs returned questionnaires (65% response rate), and, of these, 792 (94%) saw children 0-12 years. Attitudes to and involvement in public health promotion; predictive factors for GPs' involvement. The odds of GPs' involvement in child public health issues were increased by being female (odds ratio [OR], 1.88), receiving basic medical qualifications outside Australia (OR, 1.55), attending continuing education and postgraduate training (OR, 1.60), and having confidence in dealing with newborns and infants (OR, 1.93) and preschool children (OR, 2.94) (both P < 0.05). Older GPs, compared with younger GPs, had significantly lower odds of involvement (P < 0.01). After adjustment, GPs had higher odds of involvement if they agreed it was important for them to take part in health promotion, or in screening and surveillance (OR, 2.76 and 1.94, respectively; P < or = 0.05); and lower odds if they agreed that screening and surveillance should be mainly done by maternal and child health nurses (OR, 0.60). The most common barriers to involvement were insufficient time, inadequate financial reimbursement for long consultations, inappropriateness of raising these issues in children presenting with illness, and lack of community resources. Increasing GPs' involvement in child public health will require attention to barriers (time, remuneration and perceived appropriateness), continuing education and changes in workforce composition and patterns.


A contemplative care approach to training and supporting hospice volunteers: a prospective study of spiritual practice, well-being, and fear of death.
Inspired by a 2,500-year-old Buddhist tradition, the Zen Hospice Project (ZHP) provides residential hospice care, volunteer programs, and educational efforts that cultivate wisdom and compassion in service. The present study was designed to understand how being with dying hospice residents affects hospice volunteers well-being and the role of spiritual practice in ameliorating the fear of death. A one-year longitudinal study of two volunteer cohorts (N = 24 and N = 22) with repeated measures of spiritual practice, well-being, and hospice performance during one-year service as volunteers. The Zen Hospice Guest House and Laguna Honda Residential Hospital of San Francisco, CA. All 46 individuals who became ZHP volunteers during two years. A 40-hour training program for beginning hospice volunteers stressing compassion, equanimity, mindfulness, and practical bedside care; a one-year caregiver assignment five hours per week; and monthly group meeting. Self-report FACIT spiritual well-being, general well-being, self-transcendence scale, and a volunteer coordinator-rated ZHP performance scale. The volunteers had a high level of self-care and well-being at baseline and maintained both throughout the year; they increased compassion and decreased fear of death. Those (n = 20) practicing yoga were found to have consistently lower fear of death than the group average (P = .04, P = .008, respectively). All rated the training and program highly, and 63% continued to volunteer after the first year's commitment. The results suggest that this approach to training and supporting hospice volunteers fosters emotional well-being and spiritual growth.


Increased blood pressure induced by central application of aminopeptidase inhibitors is angiotensinergic-dependent in normotensive and hypertensive rat strains.
Two aminopeptidase inhibitors, amastatin (AM) and bestatin (BE), were employed in 3 strains of rats, spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD), to investigate the central angiotensinergic system. The results indicate that intracerebroventricular (i.c.v.) injections of AM and BE induced pressor elevations in all 3 strains of rats. In order to test for the possibility of spillage into peripheral vasculature, members from all 3 strains were peripherally infused with AM, BE, or 0.15 NaCl via jugular vein catheters. The SHRs were significantly more responsive to the aminopeptidases than the normotensive strains, however their overall pressor responses were only 33% of those to i.c.v. infusion. Next, in order to test the notion that these aminopeptidase inhibitors are having their effect via the central angiotensinergic system, and not some other peptidergic system, the specific angiotensin receptor antagonist, Sar1, Thr8-AII (sarthran) was employed. Intracerebroventricular pretreatment with sarthran prevented subsequent pressor responses to i.c.v. AM and BE in members of all 3 strains, thereby suggesting that these aminopeptidase inhibitors are having their effect via the central angiotensinergic system.


STARC-SUD - Adaptation of a Transdiagnostic Intervention for Refugees With Substance Use Disorders.
Refugees often suffer from multiple mental health problems, which transdiagnostic interventions can address. STARC (Skills-Training of Affect Regulation - A Culture-sensitive Approach) is a culturally sensitive transdiagnostic group intervention that has been developed for refugees to improve affect regulation. In refugees with substance use disorders (SUD), the consideration of SUD-specific elements might improve the acceptance and effectiveness of such an intervention. We aimed to adapt the STARC program for refugees with SUD in a culturally sensitive way. The conceptual framework of Heim and Kohrt (2019) was used to culturally sensitively adapt the STARC program to the needs of Syrian refugees with SUD. The results of five focus group discussions with refugees on cultural concepts of SUD and their treatment informed the adaption. An expert group suggested adaptions and decided by consensus on their implementation. Two pilot groups were conducted with the adapted STARC-SUD program. Interviews with the therapists of these pilot groups informed further adaption. The concepts related to SUD identified in focus groups and therapists' interviews that differed from Western concepts were integrated into the STARC intervention. Further studies should assess the acceptance and effectiveness of the culturally sensitive STARC-SUD program for refugees with SUD.


Ellipticine-induced alteration of model and natural membranes.
The modification of certain membrane properties by ellipticine derivatives was examined. The amphiphilic 9-methoxyellipticine was the most efficient in disorganizing membrane structure and in inducing leaks of liposomes, haemolysis of intact human erythrocytes. This drug and the dipolar 9-amino- and 9-hydroxyellipticine were equally efficient in decreasing the surface charge of membranes and in inhibiting the respiration of an isolated bacterial membrane.


Editorial Commentary: Machine Learning and Artificial Intelligence Are Tools Requiring Physician and Patient Input When Screening Patients at Risk for Extended, Postoperative Opioid Use.
As the implementation of artificial intelligence in orthopedic surgery research flourishes, so grows the need for responsible use. Related research requires clear reporting of algorithmic error rates. Recent studies show that preoperative opioid use, male sex, and greater body mass index are risk factors for extended, postoperative opioid use, but may result in high false positive rates. Thus, to be applied clinically when screening patients, these tools require physician and patient input, and nuanced interpretation, as the utility of these screening tools diminish without providers interpreting and acting on the information. Machine learning and artificial intelligence should be viewed as tools that can facilitate these human conversations among patients, orthopedic surgeons, and health care providers.


HIV increases HCV replication in a TGF-beta1-dependent manner.
Human immunodeficiency virus (HIV) coinfection increases hepatitis C virus (HCV)-related progression of hepatic fibrosis, increases HCV persistence, and decreases response rates to interferon-based anti-HCV therapy. It has remained unclear how HIV, a nonhepatotropic virus, accelerates the progression of liver disease by HCV. We explored the possibility that circulating HIV and/or its proteins contribute to the pathogenesis of HCV through engagement of extracellular coreceptors on hepatocytes. In this study, we found that inactivated HIV or gp120 increases HCV replication and enhances HCV-regulated transforming growth factor (TGF)-beta1 expression in both a replicon and an infectious model of HCV. This proviral effect of HIV and gp120 on HCV replication is neutralized by antibodies to CCR5 or CXCR4. However, HIV and gp120 did not alter type I interferon-mediated signaling in these HCV models, indicating that HIV regulates HCV replication through an alternative mechanism. Interestingly, we found that human TGF-beta1 also enhanced HCV replication. The effect of HIV on HCV replication was blocked by a neutralizing antibody to TGF-beta1, indicating that its effects on HCV replication are TGF-beta1 dependent. These results suggest a novel mechanism by which HIV not only enhances HCV replication but also contributes to progression of hepatic fibrosis.


Plantar pressures in children with congenital talipes equino varus--a comparison between surgical management and the Ponseti technique.
The Ponseti technique for treatment for Congenital Talipes Equinovarus (CTEV) was introduced in the authors' institution in 2001, substituting a more traditional orthopaedic approach which involved surgery. There is currently limited published information regarding the differences in clinical outcomes between these two techniques, particularly in relation to plantar pressure analysis. This study aims to determine differences in pedobarographic outcome in children with CTEV, treated with either a surgical or Ponseti approach. A high resolution pedobarograph was used to record plantar pressure distribution in 52 children with CTEV and 26 children with typical development. Data were imported into Matlab where a custom programme was developed for processing and analysing pedobarographic recordings. There were significant differences in both treatment groups compared to the typically developed group (p<0.05) for most measurements. The most salient differences between treatment groups were (i) at the hind-foot where the Ponseti group had significantly lower maximum peak pressures (p<0.05); (ii) at the lateral mid-foot where children treated by the Ponseti approach showed significantly larger peak force (p<0.001), average peak pressure (p<0.001) and maximum peak pressure (p<0.01); (iii) at the lateral fore-foot where the surgical group showed lower average peak pressure (p<0.05); and (iv) in the medial/lateral fore-foot ratio where the Ponseti group showed significantly lower values (p<0.05). Plantar pressure analysis is a complementary measurement for the assessment of gait in children with CTEV. Data presented in this study showed that while there were deviations in children with CTEV, the differences observed between treatment groups suggest children in the Ponseti group have some level of under correction or recurrence.


CDC17: an essential gene that prevents telomere elongation in yeast.
The CDC17 gene product performs an essential stage-specific function during the Saccharomyces cerevisiae cell cycle. When cdc17-1 strains are grown at the maximum permissive temperature, recombination is induced preferentially in the genetic interval of the chromosome closest to the telomere. Telomeres are longer in cdc17 strains than in CDC17 strains at the permissive temperature because of addition of sequence near or in the poly (C1-3A) telomeric DNA and become even longer when cells are propagated at elevated temperatures. The mitotic recombination events require RAD52 function, but telomere growth does not. Long telomeres are maintained for many generations when crossed into a CDC17+ background, suggesting that telomere length is largely conserved during replication. The altered telomere length phenotype of cdc17 mutations is recessive and coreverts and cosegregates with the temperature-sensitive lethal phenotype.


[pericarditis following 5-fluorouracil administration].
We report a case of pericarditis supervening after 5-fluorouracil infusion in a 52-year-old patient suffering from metastatic rectal cancer. Besides its well-known side-effects (mucitis, diarrhea, nausea, hematotoxicity), this molecule sometimes induces cardio-toxicity, which can take different clinical forms, pericarditis being one of the most uncommon. Several risk factors have been described and have to be kept in mind when initiating this therapy. Prevention may consist of close monitoring of patients considered at risk. Treatment of 5-FU induced cardiotoxicity basically consists in stopping the use of this drug and replacing it with another chemotherapy agent.


Effects of sodium tanshinone IIA sulfonate against Marek's disease virus in experimentally infected chickens.
Chickens experimentally infected with Marek's disease virus J-1 strain were used to evaluate the anti-Marek's disease virus (MDV) activity of sodium tanshinone IIA sulfonate (STS) in vivo. Chickens in same group were kept in one pen and control group chickens were housed in negative pressure isolator. Chickens were treated with different dose of STS or ABOB for 21 consecutive days. Peripheral T lymphocyte proliferation, expression level of IFN-γ and IL-10 in serum, and MDV load in spleen were determined. The results showed that the treatments with STS and ABOB could significantly increase stimulating index (SI) of peripheral T lymphocytes while the SI is dropping due to the MDV infection, SI of chickens in STS prevention groups were significantly higher than that in STS treatment group and ABOB group (P<0.05 or P<0.01); IFN-γ and IL-10 level of chickens in STS groups were higher than that in other groups (P<0.05 or P<0.01). The results of qPCR demonstrated that STS could inhibit the virus replication in spleen of chickens infected with MDV. These findings indicated that STS can be potentially applied as an anti-MDV drug and set a solid basis for further investigating the antiviral mechanisms of STS.


Synergistic utilization of red mud for flue-gas desulfurization and fly ash-based geopolymer preparation.
As an industrial waste characterized by huge volume and high alkalinity, red mud has become a serious environmental problem. The reuse of red mud has been explored in previous studies, including as building materials and for soil and waste water treatment. In this study, an innovation was made for the reuse of red mud to create a synergistic effect. Red mud was first used in flue gas desulfurization (FGD), and then the desulfurized red mud was again reused to make a geopolymer material. By using one type of original red mud and three types of fly ash, this study revealed that with high alkalinity and desulfurization capacity, the red mud could serve as an excellent FGD sorbent. After FGD, the sodium sulfate in the desulfurized red mud acted as a chemical activator for geopolymer made with class C fly ash. A 25% increase in strength was observed between the geopolymers with the red mud after FGD and with the original one. There are no significant benefits of FGD on the class F fly ash-based geopolymers and further study is required.


Changes of the immune response due to the absorption of antigenic protein or peptides.
Rabbits immunized against human gammaglobulin (HGG) were fed with either intact HGG or pepsin-digested HGG. Circulating antibodies were determined over an absorption time of 4 h. The oral application of antigenic peptides reduced circulating antibodies from 550 micrograms/ml to 120 micrograms/ml. A further parenteral antigen exposure to 50 mg HGG revealed that orally pretreated animals are protected against a marked blood pressure decrease due to antigen antibody reactions. One possible explanation for this phenomenon is that circulating antibodies are fixed in the wall of the gut by enterally applied antigenic peptides and eliminated into the lumen of the gastrointestinal tract. If this phenomenon can be extrapolated to human beings it would be a new therapeutic concept for the treatment of diseases in which circulating antibodies are of importance.


Toxicology of frequently encountered nonsteroidal anti-inflammatory drugs in dogs and cats.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of heterogeneous compounds extensively used in both human and veterinary medicine for their antipyretic, anti-inflammation, and analgesic properties. NSAIDs consist of a wide range of pharmacologically active agents with different chemical structures, with similar therapeutic and adverse effects. The ASPCA Animal Poison Control Center received 22,206 NSAID incidents in dogs and cats (3% of total cases; dogs [15,823] and cats [1244]) during 2005 to 2010. This is roughly equivalent to 4% NSAID incidents reported in humans. The most common NSAID involved was ibuprofen, followed by aspirin, naproxen, deracoxib, meloxicam, diclofenac, piroxicam, indomethacin, nabumetone, and etodolac. This article provides a brief overview of classification, mechanism of action, pharmacologic and toxicologic properties, and treatment information involving frequently encountered human and veterinary NSAIDs in dogs and cats.


High-intensity walking in midlife is associated with improved memory in physically capable older adults.
Little is known about the associations of midlife- and late life-initiated walking with Alzheimer's disease (AD)-related cognitive decline in humans. We aimed to investigate whether high-intensity, prolonged, midlife-initiated walking is associated with changes in AD-related cognitive decline in physically capable older adults. We studied 188 physically capable participants aged 65-90 years without dementia who underwent comprehensive clinical assessment, including of their walking modality (i.e., intensity, duration, midlife- or late life-onset), memory- or non-memory and total cognitive performance, and blood or nutritional biomarkers. The walking group showed better episodic memory (B = 2.852, SE = 1.214, β = 0.144, p = 0.020), but not non-memory cognition, than the non-walking group. High-intensity walking starting in midlife was significantly associated with better episodic memory (B = 9.360, SE = 3.314, β = 0.446, p = 0.005) compared to the non-walking group. In contrast, there were no differences in cognition according to walking duration, regardless of the onset time. The walking group also showed a similar association with overall cognition. Among physically capable older adults without dementia, walking, particularly at high intensity and starting in midlife, is associated with improved episodic memory, an AD-related cognitive domain. Further attention should be paid to the role of walking in terms of AD prevention.


Bivalirudin is inferior to heparin in preservation of intraoperative autologous blood.
Bivalirudin is used as an alternative to heparin in cardiac surgery, and may be superior to heparin with regard to platelet function. Bivalirudin however, is prone to cleavage by thrombin resulting in coagulation in areas of stasis. We compared the preservation of platelet function and the quality of anticoagulation in autologous blood of 26 cardiac surgical patients collected intraoperatively and anticoagulated ex vivo with either bivalirudin or heparin, with supplementation of bivalirudin over time and prevention of stasis. We found in both preservatives a reduction in ADP-induced platelet aggregation response over a period of 105 minutes (median, IQR: 73-141) as measured by Multiplate®. Supplementation of additional bivalirudin (23 ± 1.1 μg/ml/hr) and prevention of stasis was not able to prevent thrombin generation. We found a 5-fold increase in levels of prothrombin fragment 1+2 in bivalirudin preserved autologous blood as compared to heparin preserved blood (F(1+2) levels median 8.9 nM [quartile percentiles 4.2-12.4] vs 1.3 nM [0.6-2.1], P=0.001 Mann-Whitney, n=10). Our study suggests that preservation of platelet function in autologous blood anticoagulated with bivalirudin is not a suitable alternative to heparin.


Prognostic and immunological role of cancer-associated fibroblasts-derived exosomal protein in esophageal squamous cell carcinoma.
Cancer-associated fibroblasts (CAFs) are a crucial component of the tumor microenvironment (TME) and play significant roles in tumor initiation, progression, and immune evasion. Despite this, the specific exosomal proteins derived from CAFs and their functions in esophageal squamous cell carcinoma (ESCC) remain unknown. Therefore, this study aims to investigate the impact and prognostic significance of CAFs-derived exosomal proteins in ESCC. Exosomes obtained from CAFs and normal fibroblasts (NFs) were isolated using ultracentrifugation, and the protein expression profiles of the exosomes were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tumor proliferation was assessed using CCK-8 and colony formation assays, while cell invasion and migration were evaluated using transwell assays. Lasso regression analysis was employed to establish a signature based on CAFs-derived exosomal proteins using the TCGA database. The immunological and prognostic roles of this signature were comprehensively investigated through survival analysis, gene set enrichment analysis (GSEA), immune analysis, immunotherapy response analysis, and drug sensitivity analysis. The GSE160269 dataset was utilized for single-cell transcriptome analysis to further elucidate the role of the signature in the TME. Additionally, cDNA microarray analysis was utilized to validate the prognostic value of the signature. Our findings demonstrate that exosomes derived from CAFs significantly enhance the proliferation, invasion, and migration of esophageal cancer cells. We identified 842 differentially expressed exosomal proteins through LC-MS/MS analysis, and two key proteins were utilized to establish a risk signature. Survival analysis revealed a significantly worse prognosis in the high-risk group, with multivariate analysis indicating that the risk score serves as an independent prognostic factor. Moreover, we observed a significant correlation between the risk score and immune cell infiltration, immunotherapy response, and sensitivity to chemotherapeutic treatments in the study population. Lastly, single-cell transcriptome analysis further revealed the expression patterns of TNFRSF10B and ILF3 in different cell subpopulations. In conclusion, our study has successfully established a robust prognostic signature based on CAFs-derived exosomal proteins, which can serve as a reliable biomarker for predicting prognosis and evaluating the immune microenvironment in ESCC.


[Endovascular treatment of non-ruptured intracranial aneurysms: critical analysis of the literature].
The goal was to evaluate, from the published data, the results of the endovascular treatment of unruptured aneurysms. We have searched Medline for studies publishing results for endovascular coiling of unrupured aneurysms. Studies were classified as single-center, multicenter, or meta-analysis. Single-center studies always underestimate morbidity and mortality rates. However, it is possible to estimate mortality rate around 1.5% and morbidity rate between 3 and 6%. Some published series have directly compared results of endovascular treatment with surgical treatment. The results are always in favour of endovascular treatment, demonstrating a lower rate of complications and lower total hospital charges. All published series of unruptured aneurysms favour the endovascular treatment instead of surgery. However, there is a lack of multicenter prospective series evaluating the results of the endovascular treatment of unruptured aneurysms. Likewise, there is no scientific arguments demonstrating that preventive treatment of unruptured aneurysms decreases the mortality and allows to decrease the risk of neurologic sequellae.


Concurrent medulloblastoma and cardiac fibroma: a rare presentation of Gorlin-Goltz syndrome.
Gorlin-Goltz syndrome is a rare autosomal dominant disorder resulting from PTCH1 gene mutation and presents with variable clinical manifestations. The co-occurrence of medulloblastoma and cardiac fibroma in Gorlin-Goltz syndrome is extremely rare. The present article discusses a patient diagnosed with Gorlin-Goltz syndrome and concurrent medulloblastoma and cardiac fibroma. A 19-month-old boy transferred to our hospital after a radiological finding of posterior fossa lesion and hydrocephalus. A pericardial mass was noted after persistent arrhythmias. Both tumors were excised for definitive management. The histopathological sections were diagnostic of desmoplastic nodular medulloblastoma, WHO grade 4 and cardiac fibroma. Molecular and genetic investigations confirmed a pathogenic variant of PTCH1 gene, suggestive of autosomal dominant Gorlin-Goltz syndrome. Co-occurrence of medulloblastoma and cardiac fibroma is extremely rare and poses a management dilemma. Genetic counseling and antenatal screening are of utmost importance to early detect and manage patients with Gorlin-Goltz syndrome.


The potential role of microvascular pathology in the neurological manifestations of coronavirus infection.
Human coronaviruses are highly pathogenic viruses that pose a serious threat to human health. Examples include the severe acute respiratory syndrome outbreak of 2003 (SARS-CoV-1), the Middle East Respiratory Syndrome (MERS-CoV) outbreak of 2012, and the current SARS-CoV-2 (COVID-19) pandemic. Herein, we review the neurological manifestations of coronaviruses and discuss the potential pathogenic role of blood-brain barrier dysfunction. We present the hypothesis that pre-existing vascular damage (due to aging, cardiovascular disease, diabetes, hypertension or other conditions) facilitates infiltration of the virus into the central nervous system (CNS), increasing neuro-inflammation and the likelihood of neurological symptoms. We also discuss the role of a neuroinflammatory cytokine profile in both blood-brain barrier dysfunction and macrovascular disease (e.g. ischemic stroke and thromboembolism). Future studies are needed to better understand the involvement of the microvasculature in coronavirus neuropathology, and to test the diagnostic potential of minimally-invasive screening tools (e.g. serum biomarkers, fluorescein retinal angiography and dynamic-contrast MRI).


Genome-wide co-occupancy of AML1-ETO and N-CoR defines the t(8;21) AML signature in leukemic cells.
Many leukemias result from chromosomal rearrangements. The t(8;21) chromosomal translocation produces AML1-ETO, an oncogenic fusion protein that compromises the function of AML1, a transcription factor critical for myeloid cell differentiation. Because of the pressing need for new therapies in the treatment of acute myleoid leukemia, we investigated the genome-wide occupancy of AML1-ETO in leukemic cells to discover novel regulatory mechanisms involving AML-ETO bound genes. We report the co-localization of AML1-ETO with the N-CoR co-repressor to be primarily on genomic regions distal to transcriptional start sites (TSSs). These regions exhibit over-representation of the motif for PU.1, a key hematopoietic regulator and member of the ETS family of transcription factors. A significant discovery of our study is that genes co-occupied by AML1-ETO and N-CoR (e.g., TYROBP and LAPTM5) are associated with the leukemic phenotype, as determined by analyses of gene ontology and by the observation that these genes are predominantly up-regulated upon AML1-ETO depletion. In contrast, the AML1-ETO/p300 gene network is less responsive to AML1-ETO depletion and less associated with the differentiation block characteristic of leukemic cells. Furthermore, a substantial fraction of AML1-ETO/p300 co-localization occurs near TSSs in promoter regions associated with transcriptionally active loci. Our findings establish a novel and dominant t(8;21) AML leukemia signature characterized by occupancy of AML1-ETO/N-CoR at promoter-distal genomic regions enriched in motifs for myeloid differentiation factors, thus providing mechanistic insight into the leukemic phenotype.


Wnt signaling pathways participate in Astragalus injection-induced differentiation of bone marrow mesenchymal stem cells.
Bone marrow mesenchymal stem cells (MSCs) have the capacity for self-renewal and multi-directional differentiation, and MSCs can differentiate into neuron-like cells under certain conditions. In this study, we used the traditional Chinese medicine Astragalus as an inducer. After 7 days of induction, the expression of specific markers was detected in each induced group by immunocytochemical staining. The results of real-time quantitative PCR and Western blot confirmed the immunocytochemistry analysis. We also tested some key genes and proteins of the Wnt signaling pathway, and found that they were increased in Astragalus-treated groups. After treatment with lithium chloride (LiCl), the protein expression of phospho GSK-3β and β-catenin was increased in each group compared to the corresponding group without LiCl. These findings demonstrate that Astragalus injection can induce differentiation of MSCs into neuron-like cells and suggest that the process of differentiation might be mediated by activation of Wnt signaling pathways.


Multimodal imaging and treatment of bone metastasis.
The role of molecular imaging in pre-clinical research is continuously evolving. Particularly in small animal models in biomedical research, optical imaging technologies are frequently used to visualize normal as well as aberrant cellular processes at a molecular-genetic or cellular level of function. Also in cancer metastasis research, whole body bioluminescent and fluorescent imaging techniques have become indispensable tools that allow non-invasive and real-time imaging of gene expression, tumor progression and metastasis, and response to therapeutic intervention. In this paper, we discuss the use of optical imaging strategies--either alone or in combination with CT--to study intrabone tumor growth, tumor progression and to monitor efficacy of therapeutic agents in metastatic bone disease.


Tumor-induced Osteomalacia: A Comprehensive Review.
Tumor-induced osteomalacia (TIO) is an ultrarare paraneoplastic syndrome due to overproduction of fibroblast growth factor 23 (FGF23), with profound effects on patient morbidity. TIO is an underdiagnosed disease, whose awareness should be increased among physicians for timely and proper management of patients. Symptoms reported by patients with TIO are usually nonspecific, thus rendering the diagnosis elusive, with an initial misdiagnosis rate of more than 95%. Biochemical features of TIO are represented by hypophosphatemia, increased or inappropriately normal levels of FGF23, and low to low normal circulating 1,25-dihydroxyvitamin D (1,25(OH)2D). Phosphaturic mesenchymal tumors are the pathological entities underlying TIO in most affected patients. There is now evidence that FN1-FGFR1 and FN1-FGF1 fusion genes are present in about half of tumors causing this paraneoplastic syndrome. Tumors causing TIO are small and grow slowly. They can occur in all parts of the body from head to toe with similar prevalence in soft tissue and bone. There are a number of functional and anatomical imaging techniques used for tumor localization; 68Ga DOTA-based technologies have better sensitivity. Surgery is the treatment of choice; several medical treatments are now available in case of inability to locate the tumor or in case of incomplete excision.


Cognitive function in toddlers with congenital heart disease: The impact of a stimulating home environment.
Infants born with congenital heart disease (CHD) are at increased risk of neurodevelopmental difficulties in childhood. The extent to which perioperative factors, cardiac physiology, brain injury severity, socioeconomic status, and home environment influence early neurodevelopment is not clear. Sixty-nine newborns with CHD were recruited from St Thomas' Hospital. Infants underwent presurgical magnetic resonance imaging on a 3-Tesla scanner situated on the neonatal unit. At 22 months, children completed the Bayley Scales of Infant and Toddler Development-3rd edition and parents completed the cognitively stimulating parenting scale to assess cognitive stimulation at home. Level of maternal education and total annual household income were also collected. Hospital records were reviewed to calculate days on the intensive care unit post-surgery, time on bypass during surgery, and days to corrective or definitive palliative surgical intervention. In the final analysis of 56 infants, higher scores on the cognitively stimulating parenting scale were associated with higher cognitive scores at age 22 months, correcting for gestational age at birth, sex, and maternal education. There were no relationships between outcome scores and clinical factors; socioeconomic status; or brain injury severity. Supporting parents to provide a stimulating home environment for children may promote cognitive development in this high-risk population.


Nonsense mutation in the CRYBB2 gene causing autosomal dominant progressive polymorphic congenital coronary cataracts.
We sought to identify the genetic defect in a large, five-generation Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts and to examine the clinical features in detail. Clinical and ophthalmologic examinations were conducted on family members. All members were genotyped with microsatellite markers at loci previously associated with cataracts. Two-point LOD scores were calculated using a linkage package after genotyping. A mutation was detected by direct sequencing and verified by denaturing high-performance liquid chromatography (DHPLC). Clinical observations showed that all affected family members had progressive polymorphic coronary cataracts. Linkage analysis was obtained at markers, D22S303 (LOD score [Z]=2.11, recombination fraction [theta]=0.0) and D22S1167 (Z=1.20, theta=0.0). Haplotype analysis indicated that the cataract gene was closely linked with these two markers. Sequencing the betaB-crystallin gene (CRYBB2) revealed a C --> T transition in exon 6, which changed a codon from Gln to a stop codon (P.Q155X). This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals. This study identified a mutation in CRYBB2 in a large Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts. These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.


Haploinsufficiencies of FOXF1, FOXC2 and FOXL1 genes originated from deleted 16q24.1q24.2 fragment related with alveolar capillary dysplasia with misalignment of pulmonary veins and lymphedema-distichiasis syndrome: relationship to phenotype.
We describe a fetus with a 2.12-Mb terminal deleted fragment in 16q associated with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) and lymphedema-distichiasis syndrome (LDS) and intend to provide a comprehensive prenatal management strategy for the fetuses with ACDMPV and LDS through reviewing other similar published studies. The fetus presented a series of diverse structural malformations including congenital cardiovascular, genitourinary and gastro-intestinal anomalies in ultrasound at 23 + 5 weeks of gestation (GA). Amniocentesis was conducted for karyotype analysis and copy number variation sequencing (CNV-seq) after informed consent. The fetal karyotype was 46,XX, however the result of CNV-seq showed an approximately 2.12-Mb deletion in 16q24.1q24.2 (85220000-87340000) × 1 indicating pathogenicity. Genomic testing should be recommend as a first line diagnostic tool for suspected ACDMPV and/or LDS or other genetic syndromes for the fetuses with structural abnormalities in clinical practice.


Grey matter loss in relapsing-remitting multiple sclerosis: a voxel-based morphometry study.
Global grey matter (GM) loss has been reported in multiple sclerosis (MS). We addressed the question of if and where GM loss is localized by means of optimized voxel-based morphometry, applied to MRI studies of 51 patients with clinically defined relapsing-remitting MS and 34 age-matched normal subjects, segmented into normal and abnormal brain tissues using a multiparametric approach. Segmented GM volumes were subsequently compared on a voxel-by-voxel basis to highlight regions of relative GM loss (P < 0.05, corrected for multiple comparisons at AnCova). Additionally, localized differences in brain asymmetry between the MS and the control groups were assessed by comparing on a voxel-by-voxel basis maps of GM differences between the two hemispheres (P < 0.05 corrected for multiple comparisons). In MS patients, GM volume was significantly decreased at the level of the left fronto-temporal cortex and precuneus, as well as of anterior cingulate gyrus and of caudate nuclei bilaterally. The only cortical region of significant GM loss in the right hemisphere was located in the postcentral area. Furthermore, GM loss regions were colocalized with increased GM asymmetries (Left < Right) in MS, confirming a preferential left-sided GM loss. Caudate atrophy correlated with lesion load, while no correlation between cortical regional GM loss and disease duration, clinical status or lesion load emerged. Our findings suggest that in RR-MS cortical GM reduction preferentially involves left fronto-temporal structures and deep GM, the latter correlating preferentially to global lesion load.


Vaccines in pediatric transplant recipients-Past, present, and future.
Infections significantly impact outcomes for solid organ and hematopoietic stem cell transplantation in children. Vaccine-preventable diseases contribute to morbidity and mortality in both early and late posttransplant time periods. Several infectious diseases and transplantation societies have published recommendations and guidelines that address immunization in adult and pediatric transplant recipients. In many cases, pediatric-specific studies are limited in size or quality, leading to recommendations being based on adult data or mixed adult-pediatric studies. We therefore review the current state of evidence for selected immunizations in pediatric transplant recipients and highlight areas for future investigation. Specific attention is given to studies that enrolled only children.


[Genetic polymorphism of erythrocytic enzymes in Yakut populations].
Polymorphism of the erythrocytic enzymes PGM1, ACP1, ESD, and GLO1 was found in Yakut populations. The allelic frequencies of the polymorphic systems studied varied within the following ranges: PGM1*1+, 0.5833-0.7791; PGM1*1-, 0.0345-0.1176; PGM1*2+, 0.1250-0.2813; ACP1*A, 0.1429-0.3382; ACP1*B, 0.6548-0.8571; ESD*2, 0.1250-0.4643; and GLO1*1, 0.0116-0.2845.


[Effect of splenectomy in gastric carcinoma surgery on cell-mediated immunity; evaluation with alteration of peripheral blood lymphocyte subsets].
Peripheral blood lymphocyte subsets were studied in 70 patients who underwent gastrectomy for gastric carcinoma. Lymphocyte subsets were analysed before and after gastrectomy by use of monoclonal antibody for cell membrane markers. There were significant differences in the gastrectomized patients with splenectomy compared to the patients without splenectomy in postoperative changes of lymphocyte subsets as follows. Decrease of OKT4 and increase of OKT8. Temporary decrease of B-1. Continuous increase of Leu-7. These results suggest that gastrectomized patients with splenectomy show a decrease in helper activity, an increase of suppressor activity of T lymphocytes and a compensatory increase of population of natural killer cells in association with suppression of natural killer activity.


Evaluating the extent of protein damage in dairy products: simultaneous determination of early and advanced glycation-induced lysine modifications.
An isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine lysine (Lys), N(epsilon)-fructosyllysine (FL), N epsilon-carboxymethyllysine (CML), and pyrraline (Pyr) in dairy products. The presented approach entails protein cleavage via enzymatic digestion to liberate the aforementioned compounds, which were then quantified using a stable isotope dilution assay. LC-MS/MS analysis was performed by positive electrospray ionization recording two transition reactions per analyte in selected reaction monitoring mode. The CML and Lys values obtained with enzymatic digestion were compared to those acquired with acid hydrolysis HCl (6 mol/L), and the two proteolysis methods yielded comparable quantifications. Allowing for the fact that the investigated compounds are formed during different stages of the glycation process, the method is able to reveal the progress of protein glycation in dairy products.


Proteotyping: Proteomic characterization, classification and identification of microorganisms--A prospectus.
Modern microbial systematics requires a range of methodologies for the comprehensive characterization, classification and identification of microorganisms. While whole-genome sequences provide the ultimate reference for defining microbial phylogeny and taxonomy, selected biomarker-based strategies continue to provide the means for the bulk of microbial systematic studies. Proteomics, the study of the expression of genes, as well as the structure and function of the resulting proteins, offers indirect measures of genome sequence data. Recent developments in applications of proteomics for analyzing microorganisms have paralleled the growing microbial genome sequence database, as well as the evolution of mass spectrometry (MS) instrumentation and bioinformatics. MALDI-TOF MS, which generates proteomic mass patterns for 'fingerprint'-based characterizations, has provided a marked breakthrough for microbial identification. However, MALDI-TOF MS is limited in the number of targets that can be detected for strain characterization. Advanced methods of tandem mass spectrometry, in which proteins and peptides generated from proteins, are characterized and identified, using LC-MS/MS, provide the ability to detect hundreds or thousands of expressed microbial strain markers for high-resolution characterizations and identifications. Model studies demonstrate the application of proteomics-based analyses for bacterial species- and strain-level detection and identification and for characterization of environmentally relevant, metabolically diverse bacteria. Proteomics-based approaches represent an emerging complement to traditional methods of characterizing microorganisms, enabling the elucidation of the expressed biomarkers of genome sequence information, which can be applied to 'proteotyping' applications of microorganisms at all taxonomic levels.


Primary cutaneous B-cell lymphoma successfully treated with highly active antiretroviral therapy alone: a case report and review of the literature.
Cutaneous B-cell lymphoma (CBCL) is an unusual skin neoplasm with a great range of clinical presentations. Here, we report a case of CBCL in an AIDS patient presented as a single and nodular/ulcerative lesion in the perianal area. The patient was started on highly active antiretroviral therapy alone with a good clinical and oncological response. Two years later, the patient is asymptomatic with undetectable viral load and immune reconstitution.


Characteristics of hospitalized patients with hypercalcemia in the province of Malaga: a longitudinal, retrospective, multicenter study.
There are limited studies analyzing hypercalcemia in hospitalized patients. Our objectives were to describe the clinical characteristics of hospitalized patients with hypercalcemia, estimate its prevalence in the hospital setting, analyze the rate of correction of hypercalcemia, and identify prognostic variables. Observational, longitudinal, retrospective, and bicentric study. Adult patients admitted to two hospitals in Málaga (2014-2018) with a diagnosis of hypercalcemia were included. The minimum follow-up was 2 years or until death. A total of 205 patients with hypercalcemia were included (incidence: 0.13%). The mean age (SD) was 68.2 (13.1) years, with a predominance of males (55.1%). The median (IQR) serum calcium at admission was 13.1 (11.8-14.6) mg/dl. The most common etiologies were neoplasms (75.1%), primary hyperparathyroidism, and medications (both 8.8%). The median (IQR) follow-up period was 5.1 (1.7-60.3) weeks. The most commonly used treatments were fluid therapy (86.8%), loop diuretics (70.9%), bisphosphonates (60.7%), and glucocorticoids (46.2%). The rate of correction of hypercalcemia was 65.2%, with a median (IQR) of 6 (3-10) days. The mortality rate was 81.5%. The median (95% CI) survival was 5.1 (3-7.3) weeks. Factors associated with higher mortality were advanced age, neoplastic etiology, serum calcium at admission, and failure to correct hypercalcemia. Hypercalcemia in hospitalized patients is mainly due to neoplastic processes and is associated with high mortality. We observed a low rate of adherence to recommendations for the management of hypercalcemia.


Research on AIDS patients' survival time after highly active antiretroviral therapy, treatment effect and treatment modes.
To fully define clinical efficacy of highly active antiretroviral therapy for AIDS, analyze patients' survival time and treatment mode after receiving treatment, and provide scientific theory to guide improvement of antiviral therapy, this paper selected 3100 cases of patients diagnosed with AIDS during April 2006 and April 2014 as object of this study. All patients were treated with highly active antiretroviral therapy. The main analysis contents of this study include CD4 + T lymphocyte count, viral load changes, incidence of opportunistic infections, specific cause of death and the like. The results show that patients' CD4 + T lymphocyte levels are significantly increased 3, 18, and 24 months after treatment, difference between the situation after and before receiving treatment, P < 0.05, with statistically significant difference. Analyzed from effective inhibition of virus, effective inhibition rate is 72.58.0% (2250/3100). Main causes of death in patients is usually respiratory failure. It thus can be concluded that highly active antiretroviral therapy for AIDS is with good clinical effect, which can effectively improve survival time of patients. So it enjoys application value of being widely used in clinical treatment of AIDS.


2017 ACC/AHA Blood Pressure Classification and Cardiovascular Disease in 15 Million Adults of Age 20-94 Years.
The 2017 American College of Cardiology/American Heart Association (ACC/AHA) high blood pressure (BP) guideline lowered the cut-off for hypertension, but its age-specific association with cardiovascular disease (CVD) remains inconclusive in different populations. We evaluated the association between high BP according to the 2017 ACC/AHA guideline and CVD risks in Koreans aged 20-94 years. In a nationwide health screening cohort, we included 15,508,537 persons aged 20-94 years without prior CVD. BP was categorized into normal, elevated, stage 1 hypertension, or stage 2 hypertension. The primary outcome was a composite CVD hospitalization (myocardial infarction, stroke, and/or heart failure). Over 10 years of follow-up, CVD incidence rates per 100,000 person-years were 105.4, 168.3, 215.9, and 641.2 for normal, elevated BP, stage 1, and stage 2 hypertension, respectively. The age-specific hazard ratios of stage 1 hypertension compared to normal BP were 1.41 (1.34-1.48) at ages 20-34, 1.54 (1.51-1.57) at ages 35-49, 1.38 (1.35-1.40) at ages 50-64, 1.21 (1.19-1.24) at ages 65-79, and 1.11 (1.03-1.19) at ages 80-94 years. With the lowered BP cut-off, 130/80 mmHg, population attributable fraction for CVD was 32.2%. In conclusion, stage 1 hypertension was significantly associated with a higher CVD risk across entire adulthood. The new definition of hypertension may have a substantial population impact on primary CVD prevention.


Association between SLCO1B1 polymorphism and methotrexate-induced hepatotoxicity: a systematic review and meta-analysis.
Reports on the association between the solute carrier organic anion transporter 1B1 (SLCO1B1) T521C polymorphism and methotrexate-induced hepatotoxicity in patients with malignancies are inconsistent. This meta-analysis evaluated the association between the SLCO1B1 T521C polymorphism and methotrexate-induced hepatotoxicity. We performed a systematic review of previous reports from the PubMed, Web of Science, and EMBASE databases, and a meta-analysis was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate the effect of the SLCO1B1 T521C polymorphism on the occurrence of methotrexate-induced hepatotoxicity. In total, data from five studies including 465 patients were analyzed. Patients had received a high-dose methotrexate regimen (1-5 g/m2). The SLCO1B1 variant allele (C allele) carriers had a 1.9-fold higher risk of hepatotoxicity than wild-type homozygote carriers (TT; OR, 1.94; 95% CI, 1.14-3.31). This meta-analysis demonstrated that C allele carriers of the SLCO1B1 polymorphism had a higher risk of hepatotoxicity than patients with the TT genotype. The SLCO1B1 T521C polymorphism may be a useful predictor for methotrexate-induced hepatotoxicity in patients with malignancies.


Selection of stabilizing additive for lipase immobilization on controlled pore silica by factorial design.
Candida rugosa lipase was covalently immobilized on silanized controlled pore silica (CPS) previously activated with glutaraldehyde in the presence of several additives to improve the performance of the immobilized form in long-term operation. Proteins (albumin and lecithin) and organic molecules (beta-cyclodextrin and polyethylene glycol [PEG]-1500) were added during the immobilization procedure, and their effects are reported and compared to the behavior of the immobilized biocatalyst in the absence (lacking) of additive. The selection of the most efficient additive at different lipase loadings (150-450 U/g of dry support) was performed by experimental design. Two 22 full factorial designs with two repetitions at the center point were employed to evaluate the immobilization yield. A better stabilizing effect was found when small amounts of albumin or PEG-1500 were added simultaneously to the lipase onto the support. The catalytic activity had a maximum (193 U/mg) for lipase loading of 150 U/g of dry support using PEG-1500 as the stabilizing additive. This immobilized system was used to perform esterification reactions under repeated batch cycles (for the synthesis of butyl butyrate as a model). The half-life of the lipase immobilized on CPS in the presence of PEG-1500 was found to increase fivefold compared with the control (immobilized lipase on CPS without additive).


Quality of life assessments in dermatology.
This review describes the many ways in which skin disease can adversely affect the quality of life (QOL) of patients with skin disease. Measurement of this impact is required for clinical and health service research, and may be valuable in clinical practice and in the evaluation of new drug therapy. Methods of measuring QOL in dermatology are described. These include general health measures, dermatology specific measures such as the Dermatology Life Quality Index (DLQI), the Dermatology Quality of Life Scales (DQOLS), the Dermatology Specific Quality of Life (DSQL), and Skindex, and disease specific measures such as the Psoriasis Disability Index (PDI), the Psoriasis Life Stress Inventory (PLSI), and the Acne Disability Index (ADI). Instruments used for measuring QOL in children (the Children's Dermatology Life Quality Index (CDLQI)) and for measuring the impact of atopic dermatitis on the families of affected children (the Dermatitis Family Impact (DFI) questionnaire) are described. Reasons are given for the use of such measures in clinical practice.


K579, a slow-binding inhibitor of dipeptidyl peptidase IV, is a long-acting hypoglycemic agent.
Dipeptidyl peptidase IV inhibitors are expected to be categorized in a new type of antidiabetic drugs. We had developed a long-acting dipeptidyl peptidase IV inhibitor, K579 [(S)-1-[4-methyl-1-(2-pyrimidinyl)-4-piperidylamino]acetyl-2-pyrrolidinecarbonitrile]. The aim of present study was to characterize the pharmacological profiles of K579. In normal rats, K579 suppressed the blood glucose elevation after an oral glucose tolerance test with the increment of plasma insulin and active forms of glucagon-like peptide-1 (GLP-1). During repetitive glucose loading using Zucker fatty rats, pretreatment with K579 attenuated the glucose excursion after the second glucose loading as well as the first glucose loading without inducing hypoglycemia. The kinetic study using cell extract revealed that K579 was a more potent and slower binding inhibitor than the existing dipeptidyl peptidase IV inhibitor (NVP-DPP728, 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine). These profiles of K579 might be advantageous over the existing dipeptidyl peptidase IV inhibitor with respect to less dosing frequency.


Neuronal and non-neuronal components in the overflow of labelled adenyl compounds from guinea-pig taenia coli.
Guinea-pig taenia coli preprations were pre-incubated in 3H-adenosine and the overflow of 3H-compounds to a superfusing medium was measured during transmural field stimulation in the presence and absence of tetrodotoxin. The fractional overflow of 3H-compounds on stimulation of taenia coli pre-incubated in 3H-adenosine at 10(-7) M was greater than after incubation at 10(-5) M. About half of the releasable store was blocked by tetrodotoxin. It is proposed that at lower concentrations, there is selective loading of a releasable store, while at higher concentrations thare is a greater loading of non-releasable stores, and that neuronal stores account for about 33% of the 3H-compounds released by transmural stimulation.


PET study on mice bearing human colon adenocarcinoma cells using [11C]GF120918, a dual radioligand for P-glycoprotein and breast cancer resistance protein.
To evaluate the functions of P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) in human colon adenocarcinoma (Caco-2), we carried out an in-vitro study and a small animal positron emission tomography (PET) study using [C]GF120918 (elacridar). [C]GF120918 was synthesized by reacting the desmethyl precursor with [C]CH3I. An in-vitro study using [C]GF120918 was carried out in Caco-2 and Madin-Darby canine kidney cells in the presence or absence of a transporter inhibitor (cyclosporine A and unlabeled GF120918). The biodistribution of radioactivity after the injection of [C]GF120918 was determined in Caco-2-bearing mice using a small animal PET scanner. In Caco-2 cells expressing Pgp and BCRP, coincubation with unlabeled GF120918 caused an approximately two-fold increase in [C]GF120918 uptake compared with that of the control ([C]GF120918 only). In Caco-2-bearing mice, PET results indicated that [C]GF120918 uptake in the tumor was low, but was significantly increased by treatment with unlabeled GF120918. In metabolite analysis, the radioactive component in the tumor almost corresponded to intact [C]GF120918. A PET study combining the administration of [C]GF120918 with unlabeled GF120918 may be a useful tool for evaluating the functions of Pgp and BCRP in tumors.


In the margins of the mind: development of a projective research methodology for the study of nursing practice.
This article presents an original research method derived from the Thematic Apperception Test used in clinical psychology to understand human motivation and action. The research method is derived from the theory of projection, which states that humans will perceive stimuli in terms of their own expectations and motives and will credit others with their own attitudes, beliefs, traits, and dispositions. Projective techniques are one of a handful of methods that provide access to this type of knowledge since it resides below the level of consciousness. Use of this type of method in nursing research may be fruitful because of its capacity to make apparent the complex interplay between a clinician's beliefs and the interpretation of meaning that motivates clinical action.


Immune tolerance and protection against allergic sensitization.
Recent studies in our laboratory have focused on the nature of the primary T-cell response to inhaled allergens in the regional lymph nodes (RLN) draining the upper airways, in immunologically naive mice and rats. In general terms, the first detectable response involves activation of allergen-specific interleukin 4 (IL-4) secreting CD4+ Th-0/Th-2 cells, which triggers (at least in genetically high-immunoglobulin E (IgE)-responders) an initial burst of IgE antibody synthesis. This is followed by a rapidly expanding interferon gamma (IFN-gamma) response in the RLN, which terminates IL-4 secretion and IgE production. We have presented evidence that the initial source of IFN-gamma in this response is a population of major histocompatibility complex (MHC) class I restricted CD8+ T-cells, which respond specifically to the allergen. The initial activation of these CD8+ T-cells requires a source of exogenous IL-2, which appears to be supplied by the Th-0/Th-2 cells, which are themselves eventually suppressed by the cytokine products of the CD8+ T-cells. It is hypothesized that the IFN-gamma-rich milieu created by the allergen-specific CD8+ T-cells eventually selects for allergen-specific Th-1 cells, which, with chronic stimulation, eventually outgrow the CD8+ population and become dominant in the allergen-specific T-cell memory pool. Our most recent experiments have identified a previously covert but highly potent effector cell subset within the CD8+ T-cell population, in the form of allergen-specific TcR1 (gamma/delta) T-cells. Less than 500 of these cells, purified by positive sorting, are required to regulate the CD4 T-cell response in adult mice or rats, in adoptive transfer experiments.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of long-term release of Shh from implanted biodegradable microspheres on recovery from spinal cord injury in mice.
After spinal cord injury (SCI), loss of cells and damage to ascending and descending tracts can result in paralysis. Current treatments for SCI are based on patient stabilization, and much-needed regenerative therapies are still under development. To activate and instruct stem and progenitor cells or injured tissue to aid SCI repair, it is important to modify the injury environment for a protracted period, to allow time for cell activation, proliferation and appropriate fate differentiation. Shh plays a critical role in spinal cord formation, being involved in multiple processes: it promotes production of motor neurons and oligodendrocytes from ventral cord progenitor cells and serves as an axon guidance molecule. Hence Shh is a candidate pleiotropic beneficial environmental factor for spinal cord regeneration. Here we show that administration of biodegradable microspheres that provide sustained, controlled delivery of Shh resulted in significant functional improvement in two different mouse models of SCI: contusion and dorsal hemioversection. The mechanism is multifactorial, involving increased proliferation of endogenous NG2+ oligodendrocyte lineage cells, decreased astrocytic scar formation and increased sprouting and growth of corticospinal (CST) and raphespinal tract (RST) fibers. Thus, long-term administration of Shh is a potential valuable therapeutic intervention for SCI.


Imatinib and methylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALL AFR09 study.
Acute lymphoblastic leukemia (ALL) in the elderly is characterized by its ominous prognosis. On the other hand, imatinib has demonstrated remarkable, although transient, activity in relapsed and refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), which prompted us to assess the use of imatinib in previously untreated elderly patients. ALL patients aged 55 years or older were given steroids during 1 week. Ph+ve cases were then offered a chemotherapy-based induction followed by a consolidation phase with imatinib and steroids during 2 months. Patients in complete response (CR) after consolidation were given 10 maintenance blocks of alternating chemotherapy, including two additional 2-month blocks of imatinib. Thirty patients were included in this study and are compared with 21 historical controls. Out of 29 assessable patients, 21 (72%, confidence interval (CI): 53-87%) were in CR after induction chemotherapy vs 6/21 (29%, CI: 11-52%) in controls (P=0.003). Five additional CRs were obtained after salvage with imatinib and four after salvage with additional chemotherapy in the control group. Overall survival (OS) is 66% at 1 year vs 43% in the control group (P=0.005). The 1-year relapse-free survival is 58 vs 11% (P=0.0003). The use of imatinib in elderly patients with Ph+ ALL is very likely to improve outcome, including OS.


Ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve.
Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal demyelination in the brain and spinal cord. Studies showed that iron released during the course of myelin breakdown exacerbates tissue damage, which is in agreement with the features of iron-dependent cell death, ferroptosis. Here, we aimed to investigate the possible contribution of ferroptosis in the demyelinated optic nerve, and to explore the effectiveness of ferroptosis inhibitor, deferiprone (DFP), on the extent of demyelination, inflammation and axonal damage. For this purpose, focal demyelination was induced by injection of lysolecithin (LPC), into the optic nerve of male C57BL/6J mice. Afterward, optic nerves were harvested at different time points from as early as 6 h up to 7 days post-LPC injection. Next, to evaluate the effectiveness of DFP two groups of animals received daily intraperitoneal injection of DFP for 3 or 7 continuous days. Vehicle groups received saline. Iron deposition was observed at different time points post-LPC injection from 6 h to 7 days post injection. Examining ferroptosis markers showed a significant reduction in glutathione content along with increased level of malondialdehyde and upregulated ferroptosis marker genes at early time points after injection. Besides, DFP treatment during the inflammatory phase of the model resulted in decreased microgliosis and inflammation. Reduced demyelination, microgliosis and astrogliosis was shown in mice that received DFP for 7 days. Moreover, DFP protected against axonal damage and retinal ganglion cells loss. Our results suggest the possible contribution of ferroptosis pathway in the process of demyelination. The therapeutic strategies targeting iron deposition, e.g. DFP treatment might thus represent a promising therapeutic target for patients with MS.


Cell micropatterning reveals the modulatory effect of cell shape on proliferation through intracellular calcium transients.
The mechanism by which cell shape regulates the function of the cell is one of the most important biological issues, but it remains unclear. Here, we investigated the effect of the regulation of cell shape on proliferation by using a micropatterning approach to confine MC3T3-E1 cells into specific shapes. Our results show that the proliferation rate for rectangle-, triangle-, square- and circle-shaped osteoblasts increased sequentially and was related to the nuclear shape index (NSI) but not the cell shape index (CSI). Interestingly, intracellular calcium transients also displayed different patterns, with the number of Ca2+ peaks increasing with the NSI in shaped cells. Further causal investigation revealed that the gene expression levels of the inositol 1,4,5-triphosphate receptor 1 (IP3R1) and sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), two major calcium cycling proteins in the endoplasmic reticulum (ER), were increased with an increase in NSI as a result of nuclear volume changes. Moreover, the down-regulation of IP3R1 and/or SERCA2 using shRNAs in circle-shaped or control osteoblasts resulted in changes in intracellular calcium transient patterns and cell proliferation rates towards that of smaller-NSI-shaped cells. Our results indicate that changes in cell shape changed nuclear morphology and then the gene expression of IP3R1 and SERCA2, which produced different intracellular calcium transient patterns. The patterns of intracellular calcium transients then determined the proliferation rate of the shaped osteoblasts.


Experiences of Attending Group Education to Support Insulin Initiation in Type 2 Diabetes: A Qualitative Study.
Type 2 diabetes is a progressive condition and many people require insulin therapy 5-10 years post diagnosis. Considering the global increase in type 2 diabetes, group education programmes to initiate insulin are beneficial as they are cost-effective and provide peer support. However, group education to initiate insulin has not been widely evaluated and there is a need to elicit the views and experience of people with type 2 diabetes who start insulin in groups. The aim of this study was to explore the perspectives of people with type 2 diabetes who receive nurse-led group-based insulin education. Qualitative, semi-structured interviews of people with type 2 diabetes in south London, UK, who had attended group education sessions to start insulin. Inductive thematic analysis identified themes within the data. Fifteen people with type 2 diabetes were interviewed. Three main themes were identified: creating a supportive environment; facilitator skills; and effectiveness of group. Factors which created a supportive environment included peer support, providing reassurance and printed materials. Facilitator skills associated with positive experiences included addressing negative insulin beliefs and managing group dynamics. The effectiveness of the group was determined by ongoing self-management success, need for more peer support, and insulin concerns post insulin education group. Positive experiences of insulin group education for people with type 2 diabetes were associated with sharing experiences with other people starting insulin, reassurance from healthcare professionals, appropriate supportive materials, and skill of the facilitator to address insulin concerns and manage group dynamics. People with type 2 diabetes may benefit more from education if healthcare professionals are skilled in psychological techniques to facilitate group education aimed at addressing concerns around insulin therapy. Further research needs to assess the effectiveness of structured insulin group education for people with type 2 diabetes.


The role of chromatin structure in regulating the expression of clustered genes.
Much of what we know about the chromatin-based mechanisms that regulate gene expression in mammals has come from the study of what are, paradoxically, atypical genes. These are clusters of structurally and/or functionally related genes that are coordinately regulated during development, or between different cell types. Can unravelling the mechanisms of gene regulation at these gene clusters help us to understand how other genes are controlled? Moreover, can it explain why there is clustering of apparently unrelated genes in mammalian genomes?


Environmental Surveillance of Genogroup I and II Noroviruses in Shandong Province, China in 2013.
Noroviruses are the most common cause of epidemic gastroenteritis. However, the case-based surveillance is limited in China. In this study, we analyzed the results of environmental surveillance conducted in two cities of Shandong Province, China from January to December in 2013. Twenty-four sewage samples were collected and concentrated via membrane absorption/elution method. After reverse transcription-PCR, cloning and sequencing on ORF2 region, norovirus nucleic acid was detected in all 24 sewage samples. A total of 403 norovirus sequences of 16 genotypes were detected, among which GII.3 (22.6%), GI.2 (17.1%), GI.5 (13.4%), GI.3 (11.9%), GII.4 (7.7%), and GII.6 (6.7%) were the 6 most common genotypes. Phylogenetic analysis revealed multiple lineages within most common genotypes, especially in GI.3, whereas all GII.4 sequences belonged to Sydney 2012 strain. Recombination events were observed in 5 GI and 4 GII sequences within or near the ORF1/ORF2 overlap. This is the first report on systematic environmental surveillance on norovirus in China. The data presented here reveal co-circulation and high genetic diversity of multiple norovirus genotypes in the two cities, and suggest continued environmental surveillance can provide valuable information on norovirus circulation in the population.


Castration and tolerance induces changes in the levels of the activity of acetylcholinesterase in the isolated vas deferens of the rat.
Changes in the activity of acetylcholinesterase (AChE) of the isolated vas deferens from normal, castrated, morphine and ethanol-tolerant rats were studied. Three days after the termination of treatment with morphine and on the last day of treatment with ethanol, a significant inhibition of the activity of AChE was detected. This reduction in the enzymatic activity persisted in morphine-tolerant rats for 15 days, but not for 30 days, at which time the levels of AChE were determined to be normal. However, in ethanol-tolerant rats, there were no significant changes found at days 15 or 30. The activity of AChE was decreased significantly in castrated rats, but this effect was reversed by treatment with testosterone. During withdrawal from morphine or ethanol, the levels of AChE were significantly increased. The results indicate that morphine and ethanol may be inducing changes in the feedback mechanism which regulates the levels of AChE at post-synaptic sites, and these changes could play an important role in the development of tolerance to morphine and to ethanol.


Long-term depression of inhibitory synaptic transmission induced by spike-timing dependent plasticity requires coactivation of endocannabinoid and muscarinic receptors.
The precise timing of pre-postsynaptic activity is vital for the induction of long-term potentiation (LTP) or depression (LTD) at many central synapses. We show in synapses of rat CA1 pyramidal neurons in vitro that spike timing dependent plasticity (STDP) protocols that induce LTP at glutamatergic synapses can evoke LTD of inhibitory postsynaptic currents or STDP-iLTD. The STDP-iLTD requires a postsynaptic Ca(2+) increase, a release of endocannabinoids (eCBs), the activation of type-1 endocananabinoid receptors and presynaptic muscarinic receptors that mediate a decreased probability of GABA release. In contrast, the STDP-iLTD is independent of the activation of nicotinic receptors, GABAB Rs and G protein-coupled postsynaptic receptors at pyramidal neurons. We determine that the downregulation of presynaptic Cyclic adenosine monophosphate/protein Kinase A pathways is essential for the induction of STDP-iLTD. These results suggest a novel mechanism by which the activation of cholinergic neurons and retrograde signaling by eCBs can modulate the efficacy of GABAergic synaptic transmission in ways that may contribute to information processing and storage in the hippocampus.


Group psychotherapy as an aid in the medical treatment of eczema.
The ongoing management of severe adult eczema is often difficult and problematic for both patient and doctor. A group of ten adult eczema patients were given group psychotherapy as a supplement to their regular medical regimen. Five target symptoms were rated on a biweekly basis first to establish individual baselines of disease course and later to measure treatment effect. The psychologic treatment combined behavioral and cognitive interventions with relaxation training. Patients used multiple self-rating sheets to provide feedback with the goal of increasing their skills in the management of scratching behaviors. At the end of treatment all ten patients showed significant reduction in targeted symptoms.


On the origin of termite workers: weighing up the phylogenetic evidence.
Resolving the phylogenetic history of a 'true' worker caste in termites is essential to our understanding of termite eusocial evolution. Whether this caste is ancient and monophyletic or derived and polyphyletic will have a tremendous impact on our interpretation of termite eusocial history and remains an outstanding question in termite biology. Recent work has begun to re-examine this question in light of new phylogenetic information, but new questions have now arisen about how best to model character state changes in termite caste systems. In the present paper, we compare the models of Grandcolas and D'Haese [J. Evol. Biol. 15 (2002) 885] and Thompson et al. [J. Evol Biol. 13 (2000) 8691 and attempt to make explicit how these proposals differ with respect to the number of, and homology between, character states. We highlight the support each model has for the two principal, but competing, evolutionary hypotheses outlined above.


Lanthanide coordination polymers and their Ag+-modulated fluorescence.
Four 3-D coordination polymers of lanthanide with a tetra(amino acid) ligand, 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrapropionic acid (H4L, 1), were synthesized. The structure of the Gd(III) complex was characterized. The fluorescence of the Eu(III) complex can be modulated by Ag+.


Preoperative Opioid Utilization Patterns and Postoperative Opioid Utilization: A Retrospective Cohort Study.
Among chronic opioid users, the association between decreasing or increasing preoperative opioid utilization and postoperative outcomes is unknown. The authors hypothesized that decreasing utilization would be associated with improved outcomes and increasing utilization with worsened outcomes. Using commercial insurance claims, the authors identified 57,019 chronic opioid users (10 or more prescriptions or 120 or more days supplied during the preoperative year), age 18 to 89 yr, undergoing one of 10 surgeries between 2004 and 2018. Patients with a 20% or greater decrease or increase in opioid utilization between preoperative days 7 to 90 and 91 to 365 were compared to patients with less than 20% change (stable utilization). The primary outcome was opioid utilization during postoperative days 91 to 365. Secondary outcomes included alternative measures of postoperative opioid utilization (filling a minimum number of prescriptions during this period), postoperative adverse events, and healthcare utilization. The average age was 63 ± 13 yr, with 38,045 (66.7%) female patients. Preoperative opioid utilization was decreasing for 12,347 (21.7%) patients, increasing for 21,330 (37.4%) patients, and stable for 23,342 (40.9%) patients. Patients with decreasing utilization were slightly less likely to fill an opioid prescription during postoperative days 91 to 365 compared to stable patients (89.2% vs. 96.4%; odds ratio, 0.323; 95% CI, 0.296 to 0.352; P < 0.001), though the average daily doses were similar among patients who continued to utilize opioids during this timeframe (46.7 vs. 46.5 morphine milligram equivalents; difference, 0.2; 95% CI, -0.8 to 1.2; P = 0.684). Of patients with increasing utilization, 93.6% filled opioid prescriptions during this period (odds ratio, 0.57; 95% CI, 0.52 to 0.62; P < 0.001), with slightly lower average daily doses (44.3 morphine milligram equivalents; difference, -2.2; 95% CI, -3.1 to -1.3; P < 0.001). Except for alternative measures of persistent postoperative opioid utilization, there were no clinically significant differences for the secondary outcomes. Changes in preoperative opioid utilization were not associated with clinically significant differences for several postoperative outcomes including postoperative opioid utilization.


Reduced nicotine content cigarettes and nicotine patch.
Reduced nicotine content (RNC) cigarettes have led to smoking fewer cigarettes, withdrawal relief, and facilitation of cessation. The aim of this study is to examine the effects RNC cigarettes with and without nicotine patch and patch alone on smoking behavior, toxicant exposure, withdrawal discomfort, and as an exploratory analysis, on long-term abstinence. This study involved a randomized, parallel arm design and six weeks of: (i) 0.05-0.09 mg nicotine yield cigarettes (N = 79); (ii) 21 mg nicotine patch (N = 80), or (iii) 0.05-0.09 nicotine yield cigarettes with 21 mg nicotine patch (N = 76); all groups received six weeks of additional behavioral treatment with follow-ups up to six months. Combination approach led to lower rates of smoking assigned cigarettes and hence lower carbon monoxide levels than RNC cigarettes alone. In addition, the combination approach was associated with less withdrawal severity when switching from usual brand to assigned product, and less smoking of usual brand cigarettes during treatment, but not after treatment compared with the other approaches. Combining very low nicotine content cigarettes with nicotine patch may improve the acute effects resulting from switching to either of these products alone. These findings may have implications for smoking cessation treatment or a policy measure to reduce nicotine content in cigarettes.


Imaging for the Pretreatment Staging of Small cell Lung Cancer: A Systematic Review.
Small cell lung cancer (SCLC) is an aggressive form of lung cancer. Accurate staging is essential to select the optimal treatment plan to maximize survival. No consensus exists on standard imaging modalities for pretreatment staging of SCLC. We conducted a systematic review of the literature on imaging modalities in the pretreatment staging of SCLC. A systematic search of multiple databases identified relevant studies published from 2000 through June 2015. Outcomes of interest included test concordance, staging accuracy (sensitivity and specificity), choice of treatment, timeliness of treatment, and patient outcomes. The search identified 2880 citations; 7 studies met inclusion criteria, n = 408 patients. Six of the seven studies were deemed to have moderate risk of bias, and one was deemed to have high risk of bias. One of the studies reported test concordance, three studies reported comparative accuracy of testing strategies, and four studies reported the accuracy of a single imaging modality. Analysis from these studies revealed that fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is more sensitive than multidetector CT for detecting osseous metastases, more sensitive than bone scintigraphy for detecting osseous metastases, and more sensitive for detecting any distant metastases. Evidence is sparse on the use of imaging in the pretreatment staging of SCLC. There is a lack of evidence on patient-oriented outcomes and a lack of evidence on whether comparative accuracy or effectiveness is associated with patient factors. We found low-strength evidence suggesting that FDG-PET/CT is more sensitive than CT and bone scintigraphy for detecting osseous metastases.


DeepCOVNet Model for COVID-19 Detection Using Chest X-Ray Images.
COVID-19 is an epidemic disease that has threatened all the people at worldwide scale and eventually became a pandemic It is a crucial task to differentiate COVID-19-affected patients from healthy patient populations. The need for technology enabled solutions is pertinent and this paper proposes a deep learning model for detection of COVID-19 using Chest X-Ray (CXR) images. In this research work, we provide insights on how to build robust deep learning based models for COVID-19 CXR image classification from Normal and Pneumonia affected CXR images. We contribute a methodical escort on preparation of data to produce a robust deep learning model. The paper prepared datasets by refactoring, using images from several datasets for ameliorate training of deep model. These recently published datasets enable us to build our own model and compare by using pre-trained models. The proposed experiments show the ability to work effectively to classify COVID-19 patients utilizing CXR. The empirical work, which uses a 3 convolutional layer based Deep Neural Network called "DeepCOVNet" to classify CXR images into 3 classes: COVID-19, Normal and Pneumonia cases, yielded an accuracy of 96.77% and a F1-score of 0.96 on two different combination of datasets.


Alternative methods of measuring competition applied to two Australian hermit crabs.
This article describes the intertidal hermit crab species assemblage at One Tree Island, Great Barrier Reef, Australia. Competition for shells between the two most abundant species, Clibanarius virescens and Calcinus latens, is studied in more detail. Competition appears to be primarily exploitative. The relative intensities of inter- and intra-specific competition between this pair of species are estimated using two different methods. The first is based on habitat overlap data in conjunction with a mathematical model of shell population dynamics described in Abrams (1980). The second method is more direct, and is based on following the fate of marked empty shells. Results of the two methods are very similar. This supports the validity of assumptions made in applying the first method. The relative amount of interspecific competition between these two species appears to be greater than that for other hermit crab species pairs studied previously.


Stop-signal task difficulty and the right inferior frontal gyrus.
The stop-signal paradigm is increasingly being used as a probe of response inhibition in basic and clinical neuroimaging research. The critical feature of this task is that a cued response is countermanded by a secondary 'stop-signal' stimulus offset from the first by a 'stop-signal delay'. Here we explored the role of task difficulty in the stop-signal task with the hypothesis that what is critical for successful inhibition is the time available for stopping, that we define as the difference between stop-signal onset and the expected response time (approximated by reaction time from previous trial). We also used functional magnetic resonance imaging (fMRI) to examine how the time available for stopping affects activity in the putative right inferior frontal gyrus and presupplementary motor area (right IFG-preSMA) network that is known to support stopping. While undergoing fMRI scanning, participants performed a stop-signal variant where the time available for stopping was kept approximately constant across participants, which enabled us to compare how the time available for stopping affected stop-signal task difficulty both within and between subjects. Importantly, all behavioural and neuroimaging data were consistent with previous findings. We found that the time available for stopping distinguished successful from unsuccessful inhibition trials, was independent of stop-signal delay, and affected successful inhibition depending upon individual SSRT. We also found that right IFG and adjacent anterior insula were more strongly activated during more difficult stopping. These findings may have critical implications for stop-signal studies that compare different patient or other groups using fixed stop-signal delays.


Characteristics of anoxic phosphorus removal in sequence batch reactor.
The characteristics of anaerobic phosphorus release and anoxic phosphorus uptake were investigated in sequencing batch reactors using denitrifying phosphorus removing bacteria (DPB) sludge. The lab-scale experiments were accomplished under conditions of various nitrite concentrations (5.5, 9.5, and 15 mg/L) and mixed liquor suspended solids (MLSS) (1844, 3231, and 6730 mg/L). The results obtained confirmed that nitrite, MLSS, and pH were key factors, which had a significant impact on anaerobic phosphorus release and anoxic phosphorus uptake in the biological phosphorous removal process. The nitrites were able to successfully act as electron acceptors for phosphorous uptake at a limited concentration between 5.5 and 9.5 mg/L. The denitrification and dephosphorous were inhibited when the nitrite concentration reached 15 mg/L. This observation indicated that the nitrite would not inhibit phosphorus uptake before it exceeded a threshold concentration. It was assumed that an increase of MLSS concentration from 1844 mg/L to 6730 mg/L led to the increase of denitrification and anoxic P-uptake rate. On the contrary, the average P-uptake/N denitrifying reduced from 2.10 to 1.57 mg PO4(3-)-P/mg NO3(-)-N. Therefore, it could be concluded that increasing MLSS of the DEPHANOX system might shorten the reaction time of phosphorus release and anoxic phosphorus uptake. However, excessive MLSS might reduce the specific denitrifying rate. Meanwhile, a rapid pH increase occurred at the beginning of the anoxic conditions as a result of denitrification and anoxic phosphate uptake. Anaerobic P release rate increased with an increase in pH. Moreover, when pH exceeded a relatively high value of 8.0, the dissolved P concentration decreased in the liquid phase, because of chemical precipitation. This observation suggested that pH should be strictly controlled below 8.0 to avoid chemical precipitation if the biological denitrifying phosphorus removal capability is to be studied accurately.


Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its overexpression sensitizes brain tumor cells to apoptosis following alkylation damage of DNA.
The human Dkk-1 (hDkk-1) gene, a transcriptional target of the p53 tumor suppressor, encodes a powerful inhibitor of the Wnt signaling pathway and regulates the spatial patterning/morphogenesis of the mammalian central nervous system. We investigated the p53-related functions of the hDkk-1 gene by studying its response to DNA damage and its modulation of apoptosis in human glioma cells. Various chemotherapeutic and other agents that induce DNA adducts and compromise its integrity (1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin, H(2)O(2) and UV rays) enhanced the expression of hDkk-1 significantly. The damage-induced increase in hDkk-1 mRNA levels occurred in many human tumor cell lines, irrespective of their p53 gene status. The human glioblastoma cell line, U87MG, which had undetectable hDkk-1 expression, was engineered to express moderate levels of the hDkk protein by stable transfection. The engineered cells did not show any morphological changes, but underwent marked apoptosis after ceramide treatment. Further, the DNA cross-linking drugs BCNU and cisplatin, but not the microtubule poison vincristine, induced significant cell death in U87MG/hDkk cells, and this was accompanied by altered Bcl-2/Bax expression and a reduction in the amount of telomere DNA as visualized by fluorescence in situ hybridization. These results show that hDkk-1 is a pro-apoptotic gene and suggest that it may play important roles in linking the oncogenic Wnt and p53 tumor suppressor pathways.


Levoglucosan evidence for biomass burning records over Tibetan glaciers.
Intense biomass burning (BB) events are widespread in tropical and subtropical Asia. However, the impact of BB aerosols on the Tibetan Plateau (TP), especially on Tibetan glaciers, is poorly understood. In this study, BB signals are revealed using the specific molecular tracer levoglucosan in snow and ice samples from different Tibetan glaciers. Tibetan glaciers mainly act as receptors of BB emissions from surrounding regions. Significant differences in levoglucosan concentrations in glacier samples collected from two slopes on the same mountain range indicate that high mountains can act as natural barriers to block the transport of smoke aerosols to the TP. Levoglucosan concentrations show a decreasing trend from west to east on glaciers impacted by the Indian summer monsoon on the southern edge of the TP, while the opposite pattern was observed on glaciers under the prevailing westerlies along the northern edge. The emission sources, the controlling climate system, as well as deposition and degradation during transport determined the spatial distribution regimes of levoglucosan concentration on Tibetan glaciers.


Arthroscopic Bankart repair with remplissage versus Latarjet procedure for management of engaging Hill-Sachs lesions with subcritical glenoid bone loss in traumatic anterior shoulder instability: a systematic review and meta-analysis.
A large engaging Hill-Sachs lesion (HSL) with subcritical glenoid bone loss (GBL) is approached through either increasing the glenoid arc by the Latarjet procedure or converting the HSL to an extra-articular defect by arthroscopic Bankart repair with remplissage (BRR). Until now, there has been no evidence-based consensus about which of these 2 most appropriate procedures is the better surgical choice. The purpose of this study was to analyze the current literature comparing results of BRR vs. the Latarjet procedure in the treatment of engaging HSLs with subcritical GBL. A comprehensive review of the PubMed and Cochrane databases was completed for studies that compared the clinical outcomes and complications of BRR vs. the Latarjet procedure with minimum follow-up of 2 years. The outcome measures analyzed included postoperative Rowe score, visual analog scale pain score, postoperative range of motion (ROM), and rates of recurrent instability and other complications. Overall, 4 articles (level III evidence in 3 and level II in 1) were included from an initial 804 abstracts. The study population consisted of a total of 379 patients, of whom 194 underwent BRR and 185 underwent the Latarjet procedure. There were no unacceptable differences in baseline characteristics between the 2 groups. For the rate of recurrent instability, both groups had comparable risk ratios (RRs) (N = 379; RR, 0.72; 95% confidence interval [CI], 0.37-1.41). The risk of other complications was significantly increased with the Latarjet procedure (by about 7 times) relative to the the BRR procedure (N = 379; RR, 7.37; 95% CI, 2-27). Both groups had comparable postoperative Rowe scores (n = 190; mean difference [MD], -0.9; 95% CI, -3.45 to 1.7) and visual analog scale pain scores (n = 347; MD, -0.2; 95% CI, -0.6 to 0.2). Moreover, both groups had comparable postoperative external rotation ROM (MD, -1.7°; 95% CI, -9.4° to 6°) and internal rotation ROM (MD, 1.95°; 95% CI, -5.35° to 9.25°). There was substantial heterogeneity in the effect of both procedures on postoperative pain and ROM (external rotation and internal rotation). Both the BRR and Latarjet procedures are effective for the management of engaging HSLs with subcritical GBL and give comparable clinical outcomes. However, given the fewer overall postoperative complications, remplissage may be safer. The results of the included studies were adequately consistent for most analyzed outcomes. However, for the intervention effect on postoperative pain and ROM, there was a small body of evidence, limiting the strength of the reported conclusions.


A pathway analysis of genome-wide association study highlights novel type 2 diabetes risk pathways.
Genome-wide association studies (GWAS) have been widely used to identify common type 2 diabetes (T2D) variants. However, the known variants just explain less than 20% of the overall estimated genetic contribution to T2D. Pathway-based methods have been applied into T2D GWAS datasets to investigate the biological mechanisms and reported some novel T2D risk pathways. However, few pathways were shared in these studies. Here, we performed a pathway analysis using the summary results from a large-scale meta-analysis of T2D GWAS to investigate more genetic signals in T2D. Here, we selected PLNK and VEGAS to perform the gene-based test and WebGestalt to perform the pathway-based test. We identified 8 shared KEGG pathways after correction for multiple tests in both methods. We confirm previous findings, and highlight some new T2D risk pathways. We believe that our results may be helpful to study the genetic mechanisms of T2D.


Estimates of shape by eye, or, the little invariant that could.
Five experiments were conducted to test the hypothesis that observers apprehend specific constancies under change in perspective. The constancies were projective properties of ellipses pictured to slant and tilt in depth. Observers were asked to reproduce the static upright view of a moving pair of ellipses, using a computer graphics display and interface. Projective invariants for pairs of conics were computed on the observers' productions. A few experimental conditions revealed near-perfect performance. When pairs of coplanar ellipses were viewed under dynamic transformation in perspective, then invariants calculated on the observers' productions were a match--in value on average--to the invariants of the transforming ellipse pairs. It is proposed that measures of projective properties afford a family of techniques that can be applied to gauge acuity for complex shapes in the study of visual form perception.