Knowledge acquisition and strategic action in "Mastermind" problems.
In two experiments, the strategies used by subjects playing the logical-deduction game, Mastermind, were examined. In the first experiment, subjects showed improvement resulting from the continued use of a particular strategic action, and the data suggested that the subjects learned the strategy from their transactions with the task. In the second experiment, the question of changes in underlying strategic knowledge of Mastermind was examined. The accuracy and complexity of the subjects' deductions and their use of the previously identified strategy were used to generate a model of the cognitive operations involved in Mastermind. Although there were improvements in the accuracy and complexity of the subjects' deductions resulting from continued play, these improvements were unrelated to the use of the strategy. Moreover, the likelihood of making accurate and complex deductions was well accounted for by a Markovian model, suggesting that the deployment of the strategy was not driven by any change in the subject's underlying knowledge structures. Rather, the subjects seemed to use the strategy to create Mastermind situations whose interpretation was fairly easy. The implications for previous work on the issue of Mastermind strategies and the development of logical-deduction strategies are discussed.


How do soil microbial communities respond to fire in the intermediate term? Investigating direct and indirect effects associated with fire occurrence and burn severity.
Fires transform soil microbial communities directly via heat-induced mortality and indirectly by altering plant and soil characteristics. Emerging evidence suggests the magnitude of changes to some plant and soil properties increases with burn severity, but the persistence of changes varies among plant and soil characteristics, ranging from months to years post-fire. Thus, which environmental attributes shape microbial communities at intermediate time points during ecosystem recovery, and how these characteristics vary with severity, remains poorly understood. We identified the network of properties that influence microbial communities three years after fire, along a burn severity gradient in Sierra Nevada mixed-conifer forest. We used phospholipid fatty acid (PLFA) analysis and bacterial 16S-rDNA amplicon sequencing to characterize the microbial community in mineral soil. Using structural equation modelling, we applied a systems approach to identifying the interconnected relationships among severity, vegetation, soil, and microbial communities. Dead tree basal area, soil pH, and extractable phosphorus increased with severity, whereas live tree basal area, forest floor mass, and the proportion of the ≥53 μm soil fraction decreased. Forest floor loss was associated with decreased soil moisture across the severity gradient, decreased live tree basal area was associated with increased shrub coverage, and increased dead tree basal area was associated with increases in total and inorganic soil nitrogen. Soil fungal abundance decreased across the severity gradient, despite a slightly positive response of fungi to lower soil moisture in high severity areas. Bacterial phylogenetic diversity was negatively related to severity and was driven by differences in nutrients and soil texture. The abundance of Bacteroidetes increased and the abundance of Acidobacteria decreased across the severity gradient due to differences in soil pH. Overall, we found that the effects of burn severity on vegetation and soil physicochemical characteristics interact to shape microbial communities at an intermediate time point in ecosystem recovery.


Fine structure of rat septohippocampal neurons: II. A time course analysis following axotomy.
Previous light microscopic immunocytochemical studies with antibodies against transmitter-synthesizing enzymes have suggested that septohippocampal neurons undergo retrograde degeneration following transection of their axons by cutting the fimbria-fornix. However, a fine-structural analysis of the degeneration process in these cells is lacking so far. Here we have identified septohippocampal neurons by retrograde tracing with Fluoro-Gold. Thereafter, the fimbria-fornix was transected bilaterally. Fine-structural changes in prelabeled septohippocampal neurons were then studied after varying survival times up to 10 weeks. Examination under the fluorescence microscope of Vibratome sections through the septal region revealed numerous retrogradely labeled cells after all survival times following axotomy. These neurons were then intracellularly injected with the fluorescent dye Lucifer Yellow in order to stain their dendritic arbor. Many cells were found after each survival time that displayed characteristics of septohippocampal neurons in control rats (see Naumann et al., J Comp Neurol 325:207-218, 1992). In addition, increasing with survival time, there were many shrunken neurons with a reduced dendritic arbor. Representative examples of both normal appearing and shrunken neurons were photoconverted for subsequent electron microscopic analysis. Relatively few signs of neuronal degeneration were found at each survival time analyzed. The majority of cells, including the heavily shrunken ones, displayed fine-structural characteristics of normal neurons. However, a few degenerating neurons and reactive glial cells were present in all survival stages. We conclude that axotomized septohippocampal projection neurons cease the expression of transmitter-synthesizing enzymes and shrink, but many more cells survive for extended periods of time without target-derived neurotrophic factor than was assumed in previous light microscopic studies.


Robotic-assisted laparoscopic implantation of artificial urinary sphincter in women with intrinsic sphincter deficiency incontinence: initial results.
To investigate the feasibility, safety, and functional results of robotic-assisted artificial urinary sphincter (R-AUS) laparoscopic implantation in women with stress urinary incontinence due to intrinsic sphincter deficiency. Six women underwent an R-AUS implantation between 2012 and 2013. The mean age was 65 ± 9.6 years. Five patients had previous surgery for incontinence. The mean duration of follow-up was 14.3 months. A transperitoneal approach with a lateral positioning of the robotic arms was performed. The cuff implantation, positioning of the reservoir, and the pump were carried out similarly to the laparoscopic technique. Operative time, intraoperative occurrence of injuries of the bladder or vagina, postoperative complications, and continence (pad per day) were assessed. The R-AUS implantation was feasible in all cases without intraoperative injury and 1 grade 1 postoperative complication. Mean operative time, postoperative bladder catheterization, and hospitalization time were 210 ± 32 minutes, 7 days, and 6 days, respectively. At the end of the follow-up, 83% of cases were fully continent. R-AUS implantation in incontinent women with intrinsic sphincter deficiency was feasible and safe with good functional results. More data are needed before concluding to the superiority of this new technique compared with open or laparoscopic approaches.


[Strategy for planning and execution of a large-scale SARS-CoV-2 seroprevalence study on teaching hospital workers during a pandemic situation].
To describe the planning and execution process of a massive seroprevalence study for SARS-CoV-2 in professionals of the Hospital Universitario Fundación Alcorcón (HUFA) (Spain). A description is presented of the plan designed and developed at the HUFA for the execution of the extraction of the samples for serology from all the professionals who worked in the hospital between 14 and 29 April 2020. A descriptive analysis of the participation of the professionals in the study is carried out. Extraction areas, health personnel, and execution times were planned. A total of 2326 extractions were assigned to health personnel, the remaining extractions were assigned to workers from external companies. A total of 2641 workers (90.5%) out of 2918 candidates participated in the study. The professional category most analysed was nursing with 28.3% (n = 590). The percentage of compliance with schedule planning was 28.6%. Up to a maximum of 298 daily extractions were planned. The busiest day was the 4th day of the study with 399 extractions. The organising of such a large study, with a 100% coverage of those who worked in the hospital, and with such a great response from the workers involved, has led to obtaining results of high reliability in the seroprevalence study carried out. Although the percentage of participation was very high, the level of compliance with the planning was low.


Intermittent oculomotor nerve paresis and hollow appearance on MRI manifested by pituitary adenoma.
A 71-year-old man had sustained intermittent ptosis and double vision for 2 weeks. Neurological examination found unilateral oculomotor nerve (CN III) paresis manifesting as limitations of gaze, ptosis, and mydriasis. Neither headache nor any other cranial neuropathy was noted. Cerebral magnetic resonance imaging revealed a well-circumscribed mass in the pituitary fossa extending laterally into the left cavernous sinus. The segment of the left CN III lying in the oculomotor cistern was considerably compressed by the tumor. The cisternal segments of the left CN III showed an undescribed, "hollow" appearance. The left orbit and brainstem were intact. The patient underwent tumor resection via an endoscopic transsphenoidal approach. The tumor tissue was soft in consistency, involving xanthochromic fluid. The pathological diagnosis was pituitary adenoma accompanied with considerable hemorrhagic changes. The patent's ptosis and limitations of gaze showed remarkable improvements on postoperative day 1, with resolution of the hollow appearance of the affected CN III that was confirmed on day 3. We assumed that the intralesional bleeds and lateral tumor extension into the oculomotor cistern were associated with the intermittent paresis of the CN III as the sole presentation. A hollow appearance identified in the CN III might indicate a reversible dysfunction of the nerve that can anticipate an improvement by prompt surgical intervention.


Spermatological characters of the spathebothriidean tapeworm Didymobothrium rudolphii (Monticelli, 1890).
Spermiogenesis and the spermatozoon ultrastructure of the adult Didymobothrium rudolphii (Spathebothriidea) have been examined using transmission electron microscopy for the first time. The dense material is present in the apical region of the differentiation zone in the early stage of spermiogenesis, similarly as in other basal tapeworms examined to date. The orthogonal development of the two flagella is followed by a flagellar rotation and their proximodistal fusion with the median cytoplasmic process (MCP). The two pairs of electron-dense attachment zones in the MCP mark the lines where the proximodistal fusion of MCP with two axonemes takes place. D. rudolphii exhibits polymorphism of the intercentriolar body during spermiogenesis. The mature spermatozoon possesses the two axonemes of 9 + "1" trepaxonematan pattern, nucleus, cortical microtubules (CMs), and electron-dense granules. The anterior extremity of the gamete lacks a crested body and exhibits a centriole surrounded by a semiarc of electron-dense tubular structures. The two parallel rows of the CMs have been found in the proximal part of the two-axoneme region of the spermatozoon for the first time in the Eucestoda. The posterior extremity of the gamete exhibits pattern of the disorganized axoneme. The ultrastructural features of the sperm/spermiogenesis support a view about the close relationships of the Spathebothriidea and Diphyllobothriidea and the basal position of the Spathebothriidea within the Eucestoda.


Effects of red wine on the electrical activity and functional coupling between prefrontal-parietal cortices in young men.
The effects of low-dose red wine on cortical electroencephalogram (EEG) and the functional coupling between the frontal and parietal cortices during the first minutes after ingestion were studied. In a first experiment, 38 male volunteers participated in a wine/water challenge protocol in which each subject served as his own control. Wine-induced EEG changes appeared immediately after ingestion and continued for 40 min. These changes were characterized by an increase in the absolute power (AP) and relative power (RP) of fast frequencies (alpha1, alpha2, beta1 and beta2), a decrease of low frequencies (delta and theta) and a specific decrease in the degree of coupling between cortices at 20 min after wine ingestion. To determine if EEG changes were produced by the alcohol in the red wine, in a second experiment, 24 male volunteers participated in an independent wine/placebo group protocol. At 20 min post-ingestion, the red wine group showed higher power in the alpha band, lower RP of low frequencies and decreased correlation, as compared to the placebo group. These findings show that low-dose red wine produces a rapid cortical activation and decreased synchronization between the prefrontal and parietal areas, which could be associated with aroused states or altered cognitive processes, as has been described in other studies.


Effects of chronic dietary administration of the cholinergic false precursor N-amino-N,N-dimethylaminoethanol on behavior and cholinergic parameters in rats.
The choline analog, N-amino-N,N-dimethylaminoethanol (NADe), was fed ad libitum (chloride salt; 0.5%) to weanling rats in a low choline, low methionine synthetic diet. Control rats were fed choline chloride (0.5%) in place of NADe. Initial observation and behavioral screen tests of grasp strength, startle reflex, righting reflex, analgesia (hot plate test) and body temperature did not reveal any toxic effects caused by NADe, although both experimental and control groups gained weight more slowly than rats fed standard lab chow. After 25 days on the diet, the performance of rats fed NADe in a one-trial passive avoidance test was significantly impaired compared to control rats. There was no difference between experimental and control rats in sensitivity to foot shock or in activity monitored in a closed field. A subjective, 6-component behavioral rating scale indicated rats fed NADe were resistant to handling but not aggressive. These behavioral results were similar in two separate feeding experiments using deuterium-labeled and unlabeled NADe. The twitch response of isolated rat phrenic nerve-diaphragms during stimulation did not show any impairment of neuromuscular function in rats fed NADe. Receptor binding experiments indicated there were no differences between experimental and control rats in tritiated quinuclidinyl benzilate [( 3H]QNB) binding capacity in cortex, heart and ileum. Competitive [3H]QNB binding with carbachol indicated there was no difference in the IC50's measured in cortex homogenates. Acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities in cortex were similar in experimental and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessment of porosity index of the femoral neck and tibia by 3D ultra-short echo-time MRI.
To measure the porosity index (PI) by ultrashort echo-time magnetic resonance imaging (UTE MRI) of the femoral neck and tibia; assess its correlations with age, gender, and body mass index (BMI); and analyze the PI correlations between both sites to assess whether tibial PI can reflect changes of femoral neck PI. In all, 68 healthy men and women (mean age, 45.7 ± 15.9 years) underwent 3D UTE MRI (3.0T) of the hip and mid-shaft tibia. PI of the inferior femoral neck cortex and the whole cortex of the tibia were analyzed. Associations between parameters and differences of PIs between men and women, pre- and postmenopausal women were tested. Femoral neck PI was negatively correlated with age (r = -0.385, P = 0.043) and curvilinearly correlated with BMI (R2 = 0.225, P = 0.041) in men. Tibial PI was correlated with BMI (r = -0.477, P = 0.002) in women and age (r = 0.469, P = 0.043) in postmenopausal women, although P = 0.097 (r = 0.403) after adjustment for BMI. Femoral PI was significantly higher in men than in women (P < 0.001). No significant difference in femoral and tibial PI was observed between pre- and postmenopausal women. The femoral neck and tibial PIs were not significantly correlated in any group. PIs had some correlations with age, gender, and BMI. Since femoral neck PI was not correlated with tibial PI, the tibia cannot substitute the femoral neck for estimating bone quality. Direct assessment of the femoral neck cortex is needed. 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2018;47:820-828.


Antiretinoblastoma monoclonal antibodies.
Mouse-mouse somatic hybridization techniques were used to produce monoclonal antibodies directed towards antigen expressed on retinoblastoma-derived tissue culture cell lines. Four monoclonal antibodies were produced with varying avidity which were reactive against allogeneic retinoblastoma-associated antigens. Sensitivity and specificity was demonstrated using ELISA and chromium release assays. Immunofluorescent antibody studies suggest that these monoclonal antibodies may be useful diagnostically.


Disruption of base pairing between the 5' splice site and the 5' end of U1 snRNA is required for spliceosome assembly.
A short RNA oligonucleotide comprising the 5' splice site consensus sequence (5'SS RNA) is sufficient to bind U1 small nuclear ribonucleoprotein particle (snRNP) or to induce the association of U2 snRNP and U4-U5-U6 triple snRNP. Analysis of the requirements of these interactions demonstrates that the 5'SS RNA is recognized independently by at least two different elements during spliceosome assembly: the 5' end of U1 snRNA and a component(s) of the U2-U4-U5-U6 snRNP complex. Since stable 5'SS RNA-U1 snRNA base pairing prevents interaction of the 5'SS RNA with U2-U4-U5-U6 snRNP complex, we conclude that disruption of the initial base pairing between the 5'SS RNA and the 5' end of U1 snRNA is required for subsequent spliceosome assembly.


Cryptococcosis in human immunodeficiency virus-negative patients.
To describe the clinical characteristics, treatment, and outcomes of cryptococcosis in HIV-negative patients. HIV-negative adult patients with positive culture for Cryptococcus neoformans who attended Ramathibodi Hospital between 1987 and 2003 were retrospectively reviewed. During the 17 year review period, 40 HIV-negative patients with cryptococcosis were identified. Of these, 37 patients had medical records available for study. The mean age was 49+/-18 (range 16-83) years and 73% were female. Twenty-four patients (65%) had associated underlying conditions. The most common associated conditions included immunosuppressive drug treatment (41%), presence of systemic lupus erythematosus (16%), malignancies (16%), and diabetes mellitus (14%). C. neoformans was mainly recovered from cerebrospinal fluid (32%), blood (28%), and sputum/bronchoalveolar lavage/lung tissue (28%). Twenty-three patients (62%) had disseminated cryptococcosis. Six of 14 patients with cryptococcal meningitis were asymptomatic. About half of the patients were treated with amphotericin B and subsequent fluconazole. Five patients (14%) were initially misdiagnosed and treated for tuberculosis or bacterial infection. The overall mortality rate was 27%. Cryptococcosis is not rare in HIV-negative patients. The mortality rate is high. Early recognition of cryptococcosis and use of appropriate antifungal therapy in these patients may improve clinical outcomes.


Impact of dental treatment on the oral health-related quality of life of children and adolescents with Autism Spectrum Disorder.
To evaluate the impact of dental treatment on the oral health-related quality of life (OHRQoL) of children and adolescents with Autism Spectrum Disorder (ASD), through the perception of caregivers. A prospective longitudinal study was conducted on 115 individuals with ASD, 6-14 years of age, recruited from the referral centers for special needs individuals at Teresina, Brazil. A clinical examination was carried out and the OHRQoL was measured using the Brazilian version of the Parental-Caregiver Perceptions Questionnaire (P-CPQ) before and 3 months after dental treatment. Data were analyzed using Kolmogorov-Smirnov, Levene, Mann-Whitney, Kruskall-Wallis, and Wilcoxon tests, and the Poison regression with backward method (P < .05). Treatment needs of children with ASD consisted of dental restorations (81.7%), oral prophylaxis (66.1%), endodontic treatment (10.4%), and tooth extractions (10.4%). The baseline P-CPQ total score varied from 1 to 33 (mean score = 13.2 [±6.4]), and at 3 months after treatment it ranged from 0 to 10 (mean score 3.4 [±2.2] (P < .001). The effect magnitude varied between 0.55 and 0.56. According to the perception of the caregivers, dental treatment had a positive impact on the OHRQoL of children and adolescents with ASD.


Foam fractionation of a dilute solution of bovine lactoferrin.
Lactoferrin (Lf), a protein found in human and bovine milk, tears, blood, and other secretory fluids, has been used to prevent infection from potential microbial pathogens by its ability to bind with iron (Fe3+). Currently, bovine lactoferrin can be purified from milk using ion exchange resin, which is a costly procedure making lactoferrin expensive. The purpose of this work was to investigate a low-cost foam fractionation process as the first step in separating lactoferrin from milk.


Improve the cervical cancer prevention behaviors through mobile-based educational intervention based on I-CHANGE model: study protocol for a randomized controlled trial.
Applications of mobile technologies (mHealth) have the potential to reduce health inequalities, give patients more control over their health, and improve health care's cost-effectiveness. The widespread use of mobile phones offers us a new way to prevent cervical cancer. The objective of the study was to design and develop a mobile phone application (app) that aims to conduct a behavioral intervention for women and to evaluate the efficacy of the app-based intervention. This study involves 5 phases. In the first phase, understanding women's perspectives will be identified using a qualitative approach based on the I-Change model. In phase 2, the results from the qualitative approach and requirement prioritization through providing experts' perspectives will be done. The main outputs of this phase will be resulted in prioritizing the main measurable effective variables of the I-Change model. Phase 3 will be processed for the development and psychometric of an assessment tool regarding selected constructs. In phase 4, the App framework and content development will be performed. In phase 5, a three-armed, parallel-design randomized controlled trial will be conducted on women. Two hundred ten women will be randomly assigned to three groups including two intervention groups and one control group. The intervention groups included the following: (1) a mobile application and (2) a digital book. The data will be evaluated using tools designed and constructed in phase 3 of the study at baseline in 3-month follow-up assessments. The impact of the two interventions on cervical cancer prevention behaviors through mobile-based educational intervention will then be evaluated. A theory-based health education program using a mobile app to improve cervical cancer-preventive behaviors will be implemented for the first time in Iran. With an effective health mobile-based educational design, it is very important to determine whether Iranian women will be motivated to adhere to preventive behavior related to CC. Iranian Clinical Trial Register IRCT20181205041861N3. Registered V2.0 on 26 October 2021.


T52 attenuates oncogenic STAT3 signaling and suppresses osteosarcoma.
T52 is a steroidal saponin extracted from the traditional Chinese herb Rohdea fargesii (Baill.), and it is reported to possess strong anti-proliferative capabilities in human pharyngeal carcinoma cell lines. However, whether T52 has anti-osteosarcoma properties, and its potential mechanism is remains unknown. To examine the outcome and underlying mechanism of T52 in osteosarcomas (OS). The physiological roles of T52 in OS cells were examined using CCK-8, colony formation (CF), EdU staining, cell cycle/apoptosis and cell migration/invasion assays. The relevant T52 targets against OS were assessed via bioinformatics prediction, and the binding sites were analyzed by molecular docking. Western blot analysis was carried out to examine the levels of factors associated with apoptosis, cell cycle, and STAT3 signaling pathway activation. T52 markedly diminished the proliferation, migration, and invasion of OS cells, and promoted G2/M arrest and apoptosis in a dose-dependent fashion (DDF) in vitro. Mechanistically, molecular docking predicted that T52 stably associated with STAT3 Src homology 2 (SH2) domain residues. Western blot revealed that T52 suppressed the STAT3 signaling pathway, as well as the expression of the downstream targets, such as, Bcl-2, Cyclin D1, and c-Myc. In addition, the anti-OS property of T52 were partially reversed by STAT3 reactivation, which confirmed that STAT3 signaling is critical for regulating the anti-OS property of T52. We firstly demonstrated that T52 possessed strong anti-osteosarcoma property in vitro, which was brought on by the inhibition of the STAT3 signaling pathway. Our findings provided pharmacological support for treating OS with T52.


Determining temperature ratings for children's cold weather clothing.
This study examined the physical and physiological differences between children and adults that affect body heat generation and losses and then developed a heat loss model for determining the temperature ratings of cold weather clothing designed for use by children of various ages. The thermal insulation values of selected jackets were measured using a heated manikin dressed in two base ensembles, and the temperature ratings were calculated using the model. The results indicated that the type of garments used in the base ensemble had a major effect on jacket ensemble insulation and the predicted comfort temperature. For a given level of insulation, the temperature rating decreased as the wearer's age and activity level increased. This is probably because children have a higher surface area per unit mass ratio than adults, and they lose heat faster. However, this effect is partially offset by their higher metabolic rates.


Anti-HIV activity of stilbene-related heterocyclic compounds.
Viral transcription has not been routinely targeted in the development of new antiviral drugs. This crucial step of the viral cycle depends on the concerted action of cellular and viral proteins such as NF-kappaB and Tat. In the present study, stilbene-related heterocyclic compounds including benzalphthalide, phthalazinone, imidazoindole and pyrimidoisoindole derivatives are tested for their anti-HIV activity. Original assays based on recombinant viruses were used to evaluate HIV replication inhibition and stably transfected cell lines were used to evaluate inhibition of Tat and NF-kappaB proteins. Some of the stilbene-related heterocyclic compounds analysed displayed anti-HIV activity through interference with NF-kappaB and Tat function. Moreover, compounds inhibiting both targets displayed a stronger activity on viral replication.


SPDE: a multi-functional software for sequence processing and data extraction.
Sequence Processing and Data Extraction (SPDE) has eight modules comprising 100 basic functions ranging from sequence extraction, format conversion to data reorganization and mining, and all of these functions can be completed by point-and-click icons. SPDE also incorporates eight public analyses tools; thus, SPDE is a comprehensive bioinformatics platform for big biological data analysis. SPDE built by Python can run on 32-bit, 64-bit Windows and MacOS systems. It can be downloaded from https://github.com/simon19891216/SPDEv1.2.git. Supplementary data are available at Bioinformatics online.


Low uptake of isoniazid window prophylaxis in patients exposed to a health-care worker with pulmonary tuberculosis in a paediatric ward.
A nurse on a paediatric multidisciplinary ward was diagnosed with smear-positive pulmonary tuberculosis. Children <2 years old, immunocompromised, or >40 h of contact (n = 173) were contact-traced. Children received clinical review, chest X-ray, tuberculin skin test (TST; <5 years old) and/or an interferon-gamma release assay (Quantiferon TB-Gold, ≥5 years old). Infants <6 months old or children <5 years old screened <2 months from exposure were recommended isoniazid window prophylaxis (WP) until a repeat TST at 6 months old or 8-10 weeks after the last exposure to the index case, respectively. Empiric treatment for latent tuberculosis infection (LTBI) was individually considered for immunocompromised patients. Of 173 children (135 immunocompetent, 38 immunocompromised), two were uncontactable, seven refused screening and two immunocompromised children excluded. Eight of 126 immunocompetent children were diagnosed with LTBI (initial TST positive n = 7, TST conversion n = 1); seven started isoniazid. Thirty-two of 36 immunocompetent children were recommended WP; 15 accepted (one non-compliant after 1 month). Six of seven immunocompromised children accepted empiric LTBI treatment due to severe immunosuppression/initial indeterminate Quantiferon TB-Gold result. Of 15 immunocompromised children offered WP, only five accepted. There was high acceptance of screening but low uptake of isoniazid WP in high-risk children exposed to pulmonary tuberculosis. Perception of exposure risk and chemoprophylaxis should be explored further.


Intervention of Saphenous Vein Graft Chronic Total Occlusion.
Interventions on vein graft occlusions are technically feasible procedures but carry significant risk for periprocedural complications and demonstrate questionable long-term patency. For those circumstances in which recanalization of a graft occlusion is warranted, the authors have highlighted some of the procedural considerations and available techniques that may help maximize chances for success. This should not be mistaken for a wholesale endorsement of vein graft chronic total occlusion interventions. Before undertaking a procedure of this complexity, the operator must put strong consideration into the risks, benefits, and alternatives for a given patient.


A green route for pyrolysis poly-generation of typical high ash biomass, rice husk: Effects on simultaneous production of carbonic oxide-rich syngas, phenol-abundant bio-oil, high-adsorption porous carbon and amorphous silicon dioxide.
Rice husk is a widespread agriculture waste in rice-farming country. High silica content in rice husk prevent its efficient utilization. So in this work, concept of poly-generation was introduced to improve its utilization value. This study provided CO-rich syngas, phenol-abundant bio-oil, high-adsorption porous carbon and amorphous SiO2 as four end products for first time via combination of acid washing and activated carbon catalyst. Specifically, acid washing effectively decreasedsoluble ash, which altered pyrolysis paths, increased volatiles release and reduced impurities in bio-char. After catalytic pyrolysis, phenol content of 65.56% and CO of 56.09 vol% were detected in bio-oil and syngas from AWRH. For solid products, acid washing benefited both bio-char and silica. A low-cost porous carbon with developed pores and rich surface functional groups was prepared for water absorption. And high purity amorphous SiO2 was recycled from alkali etching solution. Finally, a green process with no waste emission was proposed.


Evidence of epigenetic alterations in thrombosis and coagulation: A systematic review.
Thrombosis in the context of Cardiovascular disease (CVD) affects mainly the blood vessels supplying the heart, brain and peripheries and it is the leading cause of death worldwide. The pathophysiological thrombotic mechanisms are largely unknown. Heritability contributes to a 30% of the incidence of CVD. The remaining variation can be explained by life style factors such as smoking, dietary and exercise habits, environmental exposure to toxins, and drug usage and other comorbidities. Epigenetic variation can be acquired or inherited and constitutes an interaction between genes and the environment. Epigenetics have been implicated in atherosclerosis, ischemia/reperfusion damage and the cardiovascular response to hypoxia. Epigenetic regulators of gene expression are mainly the methylation of CpG islands, histone post translational modifications (PTMs) and microRNAs (miRNAs). These epigenetic regulators control gene expression either through activation or silencing. Epigenetic control is mostly dynamic and can potentially be manipulated to prevent or reverse the uncontrolled expression of genes, a trait that renders them putative therapeutic targets. In the current review, we systematically studied and present available data on epigenetic alterations implicated in thrombosis derived from human studies. Evidence of epigenetic alterations is observed in several thrombotic diseases such as Coronary Artery Disease and Cerebrovascular Disease, Preeclampsia and Antiphospholipid Syndrome. Differential CpG methylation and specific histone PTMs that control transcription of prothrombotic and proinflammatory genes have also been associated with predisposing factors of thrombosis and CVD, such us smoking, air pollution, hypertriglyceridemia, occupational exposure to particulate matter and comorbidities including cancer, Chronic Obstructive Pulmonary Disease and Chronic Kidney Disease. These clinical observations are further supported by in vitro experiments and indicate that epigenetic regulation affects the pathophysiology of thrombotic disorders with potential diagnostic or therapeutic utility.


A quantitative assessment of degenerative changes acceptable in the unoperated compartments of knees undergoing unicompartmental replacement.
Thirty-five unicondylar knee arthroplasties were performed on 32 patients. In the unresurfaced compartments, degenerative cartilaginous changes were observed intraoperatively and recorded. The Outerbridge grading scale was used to assess the degree of arthritic change. In addition, the surface area involved was estimated. Grade III and limited grade IV changes in the unresurfaced tibiofemoral compartment and the patellofemoral joint did not preclude excellent results at a follow-up interval of 2 to 4 years.


Crystal structure, Hirshfeld surface and photo-physical analysis of 2-nitro-3-phenyl-9H-carbazole.
The title compound, C18H12N2O2, was synthesized from a di-nitro-biphenyl-benzene derivative using a novel modification of the Cadogan reaction. The reaction has several possible ring-closed products and the title compound was separated as the major product. The X-ray crystallographic study revealed that the carbazole compound crystallizes in the monoclinic P space group and possesses a single closed Cadogan ring. There are two independent mol-ecules in the asymmetric unit. In the crystal, the mol-ecules are linked by N-H⋯O hydrogen bonding.


Urinary amines in Tourette's syndrome patients with and without phenylethylamine abnormality.
Previous data indicated a subgroup of Tourette's syndrome patients with a beta-phenylethylamine (PEA) level that was lower than all subjects in a control group matched for age and education. The current study compared the subgroups of Tourette's syndrome patients (n = 28) from the previous study with 20 control subjects in regard to other amines and metabolites. Patients with low levels of PEA were also found to have lower levels of 3-methoxy-4-hydroxy-phenylglycol, normetanephrine, serotonin, m-tyramine, and p-tyramine. There was also some evidence of dopaminergic abnormalities in the low-PEA subgroup. These data provide suggest a role of PEA in the pathophysiology of some patients with Tourette's syndrome. This effect may be mediated through other neurotransmitter systems.


The relationship between HLA class II polymorphisms and somatic deletions in testicular B cell lymphomas of Dutch patients.
Several risk factors including immune deficiencies, infections, and autoimmune diseases have been established for non-Hodgkin's lymphoma (NHL). For diffuse large B cell lymphoma (DLBCL), the most common type of lymphoma, no risk factors have been described, which may be due to the intrinsic heterogeneity of this disorder. Previously we reported that, in contrast to nodal DLBCLs, the majority of testicular DLBCLs manifested complete loss of HLA-DR and -DQ expression associated with homozygous deletions of the corresponding genes. To determine the correlation between HLA class II polymorphisms and these lymphomas, we applied DNA typing for HLA-DRB1 and HLA-DQB1 on 50 Dutch patients with testicular and 48 with nodal DLBCL and compared the frequencies with a cohort of healthy Dutch controls. Both the patients with nodal and those with testicular DLBCL manifested significantly higher frequencies of HLA-DRB1*15 than the controls (p < 0.018, odds ratio 2.09 and p < 0.013, odds ratio 2.12, respectively). Moreover, a positive association was seen with HLA-DRB1*12 (p = 0.043, odds ratio 4.17) in the patients with testicular DLBCL, and a negative association was seen with HLA-DRB1*07 (p = 0.022, odds ratio 0.13) in the patients with nodal DLBCL. Homozygous deletions of the HLA-DR/DQ region, evaluated by interphase fluorescence in situ hybridization were seen in 20 of 48 testicular tumors. No preferential loss or retention of a particular HLA-DR or -DQ allele was seen because all alleles were at least once retained or involved in a homozygous deletion.


Reference voluntary jitter values using disposable monopolar needle electrodes in the extensor digitorum communis muscle.
To measure normal variability in neuromuscular transmission in the extensor digitorum communis (EDC) muscle voluntarily activated using a disposable monopolar needle electrode (MNPE). We examined the EDC muscle using MNPE in 50 healthy volunteers (12 male and 38 female, mean age: 41.5+/-12.9 years, age range: 18-74 years). The high-pass filter setting was 3 kHz. Jitter values are expressed as the mean consecutive difference (MCD) of 20 potential pairs. Mean MCD (n=50) was 21.3+/-3 micros (upper 95% confidence limit (CL): 27.3 micros). Mean MCD in all potential pairs (n=1000) was 21.3+/-6.6 micros (upper 95% CL: 34 micros). Mean MCD for the 18th highest value was 28+/-4.7 micros (upper 95% CL: 37.5 micros). The suggested practical upper limit for mean MCD was set to 28 micros; for outliers it was 38 micros. The present study defines the normative value for jitter recorded with disposable MNPE, which is a low-cost alternative for the evaluation of neuromuscular transmission, although certain precautions must be taken.


Risk of Anterior Abdominal Wall Adhesions Increases with Number and Type of Previous Laparotomy
Adhesions to the anterior abdominal wall after previous midline vertical laparotomy were found in 68% of patients undergoing laparoscopy (Childers et al: Gynecol Oncol 50:221, 1993). We reviewed the prevalence of anterior wall adhesions in patients with previous laparotomy incisions who underwent laparoscopy (>95% of patients) or laparotomy. The prevalence of omental and/or bowel adhesions to the anterior abdominal wall in proximity to the umbilicus were tallied and analyzed by incision site (midline vertical or suprapubic transverse) and number of previous laparotomies (one or more than one). The following table illustrates the number of patients in each category with anterior abdominal wall adhesions. While the prevalence of adhesions is increased with more than one previous laparotomy this did not reach statistical significance (Chi-square test). A midline vertical laparotomy does significantly increase the risk for anterior wall adhesions compared to a transverse incision (p<0.05). However, it should be noted that 28% of patients with a previous suprapubic transverse incision (Pfannenstiel or Maylard) had omental and/or bowel adhesions. In this series, one patient with two previous transverse incisions had an incidental enterotomy. We currently employ the technique of LUQ trocar placement in patients with previous midline and suprapubic transverse incisions.


Effects of upper-extremity weight-bearing on hand-opening and prehension patterns in children with cerebral palsy.
The purpose of this study was to determine whether upper-extremity weight-bearing has an effect on hand-opening and prehension patterns of children with spastic cerebral palsy. Children at the Bobath Centre (London) were studied. Effectiveness of intervention was determined by blind scoring of video-tapes of prehension components. Computer calculations of hand surface-area were done. There was an over-all increase in surface area, indicating an increased ability to open the hand; in addition, there was an increase in the maturity of movement components of prehension. These results provide relevant information about the application of upper-extremity weight-bearing.


Lymphokine-activated killer cells in primary immunodeficiencies and acquired immunodeficiency syndrome.
Cytotoxic mechanisms (e.g., natural killer (NK) lysis, antibody-dependent cellular cytotoxicity, and cytotoxic T lymphocyte lysis) play an important role in host defense against various infections and neoplasms. Lymphokine-activated killer (LAK) cytotoxicity, induced in vitro by incubating mononuclear cells with interleukin 2 (IL-2) for 2-5 days, may also represent an important component of the body's cytotoxic repertoire. In 10 patients with congenital cellular immunodeficiencies, including 5 with severe combined immunodeficiency, the mean LAK activity in a 3-hr chromium release assay against Raji target cells was 44 +/- 8.1%, which is equivalent to that observed in normal adults and neonates. In only one case, a patient with reticular dysgenesis, was there absent LAK cell generation. Haploidentical T cell-depleted bone marrow transplantation (BMT) restored LAK activity in this patient. LAK activity was first observed in this patient and two others 3-6 weeks following BMT, prior to other evidence of immunologic engraftment such as lymphocyte proliferation to mitogens, NK activity, or interferon-gamma production. One patient with adenosine deaminase deficiency showed normal levels of LAK activity despite absent NK activity. Three patients with chronic granulomatous disease also had normal LAK activity (57 +/- 14% specific lysis). In 9 patients with acquired immunodeficiency syndrome (AIDS), IL-2 activation resulted in a mean cytotoxic activity of 56 +/- 8.7% toward Raji targets. In addition, 9 patients with pre-AIDS complex also showed normal levels of cytotoxicity (37 +/- 3.3% toward Raji targets), equivalent to that of 8 normal controls, including two healthy homosexual males (mean lysis 38 +/- 3.9%). These results indicate that LAK cells appear early in immunologic ontogeny. Further, the mechanism of lysis is not oxygen dependent since LAK activity was present in the 3 patients with chronic granulomatous disease. The ability to generate LAK in a wide spectrum of immunodeficiencies may indicate that IL-2 could be used in therapy of such disorders.


An innovative intervention to improve respectful maternity care in three Districts in Ethiopia.
Mistreatment of women during facility-based childbirth is a major violation of human rights and often deters women from attending skilled birth. In Ethiopia, mistreatment occurs in up to 49.4% of mothers giving birth in health facilities. This study describes the development, implementation and results of interventions to improve respectful maternity care. As part of a national initiative to reduce maternal and perinatal mortality in Ethiopia, we developed respectful maternity care training module with three core components: testimonial videos developed from key themes identified by staff as experiences of mothers, skills-building sessions on communication and onsite coaching. Respectful maternity care training was conducted in February 2017 in three districts within three regions. Facility level solutions applied to enhance the experience of care were documented. Safe Childbirth Checklist data measuring privacy and birth companion offered during labor and childbirth were collected over 27 months from 17 health centers and three hospitals. Interrupted time series and regression analysis were conducted to assess significance of improvement using secondary routinely collected programmatic data. Significant improvement in the percentage of births with two elements of respectful maternal care-privacy and birth companionship offered- was noted in one district (with short and long-term regression coefficient of 18 and 27% respectively), while in the other two districts, results were mixed. The short-term regression coefficient in one of the districts was 26% which was not sustained in the long-term while in the other district the long-term coefficient was 77%. Testimonial videos helped providers to see their care from their clients' perspectives, while quality improvement training and coaching helped them reflect on potential root causes for this type of treatment and develop effective solutions. This includes organizing tour to the birthing ward and allowing cultural celebrations. This study demonstrated effective way of improving respectful maternity care. Use of a multipronged approach, where the respectful maternity care intervention was embedded in quality improvement approach helped in enhancing respectful maternity care in a comprehensive manner.


Interactions of polyunsaturated fatty acids with amyloid peptides Aβ40 and Aβ42.
Polyunsaturated fatty acids (PUFAs) are reported to exert beneficial effects in Alzheimer's disease. Some PUFAs are known to reduce amyloid-beta (Aβ) toxicity by promoting its degradation and clearance. Studies on the direct interactions of PUFAs with Aβ peptides are limited and contradictory. In this study, we report the interactions of fatty acids docosahexaenoic acid (DHA), eicosatetraenoic acid (EPA), α-linolenic acid (ALA), arachidonic acid (ARA), linoleic acid (LNA) and oleic acid (OA) with Aβ peptides by carrying out fluorescence based aggregation kinetic experiments, transmission electron microscopy and molecular docking studies. Our investigations demonstrate that all the fatty acids tested exhibit anti-aggregation properties by preventing both Aβ40 and Aβ42 fibrillogenesis (∼16-84% inhibition). OA and DHA were identified as excellent inhibitors of Aβ40 or Aβ42 fibrillogenesis respectively (∼84% and 81% inhibition at 25 μM). Molecular docking studies conducted, using the dimer and oligomer models of Aβ40 peptide, suggest that these fatty acids interact in the aggregation prone Phe19-Ala21 and the β-turn region (Asp23-Lys28) whereas a similar study with Aβ42 dimer and oligomer models, indicate that the fatty acids were oriented in a hydrophobic region (Gln15, Leu16, Leu17 and Leu34). These results, suggest that DHA, EPA, ALA, ARA, LNA and OA are capable of directly interacting with both Aβ40 and Aβ42 peptides. These studies will have implications in developing potential therapeutics for Alzheimer's disease.


Development of a transcription-based bioanalytical tool to quantify the toxic potencies of hydrophilic compounds in water using the nematode Caenorhabditis elegans.
Low concentrations of environmental contaminants can be difficult to detect with current analytical tools, yet they may pose a risk to human and environmental health. The development of bioanalytical tools can help to quantify toxic potencies of biologically active compounds even of hydrophilic contaminants that are hard to extract from water samples. In this study, we exposed the model organism Caenorhabditis elegans synchronized in larval stage L4 to hydrophilic compounds via the water phase and analyzed the effect on gene transcription abundance. The nematodes were exposed to three direct-acting genotoxicants (1 mM and 5 mM): N-ethyl-N-nitrosourea (ENU), formaldehyde (HCHO), and methyl methanesulfonate (MMS). Genome-wide gene expression analysis using microarrays revealed significantly altered transcription levels of 495 genes for HCHO, 285 genes for ENU, and 569 genes for MMS in a concentration-dependent manner. A relatively high number of differentially expressed genes was downregulated, suggesting a general stress in nematodes treated with toxicants. Gene ontology and Kyoto encyclopedia of genes and genomes analysis demonstrated that the upregulated genes were primarily associated with metabolism, xenobiotic detoxification, proteotoxic stress, and innate immune response. Interestingly, genes downregulated by MMS were linked to the inhibition of neurotransmission, and this is in accordance with the observed decreased locomotion in MMS-exposed nematodes. Unexpectedly, the expression level of DNA damage response genes such as cell-cycle checkpoints or DNA-repair proteins were not altered. Overall, the current study shows that gene expression profiling of nematodes can be used to identify the potential mechanisms underlying the toxicity of chemical compounds. C. elegans is a promising test organism to further develop into a bioanalytical tool for quantification of the toxic potency of a wide array of hydrophilic contaminants.


Maturation of renal tubular transport of digoxin.
Previous data have suggested an age-related increase in renal tubular secretion of digoxin in infants and children receiving long-term digoxin therapy. This phenomenon could be the result of a maturational process or secondary to chronic substrate stimulation. To investigate this question, two groups of 2-week-old paired littermate rats received intraperitoneal injections of either digoxin or an equal volume of normal saline (control) on alternate days until sacrificed at 4, 6, and 8 wk of age. An additional group of 12-wk-old rats were studied as controls. 125I-labeled digoxin uptake was measured in renal cortical slices as the cPM/mg wet tissue slice/medium ratio (S/M). Both digoxin-treated and control rats demonstrated significant age-related increments in digoxin uptake. S/M ratios at 4, 6, 8, and 12 wk in he control group were 1.34 +/- 0.06, 1.39 +/- 0.14, 1.62 +/- 0.18 and 1.93 +/- 0.23, respectively (mean +/- S.D.) (r = 0.81; P less than 0.001). S/M ratios in the digoxin-treated animals at 4, 6, and 8 wk were 1.28 +/- 0.16, 1.33 +/- 0.09, and 1.52 +/- 0.23, respectively (r = 0.50; P less than 0.025), but did not differ significantly at each age from those in the control group. 125I uptake was significantly reduced by both dinitrophenol and sodium azide, as well as by a 100% nitrogen atmosphere. These results indicate that renal tubular transport of digoxin is an age-related energy dependent process which probably is not subject to substrate stimulation.


Disseminating tobacco control information to Asians and Pacific Islanders.
The Asian Grocery Store-Based Cancer Education Program (the Program) is a proven strategy for promoting early breast cancer detection among Asian American women. The authors sought to test whether the same public health model can become an effective strategy for increasing the Asian community's awareness of the California Smokers' Helpline (the Helpline) and thereby, potentially decreasing this community's use of tobacco products. The new module, mainly staffed by four well-trained, volunteer undergraduates, explained the risks of first- and second-hand tobacco exposure and how to access the Helpline's services. A brochure, provided in English, Chinese, Korean, and Vietnamese (the Helpline's available Asian languages), was used to guide the bicultural, bilingual students' tobacco-related discussions with shoppers. The students' repeated presence at the nine partnering Asian grocery stores served as reminders of the Helpline's availability. In its first year of operation, the student trainers reached 1,052 men and 1,419 women with tobacco cessation messages. Equally important, the participating grocery stores' managers did not object to students telling their customers to quit using the tobacco products sold in their stores. The results suggest that the Program's tobacco cessation module is a viable, community-specific, public health strategy. It is also a strategy with the potential for applications to reduce other health threats.


Ethiopia's first minimally invasive surgery program: A novel approach in global surgical education.
Complex lung diseases are among the leading causes of death in Ethiopia. Access to thoracic surgery is limited, and before 2016 no thoracic surgeons were trained in minimally invasive surgery. A global academic partnership was formed between the University of Toronto and Addis Ababa University. We describe implementation of the first minimally invasive surgery training program in sub-Sahara Africa and evaluate its safety. We performed a retrospective cohort analysis of open versus minimally invasive thoracic and upper gastrointestinal procedures performed at Addis Ababa University from January 2016 to June 2021. Baseline demographic, diagnostic, operative, and postoperative outcomes including length of stay and complications were compared. In our bilateral model of surgical education, training is provided in Ethiopia and Canada over 2 years with a focus on capacity building through egalitarian forms of knowledge exchange. Program features included certification in Fundamentals of Laparoscopic Surgery, high-fidelity lobectomy simulation, and hands-on training. Overall, 41 open and 56 minimally invasive surgery cases were included in the final statistical analysis. The average length of stay in the minimally invasive surgery group was 5.2 days versus 11.0 days in the open group (P < .001). The overall complication rate was 18% in the minimally invasive surgery group versus 39% in the open group (P = .020). We demonstrated the successful initiation of sub-Sahara Africa's first minimally invasive surgery program in thoracic and upper gastrointestinal surgery and characterize its patient safety. We envision the minimally invasive surgery program as a template to continue expanding global partnerships and improving surgical care in other resource-limited settings.


Design, Microwave-Assisted Synthesis, Antimicrobial and Anticancer Evaluation, and In Silico Studies of Some 2-Naphthamide Derivatives as DHFR and VEGFR-2 Inhibitors.
Naphthamide is a common structural framework with diverse pharmacological activities. Ten novel 2-naphthamide derivatives have been designed, synthesized, and evaluated for their in vitro antibacterial, antifungal, and anticancer activities. The title compounds were synthesized from dimethoxybenzaldehyde derivatives through a four-step microwave-assisted synthesis process. The structures were confirmed by 1H NMR, 13C NMR, and MS spectra. Compound 8b showed good antibacterial activity against Escherichia coli, Streptococcus faecalis, Salmonella enterica, MSSA, and MRSA with MIC values of 16, 16, 16, 8, and 16 μg/mL, respectively, compared to ciprofloxacin (MIC = 8-16 μg/mL). Compounds 5b (IC50 = 3.59-8.38 μM) and 8b (IC50 = 2.97-7.12 μM) exhibited good cytotoxic activity against C26, HepG2, and MCF7 cancer cell lines as compared to paclitaxel (IC50 = 2.85-5.75 μM). Moreover, compounds 5b and 8b exhibited better anticancer activity than PTX against the C26 cell line. In particular, compound 8b showed potent in vitro VEGFR-2 inhibitory activity with the IC50 value of 0.384 μM compared with sorafenib (IC50 = 0.069 μM). Therefore, compound 8b is the most potent compound for anticancer activity as indicated by in vitro cell line inhibition, in silico ADMET, molecular docking, and in vitro VEGFR-2 inhibition studies.


Effect of thermo-mechanical cycling and chlorhexidine on the bond strength of universal adhesive system to dentin.
This study evaluated the influence of thermo-mechanical cycling (TMC) on the bond strength (BS) of a universal adhesive system (UAS - Adper Single Bond Universal, 3M ESPE) to dentin treated or not with 0.2% chlorhexidine (CHX). Eighty human molars were flattened until reach the dentin and separated into 4 groups according to the bonding protocol: ENR Group: 37% phosphoric acid + 3-step etch-and-rinse adhesive system (ENR); UAS Group: UAS in self-etch mode; ENR + CHX Group: 37% phosphoric acid + CHX + ENR; UAS + CHX Group: CHX + UAS in self-etch mode. After treatments, teeth were restored (Filtek Z350, 3M ESPE). Samples (n = 10) were submitted to aging process: stored in distilled water at 37°C/30 days or TMC (ERIOS - 98N/1.6Hz + thermal cycling 5/37/55 °C - 1,200,000 cycles). Specimens were sectioned into sticks (1.0 mm2) and submitted to the microtensile test (Mechanical Test Machine - 0.5 mm/min). Fracture patterns and hybrid layer integrity were analyzed under Stereomicroscope and Scanning Electron Microscopy (SEM). The BS results (3-way ANOVA, Bonferroni's test, α = 5%) showed that groups treated with CHX presented higher BS values than control groups; significant in all cases (p < .05), except for ENR submitted to TMC (p > .05). When CHX was applied and samples were cycled, UAS revealed higher BS (p < .05) than ENR. After TMC, cohesive fractures increased for UAS, regardless of CHX application. SEM analysis demonstrated different hybridization patterns for the adhesive systems tested. The performance of the universal adhesive system used in self-etch mode was better than that of the 3-step etch-and-rinse adhesive system. Universal adhesive systems have been developed in order to simplify the dentin hybridization protocol. It is important to determine the longevity of the adhesive interface using these bonding materials after chewing.


TRIM21 inhibits porcine epidemic diarrhea virus proliferation by proteasomal degradation of the nucleocapsid protein.
Tripartite motif protein 21 (TRIM21) is an E3 ubiquitin ligase and cytosolic antibody receptor of the TRIM family. Previous reports have indicated that TRIM21 plays an important role during viral infection. This study aimed at examining the role of TRIM21 in the replication of porcine epidemic diarrhea virus (PEDV) and showed that TRIM21 inhibits PEDV proliferation by targeting and degrading the nucleocapsid (N) protein through the proteasomal pathway. Furthermore, the endogenous expression of TRIM21 was found to be downregulated by PEDV infection in Vero and LLC-PK1 cells. Overexpression of TRIM21 inhibited PEDV replication, whereas knockdown of TRIM21 increased viral titers and N protein levels. TRIM21 was found to interact and colocalize with the N protein, and the TRIM21-mediated antiviral effect was dependent on its ubiquitin ligase activity, which engages in polyubiquitination and degradation of the N protein in a proteasome-dependent manner. Taken together, these findings provide information about the role of TRIM21 in PEDV proliferation and increase our understanding of host-virus interactions.


Carcinoma cuniculatum: not a verrucous carcinoma.
Carcinoma cuniculatum and verrucous carcinoma are both very well differentiated forms of squamous carcinoma and thus difficult to separate histologically from pseudocarcinomatous hyperplasia. The diagnosis of each often requires clinical-pathologic correlation. We reviewed the literature on cases reported as carcinoma cuniculatum and compared these to the cases originally reported by Aird et al. In addition, we report an additional case of this entity that we encountered in our practice. In reviewing the literature it is evident that most authors consider carcinoma cuniculatum and verrucous carcinoma to be synonymous even though Aird's original two cases had no verrucous features. The lack of a clear conceptual distinction between these two entities may cause diagnostic confusion. The purpose of this report is to record a case of carcinoma cuniculatum which the authors believe to be similar to those reported by Aird et al., to emphasize the differences between carcinoma cuniculatum and verrucous carcinoma, and to explain how the lack of a clear conceptual distinction between these two tumors can lead to further delay in an already difficult diagnosis.


A Multidisciplinary Team-Based Approach to Improve Communication With Surrogates of Patients With Chronic Critical Illness.
Clinicians need to deliver prognostic information to surrogates of nondecisional, critically ill patients so that surrogates can make informed medical decisions that reflect the patient's values. Our objective was to implement a new approach for communicating with surrogates of patients with chronic critical illness. Surrogate decision makers of patients who were difficult to liberate from mechanical ventilation were prospectively enrolled. Surrogates met with different members of the intensive care unit treatment team for sequential 15-minute appointments to receive patient-specific assessments and education on chronic critical illness. The feasibility and acceptability of this approach were determined. A 24-question comprehension instrument was developed to assess a participant's understanding that a family member was displaying features of chronic critical illness. Each question was scored from 1 to 5, with larger scores indicating greater comprehension. Over a 15-week period, educational sessions for 9 mechanically ventilated patients were conducted. On average, 2 surrogates per patient (range: 1-4) and 6 members of the interdisciplinary team (range: 4-6) were at each meeting. Surrogates and clinicians had very positive impressions of the communication intervention. The average preintervention comprehension score was 85 of 120 (standard deviation [SD]: 8, range: 71-101). The postintervention comprehension score was greater by 5 points on average (SD: 9, range: -11 to +20 points, P = .04). Surrogates of critically ill patients approved of this novel communication approach and had a greater understanding of the patient's medical condition after the intervention.


The completion of the replication map of the Mycobacterium phlei chromosome.
New facts about the replication map of Mycobacterium phlei chromosome are summarized. Replication positions of two genes located in marginal regions of the replication map, ile close to the origin and ser near the terminus, were determined. Known positions of replication of some genes were defined with more precision within 2.5--5-min intervals using the method of sequential mutagenesis in synchronized cultures (leu, met, bac, pyr, stm, tet, cyc, his). Replication positions of genes responsible for the biosynthesis of thiamine and resistance to tetracycline and vancomycin were further identified. The contemporary replication map contains replication positions of 24 genes.


Valuing End-of-Life Care for Older People with Advanced Cancer: Is Dying at Home Important?
Most health care systems are facing the challenge of providing health services to support the increasing numbers of older people with chronic life-limiting conditions at the end of life. Many policies focus primarily on increasing the proportion of deaths at home. This study aims to investigate preferences for care throughout the latter stages of a life-limiting illness, particularly the importance of location of care, location of death, and the use of life-sustaining measures. It focuses on preferences for the care of an older person with advanced cancer in the last 3 weeks of life. A survey using discrete choice experiment (DCE) methods was completed online by a general population sample of 1548 Australians aged 45 years and over. The experiment included 12 attributes, and each respondent completed 11 choice sets. Analysis was by a mixed logit model and latent class analysis (LCA). The most important attributes influencing care preferences were cost, patient anxiety, pain control, and carer stress (relative importance scores 0.21, 0.19, 0.14, and 0.14, respectively), with less importance given to place of care and place of death (relative importance scores 0.03 and 0.01). The model predicted that 42% would consider receiving most care in hospital better than at home (58%) holding the levels of other attributes constant across the alternatives, while 42% would consider death in hospital better than at home (58%). Three population segments with different preferences were identified by the LCA, the largest (46.5%) prioritised how the patient and carer felt as well as the pain control achieved, the next largest (28.1%) prioritised cost, and the smallest segment (25.4%) prioritised a single room when an inpatient. This study shows that investment in services to support people at the end of life would be better targeted toward programmes that improve patient and carer wellbeing irrespective of the location of care and death.


A New Destination on the Palm? The Moderating Effect of Travel Anxiety on Digital Tourism Behavior in Extended UTAUT2 and TTF Models.
Digital tourism has developed rapidly, especially in museums. However, as people become increasingly familiar with digital museums, their use intentions and behavior have changed. Taking the Digital Palace Museum in China as an example, applying the PLS-SEM method, this study uncovers visitors' use intentions and actual use behavior for digital museums by integrating the new UTAUT model (UTAUT2) and TTF model (TTF under social distancing) and introduces the PATS (Pandemic Anxiety Travel Scale) model to reveal how pandemic anxiety promotes the transformation of use intentions into use behavior more easily. The results show that performance expectations, hedonic motivations, habits, and task-technology-fit positively affect use intentions for digital museums. However, the price-saving orientation negatively affects use intentions. Pandemic anxiety moderates the effect of use intentions on actual behavior. When travel anxiety is relatively high, use intentions have a greater effect on use behavior for digital museums. The results reveal the influencing factors on use intentions of digital museums and the moderating effect of pandemic anxiety on the relation between use intentions and actual behavior.


Mitogen-activated protein kinase p38 induces HDAC4 degradation in hypertrophic chondrocytes.
Histone deacetylase 4 (HDAC4) is a critical negative regulator for chondrocyte hypertrophy by binding to and inhibiting Runx2, a critical transcription factor for chondrocyte hypertrophy. It is unclear how HDAC4 expression and stability are regulated during growth plate development. We report here that inhibition of mitogen-activated protein kinase (MAPK) p38 by dominant negative p38 or p38 inhibitor prevents HDAC4 degradation. Mutation of a potential caspase-2 and 3 cleavage site Asp289 stabilizes HDAC4 in chondrocytes. In contrast, constitutively active MAPK kinase 6 (constitutive activator of p38) transgenic mice exhibit decreased HDAC4 content in vivo. We also observed that p38 stimulates caspase-3 activity in chondrocytes. Inhibition of p38 or caspases reduced HDAC4 degradation. HDAC4 inhibited Runx2 promoter activity in a dose-dependent manner and caspase inhibitors further enhanced this inhibition by preventing HDAC4 degradation. Overall, these results demonstrate that p38 promotes HDAC4 degradation by increasing caspase-mediated cleavage, which releases Runx2 from a repressive influence of HDAC4 and promotes the chondrocyte hypertrophy and bone formation.


Experimental assessment of the vector competence of Culex (Culex) neavei Theobald with West Nile and Sindbis viruses in South Africa.
Culex univittatus is the maintenance vector of West Nile (WN) and Sindbis (SIN) viruses on the inland plateau of South Africa and also transfers infection to man. Both viruses have frequently been isolated from this mosquito and human immunity is high on the plateau. In the Natal lowlands where Cx univittatus is replaced by Cx neavei, apparently the main vector there, immune rates are low and few isolations have been made from this species. Vector competence experiments were carried out with Cx neavei to compare with those previously done with Cx univittatus. It was thought that a difference in such competence might explain the contrasting epidemiological situation in the two regions. After infective feeds on chicks with high viraemias of each virus, Cx neavei showed a high transmission rate. However, the 50% infection thresholds determined by exposing birds with differing viraemias to mosquitoes of this species, were 4.4 logs per ml (WN) and 5.8 logs (SIN). These thresholds are both higher than those for Cx univittatus. It is concluded that Cx neavei is a poorer vector of both viruses which accounts for the lower viral activity, including the lower incidence of human infection, in the Natal lowlands.


The causal interaction in human basal ganglia.
The experimental study of the human brain has important restrictions, particularly in the case of basal ganglia, subcortical centers whose activity can be recorded with fMRI methods but cannot be directly modified. Similar restrictions occur in other complex systems such as those studied by Earth system science. The present work studied the cause/effect relationships between human basal ganglia with recently introduced methods to study climate dynamics. Data showed an exhaustive (identifying basal ganglia interactions regardless of their linear, non-linear or complex nature) and selective (avoiding spurious relationships) view of basal ganglia activity, showing a fast functional reconfiguration of their main centers during the execution of voluntary motor tasks. The methodology used here offers a novel view of the human basal ganglia which expands the perspective provided by the classical basal ganglia model and may help to understand BG activity under normal and pathological conditions.


Analysis of current SARS-CoV-2 infection in a large population of blood donors evidenced that RNAemia is rare in plasma.
Transmission of SARS-CoV-2 by asymptomatic individuals and by blood transfusion are important issues to understand to control the viral spread. In this work, we estimated the current SARS-CoV-2 infection rate in blood donors from Belo Horizonte, Brazil. Saliva and blood samples were collected from 4103 blood donors from June 15 to September 30, 2020. Saliva samples were tested by real-time RT-PCR for SARS-CoV-2 in mini-pools of four samples. Individual samples were tested for positive or inconclusive pools, and positive donors had their plasma tested. Twenty-seven (0.66%) blood donors were positive for SARS-CoV-2 in their saliva, but their plasma was negative, except for one, who presented a high viral load in saliva and nasopharyngeal samples and RNAemia in the plasma close to the limit of detection. Fourteen (56%) positive blood donors reported mild symptoms related to COVID-19 after donation, but the viral load levels were not statistically different between symptomatic and asymptomatic individuals. Despite the measures taken by Blood Centers to avoid blood donors with SARS-CoV-2 infection, asymptomatic or presymptomatic carriers are able to donate. The risk of the virus transmission by transfusion seems to be negligible since plasma RNAemia was seen at a very low level in only one (3.7%) of the positive donors, but other studies must be performed to confirm this finding.


A computer simulation study on the effects of input function measurement noise in tracer kinetic modeling with positron emission tomography (PET).
Tracer kinetic modeling with positron emission tomography (PET) requires measurements of the time-activity curves in both plasma (PTAC) and tissue (TTAC) to estimate physiological parameters, i.e. to fit the parameters of certain compartmental models using PTAC and TTAC as the model input and output functions, respectively. However, the estimation usually ignores the measurement noise in plasma tracer activity curves. The accuracy and reliability of the physiological parameters estimated by ignoring such noise are not well understood. In this paper, effects of noise in [18F] 2-fluoro-2-deoxy-D-glucose (FDG) tracer plasma concentration measurements on estimation of local cerebral metabolic rates of glucose (LCMRGlc) with PET is investigated systematically. The PTAC modeling approach used in this paper also provides a realistic means to filter out the noise and to improve the physiological parameter accuracy, which can be potentially used in model-based non-invasive measurements of PTAC.


Growth hormone pharmacogenetics: the interactive effect of a microsatellite in the IGF1 promoter region with the GHR-exon 3 and -202 A/C IGFBP3 variants on treatment outcomes of children with severe GH deficiency.
Insulin-like growth factor type 1 (IGF1) is a mediator of growth hormone (GH) action, and therefore, IGF1 is a candidate gene for recombinant human GH (rhGH) pharmacogenetics. Lower serum IGF1 levels were found in adults homozygous for 19 cytosine-adenosine (CA) repeats in the IGF1 promoter. The aim of this study was to evaluate the influence of (CA)n IGF1 polymorphism, alone or in combination with GH receptor (GHR)-exon 3 and -202 A/C insulin-like growth factor binding protein-3 (IGFBP3) polymorphisms, on the growth response to rhGH therapy in GH-deficient (GHD) patients. Eighty-four severe GHD patients were genotyped for (CA)n IGF1, -202 A/C IGFBP3 and GHR-exon 3 polymorphisms. Multiple linear regressions were performed to estimate the effect of each genotype, after adjustment for other influential factors. We assessed the influence of genotypes on the first year growth velocity (1st y GV) (n=84) and adult height standard deviation score (SDS) adjusted for target-height SDS (AH-TH SDS) after rhGH therapy (n=37). Homozygosity for the IGF1 19CA repeat allele was negatively correlated with 1st y GV (P=0.03) and AH-TH SDS (P=0.002) in multiple linear regression analysis. In conjunction with clinical factors, IGF1 and IGFBP3 genotypes explain 29% of the 1st y GV variability, whereas IGF1 and GHR polymorphisms explain 59% of final height-target-height SDS variability. We conclude that homozygosity for IGF1 (CA)19 allele is associated with less favorable short- and long-term growth outcomes after rhGH treatment in patients with severe GHD. Furthermore, this polymorphism exhibits a non-additive interaction with -202 A/C IGFBP3 genotype on the 1st y GV and with GHR-exon 3 genotype on adult height.


Use of reperfusion therapy and time delay in patients with ischaemic stroke by immigration status: A register-based cohort study in Denmark.
Reperfusion therapy is the mainstay of treatment for acute ischaemic stroke (AIS); however, little is known about the use of reperfusion therapy and time delay amongst immigrants. This is a Danish nationwide register-based cohort study of patients with AIS aged ≥18 years (n = 49,817) recruited from 2009 to 2018. Use of reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy) and time delay between immigrants and Danish-born residents were compared using multivariable logistics and quantile regression. Overall, 10,649 (39.8%) Danish-born residents and 452 (39.0%) immigrants with AIS were treated with reperfusion therapy in patients arriving <4.5 h following stroke onset. Compared with Danish-born residents, immigrants had lower odds of receiving reperfusion therapy after adjustment for prehospital delay, age, sex, stroke severity, sociodemographic factors and comorbidities (adjusted odds ratio 0.67; 95% confidence interval 0.49-0.92, p = 0.01). The lowest odds were observed amongst immigrants originating from Poland and non-Western countries. Similarly, immigrants had a longer prehospital delay than Danish-born residents in the fully adjusted model in patients arriving <4.5 h after stroke onset (15 min; 95% confidence interval 4-26 min, p = 0.03). No evidence was found that system delay and clinical outcome differed between immigrants and Danish-born residents in patients eligible for reperfusion therapy after adjustment for sociodemographic factors and comorbidities. Immigration status was significantly associated with lower chances of receiving reperfusion therapy and there may be differences in patient delay between immigrants and Danish-born residents in patients arriving to a stroke unit <4.5 h after stroke onset.


Oral inhalation of cannabidiol delivered from a metered dose inhaler to alleviate cytokine production induced by SARS-CoV-2 and pollutants.
Cannabidiol (CBD) was formulated as a metered dose inhaler (CBD-MDI) and evaluated in vitro for its efficacy as an inhaled dosage form against inflammation caused by the SARS-CoV-2 virus, lipopolysaccharide (LPS) from Escherichia coli, silica particles, nicotine, and coal tar. A CBD-MDI formulation was prepared with 50 mg of CBD in 10 mL for a CBD dose of 250 μg/puff. The formulation ingredients included CBD, absolute ethanol as a cosolvent, and HFA-134a as the propellant. High aerosol performance of CBD-MDI was obtained with mass median aerodynamic diameter of 1.25 ± 0.01 μm, geometric standard deviation of 1.75 ± 0.00, emitted dose of 244.7 ± 2.1 μg, and fine particle dose of 122.0 ± 1.6 μg. The cytotoxicity and anti-inflammatory effectiveness of CBD-MDI were performed in alveolar macrophage (NR8383) and co-culture of alveolar macrophage (NR8383) and human lung adenocarcinoma (A549) cell line. CBD delivered from an MDI was safe on respiratory cells and did not trigger an immune response in alveolar macrophages. CBD-MDI effectively reduced the generation of cytokines in immune cells treated with viral antigen S-RBD, bacterial antigen LPS, silica particles, and coal tar. The efficacy of CBD-MDI was comparable to budesonide. Furthermore, the findings demonstrated that the use of CBD-MDI was more effective in treatment rather than prevention when inflammation was induced by either a viral or bacterial stimulant.


Inhibition of calcite crystal growth by polyphosphates.
The inhibition of calcite crystal growth by pyrophosphate (P(2)O(7)(4-)), tripolyphosphate (P(3)O(10)(5-)), hexametaphosphate (P(6)O(18)(6-)) and binary-polyphosphate blends in calcite-seeded solutions was investigated with various solution compositions using a pH-stat system. In a single polyphosphate system, tripolyphosphate was found to be the strongest inhibitor, followed by pyrophosphate and hexametaphosphate. The inhibition can be explained by the adsorption of polyphosphates on the calcite surface conforming to a simple Langmuir adsorption model. Through a detailed speciation analysis, CaP(2)O(7)(2-) and CaP(3)O(10)(3-) were found to be the primary species of pyrophosphate and tripolyphosphate responsible for adsorption of phosphate on the calcite surface, while the responsible species for hexametaphosphate could not be determined because of a lack of published stability constants. By comparing the equilibrium constants for the adsorption reaction, the inhibitory capabilities of polyphosphates are about two orders of magnitude greater than that of orthophosphate. In binary-polyphosphate systems, the inhibition of calcite crystal growth can be described by a competitive Langmuir adsorption model using the stability constants derived from single solute systems. The inhibitory behavior of commercially available phosphate blends that are marketed to prevent calcite scale formation were demonstrated to be similar to those of laboratory-prepared blends with the same chemical composition.


Presence of an L(+)-lactate dehydrogenase in cells of Lactobacillus delbrueckii ssp. bulgaricus.
Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 was cultured in a chemostat and growth conditions were varied as required. Synthesis of L(+)-lactate was observed in all cases as well as activity of L(+)-lactate dehydrogenase in cell-free extracts. This enzyme was responsible for the formation of the L(+) isomer of lactate, since a lactate racemase was not present.


Complete response and renal cell carcinoma in the immunotherapy era: The paradox of good news.
Immune-checkpoint inhibitor-based therapy has revolutionized the natural history of metastatic renal cell carcinoma (mRCC) providing better survival outcomes, higher rates of complete responses (CR) and durable remissions. Along with these advances, new challenges have emerged. RECIST and new immune-response criteria may be equivocal identifying complete responses. How to define a durable response and what is the optimal treatment duration remains unclear. Furthermore, the real value of a complete and deep response, whether or not it can be considered curation and whether or not immunotherapy discontinuation should be considered after complete response, are questions that remain open. The present article reviews the current evidence regarding the impact and challenges of managing complete and durable responses in mRCC treated with immune-checkpoint inhibitors.


Assessing the regional biogenic methanol emission from spring wheat during the growing season: A Canadian case study.
As a volatile organic compound existing in the atmosphere, methanol plays a key role in atmospheric chemistry due to its comparatively high abundance and long lifetime. Croplands are a significant source of biogenic methanol, but there is a lack of systematic assessment for the production and emission of methanol from crops in various phases. In this study, methanol emissions from spring wheat during the growing period were estimated using a developed emission model. The temporal and spatial variations of methanol emissions of spring wheat in a Canadian province were investigated. The averaged methanol emission of spring wheat is found to be 37.94 ± 7.5 μg·m-2·h-1, increasing from north to south and exhibiting phenological peak to valley characteristics. Moreover, cold crop districts are projected to be with higher increase in air temperature and consequent methanol emissions during 2020-2099. Furthermore, the seasonality of methanol emissions is found to be positively correlated to concentrations of CO, filterable particulate matter, and PM10 but negatively related to NO2 and O3. The uncertainty and sensitivity analysis results suggest that methanol emissions show a Gamma probabilistic distribution, and growth length, air temperature, solar radiation and leafage are the most important influencing variables. In most cases, methanol emissions increase with air temperature in the range of 3-35 °C while the excessive temperature may result in decreased methanol emissions because of inactivated enzyme activity or increased instant methanol emissions due to heat injury. Notably, induced emission might be the major source of biogenic methanol of mature leaves. The results of this study can be used to develop appropriate strategies for regional emission management of cropping systems.


Exploring the role of homeobox and zinc finger proteins in pancreatic cell proliferation, differentiation, and apoptosis.
Transcription factors are DNA binding proteins that regulate gene expression in response to a large variety of extracellular stimuli, and thereby act as key molecular switches for controlling cell differentiation, proliferation, and apoptosis. During the last decade, a myriad of these proteins have been identified and classified into different structural families, including homeobox, zinc finger, leucine zipper, and helix-loop-helix transcription factors. Members of the homeobox and zinc finger superfamilies are among the best-characterized transcription factors known to act as potent regulators of normal development in organisms ranging from insects to humans. In addition, mutations or aberrant expression in genes encoding these proteins can result in neoplastic transformation in several different cell types, further supporting their role as "guardians" of normal cell growth and differentiation. Therefore, the purpose of this article is to review this field of research with a particular emphasis on the role of homeobox- and zinc finger-containing transcription factors in pancreatic cell growth, cell differentiation, and apoptosis. The potential participation of these proteins in neoplastic transformation is also discussed.


Evaluating a teen STD prevention Web site.
Teens are at higher risk than other age groups for acquiring sexually transmitted diseases (STDs) because of biological and behavioral risk factors, but they have few STD prevention resources. Little is known about how teens use the Internet to seek this information. A pilot study was conducted to measure audience and information-seeking characteristics of the www.iwannaknow.org Web site. In addition to a formative content analysis and a usability study, an online survey was designed, pilot tested, revised, and launched for three months. This paper briefly describes the first two formative study components, and then focuses on the online survey. The content analyses and the usability tests were useful for revising the site content and aesthetics and preparing the online survey. Fewer than half of all participants (N=3,489) were between 13 and 17 (n=1,242), the intended site demographic. Most accessed the Internet from home. The most frequent topic of interest was sexual expression, followed by teen sexuality, virginity, relationships, contraception, and then STD information and these varied by age and gender. Methods and findings will assist researchers, Web site developers, and health educators to refine these evaluation methods, develop effective Web sites, and tailor STD prevention messages by age group and gender. The Internet is a cost-effective method for educating teens and those who care for or work with teens about STD risks and prevention, however, more research is needed to assess the behavioral effects of online interventions.


Detection of N,N-diacetyllactosamine (LacdiNAc) containing free prostate-specific antigen for early stage prostate cancer diagnostics and for identification of castration-resistant prostate cancer patients.
Prostate cancer (PCa) is one of the most common cancer types among men and also acommon cause of death globally. With an increasing incidence, there is aneed for low-cost, reliable biomarkers present in samples, which could be provided non-invasively (without a need to perform prostate biopsy). Glycosylation changes of free-PSA (fPSA) are considered cancer-specific, while the level of different PSA forms can increase under other than cancerous conditions. In the present study, we investigated the role ofN,N-diacetyllactosamine (LacdiNAc) epitope of fPSA (i.e. glycoprofile of fPSA or gPSA) in combination with total-PSA (tPSA), prostate volume, and tPSA density (tPSA level divided by prostate volume i.e. PSAd) as biomarkers for monitoring of PCa development and progression in 105 men. Furthermore, we applied an genetic (evolutionary) algorithm to identify any suspicious individuals in abenign cohort having benign prostatic hyperplasia (BPH). We identified 3 suspicious men originally diagnosed with BPH using gPSA analysis. In thefollow-up we found out that two men should not be considered as BPH patients since multiparametric magnetic resonance imaging (mpMRI) identified one man with clinically significant PCa via Prostate Imaging - Reporting and Data System (PI RADS v2 = 4) and the second man was with High-gradeprostatic intraepithelial neoplasia (HG PIN), commonly described as apre-cancerous stage. Moreover, in the study we described for the first time that changed LacdiNAc on PSA can be applied to identify prostatitis patients and most importantly this is the first study suggesting that changed glycosylation on PSA can be applied to identify castration-resistant prostate cancer (CRPCa) patients.


Critical care problems in neonates. Colloid osmotic pressure in healthy and sick neonates.
Clinical usefulness of colloid osmotic pressure (COP) measurements in adults has been well established. However, data in healthy and sick neonates are sparse. The present study established the COP changes in healthy term and preterm infants and in critically ill neonates. COP in healthy term (16.9 +/- 1.9 mm Hg) and preterm (15.4 +/- 1.3) infants was significantly lower than adults (21.6 +/- 3.6). Even in sick neonates, COP correlated with gestational age (n = 78, r = 0.63, p less than 0.001 , birth weight (r = 0.58, p less than 0.001) and total protein (n = 71, r = 0.58, p less than 0.001). Critically ill preterm infants with hyaline membrane disease had the lowest COP (11.5 +/- 1.2). Administration of 10% albumin failed to increase the COP significantly. In critically ill preterm infants who survived, the COP increased during the first postnatal week, whereas in nonsurvivors COP decreased significantly to less than 10 mm Hg.


Data on the activity of place cells in the hippocampal CA1 subfield of a monkey performing a shuttling task.
This data article provides spike-timestamps of place cells recorded in a male Japanese monkey and the animal's sequential positions during the performance of a shuttling task on a rectangular track. All data were recorded in the right hippocampal CA1 subfield, while the monkey performed the task under a freely behaving condition. These were the source data on the monkey place cells in our related research article entitled "Effects of self-locomotion on the activity of place cells in the hippocampus of a freely behaving monkey" [1]. In addition, here we show a movement directional activity of a place cell in two-dimensional space as an example of data utilization. The source data are freely accessible [2] and can be used by other researchers to obtain new insights into place cells, such as functional differences between animal species.


MXene-Derived Tin O2 n- 1 Quantum Dots Distributed on Porous Carbon Nanosheets for Stable and Long-Life Li-S Batteries: Enhanced Polysulfide Mediation via Defect Engineering.
The application of Li-S batteries has been hindered by the shuttling behavior and sluggish reaction kinetics of polysulfides. Here an effective polysulfide immobilizer and catalytic promoter is developed by proposing oxygen-vacancy-rich Tin O2 n -1 quantum dots (OV-Tn QDs) decorated on porous carbon nanosheets (PCN), which are modulated using Ti3 C2 Tx MXene as starting materials. The Tn QDs not only confine polysulfides through strong chemisorption but also promote polysulfide conversion via redox-active catalysis. The introduction of oxygen vacancies further boosts the immobilization and conversion of polysulfides by lowering the adsorption energy and shortening the bond lengths. The PCN provides a physical polysulfide confinement as well as a flexible substrate preventing OV-Tn QDs from aggregation. Moreover, the two building blocks are conductive, thereby effectively improving the electron/charge transfer. Finally, the ultrasmall size of QDs along with the porous structure endows OV-Tn QDs@PCN with large specific surface area and pore volume, affording adequate space for S loading and volume expansion. Therefore, the OV-Tn QDs@PCN/S delivers a high S loading (79.1 wt%), good rate capability (672 mA h g-1 at 2 C), and excellent long-term cyclability (88% capacity retention over 1000 cycles at 2 C). It also exhibits good Li+ storage under high S-mass loading and lean electrolyte.


Tirbanibulin: Topical Treatment for Actinic Keratosis.
We review here the pharmacology, pharmacokinetics, efficacy, dosage and administration, and place in therapy of tirbanibulin for the treatment of actinic keratosis (AK). A literature search using PubMed was conducted using the terms tirbanibulin (tirbanibulin) and actinic keratosis from September 2014 to February 2021. All English-language articles evaluating tirbanibulin were analyzed for this review. Tirbanibulin was granted approval for the treatment of AK of the face or scalp as a first-line therapy. It is administered at a dose of 2.5 mg in 250 mg of white or off-white ointment for a 25 cm2 contiguous treatment surface for 5 consecutive days. Adverse effects include flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. This article discusses the clinical trials that led to the approval of tirbanibulin and comparison with other approved topical ointments indicated for the treatment of AK. In the clinical trials, all participants experienced a decrease in lesion size or saw complete clearance with minimal adverse effects.


Negative-Pressure Wound Therapy Improves Take Rate of Skin Graft in Irregular, High-Mobility Areas: A Randomized Controlled Trial.
Tie-over bolster dressing to secure a skin graft is associated with low graft take rates in irregular, high-mobility areas and suboptimal recipient wound beds. Negative-pressure wound therapy has become a well-established method to secure the graft, with a graft take rate of this method reported to be 96.7 percent. However, comparative efficacies between the two methods on irregular, high-mobility areas are yet to be determined. Patients eligible for skin graft were randomly assigned to receive either negative-pressure wound therapy or tie-over bolster dressing between December of 2014 and December of 2015. The primary outcome was determined by the take rate of skin grafts between postoperative days 5 and 7. The secondary outcomes were dressing time and postoperative complications, including hematoma, seroma, infection, displacement, and necrosis. A total of 86 patients were assigned to receive either negative-pressure wound therapy ( n = 43) or tie-over bolster dressing ( n = 43) for skin graft treatment. Negative-pressure wound therapy significantly improved the take rate of grafts as compared with tie-over bolster dressing (97.2 versus 90.2 percent; p = 0.005). The improvements came from the grafts in irregular, high-mobility areas in the respective groups (97.6 versus 81.7 percent; p < 0.001). Negative-pressure wound therapy reduced skin graft displacement as a postoperative complication as compared with tie-over bolster dressing (one versus nine patients; p = 0.007). Dressing time using negative-pressure wound therapy was significantly shorter compared with tie-over bolster dressing (15.2 ± 4.2 versus 27.4 ± 4.3 minutes; p = 0.001). Negative-pressure wound therapy can improve the take rate of skin grafts in irregular, high-mobility areas and shorten the dressing time. Therapeutic, I.


Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptors in chick cerebral cortex.
In this study receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) were characterized in chick cerebral cortex by an in vitro binding technique, using 125I-labeled VIP ([125I]-VIP) as a ligand. The specific binding of [125I]-VIP to chick cerebral cortical membranes was found to be rapid, stable, saturable, reversible, and of high affinity. Saturation analysis resulted in a linear Scatchard plot, suggesting binding to a single class of receptor binding sites with high affinity (Kd = 0.21 nM) and low capacity (Bmax = 19.5 fmol/mg protein). The relative rank order of potency of the tested peptides to inhibit [125I]-VIP binding to chick cerebrum was VIP (chicken) > or = VIP (mammalian) > or = PACAP27 > or = PACAP38 >> VIP6-28 (mammalian) > PHI (porcine) >> neurotensin6-11-chicken VIP7-28 > neurotensin6-11-mammalian VIP7-28 >>> VIP16-28 (chicken; inactive) approximately secretin (inactive). About 60% of [125I]-VIP-binding sites in chick cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. It has been concluded that the cerebral cortex of chick, in addition to PAC1 receptors, contains a population of VPAC-type receptors.


Significance of serum bilirubin level in response of hepatocellular carcinoma to doxorubicin.
To determine which of several clinical and laboratory features could be of significance in the response of hepatocellular carcinoma to doxorubicin we have analysed the frequency of remission in 143 patients treated with this drug. Of those features investigated including age, sex, presence and aetiology of underlying cirrhosis, duration of symptoms, performance grade and liver function tests, a normal serum bilirubin level was shown to be the only one on logistic regression analysis to predict a greater change of response (response rate = 46% with serum bilirubin less than 20 mumol/l and 10% with bilirubin greater than 20 mumol/l). The most likely explanation is that reduction in doxorubicin dosage according to the serum bilirubin level, based on the view that the risk of myelosuppression is thereby lessened, may lead to suboptimal dose administration.


What about the relatives?
Dealing with a relative or friend's terminal illness is an extremely stressful experience. How well are patients' relatives and friends cared for by healthcare staff?


3-(4-Chloro-phen-oxy)-1-(4-meth-oxy-phen-yl)-4-(4-nitro-phen-yl)azetidin-2-one.
In the title compound, C(22)H(17)ClN(2)O(5), the nearly planar four-membered β-lactam ring [maximum deviation of 0.016 (1) for the N atom] makes dihedral angles of 53.07 (9), 73.19 (9) and 6.61 (9)° with the chloro-, nitro- and meth-oxy-benzene rings, respectively. The crystal structure is stabilized by C-H⋯O hydrogen bonds, a weak C-H⋯π inter-action and a π-π stacking inter-action [centroid-centroid distance = 3.6513 (8) Å] between the meth-oxy-benzene rings of inversion-related mol-ecules.


Brain-Derived Neurotrophic Factor, Kynurenine Pathway, and Lipid-Profiling Alterations as Potential Animal Welfare Indicators in Dairy Cattle.
Complete animal welfare evaluation in intensive farming is challenging. With this study, we investigate new biomarkers for animal physical and mental health by comparing plasma expression of biochemical indicators in dairy cows reared in three different systems: (A) semi-intensive free-stall, (B) non-intensive tie-stall, and (C) intensive free-stall. Additionally, protein levels of mature brain-derived neurotrophic factor (mBDNF) and its precursor form (proBDNF) and indoleamine 2,3-dioxygenase (IDO1) specific activity were evaluated in brain samples collected from 12 cattle culled between 73 and 138 months of age. Alterations in plasma lipid composition and in the kynurenine pathway of tryptophan metabolism were observed in the tie-stall-reared animals. The total plasma BDNF concentration was higher in tie-stall group compared to the two free-housing groups. Brain analysis of the tie-stall animals revealed a different mBDNF/proBDNF ratio, with a higher level of proBDNF (p < 0.001). Our data are similar to previous studies on animal models of depression, which reported that inhibition of the conversion of proBDNF in its mature form and/or elevated peripheral kynurenine pathway activation may underlie cerebral biochemical changes and induce depressive-like state behavior in animals.