The treatment of metastatic germ-cell testicular tumours with bleomycin, etoposide and cis-platin (BEP).
Between July 1979 and December 1981, 43 patients with metastatic germ-cell tumours (36 testicular non-seminomas and 7 testicular seminomas) were treated with 2-6 cycles of bleomycin, etoposide and cis-platin (BEP). Forty (93%) are alive, 37 (86%) with no evidence of disease. Of 36 men with testicular non-seminoma 30 (83.3%) are alive and disease-free at 8-38 months (median 17.0 months). In the latter group 25/28 (89.3%) who had had no prior irradiation are alive and disease-free. Fourteen non-seminoma patients had small volume metastases and 13 are in complete remission, as are 12/14 patients with bulky disease. All 7 patients with advanced seminoma are alive and disease-free. It is concluded that BEP is a well tolerated and effective first line treatment for patients with metastatic germ-cell tumours.


Enhanced photocatalysis by coupling of anatase TiO2 film to triangular Ag nanoparticle island.
In order to overcome the low utilization ratio of solar light and high electron-hole pair recombination rate of TiO2, the triangular Ag nanoparticle island is covered on the surface of the TiO2 thin film. Enhancement of the photocatalytic activity of the Ag/TiO2 nanocomposite system is observed. The increase of electron-hole pair generation is caused by the enhanced near-field amplitudes of localized surface plasmon of the Ag nanoparticles. The efficiently suppressed recombination of electron-hole pair caused by the metal-semiconductor contact can also enhance the photocatalytic activity of the TiO2 film.


Serum and meat antioxidative status of broiler chickens fed diets supplemented with garlic rhizome meal, moringa leaf meal and their composite.
Serum and breast meat antioxidative status of broiler chickens fed diets supplemented with moringa leaf meal (MLM), garlic rhizome meal (GRM) and their composite were assessed. Ninety-six-day old Cobb 500 broiler chickens were randomly allotted to four treatment diets: Diet 1 (control), Diet 2 (2.5 g/kg MLM), Diet 3 (2.5 g/kg GRM) and Diet 4 (1.25 g/kg MLM + 1.25 g/kg GRM). Serum superoxide dismutase concentrations were not significantly (P > 0.05) influenced by the diets, whereas there were increased serum catalase concentrations across all the treatment diets with birds on Diet 4 showing significantly (P < 0.05) higher means than those on the control. For the serum glutathione peroxidase, significant (P < 0.05) increases were observed among the broilers on Diets 2 to 4 with those on Diet 2 showing the highest significant difference (P < 0.05) with birds on the control diet. The meat catalase and cholesterol concentrations of the breast meat were not significantly (P > 0.05) influenced by the phytoadditives. However, significant (P < 0.05) decrease in lipid peroxidation was observed across the treatment diets when compared with the control, while the phytoadditives enhanced the breast meat glutathione peroxidase among the broilers on the Diets 2 and 4.


Wood cellulose microfibrils have a 24-chain core-shell nanostructure in seed plants.
Wood cellulose microfibril (CMF) is the most abundant organic substance on Earth but its nanostructure remains poorly understood. There are controversies regarding the glucan chain number (N) of CMFs during initial synthesis and whether they become fused afterward. Here, we combined small-angle X-ray scattering, solid-state nuclear magnetic resonance and X-ray diffraction analyses to resolve CMF nanostructures in native wood. We developed small-angle X-ray scattering measurement methods for the cross-section aspect ratio and area of the crystalline-ordered CMF core, which has a higher scattering length density than the semidisordered shell zone. The 1:1 aspect ratio suggested that CMFs remain mostly segregated, not fused. The area measurement reflected the chain number in the core zone (Ncore). To measure the ratio of ordered cellulose over total cellulose (Roc) by solid-state nuclear magnetic resonance, we developed a method termed global iterative fitting of T1ρ-edited decay (GIFTED), in addition to the conventional proton spin relaxation editing method. Using the formula N = Ncore/Roc, most wood CMFs were found to contain 24 glucan chains, conserved between gymnosperm and angiosperm trees. The average CMF has a crystalline-ordered core of ~2.2 nm diameter and a semidisordered shell of ~0.5 nm thickness. In naturally and artificially aged wood, we observed only CMF aggregation (contact without crystalline continuity) but not fusion (forming a conjoined crystalline unit). This further argued against the existence of partially fused CMFs in new wood, overturning the recently proposed 18-chain fusion hypothesis. Our findings are important for advancing wood structural knowledge and more efficient use of wood resources in sustainable bio-economies.


BRAF inhibition in hairy cell leukemia with low-dose vemurafenib.
The activating mutation of the BRAF serine/threonine protein kinase (BRAF V600E) is the key driver mutation in hairy cell leukemia (HCL), suggesting opportunities for therapeutic targeting. We analyzed the course of 21 HCL patients treated with vemurafenib outside of trials with individual dosing regimens (240-1920 mg/d; median treatment duration, 90 days). Vemurafenib treatment improved blood counts in all patients, with platelets, neutrophils, and hemoglobin recovering within 28, 43, and 55 days (median), respectively. Complete remission was achieved in 40% (6/15 of evaluable patients) and median event-free survival was 17 months. Response rate and kinetics of response were independent of vemurafenib dosing. Retreatment with vemurafenib led to similar response patterns (n = 6). Pharmacodynamic analysis of BRAF V600E downstream targets showed that vemurafenib (480 mg/d) completely abrogated extracellular signal-regulated kinase phosphorylation of hairy cells in vivo. Typical side effects also occurred at low dosing regimens. We observed the development of acute myeloid lymphoma (AML) subtype M6 in 1 patient, and the course suggested disease acceleration triggered by vemurafenib. The phosphatidylinositol 3-kinase hotspot mutation (E545K) was identified in the AML clone, providing a potential novel mechanism for paradoxical BRAF activation. These data provide proof of dependence of HCL on active BRAF signaling. We provide evidence that antitumor and side effects are observed with 480 mg vemurafenib, suggesting that dosing regimens in BRAF-driven cancers could warrant reassessment in trials with implications for cost of cancer care.


Transcriptomic dataset of Mycolicibacterium smegmatis exposed to an imidazo[1,2-b][1,2,4,5]tetrazine.
Deciphering the mechanism of action of novel anti-tuberculosis compounds is a key step in the drug development process. We have previously described a number of imidazo[1,2-b][1,2,4,5]tetrazines with a promising activity on Mycobacterium tuberculosis[1]. These compounds had predicted activity as serine‑threonine protein kinase inhibitors, however spontaneous drug resistant Mycolicibacterium smegmatis mc 2 155 (formerly Mycobacterium smegmatis) revealed only the mycobacterial mechanism of resistance to imidazo[1,2-b][1,2,4,5]tetrazines: mutations in MSMEG_1380 gene lead to overexpression of the mmpS5-mmpL5 operon in M. smegmatis, thus providing resistance to imidazo[1,2-b][1,2,4,5]tetrazines via enhanced efflux [2]. Here we report the RNA sequencing data of M. smegmatis mc 2 155 culture treated with one of the imidazo[1,2-b][1,2,4,5]tetrazines for 1.5 h and the untreated culture as a control. The mapped reads showed that a total of 1386 genes are differentially expressed in this experiment. A further analysis of these data can shed light of the mechanism of action of imidazo[1,2-b][1,2,4,5]tetrazines. The data generated by RNA-seq (raw reads) have been deposited to NCBI sequence read archive (SRA) and have been assigned a BioProject accession number PRJNA615922.


Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer.
As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy. Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions. From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks. This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach. German Clinical Trials Register DRKS00003273.


Measurement of human plasma proteome dynamics with (2)H(2)O and liquid chromatography tandem mass spectrometry.
Dysfunction of protein turnover is a feature of many human diseases, and proteins are substrates in important biological processes. Currently, no method exists for the measurement of global protein turnover (i.e., proteome dynamics) that can be applied in humans. Here we describe the use of metabolic labeling with deuterium ((2)H) from (2)H(2)O and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of mass isotopomer patterns to measure protein turnover. We show that the positions available for (2)H label incorporation in vivo can be calculated using peptide sequence. The isotopic incorporation values calculated by combinatorial analysis of mass isotopomer patterns in peptides correlate very closely with values established for individual amino acids. Inpatient and outpatient heavy water labeling protocols resulted in (2)H label incorporation sufficient for reproducible quantitation in humans. Replacement rates were similar for peptides deriving from the same protein. Using a kinetic model to account for the time course of each individual's (2)H(2)O enrichment curves, dynamics of approximately 100 proteins with half-lives ranging from 0.4 to 40 days were measured using 8 μl of plasma. The measured rates were consistent with literature values. This method can be used to measure in vivo proteome homeostasis in humans in disease and during therapeutic interventions.


Opinions of 12 to 13-year-olds in Austria and Australia on the concern, cause and imminence of climate change.
Early adolescence (12-13 years old) is a critical but under-researched demographic for the formation of attitudes related to climate change. We address this important area by exploring adolescent views about climate change. This paper presents opinions collected from surveys of 463 1st-year secondary school students (12-13 years old) in public secondary schools in inner-urban centres in Austria and Australia on whether climate change is (1) something about which to worry, (2) caused by humans and (3) happening now. Eligible respondents in both countries showed similar levels of agreement that climate change was probably or definitely something we should (1) worry about (84.6% Austria, 89.1% Australia), which is significantly higher than either country's adult population. Eligible respondents agreed that climate change probably or definitely is (2) caused by humans (75.6% Austria, 83.6% Australia) and that climate change is probably or definitely something that is (3) happening now (73.1% Austria, 87.5% Australia). Their response differed from the respective adult populations, but in opposite directions. Our results suggest that socio-cultural worldview may not have as much influence on this age group as it does on the respective adult populations and suggests that this age group would be receptive and ready for climate science education and engagement initiatives.


Activation of G protein coupled estrogen receptor prevents chemotherapy-induced intestinal mucositis by inhibiting the DNA damage in crypt cell in an extracellular signal-regulated kinase 1- and 2- dependent manner.
Chemotherapy-induced intestinal mucositis (CIM) is a common adverse reaction to antineoplastic treatment with few appropriate, specific interventions. We aimed to identify the role of the G protein coupled estrogen receptor (GPER) in CIM and its mechanism. Adult male C57BL/6 mice were intraperitoneally injected with 5-fluorouracil to establish the CIM model. The selective GPER agonist G-1 significantly inhibited weight loss and histological damage in CIM mice and restored mucosal barrier dysfunction, including improving the expression of ZO-1, increasing the number of goblet cells, and decreasing mucosal permeability. Moreover, G-1 treatment did not alter the antitumor effect of 5-fluorouracil. In the CIM model, G-1 therapy reduced the expression of proapoptotic protein and cyclin D1 and cyclin B1, reversed the changes in the number of TUNEL+ cells, Ki67+ and bromodeoxyuridine+ cells in crypts. The selective GPER antagonist G15 eliminated all of the above effects caused by G-1 on CIM, and application of G15 alone increased the severity of CIM. GPER was predominantly expressed in ileal crypts, and G-1 inhibited the DNA damage induced by 5-fluorouracil in vivo and vitro, as confirmed by the decrease in the number of γH2AX+ cells in the crypts and the comet assay results. Referring to the data from GEO dataset we verified GPER activation restored ERK1/2 activity in CIM and 5-fluorouracil-treated IEC-6 cells. Once the effects of G-1 on ERK1/2 activity were abolished with the ERK1/2 inhibitor PD0325901, the effects of G-1 on DNA damage both in vivo and in vitro were eliminated. Correspondingly, all of the manifestations of G-1 protection against CIM were inhibited by PD0325901, such as body weight and histological changes, the mucosal barrier, the apoptosis and proliferation of crypt cells. In conclusion, GPER activation prevents CIM by inhibiting crypt cell DNA damage in an ERK1/2-dependent manner, suggesting GPER might be a target preventing CIM.


Synergistic strengthening mechanisms of mechanical activation-microwave reduction for selective lithium extraction from spent lithium batteries.
Carbothermal reduction of cathode materials is an effective method to selectively extract lithium carbonate, both mechanical activation and microwave heating can enhance thermal reduction of mixed electrode materials. However, the mechanism of enhanced lithium extraction has not been fully revealed. This study attempts to uncover the synergistic strengthening mechanisms of mechanical activation-microwave reduction from the aspects of material structure, dielectric properties, reduction kinetics and lithium recovery rate. Mechanical activation induces amorphization and structural defects. The enhanced dielectric properties of materials and the induced hotspots/arc plasmas are also responsible for the enhancement of the reduction reaction. The average dissociation activation energy in the activated sample is 18.0 kJ·mol-1, which is 20.3 kJ·mol-1 lower than that of unactivated sample. The model-free method reveals that the carbothermic reduction process can be divided into three stages: (I) initial stage (α < 0.4(0.6)): the activation energy gradually decreases with the formation of strong microwave acceptor-reduction products; (II) transitional stage (0.4(0.6) < α < 0.7): the increase in mass transfer resistance leads to gradual increase in activation energy. Mechanical activation shortens the transitional reaction stage; (III) later reaction stage (α > 0.7), the decrease in activation energy may be attributed to the enhanced microwave absorption and CO reduction. The model-fitting method reveals that after mechanical activation, the reaction kinetic changes from reaction-order model to Ginstling-Brounshtein diffusion model. The optimized lithium extraction process parameters were: activation 300 rpm for 1.5 h, reduction temperature 550 °C. The research results can provide theoretical support for the enhanced extraction of cathode materials.


Consequences of Curvature on Induced Magnetic Field: The Case of Helicenes.
Helicenes consist of several fused rings twisted around an axis, forming a cylindrical helix, with π-delocalized electrons in the non-planar rings. Induced magnetic fields dissecting the orbital contributions of [6]-, [7]-, and [14]helicene are discussed. Computations show a deshielding cone produced by the π-electrons along the helical axis. Unexpectedly, the response of the core electrons produces a shielding cone, which is cumulative and sensitive to the curvature of the systems owing to the overlap of the other ring responses. A warning is provided regarding the evaluation of the delocalization in curved systems in which the x- and y-components of the induced magnetic field become relevant.


Prevalence of mycoplasma in the genital tract of pregnant women. Preliminary data.
The prevalence of Myoplasma hominis and "T" strains was investigated in 175 pregnant women in the 12th--40th week of pregnancy. It was possible to isolate the "T" strain from 30.3%, M. hominis from 11.4% and both strains from 9.7% of the women.


Total theophylline clearance in childhood: the influence of age-dependent changes in metabolism and elimination.
Theophylline metabolism and elimination during childhood are age-dependent. The total clearance, which is the sum of metabolic and renal clearances is highest in infants and young children. To differentiate between the two pathways, theophylline concentrations were measured in both serum and urine in 16 children aged 2 weeks-16 years using the fluorescence polarization immunoassay. It was found that both partial clearances assume maximal values at about the same age, but the fraction of total clearance attributable to the renal route decreases continuously.


Thoracoscopic pericardial fenestration after cardiac transplantation.
A patient suffered from recurrent pericardial effusions following heart transplantation. Repeated pericardiocentesis and insertion of pericardial drains could not resolve the problem and therefore surgical intervention was necessary. The procedure was performed as a minimally invasive thoracoscopic pericardial fenestration. Four months postoperative the patient was without recurrences. This method of pericardial fenestration after heart transplantation has been used for the first time.


B(C6F5)3-mediated direct intramolecular C7-alkenylation of N-propargylindoles.
B(C6F5)3-mediated direct C7-alkenylation of N-propargylindoles without directing groups was developed. This reaction proceeds via the π-activation of the alkynyl group with B(C6F5)3/Friedel-Crafts alkenylation/proton transfer reaction sequence. Interestingly, C7-alkenylation products could further convert into the fused indoles by deprotonation and finally polyaromatic N-heterocycles by the hydride abstraction.


Amorfrutin B Protects Mouse Brain Neurons from Hypoxia/Ischemia by Inhibiting Apoptosis and Autophagy Processes Through Gene Methylation- and miRNA-Dependent Regulation.
Amorfrutin B is a selective modulator of the PPARγ receptor, which has recently been identified as an effective neuroprotective compound that protects brain neurons from hypoxic and ischemic damage. Our study demonstrated for the first time that a 6-h delayed post-treatment with amorfrutin B prevented hypoxia/ischemia-induced neuronal apoptosis in terms of the loss of mitochondrial membrane potential, heterochromatin foci formation, and expression of specific genes and proteins. The expression of all studied apoptosis-related factors was decreased in response to amorfrutin B, both during hypoxia and ischemia, except for the expression of anti-apoptotic BCL2, which was increased. After post-treatment with amorfrutin B, the methylation rate of the pro-apoptotic Bax gene was inversely correlated with the protein level, which explained the decrease in the BAX/BCL2 ratio as a result of Bax hypermethylation. The mechanisms of the protective action of amorfrutin B also involved the inhibition of autophagy, as evidenced by diminished autophagolysosome formation and the loss of neuroprotective properties of amorfrutin B after the silencing of Becn1 and/or Atg7. Although post-treatment with amorfrutin B reduced the expression levels of Becn1, Nup62, and Ambra1 during hypoxia, it stimulated Atg5 and the protein levels of MAP1LC3B and AMBRA1 during ischemia, supporting the ambiguous role of autophagy in the development of brain pathologies. Furthermore, amorfrutin B affected the expression levels of apoptosis-focused and autophagy-related miRNAs, and many of these miRNAs were oppositely regulated by amorfrutin B and hypoxia/ischemia. The results strongly support the position of amorfrutin B among the most promising anti-stroke and wide-window therapeutics.


Reliability of the family impact of assistive technology scale for families of young children with cerebral palsy.
To examine the internal consistency and test-retest reliability of the Family Impact of Assistive Technology Scale (FIATS) when used to measure the perceptions of parents about important aspects of family life that may be influenced by their children's use of assistive devices. Repeated measure. Homes of 50 participating families. Parents of young children with cerebral palsy. Not applicable. The FIATS. Through an a priori item-reduction process, we reduced the length of the FIATS from 89 to 64 items. We retained 8 of the 9 original subscales. The 8 subscales included the following: autonomy, caregiver relief, contentment, doing activities, effort, family and social interaction, caregiver supervision, and safety. Remaining items of the removed subscale (technology acceptance) correlated well with the subscale total, but did not relate well to the FIATS total score. This construct was retained as a separate but noncontributing scale within the FIATS. The overall FIATS and its 8 contributing subscales had acceptable internal consistencies and test-retest reliabilities. The FIATS shows promise as a homogeneous and reproducible multidimensional measure of dimensions of child and family life. We plan further testing to examine the sensitivity and clinical meaningfulness of change scores on the FIATS.


Variations in Age-Adjusted Prostate Cancer Incidence Rates by Race and Ethnicity After Changes in Prostate-Specific Antigen Screening Recommendation.
After publication of US Preventive Task Force Prostate-Specific Antigen (PSA) screening guidelines in 2008 and 2012, there have been documented associations with incidence and stage distributions of prostate cancer. It is unclear if these changes were temporary or differed by age or race and ethnicity. To assess the association of 2008 and 2012 PSA guidelines with prostate cancer incidence by age and race and ethnicity in the US. This cross-sectional study evaluated prostate cancer incidence from 2005 to 2018 in the US using data from the US Cancer Statistics public use database. Data were analyzed from August 2020 through June 2022. The primary outcome was the year when rates of prostate cancer incidence changed directionality by age and race and ethnicity. Age-adjusted incidence rates of prostate cancer and corresponding 95% CIs were created, followed by join point regression analysis to evaluate trends of age-adjusted incidence rates of prostate cancer by age, race, Hispanic ethnicity, and stage of diagnosis. Among 2 944 387 men with prostate cancer, 2 869 943 (97.5%) men were aged 50 years and older. Men aged 50 years and older accounted for 185 476 of 191 533 Hispanic individuals (96.8%) and 2 684 467 of 2 752 854 non-Hispanic individuals (97.5%). Men aged 50 years and older accounted for 427 016 of 447 847 African American individuals (95.4%), 12 141 of 12 470 American Indian or Alaska Native individuals (97.4%), 61 126 of 62 159 Asian or Pacific Islander individuals (98.3%), and 2 294 171 of 2 344 392 White individuals (97.9%). Men with unknown race (77 519 men) were excluded from the analysis. A decrease in age-adjusted rate of prostate cancer after the 2008 guideline change was observed in all age groups by race and ethnicity. For example, among African American men ages 65 to 74 years, 10 784 of 807 080 men (1.34%) had a prostate cancer diagnosis in 2007 vs 10 714 of 835 548 men in 2008 (1.28%). The mean annual age-adjusted incidence rates of prostate cancer per 100 000 men were 157.7 men (95% CI, 157.4-158.0 men) in 2005 to 2008 and 131.9 men (95% CI, 131.6-132.2 men) in 2009 to 2012. The number of inflections and annual percent changes (APCs) for segments separated by inflections varied by age, race, and Hispanic ethnicity. For men ages 65 to 74 years, the APC was -6.53 (95% CI, -9.28 to -3.69) for 2009 to 2014 among African American men (2 join points), -5.96 (95% CI, -6.84 to -5.07) for 2007 to 2018 among American Indian or Alaska Native men (1 join point), -6.52 (95% CI, -9.22 to -3.74) for 2007 to 2014 among Asian or Pacific Islander men (2 join points), -7.92 (95% CI, -11.36 to -4.35) for 2009 to 2014 among Hispanic men (2 join points), and -7.02 (95% CI, -9.41 to -4.57) for 2007 to 2014 among White men (2 join points).. In this study, men in different age, race, and ethnicity groups had different APC patterns after 2008 and 2012 PSA screening guideline changes. These findings may provide important data on the timing and durations of changes in cancer diagnoses that are associated with changes in PSA screening recommendations and may be valuable for targeted strategies to reduce regional- and distant-staged cancers.


Assessing inhibitors of mutant isocitrate dehydrogenase using a suite of pre-clinical discovery assays.
Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that are mutated in a variety of cancers to confer a gain-of-function activity resulting in the accumulation of an oncometabolite, D-2-hydroxyglutarate (2-HG). Accumulation of 2-HG can result in epigenetic dysregulation and a block in cellular differentiation, suggesting these mutations play a role in neoplasia. Based on its potential as a cancer target, a number of small molecule inhibitors have been developed to specifically inhibit mutant forms of IDH (mIDH1 and mIDH2). We present a comprehensive suite of in vitro preclinical drug development assays that can be used as a tool-box to identify lead compounds for mIDH drug discovery programs, as well as what we believe is the most comprehensive publically available dataset on the top mIDH inhibitors. This involved biochemical, cell-based, and tier-one ADME techniques.


Etiological Analysis of Fungal Keratitis and Rapid Identification of Predominant Fungal Pathogens.
Fungal keratitis is a worldwide-distributed refractory and potentially blinding ocular infection caused by various fungi. It is necessary to investigate the etiological and epidemiological characteristics of this disease and establish a rapid and specific pathogenic identification method. Here, we isolated and identified fungal pathogens of 275 patients with presumed fungal keratitis from Jilin Province, China, and conducted statistical analyses of epidemiological information. The positive rate of fungal culture was 72.0 %. Fusarium sp. was the most common genus among 210 fungal isolates. The predominant species were Fusarium solani, Aspergillus fumigatus, and Candida glabrata, which accounted for over 50 % of the isolated organisms. Corneal trauma and previous use of drugs were the most important predisposing factors. In addition, a multiplex polymerase chain reaction (PCR) was designed with species-specific primers of the three species that could identify them with amplicons of approximately 330 bp from F. solani, 275 bp from A. fumigatus, and 230 bp from C. glabrata. Additionally, PCR with fungal universal primers and multiplex PCR were performed using DNA prepared by an improved DNA extraction method from corneal scrapings. With this method, fungal pathogens from corneal scrapings could be specifically and rapidly identified within 8 h. The culture-independent rapid identification of corneal scrapings may have great significance for the early diagnosis and treatment of fungal keratitis.


Association between practice patterns and body mass index percentile in infants and young children with cystic fibrosis.
Few guidelines focus on the preventive and maintenance care of infants with cystic fibrosis (CF). We explored how practice variability at accredited CF centers affected nutritional outcomes. A retrospective cohort study using Cystic Fibrosis Foundation registry data (1993-2004) from three CF centers compared the initial management with respiratory, antimicrobial, and nutritional agents in infants. Further, we examined the association between dornase alpha use prior to two years of age and BMI percentile over time accounting for several possible factors including gender, race, CF center, presentation, age at diagnosis, sweat value, F508del status, first Pseudomonas aeruginosa infection age, second-year weight percentile, supplemental feedings use, and pancreatic enzymes use. Patient characteristics and prescribed therapies were similar at all sites for 165 patients who met inclusion criteria. However, one CF center prescribed dornase alpha significantly more frequently, 82% vs. 10% (p<0.001), and supplemental feeds significantly less frequently, 56% vs. 78% (p=0.04). Dornase alpha prescription prior to age two was associated with a 10-percentile increase in BMI through age six compared to infants not prescribed dornase alpha. Treating infants less than two years old with dornase alpha may improve nutritional outcome through age six.


Influence of operative trauma on factor XII and inhibitor of plasminogen activator.
A parallel decrease of factor (F) XII and a fibrinolytic inhibitor of plasminogen activation (PA inhibitor) was found in a series of 52 patients subjected to vascular surgery. It was at a maximum on days 2-4 postoperatively. The most extensive decrease was found in patients undergoing aortoiliac bypass operation. These patients had the highest blood loss and the longest operation times indicating that the changes were correlated to the magnitude of surgical procedure. The parallel decrease of F XII and the fibrinolytic inhibitor suggests an association between these two proteins in vivo.


An Optimization-based Framework to Learn Conditional Random Fields for Multi-label Classification.
This paper studies multi-label classification problem in which data instances are associated with multiple, possibly high-dimensional, label vectors. This problem is especially challenging when labels are dependent and one cannot decompose the problem into a set of independent classification problems. To address the problem and properly represent label dependencies we propose and study a pairwise conditional random Field (CRF) model. We develop a new approach for learning the structure and parameters of the CRF from data. The approach maximizes the pseudo likelihood of observed labels and relies on the fast proximal gradient descend for learning the structure and limited memory BFGS for learning the parameters of the model. Empirical results on several datasets show that our approach outperforms several multi-label classification baselines, including recently published state-of-the-art methods.


Does electron-correlation has any role in the quantitative structure-activity relationships?
For developing quantitative structure-activity relationships (QSARs), quantum-mechanical molecular descriptors based on the state-of-the-art quantum-mechanical methods such as Hartree-Fock (HF) method and density-functional theory (DFT), are now routinely employed. The validity of these quantum-mechanical methods, however, rests on the accurate estimation of electron-correlation energy. This work analyses the role of electron-correlation, using correlation energy as a molecular descriptor, in the QSARs. In particular, QSAR models, for the mutagenic activity of a set of nitrated polycyclic aromatic hydrocarbons (nitro-PAHs), are examined for the role of electron-correlation through state-of-the-art external validation parameters such as concordance correlation coefficient and recently proposed predictive squared correlation coefficients, namely, QF1(2), QF2(2), and QF3(2) etc. The electron-correlation contribution to the highest occupied and lowest unoccupied molecular orbital (HOMO/LUMO) energies is also analyzed. QSAR models based on the semi-empirical quantum-mechanical methods like PM6 and RM1 are also compared. It is found that the models, developed using electron-correlation contribution of the quantum-mechanical descriptors, are not only robust but also relatively more predictive than those developed with the HF and DFT descriptors. The latter are found to be even less reliable than PM6 and RM1 descriptors based models, which show comparable robustness and predictivity with those developed using electron correlation based descriptors. The external predictivity of model based on semi-empirical descriptors can be improved if electron-correlation contribution of the quantum-mechanical descriptors is explicitly included in the model. This work reports the first-ever use of electron-correlation energy and its contribution to the HOMO/LUMO energies as molecular descriptors.


VCAM-1+ hUC-MSCs Exert Considerable Neuroprotection Against Cerebral Infarction in Rats by Suppression of NLRP3-Induced Pyroptosis.
Mesenchymal stem/stromal cells (MSCs) are spindle-like heterogeneous cell populations with advantageous bidirectional immunomodulatory and hematopoietic support effects. Vascular cellular adhesion molecule-1 (VCAM-1)+ MSCs have been reported to exhibit immunoregulatory and proangiogenic capacities. Here, we studied the effects of VCAM-1+ human umbilical cord (hUC)-MSCs on neuroprotection against cerebral infarction. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO), and VCAM-1- and VCAM-1+ hUC-MSCs were intravenously injected into the rat 4 h post-MCAO surgery. Thereafter, modified neurological severity scores (mNSS) were determined, and the Morris water maze test, 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin and eosin (H&E), Nissl, TUNEL staining, and qRT-PCR were conducted. Following induction of oxygen-glucose deprivation/reoxygenation (OGD/R), SH-SY5Y cells were co-cultured with VCAM-1- and VCAM-1+ hUC-MSCs. CCK-8, flow cytometry, ELISA, and western blot analyses were performed in vitro. Compared with VCAM-1- hUC-MSCs, administration of VCAM-1+ hUC-MSCs revealed improved therapeutic efficacy against cerebral infarction in rats, as confirmed by lower mNSS scores and infarct volumes, as well as improved learning and memory capacities. In addition, VCAM-1+ hUC-MSCs exhibited improved efficacy against neurological defects in rats with cerebral infarction, accompanied by inhibition of the NLRP3-mediated inflammatory response. VCAM-1+ hUC-MSC co-culture improved the viability and diminished NLRP3-mediated inflammatory response in OGD/R-treated SH-SY5Y cells. Moreover, NLRP3 overexpression in SH-SY5Y cells prevented the beneficial effects of VCAM-1+ hUC-MSC co-culture. Overall, our findings demonstrated the relevance of VCAM-1+ hUC-MSC-based cytotherapy for preclinical neuroprotection against cerebral infarction.


Characterization of ancient and modern genomes by SNP detection and phylogenomic and metagenomic analysis using PALEOMIX.
Next-generation sequencing technologies have revolutionized the field of paleogenomics, allowing the reconstruction of complete ancient genomes and their comparison with modern references. However, this requires the processing of vast amounts of data and involves a large number of steps that use a variety of computational tools. Here we present PALEOMIX (http://geogenetics.ku.dk/publications/paleomix), a flexible and user-friendly pipeline applicable to both modern and ancient genomes, which largely automates the in silico analyses behind whole-genome resequencing. Starting with next-generation sequencing reads, PALEOMIX carries out adapter removal, mapping against reference genomes, PCR duplicate removal, characterization of and compensation for postmortem damage, SNP calling and maximum-likelihood phylogenomic inference, and it profiles the metagenomic contents of the samples. As such, PALEOMIX allows for a series of potential applications in paleogenomics, comparative genomics and metagenomics. Applying the PALEOMIX pipeline to the three ancient and seven modern Phytophthora infestans genomes as described here takes 5 d using a 16-core server.


Versatile anti-infective properties of pyrido- and dihydropyrido[2,3-d]pyrimidine-based compounds.
A series of 1H-indeno[2',1':5,6]dihydropyrido[2,3-d]pyrimidine and 1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidine derivatives was prepared and screened for antiparasitic and viral RNase H inhibitory activity. Several compounds showed considerable activity against Toxoplasma gondii parasites and Leishmania major amastigotes, which warrants further investigation. Based on the structural similarities of certain derivatives with common viral RNase H inhibitors, a HIV-1 RNase H assay was used to study the RNase H inhibition by selected test compounds. Docking of active derivatives into the active site of the HIV-1 RNase H enzyme was carried out. The new compound 2a, inactive in the antiparasitic tests, showed distinct HIV-1 RNase H inhibition. Thus, ring substitution determines antiparasitic or HIV-1 RNase H inhibitory activity of this promising compound class.


Facing Time in Ischemic Stroke: An Alternative Hypothesis for Collateral Failure.
Several randomized-controlled trials could recently demonstrate that ischemic stroke which is caused by large-cerebral-artery-occlusion can be treated effectively by endovascular recanalization. Among these studies, particularly the data from the ESCAPE study further corroborated the strong association between macrovascular pial collateral flow (before recanalization) and clinical outcome after recanalization. This review briefly gives an overview on these data and on the clinical key observations demonstrating this association in practice. Since the ischemic penumbra can only be sustained by collateral flow, the collapse of collateral blood flow or poor collateral filling, observed for example by DSA or CTA before recanalization, seems to be a primary cause of rapidly progressive infarction and futile therapeutic recanalization. However, it needs to be emphasized that the true cause-effect relationship between collateral failure and rapidly progressive infarction of the penumbra, i.e. the high probability of unfavorable clinical outcome despite recanalization, remains unclear. Along this line, an alternative hypothesis is offered viewing the collapse of collateral flow not as a cause but possibly as an inevitable secondary consequence of increasing peripheral/microvascular resistance during progressive infarction.


Modified treatment of early gastric cancer: evaluation of endoscopic treatment of early gastric cancers with respect to treatment indication groups.
The results of endoscopic treatment of early gastric cancers were evaluated. The lesions were divided into two groups: the group with an absolute indication (AI) and the other with a relative indication (RI) for endoscopic treatment. Endoscopic mucosal resection (EMR) was performed on 106 lesions in 104 patients. In addition, 108 patients were treated by laser irradiation (LI). The status of the patients were serially assessed during the postoperative period. The residual rate in AI patients who underwent EMR was 30.3%, whereas the rate in RI patients was 80%. The residual rate in 70 AI patients who underwent LI was 0%. Although the recurrence rate was 4.2%, the cumulative curative rate after additional treatments was 100%. The residual rate in RI patients who underwent LI was 17.4%, and the recurrence rate was 13.2%. The cumulative curative rate after additional treatments was 97.4%. In AI patients, the initial mode of treatment use was EMR. Patients who exhibited residual cancerous tissue after EMR or those in whom EMR was difficult to perform, either technically or otherwise, underwent LI. EMR was the first choice therapeutic technique because endoscopic specimens obtained could be subjected to histopathologic examination. In RI patients, the conventional operation was the therapeutic technique of first choice. The LI procedure was performed in those who either refused surgery or who could not undergo operative treatment for various reasons.


Reactive oxygen species in biological media are they friend or foe? Major In vivo and In vitro sensing challenges.
The role of Reactive Oxygen Species (ROS) on biological media has been shifting over the years, as the knowledge on the complex mechanism that lies in underneath their production and overall results has been growing. It has been known for some time that these species are associated with a number of health conditions. However, they also participate in the immunoactivation cascade process, and can have an active role in theranostics. Macrophages, for example, react to the presence of pathogens through ROS production, potentially allowing the development of new therapeutic strategies. However, their short lifetime and limited spatial distribution of ROS have been limiting factors to the development and understanding of this phenomenon. Even though, ROS have shown successful theranostic applications, e.g., photodynamic therapy, their wide applicability has been hampered by the lack of effective tools for monitoring these processes in real time. Thus the development of innovative sensing strategies for in vivo monitoring of the balance between ROS concentration and the resultant immune response is of the utmost relevance. Such knowledge could lead to major breakthroughs towards the development of more effective treatments for neurodegenerative diseases. Within this review we will present the current understanding on the interaction mechanisms of ROS with biological systems and their overall effect. Additionally, the most promising sensing tools developed so far, for both in vivo and in vitro tracking will be presented along with their main limitations and advantages. This review focuses on the four main ROS that have been studied these are: singlet oxygen species, hydrogen peroxide, hydroxyl radical and superoxide anion.


Ocular surface squamous neoplasia as the first apparent manifestation of HIV infection in Malawi.
To evaluate the prevalence of undiagnosed and asymptomatic HIV infection in patients with ocular surface squamous neoplasia (OSSN) in an urban patient population in Malawi. A consecutive series of patients presenting with OSSN was evaluated in an African academic centre. A detailed history and physical examination in 53 consecutive patients with conjunctival squamous cell carcinoma and conjunctival intraepithelial neoplasia were performed. Thirty eight (72%) patients agreed to undergo serological HIV testing. Seventy-nine per cent (30 of 38) patients were HIV positive. None of the patients had previous HIV testing or was aware of having symptoms of HIV. Seventy per cent (n = 21) of the HIV-positive patients had no other symptoms suggestive of HIV infection or any other disease. Patients were far more likely to refuse HIV testing if they were married and male. The conjunctival tumour may be the primary and only apparent manifestation of HIV in patients presenting with OSSN in Sub-Saharan Africa.


Oral follicle-stimulating hormone receptor agonist affects granulosa cells differently than recombinant human FSH.
To determine whether TOP5300, a novel oral follicle-stimulating hormone (FSH) receptor (FSHR) allosteric agonist, elicits a different cellular response than recombinant human FSH (rh-FSH) in human granulosa cells from patients undergoing in vitro fertilization. Basic science research with a preclinical allosteric FSHR agonist. University hospital. Patients with infertility at a single academic fertility clinic were recruited under an Institutional Review Board-approved protocol. Primary granulosa cell cultures were established for 41 patients, of whom 8 had normal ovarian reserve (NOR), 17 were of advanced reproductive age (ARA), 12 had a diagnosis of polycystic ovary syndrome (PCOS), and 4 had a combination of diagnoses, such as ARA and PCOS. Primary granulosa-lutein (GL) cell cultures were treated with rh-FSH, TOP5300, or vehicle. Estradiol (E2) production using enzyme-linked immunosorbent assay, steroid pathway gene expression of StAR and aromatase using quantitative polymerase chain reaction, and FSHR membrane localization using immunofluorescence were measured in human GL cells. TOP5300 consistently stimulated E2 production among patients with NOR, ARA, and PCOS. Recombinant FSH was the more potent ligand in GL cells from patients with NOR but was ineffective in cells from patients with ARA or PCOS. The lowest level of FSHR plasma membrane localization was seen in patients with ARA, although FSHR localization was more abundant in cells from patients with PCOS; the highest levels were present in cells from patients with NOR. The localization of FSHR was not affected by TOP5300 relative to rh-FSH in any patient group. TOP5300 stimulated greater expression of StAR and CYP19A1 across cells from all patients with NOR, ARA, and PCOS combined, although rh-FSH was unable to stimulate StAR and aromatase (CYP19A1) expression in cells from patients with PCOS. TOP5300-induced expression of StAR and CYP19A1 mRNA among patients with ARA and NOR was consistently lower than that observed in cells from patients with PCOS. TOP5300 appears to stimulate E2 production and steroidogenic gene expression from GL cells more than rh-FSH in PCOS, relative to patients with ARA and NOR. It does not appear that localization of FSHR at cell membranes is a limiting step for TOP5300 or rh-FSH stimulation of steroidogenic gene expression and E2 production.


All along the watchtower: is the cilium a tumor suppressor organelle?
Cilia or flagella have been around since almost the beginning of life, and have now developed specialized cell-type specific functions from locomotion to acting as environmental sensors participating in cell signalling. Genetic defects affecting cilia result in a myriad of pathological instances, including infertility, obesity, blindness, deafness, skeletal malformations, and lung problems. However, the consistency in which the common kidney cyst is coupled with cilia dysfunction has raised interest in the possibility that ciliary dysfunction might contribute to other neoplasms as well. A suite of recent papers convincingly linking cilia to hedgehog signalling, platelet-derived growth factor signalling, Wnt signalling and the von Hippel-Lindau tumor suppressor protein has rapidly expanded the knowledge base connecting cilia to cancer. We propose that these data support the notion of the cilium as a cellular Watchtower, whose absence can be an initiating event in neoplastic growth. Furthermore, we predict that we are just now seeing the tip of the iceberg, and that the list of cancers associated with altered ciliary signalling will grow exponentially in the next few years.


A novel HLA-DRB1 allele, DRB1*01:54, identified by sequence-based typing.
The new HLA DRB1*01:54 differs from DRB1*01:02:01 by one nucleotide at exon 2.


Alteration of Ringer pH and its effects on precursor incorporation into Drosophila salivary gland nuclei.
Drosophila salivary glands were explanted and incubated with 3-H-uridine (or 3-H-thymidine) in Ringer's solution (Ephrussi-Beadle modified saline) adjusted to pH values in the integral range, 4 to 10. The results of autoradiographic investigations indicate a differential effect of altering Ringer pH on 3-H-uridine as opposed to 3-H-thymidine incorporation: a) Relatively uniform levels of chromosomal incorporation of 3-H-thymidine occured over the range of test pH. Some decrease of incorporation was noted at pH 5 and some increase at pH 9. b) Chromosomal incoroporation of 3H-uridine was severely depressed at pH 4 and 7 relative to the high incorporation levels observed at other pH values. Controlling pH of Ephrussi-Beadle Ringer's solution in such experiments a necessity. This appears especially important for studies involving 3-H-uridine incorporation.


Generation and Characterization of a New Resistance to Thyroid Hormone Mouse Model with Thyroid Hormone Receptor Alpha Gene Mutation.
Background: In humans, resistance to thyroid hormone (RTH) caused by mutations in the thyroid hormone receptor alpha (THRA) gene, RTHα, manifests as tissue-specific hypothyroidism and circulating thyroid hormone levels exhibit hypothyroid-like clinical features. Before the identification of patients with RTHα, several Thrα1 knock-in mouse models were generated to clarify the function of TRα1. However, the phenotypes of these mice were not consistent with the clinical presentation of RTHα in humans. For the present study, we generated an RTHα mouse model that carries the Thra1E403X mutation found in human RTHα patients. Here, we report the gross phenotypes of this mouse RTHα model. Methods: Traditional homologous recombination gene targeting techniques were used to introduce a mutation (Thra1E403X) in the mouse Thra gene. The phenotypes of the resulting mice were studied and compared with clinical features observed for RTHα with THRAE403X. Results: Thrα1E403X/E403X homozygous mice exhibited severe neurological phenotypes, such as spasticity and motor ataxia, which were similar to those observed in endemic cretinism. Thrα1E403X/+ heterozygous mice reproduced most clinical manifestations of patient with RTHα, such as a normal survival rate and male fertility, as well as delayed postnatal growth and development, neurological and motor coordination deficits, and anemia. The mice had typical thyroid function with a modest increase in serum triiodothyronine (T3) levels, a low thyroxine (T4)/T3 ratio, and low reverse T3 (rT3) levels. Conclusions: The Thrα1E403X/+ mice faithfully recapitulate the clinical features of human RTHα and thus can provide a useful tool to dissect the role of TRα1 in development and to determine the pathological mechanisms of RTHα.


Autonomic biofeedback therapy in epilepsy.
Pharmacological intervention is a mainstay for treatment of epilepsy. However, a third of patients with epilepsy remain drug resistant. Behavioural treatments such as biofeedback training can be potential effective alternative interventions for drug resistant epilepsy. This paper describes a biofeedback therapy in which the training of patients to control peripheral autonomic tone (galvanic skin response) changes in central control of seizure occurrence. This paper introduces; 1) the theoretical development of methodology, 2) the effect of GSR biofeedback in reducing seizure frequency in drug resistant epilepsy, 3) insights into the neural mechanisms of effective GSR biofeedback through neuromodulatory autonomic control and 3) future prospects of this approach as a therapeutic tool instantiated as an Autonomic Cognitive Rehabituation Training (ACRT).


Effect of reactive oxygen species generation in rabbit corneal epithelial cells on inflammatory and apoptotic signaling pathways in the presence of high osmotic pressure.
It is generally accepted that high osmotic pressure (HOP) of lacrimal fluid is the core mechanism causing ocular inflammation and injury. However, the association between HOP and the regulation of cell inflammatory response and apoptotic pathways remains unclear. In the present study, we used HOP to interfere with in vitro cultured rabbit corneal epithelial cells, and found that HOP increased the generation of reactive oxygen species (ROS) in rabbit corneal epithelial cells, and increased ROS in turn induced the activation of JNK inflammatory signaling pathway, which further promoted the expression of pro-inflammatory factor NF-κβ and induced the generation of inflammatory factor IL-1β and TNF-α. In addition, HOP-induced ROS in rabbit corneal epithelial cells regulated the CD95/CD95L-mediated cell apoptotic signaling pathway by activating JNK inflammatory signaling pathway. These findings may serve as new theoretical basis and a new way of thinking about the treatment of ocular diseases, especially dry eye.


Injustice Through Cultural Lens: A Pilot Qualitative Exploration of Pain-Related Injustice Appraisals Among Arab-Americans with Chronic Low Back Pain.
The current qualitative study sought to obtain an in-depth understanding of how Arab-Americans conceptualize perceived injustice concerning their chronic low back pain (CLBP) by reflecting on the Injustice Experience Questionnaire (IEQ). Twelve Arab-American adults with CLBP were recruited from a metropolitan area in Alabama using a purposive sampling technique. Participants took part in individual, face-to-face, semi-structured interviews reflecting on each statement from the IEQ. Descriptive data analysis was generated for demographic and pain variables. Directed content analysis was conducted to identify themes and sub-themes. 'Blame and unfairness' and 'severity and irreparability of loss,' the 2 established theoretical factors comprising pain-related injustice appraisal were used as predominant themes. Acceptance emerged as an inductive theme with the following sub-themes: positive appraisal and resilience, attempts to reduce pain, religious values and fate, and belief that everything happening for a reason. The influence of religion was noted across all themes. The current pilot findings suggest that Arabic culture, heavily infused with Islamic beliefs, influences how Arab-Americans conceptualize pain-related injustice appraisals. Additional exploration of the cultural appropriateness of the IEQ among individuals of Arab background is needed to further elaborate on the subject of faith and religious belief suggested by the current study. Perspective: Although the study findings largely reflected established injustice literature constructs, several emergent themes regarding pain-related injustice appraisal were influenced by the participants' culture and religious beliefs. These findings may indicate that specific psychotherapeutic approaches that have been proven effective among some groups may not function similarly in other populations.


Diagnostic Associations of Processing Speed in a Transdiagnostic, Pediatric Sample.
The present study examines the relationships between processing speed (PS), mental health disorders, and learning disorders. Prior work has tended to explore relationships between PS deficits and specific diagnoses in isolation of one another. Here, we simultaneously investigated PS associations with five diagnoses (i.e., anxiety, autism, ADHD, depressive, specific learning) in a large-scale, transdiagnostic, community self-referred sample. 843 children, ages 8-16 were included from the Healthy Brain Network (HBN) Biobank. Principal component analysis (PCA) was employed to create a composite measure of four PS tasks, referred to as PC1. Intraclass correlation coefficient (ICC) between the four PS measures, as well as PC1, were calculated to assess reliability. ICCs were moderate between WISC-V tasks (0.663), and relatively modest between NIH Toolbox Pattern Comparison and other PS scales (0.14-0.27). Regression analyses revealed specific significant relationships between PS and reading and math disabilities, ADHD-inattentive presentation (ADHD-I), and ADHD-combined presentation (ADHD-C). After accounting for inattention, the present study did not find a significant relationship with Autism Spectrum Disorder. Our examination of PS in a large, transdiagnostic sample suggested more specific associations with ADHD and learning disorders than the literature currently suggests. Implications for understanding how PS interacts with a highly heterogeneous childhood sample are discussed.


[Current approach in surgical treatment for liver metastases from colorectal cancer].
Surgical treatment of liver metastases colorectal, cancel increases the survival rate of patients, accompanied by low frequency of postoperative complications and mortality. The article presents a retrospective analysis of surgical treatment of 107 patients with metastatic colorectal cancer to the liver.


Cardiovascular Magnetic Resonance in Right Heart and Pulmonary Circulation Disorders.
Right heart and pulmonary circulation disorders are generally caused by right ventricle (RV) pressure overload, volume overload, and cardiomyopathy, and they are associated with distinct clinical courses and therapeutic approaches, although they often may coexist. Cardiac magnetic resonance (CMR) provides a noninvasive accurate and reproducible multiplanar anatomic and functional assessment, tissue characterization, and blood flow evaluation of the right heart and pulmonary circulation. This article reviews the current status of the CMR, the most recent techniques, the new parameters and their clinical utility in diagnosis, prognosis, and therapeutic management in the right heart and pulmonary circulation disorders.


Posture monitoring in healthcare: a systematic mapping study and taxonomy.
Palliative treatments for back pain usually include exercise, analgesics, physiotherapy, prostheses, and surgery in severe cases. Technologies for postural monitoring are growing, and they are important in preventing back pain and mitigating permanent damage. Remote work, especially after the COVID-19 pandemic, made people spend more time than usual in chairs and environments not certified by the health aspects of work. This research investigated through a Systematic Mapping Study (SMS) contributions in posture monitoring for healthcare in smart environments, including the different methods to obtain the posture, the limitations, and the target audience of the proposed models. The SMS was conducted in eight databases, including articles from January 2012 to March 2022. The initial search yielded 3161 articles, of which 34 were selected after applying the filtering criteria. Moreover, this study presents the challenges related to posture behavior monitoring, identifying studies and implementations that apply assistive technology for postural monitoring and improving the health and life of remote workers. In addition, three commercial postural devices are presented, and what challenges they currently face. Regarding healthcare, results showed a prevalence of using the Internet of Things (IoT) devices such as wireless sensor networks and inertial measurement unit (IMU) sensors. This article also proposes a taxonomy, showing the most used technologies and algorithms for improving posture, besides the posture-monitoring hierarchy classifying into three important branches: (a) Data Collect; (b) Data Transmission; and (c) Data Analysis.


Feasibility evaluation of psychosocial intervention for internally displaced youth in Kenya.
There is limited evidence on the cultural appropriateness of first-stage psychosocial interventions for youth with mental health problems who experience conflict and disadvantage in low- and middle-income countries (LMIC). To evaluate the feasibility of such an intervention (Writing for Recovery - WfR) among youth with emerging emotional problems following internal displacement in Kenya. Fifty-four youth aged 14-17 years were randomly allocated to a six-session intervention or a waiting list control group. They completed measures of stressful life events; post-traumatic stress, depressive and anxiety symptoms; quality of life; and free text on their experience of the intervention. Young participants reported high levels of trauma exposure and emotional problems. The intervention was perceived as flexible and culturally acceptable, with reported short-term impact. This was found to have promising post-intervention effect in reducing post-traumatic stress, but not depressive or anxiety symptoms; and in enhancing quality of life scores. Similar psychosocial interventions that can be delivered by paraprofessionals are important for resource-constrained LMIC settings, but need to be integrated within a comprehensive scaled service model.


Cell surface galactosyltransferase acts as a general modulator of rat acinar cell proliferation.
Several physiological parameters were examined for inducing acinar cell proliferation and corresponding increased expression of beta 1-4 galactosyltransferase. In this study, dietary changes causing acinar cell proliferation included the following: the introduction of animals to a liquid diet (causing gland atrophy) followed by reintroduction of solid chow, gustatory stimulation provided by the introduction of 0.5% citric acid to animal drinking water, and removal of the submandibular gland with subsequent reliance on the parotid gland for salivary protein. Alterations in growth factor levels were produced by injecting animals with a chronic (3 day) regimen of either nerve growth factor or epidermal growth factor. Parotid gland proliferation could be blocked in all cases except EGF by the injection of propranolol, a beta-adrenoceptor antagonist, or the galactosyltransferase specific modifier protein, alpha-lactalbumin. EGF-induced proliferation could, however, be prevented by treating the animals with monoclonal antibody to EGF receptor or galactosyltransferase modifier protein alpha-lactalbumin. These results for normal acinar cell proliferation suggest a direct role for cell surface beta 1-4 galactosyltransferase in signalling and maintaining active cell growth.


Twinning frequency of Japanese Macaques (Macaca fuscata) at Takasakiyama.
In a wild-living, artificially provisioned population of Japanese macaques at Takasakiyama in southern Japan, nine sets of twins were recorded from 12,392 known deliveries over a 56-year study period. Recorded twinning frequency was 0.073%. During the first 28-year period, artificial food was given until macaques were satiated and population size increased rapidly. In the second 28-year period, provisioned food was restricted to about half of the former period's calorific content. Seven sets of twins were born in the first period and two sets in the second. Twining frequency in the two periods was 0.137 and 0.027%, respectively. In comparing studies of other Catarrhine primate samples, we hypothesize that twinning frequency is influenced by living conditions, and we suggest that living conditions should be carefully evaluated in studies of twinning frequency.


The dynamics of flap movement: effect of pivotal restraint on flap rotation and transposition.
Flaps that rotate or transpose around a cutaneous pedicle are restrained by the tethering effect of that base of tissue. Flap design that fails to adjust for this force may eventuate in unwanted degrees of tension and/or surrounding tissue displacement. This concept is discussed and illustrated for the rotation, rhombic, and bilobed flap.


Serum alkaline phosphatase as a predictor of worsening renal function in patients with acute decompensated heart failure.
Venous congestion has come into focus as an important hemodynamic factor for worsening renal function (WRF) in patients with acute decompensated heart failure (ADHF). Serum alkaline phosphatase (ALP) was reported as a biological marker of liver congestion in ADHF. The purpose of this study was to determine whether ALP is a predictor of WRF in patients with ADHF. We enrolled consecutive patients admitted to a single cardiovascular center with ADHF, and defined WRF as an increase in creatinine of >0.3 mg/dl during hospitalization and chronic kidney disease (CKD) as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2). The patients were classified into tertiles by ALP level (<203, 203-278, and >278 IU/L). A total of 972 patients (mean age, 76±13 years; 54% male) were retrospectively analyzed. WRF was identified in 132 patients (13.6%). In multivariate logistic regression analysis, baseline CKD [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.48-4.08, p<0.001], serum albumin (OR 0.52, 95% CI 0.35-0.77, p=0.001), and diabetes (OR 2.07, 95% CI 1.37-3.12, p<0.001) were associated with WRF. Compared with the lowest tertile (ALP <203 IU/L), an adjusted OR of WRF was 1.69 (95% CI 1.02-2.79, p=0.04) in the middle tertile (ALP, 203-278 IU/L) and 1.95 (95% CI 1.20-3.21, p=0.008) in the highest tertile (ALP >278 IU/L). Serum ALP is an independent predictor of WRF in the clinical course of ADHF.


Preliminary evaluation of the utility of comparing SpO2 /FiO2 and PaO2 /FiO2 ratios in dogs.
To determine whether the ratio of pulse oximetry saturation/fraction of inspired oxygen (SpO2 /FiO2 , [SF]) correlates with the ratio of partial pressure of oxygen in arterial blood/FiO2 (PaO2 /FiO2 , [PF]) in dogs. Prospective, observational pilot study. Urban tertiary veterinary referral center. Thirty-eight client-owned dogs requiring assessment of oxygenation. None. Arterial blood gas analysis with co-oximetry was performed on samples obtained from the dorsal pedal artery. Median SpO2 was 91.5% (range 80-97%) and median PaO2 was 70.1 mmHg (range 44.5-103.8 mmHg). Hypoventilation was uncommon and venous admixture was the predominant cause of hypoxemia in this population. Median SF was 435.7 (range 381.0-461.9) and median PF was 334.0 (range 211.9-494.3). Nine dogs (23.6%) had PF <300; no dogs had PF below 200. SF and PF were correlated (ρ = 0.618, P < 0.01). SF and PF in dogs spontaneously breathing room air have good correlation, suggesting that SF may be a useful, noninvasive surrogate for PF when assessing oxygenation in canine patients. Further studies are warranted to confirm and validate this relationship in spontaneously breathing and mechanically ventilated dogs on varying levels of FiO2 and to assess the ability of SF to predict outcome.


Computer automated structure evaluation of the carcinogenicity of N-nitrosothiazolidine and N-nitrosothiazolidine 4-carboxylic acid.
N-Nitrosothiazolidine 4-carboxylic acid (NTCA), a sulphur-containing nitrosamine present in human urine, was predicted to be non-carcinogenic by CASE, the newly developed Computer Automated Structure Evaluating system. On the other hand, N-nitrosothiazolidine (NTHZ), a nitrosamine present in food products, was predicted to be carcinogenic. The putative non-carcinogenic NTCA may be metabolized to NTHZ, a predicted carcinogen.


Histopathologic Evolution of Melanocytes Associated With Rapid Clinical Progression of Melanoma: Clinicopathologic Presentation of Hyperprogressive Disease in a Patient Treated With Immunotherapy.
This report describes the case of a 71-year-old woman with nodular melanoma who experienced rapid clinical deterioration 3 weeks after receiving immunotherapy treatment. Given this presentation, there was high suspicion for tumor hyperprogression, which has been observed as a paradoxical response to the use of immunotherapy in the treatment of melanoma. Histopathologic and genomic changes of primary tumor are documented at several different timepoints relative to immunotherapy treatment that may depict important alterations associated with hyperprogressive disease. To our knowledge, this case is the first to document the evolution of histopathologic features of melanoma associated with hyperprogressive disease.


Edge-based analysis of networks: curvatures of graphs and hypergraphs.
The relations, rather than the elements, constitute the structure of networks. We therefore develop a systematic approach to the analysis of networks, modelled as graphs or hypergraphs, that is based on structural properties of (hyper)edges, instead of vertices. For that purpose, we utilize so-called network curvatures. These curvatures quantify the local structural properties of (hyper)edges, that is, how, and how well, they are connected to others. In the case of directed networks, they assess the input they receive and the output they produce, and relations between them. With those tools, we can investigate biological networks. As examples, we apply our methods here to protein-protein interaction, transcriptional regulatory and metabolic networks.


Peripheral nerve grafts to the frog optic tectum: a morphological study of foreign axon regeneration in the central nervous system.
The proximal stump of a transected mandibular nerve was grafted onto the rostrodorsal surface of the optic tectum in adult Rana pipiens to investigate the morphologic characteristics of nonspecific axonal regeneration in a highly organized region of central nervous system (CNS). Within the first 3 weeks postgraft surgery (WPS), the nerve-tectum interface became firmly established. Concomitant with this was an invasion of the host tectum by a small number of fine "pioneerlike" axons from the nerve. By 6 WPS there developed a concerted instreaming of a large number of peripheral fibers. Once within the CNS, the foreign axons distributed themselves throughout the rostrocaudal extent of the tectum, but primarily its dorsal aspect within superficial layers 8 and 9. Presence of intact optic fibers at the time of mandibular fiber invasion served somewhat to restrict the regenerating aberrant axons in their course through layer 9. This restriction could be avoided by removal of the optic input either before or during peripheral ingrowth. However, once peripheral fibers had entered and established themselves in the host environment, no subsequent manipulation of the retinotectal projection had any effect. The aberrant growth pattern, which appeared remarkably stable after 6 WPS, consisted of a plexus of medium- and fine-caliber peripheral axons. Many of these fibers had numerous branches and "en passant" varicosities, the latter encompassing a variety of shapes and sizes. Terminal swellings and arborizations were also found. When comparing the regeneration of optic and mandibular nerve fibers in the tectum, two distinctions were made. Whereas optic axons revealed a fascicular and layered organization, mandibular axons showed a highly segregated and disordered growth pattern. These characteristic differences were maintained even when the two fiber systems were allowed to coregenerate into the same target tectum. Thus, each of the two groups of axons interacts with the tectal substrate in a distinct manner, apparently independent of the other.


Anatomic bases of vascularized elbow joint harvesting to achieve vascularized allograft.
In order to later make precise the operative technique of free vascularized elbow allograft transfer, the anatomic conditions necessary for the success of such an operation are reviewed. The exact topography of the nutrient foramina of the humerus, radius, and ulna has been specified on 102 dry bones. The osseous resection at the recipient will have to be carried out on these aspects: nutrient foramina of the three bones of the elbow (at 9 cm from medial epicondyle for the humerus; at 8 cm for the two bones of forearm) in order to preserve diaphysary vascularization of the recipient. A study of arterial and venous vascularization carried out on 18 anatomic specimens showed that the osseous ends were irrigated by a periosteal arterial network and were drained in the centromedullary cavities. Systematization of the arteriovenous blood supply of the distal end of the humerus and proximal ends of the two forearm bones is proposed after dissection of 18 anatomic specimens. Arterial periosteal territories are defined. The importance of each peri articular arteriole is estimated according to the surface of its respective section. A radial, constant, and musculoperiosteal collateral artery from the brachial artery is described. It accounts for 12% (+/- 3%) of the total contribution. The recurrent radial artery is the most significant: 31% (+/- 9%) of the total contribution. The profunda brachii artery is negligible: 4% (+/- 2%) of the total contribution. As well for vascular as mechanical reasons, osteosynthesis will have to be carried out using screwed plates, the optimal location of which is specified according to the arterial periosteal cartography. Ulnar and radial nerves and, to a lesser extent, the median nerve can be harvested "en bloc" preserving their vascular supply in order to make vascularized grafts of them. Free vascularized elbow allograft transfer is technically possible, if one respects these anatomic bases.


[Impact of the new European regulation 2017/745 on medical devices on hospital pharmacies activity: Example on pharmaceutical supply function within a French university hospital center].
The new European regulation (MDR) on medical devices (MD) is expected to have major impacts on the industrial sector, but also consequences on healthcare professionals. Our objective was to evaluate the impact of the MDR on the supply of MDs in hospital pharmacies at the level of a French university hospital. We conducted a prospective follow-up of marketing cessations and supply disruptions directly related to the MDR between November 2019 and September 2020. The data were analyzed accounting for the nature of the suppliers (status/size), the nature of the MDs (route/class), and the proposed alternatives. The economic impact on hospital pharmacies was also estimated. Over this period, 96 MD product designations were declared out of stock or in cessation (total of 402 references), of which half corresponded to class IIa MDs, mainly used for surgical procedures. Of the 14 companies concerned (36% French), the majority were manufacturers, of small/medium-size or intermediate size. Substitutions were proposed for only 15 products (15.6%). The cost of pharmaceutical management of these disruptions/marketing cessations was estimated at 3052€. Even before the official date of its application, the impacts of the MDR on the supply function of hospital pharmacies are already visible. In the short, medium and long term, prospective monitoring of the impacts, positive or negative, would seem to be justified at the level of manufacturers, healthcare professionals and end users of MDs.


Reliability and validity of simulated problems as measures of change in problem-solving skills.
Two contruct validity studies and two reliability studies for Diagnostic Management Problems are reported. Construct validity was confirmed, internal consistency was partially demonstrated, and two test packages were found to differ substantially on all five subscores.


Synthesis of tetrachalcogenide-substituted phenalenyl derivatives: preparation and solid-state characterization of bis(3,4,6,7-tetrathioalkyl-phenalenyl)boron radicals.
We report the synthesis and properties of a series of spiro-bis(3,4,6,7-tetrachalcogenide-substituted-phenalenyl)boron salts and two of the corresponding tetrathioalkyl-substituted spiro-bis(phenalenyl)boron radicals [tetrathiomethyl (10) and tetrathioethyl (11)] in which all of the active positions of the phenalenyl (PLY) nucleus are functionalized. In the solid state, radicals 10 and 11 exist as a weak π-dimers due to the steric congestion of the thioalkyl groups in the superimposed PLY units. As a result, the spins are localized in the isolated (nonsuperimposed) PLY rings, and the structure, magnetic susceptibility measurements, and band structure calculations confirm that these PLY units are unable to undergo strong intermolecular interaction as a result of the orientation of the thioalkyl groups.


Catalytic Formation of α-Aryl Ketones by C-H Functionalization with Cyclic Alkenyl Carbonates and One-Pot Synthesis of Isocoumarins.
We report here a method for direct catalytic introduction of simple α-acylalkyl groups via rhodium-catalyzed C-H functionalization with cyclic alkenyl carbonates, synthetic equivalents to enolates bearing leaving groups. The reaction proceeded smoothly without using bases to give α-aryl ketones in high yields. Various nitrogen-containing aromatic rings and amide groups serve as directing groups. 3-Substituted isocoumarins can also be prepared by one-pot C-H functionalization/cyclization.


A convenient approach to synthesizing peptide C-terminal N-alkyl amides.
Peptide C-terminal N-alkyl amides have gained more attention over the past decade due to their biological properties, including improved pharmacokinetic and pharmacodynamic profiles. However, the synthesis of this type of peptide on solid phase by current available methods can be challenging. Here we report a convenient method to synthesize peptide C-terminal N-alkyl amides using the well-known Fukuyama N-alkylation reaction on a standard resin commonly used for the synthesis of peptide C-terminal primary amides, the peptide amide linker-polyethylene glycol-polystyrene (PAL-PEG-PS) resin. The alkylation and oNBS deprotection were conducted under basic conditions and were therefore compatible with this acid labile resin. The alkylation reaction was very efficient on this resin with a number of different alkyl iodides or bromides, and the synthesis of model enkephalin N-alkyl amide analogs using this method gave consistently high yields and purities, demonstrating the applicability of this methodology. The synthesis of N-alkyl amides was more difficult on a Rink amide resin, especially the coupling of the first amino acid to the N-alkyl amine, resulting in lower yields for loading the first amino acid onto the resin. This method can be widely applied in the synthesis of peptide N-alkyl amides.


Evidence that the spasmogenic action of tetraethylammonium in guinea-pig trachealis is both direct and dependent on the cellular influx of calcium ion.
1 Tetraethylammonium (TEA, 1-8 mmol/l) evoked spasm of guinea-pig trachealis which was unaffected by atropine (1 mumol/l), mepyramine (1 mumol/l) or tetrodotoxin (3 mumol/l). 2 The spasm evoked by TEA was markedly suppressed in Ca2+-free Krebs solution while that evoked by acetylcholine was much less affected. 3 Extracellular electrical recording showed that exposure to Ca2+-free Krebs solution suppressed both spontaneous electrical slow wave activity of the trachea and the spasm and slow waves induced by TEA. These effects were reversible. 4 TEA (2 and 8 mmol/l) increased the lanthanum-resistant calcium fraction of trachea. 5 It is concluded that TEA acts directly on the smooth muscle of guinea-pig trachea, that the spasm and electrical slow waves evoked are Ca2+-dependent and that the cellular influx of Ca2+ is increased.


Plasminogen activator inhibitor-1 increases the expression of VEGF in human glioma cells.
The level of plasminogen activator inhibitor-1 (PAI-1) in tumor tissue has been shown to be an independent negative prognostic factor in different cancers. There are several proposed reasons for this, among these, the influence of PAI-1 on tumor neovascularization and cell migration. We report that PAI-1 stimulates expression and release of vascular endothelial growth factor (VEGF) in the human glioma cell line D54Mg, and thereby stimulates the proliferation of human umbilical vein endothelial cells (HUVEC) in vitro. To search for possible molecular effects of PAI-1 on malignant cells, cDNA array hybridization analysis of D54Mg glioma cells transfected with an adenoviral PAI-1 expression vector was performed. This revealed that the VEGF response was accompanied with the simultaneous upregulation of GADD153, Rho GTPase activating protein 4 (p115), Collagen type VI alpha 1 and cell division cycle 42 (CDC42) transcripts. Exogenous treatment of D54Mg cells with a constitutively active recombinant PAI-1 protein confirmed an upregulation of VEGF expression in a time- and dose-dependent manner, and supernatants from such cultures stimulated the proliferation of human umbilical vein endothelial cells in vitro. In 44 human glioma biopsies, patients, the protein levels of PAI-1 correlated strongly with the levels of VEGF in the tumor tissues. Whereas VEGF expression correlated inversely with survival, there was no statistically significant prediction of survival by PAI-1 in this group of patients. These clinical data support and strengthen the hypothesis that PAI-1 is one of the factors regulating and inducing the VEGF expression in human gliomas. The induction of VEGF expression and thus endothelial cell proliferation may represent an as yet undiscovered mechanism whereby PAI-1 contributes to tumor neoangiogenesis.


Molecular genetic screening of full-term small for gestational age.
To examine the clinical application of genomic screening in newborns small for gestational age (SGA), hoping to provide an efficient technique for early discovery of neonatal diseases, which is necessary to elevate survival rates and the quality of life in infants. Totally 93 full-term SGA newborns were assessed. Dried blood spot (DBS) samples were obtained at 72 h after birth, and tandem mass spectrometry (TMS) and Angel Care genomic screening (GS, using Targeted next generation sequencing) were carried out. All 93 subjects were examined by Angel Care GS and TMS. No children showing inborn errors of metabolism (IEM) were detected by TMS, while 2 pediatric cases (2.15%, 2/93) were confirmed as thyroid dyshormonogenesis 6 (TDH6) by Angel Care GS. Additionally, 45 pediatric cases (48.4%) had one or more variants conferring a carrier status for recessive childhood-onset disorders, with 31 genes and 42 variants associated with 26 diseases. The top three gene-related diseases with carrier status were autosomal recessive deafness (DFNB), abnormal thyroid hormone and Krabbe disease. SGA is tightly associated with genetic variation. Molecular Genetic Screening allows early detection of congenital hypothyroidism and may be a potent genomic sequencing technique for screening newborns.


Effective absorption correction for energy dispersive X-ray mapping in a scanning transmission electron microscope: analysing the local indium distribution in rough samples of InGaN alloy layers.
We have applied our previous method of self-consistent k*-factors for absorption correction in energy-dispersive X-ray spectroscopy to quantify the indium content in X-ray maps of thick compound InGaN layers. The method allows us to quantify the indium concentration without measuring the sample thickness, density or beam current, and works even if there is a drastic local thickness change due to sample roughness or preferential thinning. The method is shown to select, point-by-point in a two-dimensional spectrum image or map, the k*-factor from the local Ga K/L intensity ratio that is most appropriate for the corresponding sample geometry, demonstrating it is not the sample thickness measured along the electron beam direction but the optical path length the X-rays have to travel through the sample that is relevant for the absorption correction.


SLC39A4 expression is associated with enhanced cell migration, cisplatin resistance, and poor survival in non-small cell lung cancer.
The zinc transporter SLC39A4 influences epithelial cell morphology and migration in various cancers; however, its role in regulating cell invasion and chemotherapeutic resistance in human lung cancer is not yet clear. Here, integrated analysis of gene expression in non-small cell lung cancer revealed that SLC39A4 expression is significantly correlated with increased tumour size and regional lymph node spread, as well as shorter overall survival (OS) and disease-free survival (DFS). SLC39A4 silencing by lentivirus-mediated shRNA blocked human lung cancer cell epithelial-mesenchymal transition and metastasis in vitro and in vivo, respectively. Moreover, SLC39A4 knockdown enhanced cancer cell sensitivity to cisplatin-induced death by inhibiting stemness in lung cancer cells. Collectively, these data suggest that SLC39A4 may be a novel therapeutic target and predictive marker of tumour metastasis in non-small cell lung cancer.


Effect of low dose of vinclozolin on reproductive tract development and sperm parameters in CD1 outbred mice.
The effect of a low dose of vinclozolin within the development of the reproductive tract during gestation (VIN-GD 15-22) and puberty (VIN-PND 23-44) in CD1 mice was tested. We found a decrease in the anogenital distance, prostate weight and pathology of testes in both experimental groups. Sperm counts decreased to 46% (VIN-GD) and to 81% (VIN-PND), and also the acrosomal state (evaluated by antiacrosomal antibody) decreased in both groups to 89% in comparison to the control group (100%). Sperm head abnormalities increased by approximately 18% and 13%, respectively. In this connection, the expression of some genes was changed (arosome-related gene (Acr), apoptosis related genes (p53, p21)). In conclusion, a low dose of vinclozolin affected the reproductive tract, sperm parameters and expression of selected genes in both experimental groups.


Phytoremediation of heavy metals--concepts and applications.
The mobilization of heavy metals by man through extraction from ores and processing for different applications has led to the release of these elements into the environment. Since heavy metals are nonbiodegradable, they accumulate in the environment and subsequently contaminate the food chain. This contamination poses a risk to environmental and human health. Some heavy metals are carcinogenic, mutagenic, teratogenic and endocrine disruptors while others cause neurological and behavioral changes especially in children. Thus remediation of heavy metal pollution deserves due attention. Different physical and chemical methods used for this purpose suffer from serious limitations like high cost, intensive labor, alteration of soil properties and disturbance of soil native microflora. In contrast, phytoremediation is a better solution to the problem. Phytoremediation is the use of plants and associated soil microbes to reduce the concentrations or toxic effects of contaminants in the environments. It is a relatively recent technology and is perceived as cost-effective, efficient, novel, eco-friendly, and solar-driven technology with good public acceptance. Phytoremediation is an area of active current research. New efficient metal hyperaccumulators are being explored for applications in phytoremediation and phytomining. Molecular tools are being used to better understand the mechanisms of metal uptake, translocation, sequestration and tolerance in plants. This review article comprehensively discusses the background, concepts and future trends in phytoremediation of heavy metals.


Role of Complement Activation in Allograft Inflammation.
Novel paradigms have broadened our understanding of mechanisms through which complement mediates allograft inflammation/injury. Herein we review advances in the field and highlight therapeutic implications. Pre-clinical and translational human trials have elucidated complement-dependent mechanisms of post-transplant ischemia-reperfusion (I/R) injury. Immune cell-derived, and intracellular, complement activation are newly linked to proinflammatory T cell immunity relevant to allograft rejection. Complement-induced immune regulation, including C5a ligation of C5a receptor 2 on T cells, C5a/C5a receptor 1 interactions on regulatory myeloid cells, and C1q binding to CD8+ T cells can inhibit proinflammatory T cells and/or prolong murine allograft survival. Pilot trials of complement inhibition to treat/prevent human I/R- or antibody-initiated allograft injury show promise. The complement system participates in allograft injury through multiple context- dependent mechanisms involving various components and receptors. These new insights along with development and implementation of individualized complement inhibitory strategies have potential to improve transplant outcomes.


Analysis of clinicopathological and molecular features of ELOC(TCEB1)-mutant renal cell carcinoma.
This study aimed to investigate the clinicopathological and molecular characteristics of ELOC(TCEB1)-mutant renal cell carcinoma. Sanger sequencing was used to assess 32 cases originally diagnosed as clear cell renal cell carcinoma with CK7 positive and/or fibromyomatous stroma. Of these, 4 patients with ELOC(TCEB1) gene mutation were screened, and their clinicopathological data were collected for histomorphological observation, immunohistochemical staining, and follow-up, and relevant pieces of literature were reviewed. The 4 patients with ELOC(TCEB1) mutations were all males and aged between 57 and 64 years (median age: 59 years old). The tumor was located in the renal cortex, with a diameter of 2-3.5 cm. The cross-section was grayish-yellow and grayish brown, solid and nodular, and clearly demarcated from the surrounding tissues. Of the 4 patients, 3 harbored a thick fibrous pseudocapsule rich in smooth muscle and were separated from the surrounding normal renal tissue, and 2 of them showed focal invasion into the pseudocapsule, whereas 1 patient had no capsule but had focal invasion into the surrounding renal parenchyma. The tumor tissues mainly exhibited elongated or branched aciniform or tubular structures, commonly accompanied by interspersed small cystic and focal clustered short papillary structures. The cytoplasm of the tumor cells was rich and lightly stained, and the nuclear grading ranged from 1 to 2. All patients showed loose edema in the stroma, and 2 patients showed a small number of interspersed smooth muscle bundles. All 4 patients showed EMA, CA9, AMACR, and TCEB1 expression, and TCEB1 was mainly located in the nucleus. Vimentin, CK7, and CD10 expressions were observed in most cases; CD117, TFE3, HMB45, and melanA were not expressed in all tumors; the expression rate of Ki67 was 3%- 8%. All 4 patients had a point mutation in ELOC(TCEB1) Y79C. The patients were followed up for 24-93 months (mean 49 months), and all of them survived to date without recurrence or metastasis. ELOC(TCEB1)-mutant renal cell carcinoma is a rare type of renal cell carcinoma, which tends to occur in middle-aged and elderly men. The main characteristics of this tumor are the branching alveolar or tubular structure with clustered short papillae, presence of fibromyomatous stroma, and the expression of CK7, CA9, CD10, and AMACR. Positive TCEB1 nuclear staining may be an important marker and the Sanger sequencing method is helpful for the diagnosis of this type of RCC. Most patients harbor tumors exhibiting low nuclear grade and inert clinical behavior, and a few tumors exhibit high nuclear grade and aggressive characteristics.


Electrochemical deoxyribonucleic acid biosensor based on the self-assembly film with nanogold decorated on ionic liquid modified carbon paste electrode.
An electrochemical DNA biosensor was fabricated by self-assembling probe single-stranded DNA (ssDNA) with a nanogold decorated on ionic liquid modified carbon paste electrode (IL-CPE). IL-CPE was fabricated using 1-butylpyridinium hexafluorophosphate as the binder and the gold nanoparticles were electrodeposited on the surface of IL-CPE (Au/IL-CPE). Then mercaptoacetic acid was self-assembled on the Au/IL-CPE to obtain a layer of modified film, and the ssDNA probe was further covalently-linked with mercaptoacetic acid by the formation of carboxylate ester with the help of N-(3-dimethylamino-propyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. The hybridization reaction with the target ssDNA was monitored with methylene blue (MB) as the electrochemical indicator. Under the optimal conditions, differential pulse voltammetric responses of MB was proportional to the specific ssDNA arachis sequences in the concentration range from 1.0×10(-11) to 1.0×10(-6) mol L(-1) with the detection limit as 1.5×10(-12) mol L(-1) (3σ). This electrochemical DNA sensor exhibited good stability and selectivity with the discrimination ability of the one-base and three-base mismatched ssDNA sequences. The polymerase chain reaction product of arachis Arabinose operon D gene was successfully detected by the proposed method, which indicated that the electrochemical DNA sensor designed in this paper could be further used for the detection of specific ssDNA sequence.


Academic misconduct among medical students in a post-communist country.
To assess the prevalence of, attitudes towards and willingness to report different forms of academic dishonesty among medical students in a post-communist transitional country. An anonymous, self-administered questionnaire was distributed to medical students in Years 2-6 at the Zagreb University School of Medicine; 827 (70%) valid questionnaires were returned and analysed. Most of the students (94%) admitted cheating at least once during their studies. The most frequent type of misconduct was 'signing in an absent student on a class attendance list' (89.1%), and the least frequent 'paying for passing an examination' (0.7%). The number of committed types of misconduct out of 11 listed types increased from Year 2 (median 2) to Year 6 (median 4). Cheating behaviours could be clustered into 4 groups based on self-reported cheating, perceived prevalence of cheating, attitude towards cheating, and willingness to report cheating. The clustered behaviours that most students admitted to were perceived as the most frequent, more approved of and less likely to be reported. The strongest predictors of dishonest behaviour were attitude, perception of peer group behaviour and study year. Almost half (44%) the students said they would never report any form of cheating. Academic misconduct is widespread among medical students at the largest medical school in Croatia and its prevalence is greater than that reported for developed countries. This may be related to social and cultural factors specific to a country in the midst of a post-communist transition to a market economy, and calls for measures to be instigated at an institutional level to educate against and prevent such behaviour.


Irreversible inhibition of the cytosolic metabolism of N-hydroxy-2-acetylaminofluorene by its glycolyl analog.
The glycolyl hydroxamic acid derivative of 2-aminofluorene was found to be a potent inhibitor of its own metabolism and the metabolism of N-hydroxy-2-acetylaminofluorene by rat liver cytosol. The inhibition was irreversible, as well as time and concentration dependent, which indicates a suicide-inhibition type of metabolism. There was a direct correlation between the inhibition of N-hydroxy-2-acetylaminofluorene disappearance and 2-acetylaminofluorene formation. In contrast, both the glycolyl and acetyl hydroxamic acid derivatives were metabolized to a similar extent by enzymes in the microsomal fraction.


Clinical practice to address tamoxifen nonadherence.
The primary and secondary benefits of tamoxifen as adjuvant therapy in women with hormone-receptor-positive breast cancer are substantial: a 1% decrease in the risk of death each year for 10 years with each additional year of treatment during the first 5 years. Considerable data, however, indicate that these benefits are lost to many patients because of treatment nonadherence. Nonadherence is examined within the framework of the Common-Sense Model of Self-Regulation to describe patients' models of disease and treatment that organize their thinking and behavior, and the crucial role of the practitioner in addressing and altering these models. Common patient education and social communications about patients' hormone-receptor-positive breast cancer and tamoxifen treatment promote an acute disease paradigm in which cancer occurs within specific locations and is either present or absent. We recommend that clinicians communicate the concepts of hormone-receptor-positive breast cancer as follows: i. a non-dichotomous systemic disorder entailing a treatment goal of homeostasis and disease quiescence and ii. a disorder undetectable by currently available tests in subclinical states. Equally important, the clinician can provide a comprehensive picture of the well-documented secondary effects of tamoxifen, noting in particular the beneficial effects. Specific action plans, grounded in individual patient understanding, can be developed and reinforced, in an ongoing process that validates and integrates patient values and goals as they change over time.


Minimally invasive system to reliably characterize ventricular electrophysiology from living donors.
Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. However, access to human ventricular samples is scarce. We aim to demonstrate that slices from small transmural core biopsies collected from living donors during routine cardiac surgery preserve structural and functional properties of larger myocardial specimens, allowing accurate electrophysiological characterization. In pigs, we compared left ventricular transmural core biopsies with transmural tissue blocks from the same ventricular region. In humans, we analyzed transmural biopsies and papillary muscles from living donors. All tissues were vibratome-sliced. By histological analysis of the transmural biopsies, we showed that tissue architecture and cellular organization were preserved. Enzymatic and vital staining methods verified viability. Optically mapped transmembrane potentials confirmed that action potential duration and morphology were similar in pig biopsies and tissue blocks. Action potential morphology and duration in human biopsies and papillary muscles agreed with published ranges. In both pigs and humans, responses to increasing pacing frequencies and β-adrenergic stimulation were similar in transmural biopsies and larger tissues. We show that it is possible to successfully collect and characterize tissue slices from human myocardial biopsies routinely extracted from living donors, whose behavior mimics that of larger myocardial preparations both structurally and electrophysiologically.