Management of Mechanical Nasal Obstruction Isolated or Associated to Upper Airway Inflammatory Diseases in Real Life: Use of both Subjective and Objective Criteria.
Mechanical nasal obstruction (MNO) is a prevalent condition with a high impact on patient's quality-of-life (QoL) and socio-economic burden. The aim of this study was to determine the usefulness of both subjective and objective criteria in the appropriate management of MNO, either alone or associated to upper airway inflammatory diseases such as allergic rhinitis (AR) or chronic rhinosinusitis with nasal polyps (CRSwNP). A long debate persists about the usefulness of subjective and objective methods for making decisions on the management of patients with nasal obstruction. Establishing standards and ranges of symptom scales and questionnaires is essential to measure the success of an intervention and its impact on QoL. To our knowledge this is the first real-life study to describe the management of MNO using both subjective and objective criteria in MNO isolated or associated to upper airway inflammatory diseases (AR or CRSwNP). Medical treatment (intranasal corticosteroids) has a minor but significant improvement in MNO subjective outcomes (NO, NOSE, and CQ7) with no changes in loss of smell and objective outcomes. After surgery, all MNO patients reported a significant improvement in both subjective and objective outcomes, this improvement being higher in CRSwNP. We concluded that in daily clinical practice, the therapeutic recommendation for MNO should be based on both subjective and objective outcomes, nasal corrective surgery being the treatment of choice in MNO, either isolated or associated to upper airway inflammatory diseases, AR or CRSwNP.


Shifting in the global flood timing.
Climate change will have an impact on not only flood magnitude but also on flood timing. This paper studies the shifting in flood timing at 6167 gauging stations from 1970 to 2010, globally. The shift in flood timing and its relationship with three influential factors (maximum 7-day precipitation, soil moisture excess, and snowmelt) are investigated. There is a clear global pattern in the mean flooding date: winter (Dec-Feb) across the western Coastal America, western Europe and the Mediterranean region, summer (Jun-Aug) in the north America, the Alps, Indian Peninsula, central Asia, Japan, and austral summer (Dec-Feb) in south Africa and north Australia area. The shift in flood timing has a trend from - 22 days per decade (earlier) to 28 days per decade (delayed). Earlier floods were found extensively in the north America, Europe and northeast Australia while delayed floods were prevailing in the Amazon, Cerrado, south Africa, India and Japan. Earlier flood timing in the north America and Europe was caused by earlier snowmelt while delayed extreme soil moisture excess and precipitation have jointly led to delayed floods around the monsoon zone, including south Africa, India and Japan. This study provides an insight on the shifting mechanism of flood timing, and supports decisions on the global flood mitigation and the impact from future climate change.


Inflammatory Cytokines, but Not Dietary Patterns, Are Related to Somatic Symptoms of Depression in a Sample of Women.
Depression is a heterogenous disorder with both cognitive and somatic symptom dimensions that may differentially relate to systemic inflammation. Diet, which has the potential to modulate both inflammation levels and mood, is yet to be studied within the context of individual depression dimensions. This study examined the associations between inflammatory cytokines and dietary patterns with depressive symptom dimension profiles among a sample of women recruited in a non-clinical setting. Inflammatory cytokines (IL-6 and TNF-α), inflammatory diet (Diet Inflammatory Index; DII), and depressive symptoms (Beck Depression Inventory-II; BDI-II) were measured in 136 females (M age = 22.01 ± 4.02, range 18-59 years). Multiple linear regressions were used to investigate the relationships between inflammatory cytokines and diet with self-reported cognitive, somatic, and total depressive symptoms, adjusting for demographic factors. Findings showed that increased somatic dimension scores were positively associated with IL-6 (ß = 0.273, p = 0.002) and TNF-α (ß = 0.215, p = 0.017), but not inflammatory diet (p = 0.300). Total BDI-II scores were only positively associated with IL-6 (ß = 0.221, p = 0.012), and cognitive dimension scores were not associated with any inflammation measures. These findings contribute to existing evidence that inflammatory cytokines are associated with the somatic symptoms of depression. Inflammatory diet index was not associated with depression measures.


Mitochondrial translational defect extends lifespan in C. elegans by activating UPRmt.
Aminoacyl-tRNA synthetases (aaRSs) are indispensable players in translation. Usually, two or three genes encode cytoplasmic and mitochondrial threonyl-tRNA synthetases (ThrRSs) in eukaryotes. Here, we reported that Caenorhabditis elegans harbors only one tars-1, generating cytoplasmic and mitochondrial ThrRSs via translational reinitiation. Mitochondrial tars-1 knockdown decreased mitochondrial tRNAThr charging and translation and caused pleotropic phenotypes of delayed development, decreased motor ability and prolonged lifespan, which could be rescued by replenishing mitochondrial tars-1. Mitochondrial tars-1 deficiency leads to compromised mitochondrial functions including the decrease in oxygen consumption rate, complex Ⅰ activity and the activation of the mitochondrial unfolded protein response (UPRmt), which contributes to longevity. Furthermore, deficiency of other eight mitochondrial aaRSs in C. elegans and five in mammal also caused activation of the UPRmt. In summary, we deciphered the mechanism of one tars-1, generating two aaRSs, and elucidated the biochemical features and physiological function of C. elegans tars-1. We further uncovered a conserved connection between mitochondrial translation deficiency and UPRmt.


Species traits and environmental conditions govern the relationship between biodiversity effects across trophic levels.
Changing environments can have divergent effects on biodiversity-ecosystem function relationships at alternating trophic levels. Freshwater mussels fertilize stream foodwebs through nutrient excretion, and mussel species-specific excretion rates depend on environmental conditions. We asked how differences in mussel diversity in varying environments influence the dynamics between primary producers and consumers. We conducted field experiments manipulating mussel richness under summer (low flow, high temperature) and fall (moderate flow and temperature) conditions, measured nutrient limitation, algal biomass and grazing chironomid abundance, and analyzed the data with non-transgressive overyielding and tripartite biodiversity partitioning analyses. Algal biomass and chironomid abundance were best explained by trait-independent complementarity among mussel species, but the relationship between biodiversity effects across trophic levels (algae and grazers) depended on seasonal differences in mussel species' trait expression (nutrient excretion and activity level). Both species identity and overall diversity effects were related to the magnitude of nutrient limitation. Our results demonstrate that biodiversity of a resource-provisioning (nutrients and habitat) group of species influences foodweb dynamics and that understanding species traits and environmental context are important for interpreting biodiversity experiments.


[Contrast-enhanced ultrasound for characterisation of focal liver lesions, practical advice].
This review article reports on evidence-based and clinical aspects of contrast-enhanced ultrasound of liver masses. The advanced possibilities of contrast-enhanced ultrasound to detect and characterise liver tumors are described as well as limitations and pitfalls of the method. The choice of the ultrasound device and contrast agents as well as the qualifications of the examiners according to guidelines are discussed.


Chemical defenses and the susceptibility of tropical marine brown algae to herbivores.
I assayed phenolic and tannin concentrations in a number of species of temperate and tropical brown algae of the genera Sargassum and Turbinaria. Tropical species in both genera contained consistently low levels of phenolics and tannins (species means ranged between 0 and 1.6% [measured as % dry weight of the thallus]). Levels of phenolics in temperate species of Sargassum were variable and consistently much higher than in tropical species (species means ranged between 3 and 12% by dry weight). This pattern of latitudinal variation in phenolic levels in Sargassum conflicts with previous predictions for latitudinal variation in the chemical defenses of marine organisms. The low levels of phenolics present in the tropical species that I analyzed may also explain recent results (Hay 1984; Lewis 1985) demonstrating that tropical Sargassum and Turbinaria are often preferentially consumed by herbivorous fishes and echinoids.


Thromboembolic prophylaxis with intermittent pneumatic compression devices in trauma patients: a false sense of security?
Intermittent pneumatic compression devices provide a safe and attractive means of venous thromboembolism prophylaxis. We hypothesized that intermittent pneumatic compression devices were inadequate prophylaxis secondary to noncompliance. This was a prospective double-blind study evaluating compliance with intermittent pneumatic compression devices in nonambulatory adult trauma patients. Compliance was evaluated for the first 3 days of admission. The study consisted of two 3-month stages (before and after hospital personnel education on the importance of venous thromboembolism prophylaxis). During the first stage, device compliance was 85%, 59%, and 74% in the intensive care unit, surgical ward, and overall, respectively. Following hospital personnel education, device compliance was 82%, 65%, and 77% in the intensive care unit, surgical ward, and overall, respectively. There was no significant difference in compliance between the 2 stages. With inadequate compliance and the cost attributed with intermittent pneumatic compression devices, other means of venous thromboembolism prophylaxis should be considered first, specifically low-molecular-weight heparin if not contraindicated.


DFT and TD-DFT insights, photolysis and photocatalysis investigation of three dyes with similar structure under UV irradiation with and without TiO2 as a catalyst: Effect of adsorption, pH and light intensity.
TiO2-mediated photocatalytic degradation of three triphenylmethane dyes (basic fuchsin, acid fuchsin and Gentian violet), was investigated in aqueous suspensions in the presence and the absence of titanium dioxide P25 Degussa as photocatalyst. The photodegradation process was investigated using UV-A (365nm) and UV-C (254nm) light alone and UV-A in the presence of TiO2·The effects of various operational parameters were investigated such as: the effect of adsorption in the dark, the influence of pH, the influence of irradiation wavelength and the effect of light intensity. The study of the effect of various parameters reveals that the photolysis of dyes increases with the increase of light intensity, the degradation rate under UV-C (254nm) was found better than under UV-A 365nm. The photocatalytic degradation was found to follow the same order of adsorption. The decolorization and the degradation kinetics were found to follow the pseudo-first-order kinetics. The mineralization of dye was found to follow the same order of disappearance as the photocatalytic degradation and depended directly to its functional groups and its number of carbons. Additionally, density functional theory (DFT) was applied for calculations of both electronic structure and spectroscopic properties of the studied compounds, where the obtained results of the three dyes show that the theoretical electronic spectra and the experimental UV-visible ones are similar in shapes, positions and intensities.


Prognostic significance of vitamin D receptor (VDR) gene polymorphisms in liver cirrhosis.
Several polymorphisms in the vitamin D receptor (VDR) are associated with the occurrence of chronic liver disease. Here, we investigated the association between BsmI, ApaI, TaqI and FokI VDR polymorphisms and the severity of liver cirrhosis in relation to serum cytokine and lipopolysaccharide binding protein (LBP) levels and their role on survival in cirrhotic patients. We found that patients harboring the BB genotype had higher MELD score, and they were mainly at CP stage C; patients harboring the AA genotype had increased LBP, IL-1β and IL-8 levels, and they were mostly at CP stage C; TT genotype carriers had higher MELD score and they were mainly at CP stage C and FF genotype carriers had lower IL-1β levels when compared to Bb/bb, Aa/aa, Tt/tt and Ff/ff genotypes respectively. In the multivariate analysis ApaI, BsmI and TaqI polymorphisms were independently associated with liver cirrhosis severity. In the survival analysis, the independent prognostic factors were CP score, MELD and the FF genotype. Our results indicate that the ApaI, TaqI and BsmI polymorphisms are associated with the severity of liver cirrhosis, through the immunoregulatory process. Survival is related to the FF genotype of FokI polymorphism, imparting a possible protective role in liver cirrhosis.


CRY2 interacts with CIS1 to regulate thermosensory flowering via FLM alternative splicing.
Cryptochromes (CRYs) are evolutionarily conserved photolyase-like photoreceptors found in almost all species, including mammals. CRYs regulate transcription by modulating the activity of several transcription factors, but whether and how they affect pre-mRNA processing are unknown. Photoperiod and temperature are closely associated seasonal cues that influence reproductive timing in plants. CRYs mediate photoperiod-responsive floral initiation, but it is largely unknown whether and how they are also involved in thermosensory flowering. We establish here that blue light and CRY2 play critical roles in thermosensory flowering in Arabidopsis thaliana by regulating RNA alternative splicing (AS) to affect protein expression and development. CRY2 INTERACTING SPLICING FACTOR 1 (CIS1) interacts with CRY2 in a blue light-dependent manner and promotes CRY2-mediated thermosensory flowering. Blue light, CRYs, and CISs affect transcriptome-wide AS profiles, including those of FLOWERING LOCUS M (FLM), which is critical for temperature modulation of flowering. Moreover, CIS1 binds to the FLM pre-mRNA to regulate its AS, while CRY2 regulates the RNA-binding activity of CIS1. Thus, blue light regulates thermosensory flowering via a CRY2-CIS1-FLM signaling pathway that links flowering responses to both light and ambient temperature.


[Spontaneous Visibility of the Mammary Ducts in Plain Mammography (author's transl)].
Mammary ducts become visible as negative contrast in the mammogram. This is caused by an increased contents of fat or oil in the mammary secretion. The secretion of lipides can indicate hormonal disregulation.


Transcriptional and translational features of a sporulation gene of Streptomyces griseus.
The nucleotide (nt) sequence of a 2.8-kb fragment of DNA that restores sporulation to one class of bald mutants of Streptomyces griseus revealed an open reading frame (ORF) with the potential to encode a 55.5-kDa polypeptide. The presence of an in-frame TTA in the coding sequence indicated that translation is likely to require the tRNA(Leu)UUA encoded by the bldA gene. Two overlapping transcripts are initiated at transcriptional start points (tsp) separated by 258 nt and are transcribed in the same direction. The downstream tsp lies within the ORF and is followed by a second potential translation initiation site, which would encode a 49.5-kDa polypeptide in the same reading frame as the 55.5-kDa polypeptide. Transcription assays suggested that both tsp functioned during vegetative growth, but the relative abundance of the shorter transcript decreased during the early stages of submerged sporulation. Analysis of sequentially deleted subclones indicated that expression of the longer ORF was necessary to complement bald mutants. The presence of two tsp alternating with potential translation start codons suggests the temporally regulated synthesis of two polypeptides that have identical C termini but different N termini.


Intelligent Electromagnetic Sensing with Learnable Data Acquisition and Processing.
Electromagnetic (EM) sensing is a widespread contactless examination technique with applications in areas such as health care and the internet of things. Most conventional sensing systems lack intelligence, which not only results in expensive hardware and complicated computational algorithms but also poses important challenges for real-time in situ sensing. To address this shortcoming, we propose the concept of intelligent sensing by designing a programmable metasurface for data-driven learnable data acquisition and integrating it into a data-driven learnable data-processing pipeline. Thereby, a measurement strategy can be learned jointly with a matching data post-processing scheme, optimally tailored to the specific sensing hardware, task, and scene, allowing us to perform high-quality imaging and high-accuracy recognition with a remarkably reduced number of measurements. We report the first experimental demonstration of "learned sensing" applied to microwave imaging and gesture recognition. Our results pave the way for learned EM sensing with low latency and computational burden.


Postoperative fasting plasma glucose and family history diabetes mellitus can predict post-transplantation diabetes mellitus in kidney transplant recipients.
To explore whether glycated albumin (GA) or fasting plasma glucose (FPG), both routinely monitored during patients' hospital stay, can be used to predict post-transplantation diabetes mellitus (PTDM). All kidney transplantation recipients (KTRs) from January 2017 to December 2018 were followed-up for 1 year. PTDM was diagnosed from day 45 post-operation to 1 year. When the completeness was above 80%, FPG or GA data on the day was selected, analyzed, and presented as range parameters and standard deviation (SD) and compared between PTDM and non-PTDM groups in fluctuation and stable periods. The predictive cut-off values were determined via receiver operating characteristic (ROC) analysis. The PTDM combined predictive mode, formed by the independent risk factors derived from logistic regression analyses, was compared with each independent risk factor with the independent ROC curve test. Among 536 KTRs, 38 patients developed PTDM up to 1 year post-operatively. The family history diabetes mellitus (OR, 3.21; P = 0.035), the FPG SD in fluctuation period >2.09 mmol/L (OR, 3.06; P = 0.002), and the FPG maximum in stable period >5.08 mmol/L (OR, 6.85; P < 0.001) were the PTDM independent risk factors. The discrimination of the combined mode (area under the curve = 0.81, sensitivity = 73.68%, and specificity = 76.31%) was higher than each prediction (P < 0.05). The FPG standard deviation during the fluctuation period, FPG maximum during the stable period, and family history diabetes mellitus predicted PTDM with good discrimination and potential routine clinical use.


Strategy to avoid vascular injuries in revision total hip arthroplasty with intrapelvic implants.
Our objective was describing an algorithm to identify and prevent vascular injury in patients with intrapelvic components. Patients were defined as at risk to vascular injuries when components or cement migrated 5 mm or more beyond the ilioischial line in any of the pelvic incidences (anteroposterior and Judet view). In those patients, a serial investigation was initiated by a CT angiography, followed by a vascular surgeon evaluation. The investigation proceeded if necessary. The main goal was to assure a safe tissue plane between the hardware and the vessels. In ten at-risk patients undergoing revision hip arthroplasty and submitted to our algorithm, six were recognized as being high risk to vascular injury during surgery. In those six high-risk patients, a preventive preoperative stent was implanted before the orthopaedic procedure. Four patients needed a second reinforcing stent to protect and to maintain the vessel anatomy deformed by the intrapelvic implants. The evaluation algorithm was useful to avoid blood vessels injury during revision total hip arthroplasty in high-risk patients.Cite this article: Bone Jt Open 2022;3(11):859-866.


The use of observational diaries in in-training evaluation: student perceptions.
In health science education clinical clerkships serve the twofold purpose of guiding student learning and assessment of performance. Evidently, both formative and summative assessment procedures are needed in clerkship assessment. In-training evaluation (ITE) has the potential to serve both assessment functions. Implementation of effective ITE, however, has been shown to be problematic, partly because integration of assessment functions may have negative consequences for teaching and learning. This study investigates student perceptions of the impact of an integrated assessment approach, seeking to refine criteria for effective ITE. In the curriculum of Maastricht Midwifery School (MMS), clerkship assessment is based on ITE serving both assessment functions. The ITE model is based on principles of extensive work sampling, and frequent documentation of performance. A focus group technique was used to explore student perceptions on the impact of the ITE approach on student learning and supervisor teaching behaviour, and on the usefulness of information for decision making. Results indicate that the assessment approach is effective in guidance of student learning. Furthermore, students consider the frequent performance documentation essential in clerkship grading. Acceptance and effectivity of ITE requires a learning environment which is safe and respectful. Transparency of assessment processes is the key to success. Suggestions for improvement focus on variation in evaluation formats, improvement of feedback (narrative, complete) and student involvement in assessment. ITE can fulfill both its formative and summative purposes when some crucial conditions are taken into account. Careful training of both supervisors and students in the use of ITE for student learning and performance measurement is essential.


Isolation and culture of rabbit embryonic stem cells.
Mammalian stem cells are invaluable research resources for the study of cell and embryonic development as well as practical tools for use in the production of genetically engineered animals and further therapeutics. It is important that we further our knowledge and understanding of a variety of stem cells from several different animal species before trials in humans commence. Here we describe methods for establishing rabbit embryonic stem (rES) cell lines with indefinite proliferation potential. rES cells attain maximum proliferation potential when cultured at a feeder cell density of one-sixth of that of full confluency. Higher and lower densities of feeder cells induced ES cell differentiation or division arrest. Fibroblast growth factor (FGF)2 can maintain the undifferentiated status of rES cells; however leukemia inhibitory factor (LIF) is dispensable. Under optimized conditions, rES cells could be passaged by trypsinization 50 times. This culture system enabled efficient gene transduction and clonal expansion from single cells. rES cells grew as flat monolayer cell colonies, as reported for monkey and human ES cells, and expressed pluripotency markers. Embryoid bodies and teratomas formed readily in vitro and in vivo, respectively. Characterization of ES cells from different species is important for establishing common features of pluripotency. We have demonstrated the similarity of ES cells between rabbit and humans. These cell lines could be applied directly using gene-targeting techniques, or in combination with induced pluripotent stem cells. Thus, rES cells are a suitable model for studying human transplantation therapy and disease treatments.


Cytological, genetic, and proteomic analysis of a sesame (Sesamum indicum L.) mutant Siyl-1 with yellow-green leaf color.
Both photosynthetic pigments and chloroplasts in plant leaf cells play an important role in deciding on the photosynthetic capacity and efficiency in plants. Systematical investigating the regulatory mechanism of chloroplast development and chlorophyll (Chl) content variation is necessary for clarifying the photosynthesis mechanism for crops. This study aims to explore the critical regulatory mechanism of leaf color mutation in a yellow-green leaf sesame mutant Siyl-1. We performed the genetic analysis of the yellow-green leaf color mutation using the F2 population of the mutant Siyl-1. We compared the morphological structure of the chloroplasts, chlorophyll content of the three genotypes of the mutant F2 progeny. We performed the two-dimensional gel electrophoresis (2-DE) and compared the protein expression variation between the mutant progeny and the wild type. Genetic analysis indicated that there were 3 phenotypes of the F2 population of the mutant Siyl-1, i.e., YY type with light-yellow leaf color (lethal); Yy type with yellow-green leaf color, and yy type with normal green leaf color. The yellow-green mutation was controlled by an incompletely dominant nuclear gene, Siyl-1. Compared with the wild genotype, the chloroplast number and the morphological structure in YY and Yy mutant lines varied evidently. The chlorophyll content also significantly decreased (P < 0.05). The 2-DE comparison showed that there were 98 differentially expressed proteins (DEPs) among YY, Yy, and yy lines. All the 98 DEPs were classified into 5 functional groups. Of which 82.7% DEPs proteins belonged to the photosynthesis and energy metabolism group. The results revealed the genetic character of yellow-green leaf color mutant Siyl-1. 98 DEPs were found in YY and Yy mutant compared with the wild genotype. The regulation pathway related with the yellow leaf trait mutation in sesame was analyzed for the first time. The findings supplied the basic theoretical and gene basis for leaf color and chloroplast development mechanism in sesame.


The Scd6/Lsm14 protein xRAPB has properties different from RAP55 in selecting mRNA for early translation or intracellular distribution in Xenopus oocytes.
Oocytes accumulate mRNAs in the form of maternal ribonucleoprotein (RNP) particles, the protein components of which determine the location and stability of individual mRNAs prior to translation. Scd6/Lsm14 proteins, typified by RAP55, function in a wide range of eukaryotes in repressing translation and relocating mRNPs to processing bodies and stress granules. In Xenopus laevis, the RAP55 orthologue xRAPA fulfils these functions. Here we describe the properties of a variant of xRAPA, xRAPB, which is a member of the Lsm14B group. xRAPB differs from xRAPA in various respects: it is expressed at high concentration earlier in oogenesis; it interacts specifically with the DDX6 helicase Xp54; it is detected in polysomes and stalled translation initiation complexes; its over-expression leads to selective binding to translatable mRNA species without evidence of translation repression or mRNA degradation. Since both Xp54 and xRAPA are repressors of translation, activation appears to be effected through targeting of xRAPB/Xp54.


Modulation of tricarboxylic acid cycle dehydrogenases during hepatocarcinogenesis induced by hexachlorocyclohexane in mice.
The sequential distribution of key tricarboxylic acid (TCA) cycle enzymes have been investigated during hexachlorocyclohexane (HCH)-induced hepatocarcinogenesis in Swiss mice. Animals were continuously exposed to HCH (500ppm) for 2, 4, and 6 months until liver tumor developed. The activity of TCA cycle enzymes such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) have been studied. The activity of all the enzymes declined after 2 months of exposure of HCH in the liver. The neoplastic nodules and tumors developed after an exposure of HCH for 4 and 6 months, respectively. Neoplastic nodule and tumor showed wide variations in the activity and distribution of TCA cycle enzymes. The decreasing pattern in the activity of enzymes persisted in the non-neoplastic and non-tumor regions of the liver except SDH. However, the cells in nodular area and tumor showed intense enzymatic activities at cellular level. In the nodular region SDH activity declined prominently, whereas the non-nodular area showed positive reaction. Conspicuously, the tumor showed islands of positive and negative zones for TCA cycle dehydrogenases. The significance and relevance of such a distribution pattern still remains a mystery. The results are discussed in the light of HCH-induced toxicity on energy metabolism in exposed animals and possible role of such enzymes in the tumor formation.


N-acetylcysteine prevents oxidized low-density lipoprotein-induced reduction of MG53 and enhances MG53 protective effect on bone marrow stem cells.
MG53 is an important membrane repair protein and partially protects bone marrow multipotent adult progenitor cells (MAPCs) against oxidized low-density lipoprotein (ox-LDL). The present study was to test the hypothesis that the limited protective effect of MG53 on MAPCs was due to ox-LDL-induced reduction of MG53. MAPCs were cultured with and without ox-LDL (0-20 μg/mL) for up to 48 hours with or without MG53 and antioxidant N-acetylcysteine (NAC). Serum MG53 level was measured in ox-LDL-treated mice with or without NAC treatment. Ox-LDL induced significant membrane damage and substantially impaired MAPC survival with selective inhibition of Akt phosphorylation. NAC treatment effectively prevented ox-LDL-induced reduction of Akt phosphorylation without protecting MAPCs against ox-LDL. While having no effect on Akt phosphorylation, MG53 significantly decreased ox-LDL-induced membrane damage and partially improved the survival, proliferation and apoptosis of MAPCs in vitro. Ox-LDL significantly decreased MG53 level in vitro and serum MG53 level in vivo without changing MG53 clearance. NAC treatment prevented ox-LDL-induced MG53 reduction both in vitro and in vivo. Combined NAC and MG53 treatment significantly improved MAPC survival against ox-LDL. These data suggested that NAC enhanced the protective effect of MG53 on MAPCs against ox-LDL through preventing ox-LDL-induced reduction of MG53.


Dynamic mass spectrometer for studies of organic and inorganic molecules.
Experimental technique is described and relative cross-sections of direct and dissociative ionization of CO2, C4H9OH, C2H5OH, CH3OH, C6H12O6 and C7H8 molecules by electron impact in the near-threshold energy range are obtained. The experiment is performed on a setup with ion mass separation based on a monopole mass spectrometer which is proved to be successful for such a sort of experiments. For the incident electron energy range from 7 to 35 eV the energy dependences of cross-section of appearance of the main molecule ions and the fragment ions formed due to its dissociation are given.


Prosultiamine for treatment of lower urinary tract dysfunction accompanied by human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis.
To evaluate oral prosultiamine treatment in patients with overactive bladder accompanied by human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. This was a prospective, single-center, open-label study. Patients received oral prosultiamine (300 mg) once daily in the morning, and the overactive bladder symptom score and urine levels of overactive bladder-related biomarkers (nerve growth factor/creatinine and adenosine triphosphate/creatinine) 12 weeks after the initial administration were compared with the baseline values. In addition, the urodynamic parameters, including involuntary detrusor contraction and detrusor sphincter dyssynergia, were evaluated before and after treatment. A total of 16 patients were recruited for this clinical study. In the overactive bladder symptom score, night-time frequency, urgency and the total score improved after oral prosultiamine treatment (P = 0.028, 0.001 and 0.004, respectively). Both urinary nerve growth factor/creatinine and adenosine triphosphate/creatinine levels decreased significantly after the treatment (P = 0.004 and 0.017, respectively). Urodynamic studies showed that the maximum cystometric capacity increased significantly after the treatment. However, the symptoms disappeared because of the treatment in six of 10 patients with involuntary detrusor contraction (60%) and three of seven patients with detrusor sphincter dyssynergia (42.9%). There were no serious adverse events. The changes in urodynamic parameters and urine levels of overactive bladder-related markers suggest that oral prosultiamine is a safe and effective treatment for overactive bladder with human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis.


Corrigendum to "Intraoperative Imaging Modalities and Compensation for Brain Shift in Tumor Resection Surgery".
[This corrects the article DOI: 10.1155/2017/6028645.].


Should direct measurements of tumor oxygenation relate to the radiobiological hypoxic fraction of a tumor?
Numerous previous studies have attempted to relate the radiobiological hypoxic fraction (HF) to direct measures of tumor oxygenation such as HbO2 saturations, tumor pO2 levels, or hypoxic cell labeling. Although correlations have been found within tumor lines, no overall relationships were seen across tumor lines. The current objective was to examine the effect on HF of changes in the fractions of the oxygenated and anoxic tumor cells that remain clonogenic. A mathematical model was developed that relates the HF to direct measures of tumor oxygenation. The primary assumptions were that: (a) the tumor is divided into distinct compartments of either fully oxygenated or fully anoxic cells, and (b) the survival of the oxygenated cells is negligible compared to that of the anoxic cells. Based on these assumptions, the HF is plotted as a function of the fractions of clonogenic or nonclonogenic, and oxygenated or anoxic cells. If all cells are clonogenic, then the HF equals the fraction of anoxic cells. If a higher fraction of anoxic than oxygenated cells are nonclonogenic, then the HF will be overestimated by the fraction of the tumor measured to be anoxic using direct measuring techniques. If a higher fraction of the oxygenated than anoxic cells are nonclonogenic, the HF will be underestimated by the fraction of anoxic cells. Correlations between the HF and direct measures of tumor oxygenation have been described within tumor lines evaluated under different physiological condition. However, such relationships can be totally unpredictable between different tumors if the fraction of the anoxic cells that is clonogenic varies substantially. Clearly, if tumor anoxia cannot be detected using direct measures, this is an accurate indication that the tumor is well oxygenated. When tumor anoxia is present, however, the conclusions are ambiguous. Even when a small fraction of the tumor is measured as anoxic, direct measures of tumor oxygenation may not be representative of the HF if a substantial proportion of nonclonogenic cells is present.


Comparative Evaluation of Shear Bond Strength of Three Commercially Available Glass Ionomer Cements in Primary Teeth.
This study aims to comparatively evaluate the shear bond strength (SBS) of three commercially available glass ionomer cements - Miracle Mix (MM) (GC America Inc., Alsip, USA), Ketac Molar (KM) (3M Corp., Minnesota, USA) and amalgomer CR (AM) (Advanced Healthcare Ltd., Kent, England) in primary teeth and later examine the mode of the adhesive failure at the interface. Totally, 90 extracted sound primary molars were selected, and dentin on the buccal surface of crowns was exposed. Specimens were randomly assigned into three groups according to the restorative materials being tested. SBS tests were performed, and the obtained values were statistically analyzed using ANOVA and Tukey tests (P < 0.05). SBS mean values on were recorded in megapascals (MPa) and the mode of failure was assessed using a scanning electron microscope. SBS (in MPa) was - MM-5.39, KM-4.84, AM-6.38. The predominant failure mode was cohesive. Amalgomer CR exhibited statistically significant higher SBS of 6.38 MPa to primary teeth and has better adhesion to the primary teeth compared to the other test materials and can be considered as a restorative material in pediatric dentistry. However, the results of this study should be corroborated with further investigation to reach a definitive conclusion.


Effects of intestinal microbial bile salt sulfatase activity on bile salt kinetics in gnotobiotic rats.
Hepatic sulfation is thought to promote fecal excretion of lithocholate in humans by impairing the enterohepatic recirculation of the compound. Sulfatases produced by the gut flora may, at least in part, counteract this process. To investigate this interaction, female germfree rats, which are known to excrete considerable amounts of sulfated bile salts, were selectively associated with a bile salt desulfating flora. In these rats nearly all cecal, colonic, and fecal bile salt sulfate esters were hydrolyzed, resulting in a decrease of total fecal bile salt excretion of greater than 25% compared with gnotobiotic rats without a bile salt desulfating flora. Desulfation of allochenodeoxycholate, the major sulfated bile salt in germfree rats, led to an enhanced recirculation and 12 alpha-hydroxylation of the compound in the liver, resulting in an increased fecal output of allocholate. Microbial desulfation of intraperitoneally injected [24-14C]taurolithocholate-3-sulfate caused a fivefold decrease of the fecal plus urinary excretion rate of the isotope to approximately that found for unsulfated [24-14C]taurolithocholate. Coassociation of the gnotobiotic rats with a microflora that normalized the small intestinal transit time and cecal size led to a rise of total fecal bile salt excretion of greater than 30% and a twofold accelerated excretion of both sulfated and unsulfated injected [24-14C]taurolithocholate. We conclude that in rats the gut flora rapidly desulfates intestinal bile salt sulfates, enhancing the enterohepatic recirculation and subsequent hydroxylation of the desulfated bile salts. In addition, these data illustrate the importance of having a well-defined microflora to normalize intestinal transit time and cecal size of gnotobiotic animals when performing kinetic studies of enterohepatic circulating compounds.


Behavioural and anatomical studies of the posterior parietal cortex in the rat.
Primates have an area of posterior cortex characterized by multimodal sensory projections to and from the frontal association cortex and a clear behavioural syndrome resulting from lesions to this zone. The posterior association cortex of the rat was examined in two series of experiments, one anatomical and one behavioural, to see if an analogous region could be found. The anatomical connections of Krieg's area 7 in the rat were examined by placing the retrograde tracer, True blue, into the frontal or posterior cortex, and the behaviour of rats with this cortex removed was studied on a variety of tasks. This area appears to be a multimodal sensory association region. It receives projections from striate (area 17), extrastriate (areas 18a and 18b), and somatosensory cortex (area 3). It is also reciprocally connected with the posterior cingulate cortex and two frontal association zones in the medial frontal cortex, namely the anterior cingulate cortex and the frontal eye fields. Lesions produced deficits on tasks of tactile discrimination, and walking a narrow beam, two tasks requiring animals to navigate accurately to a point in space, and a task requiring the association of two spatially discontiguous cues. The animals were not impaired at navigating to a cue or in opening puzzle latches. Overall, the results show that the rat has a sensory association zone that may be analogous to the posterior parietal cortex of primates.


Coxsackie and adenovirus receptor is a critical regulator for the survival and growth of oral squamous carcinoma cells.
Coxsackie and adenovirus receptor (CAR) is essential for adenovirus infection to target cells, and its constitutive expression in various cancerous and normal tissues has been reported. Recently, the biological role of CAR in human cancers of several different origins has been investigated with respect to tumor progression, metastasis and tumorigenesis. However, its biological function in tumor cells remains controversial. Here we report the critical role of CAR in growth regulation of oral squamous cell carcinomas (SCCs) in vitro and in vivo via the specific interaction with Rho-associated protein kinase (ROCK). Loss of endogenous CAR expression by knockdown using specific small interfering RNA (siRNA) against CAR facilitates growth suppression of SCC cells due to cell dissociation, followed by apoptosis. The consequent morphological reaction was reminiscent of anoikis, rather than epithelial-mesenchymal transition, and the dissociation of oral SCC cells was triggered not by lack of contact with extracellular matrix, but by loss of cell-to-cell contact caused by abnormal translocation of E-cadherin from surface membrane to cytoplasm. Immunoprecipitation assays of the CAR-transfected oral SCC cell line, HSC-2, with or without ROCK inhibitor (Y-27632) revealed that CAR directly associates with ROCKI and ROCKII, which results in inhibition of ROCK activity and contributes to maintenance of cell-to-cell adhesion for their growth and survival. Based on these findings, in vivo behavior of CAR-downregulated HSC-2 cells from siRNA knockdown was compared with that of normally CAR-expressing cells in intraperitoneally xenografted mouse models. The mice engrafted with CAR siRNA-pretreated HSC-2 cells showed poor formation of metastatic foci in contrast to those implanted with the control siRNA-pretreated cells. Thus, CAR substantially has an impact on growth and survival of oral SCC cells as a negative regulator of ROCK in vitro and in vivo.


Picrotoxin-induced generalised convulsive seizure in rat: changes in regional distribution and frequency of the power of electroencephalogram rhythms.
It is unknown how generalised discharges in primary generalised epilepsy (PGE) develop from background brain electrical activity or how widespread these discharged are throughout the brain. Here we address this by determining which neural structures and rhythms lead to and participate in generalised discharges in the picrotoxin rat model of PGE. Rats with chronically implanted electrodes were infused with picrotoxin until a seizure occurred. This process we refer to as acute epileptogenesis. The electroencephalogram (EEG) was recorded and spectral analysis applied off-line to determine changes in the spectral power of contributing frequencies in 13 brain regions. Two types of generalised discharge occurred, spindles and seizure, which were present in all brain regions studied. None of the frequencies (1-100 Hz) were significantly increased in background EEG before either spindles or seizure. Within the generalised discharges, power changes revealed significant increases in 6-8 Hz, most powerful in ventrolateral thalamus and neocortex. Gamma frequencies were increased significantly in neocortical structures during spindles with further increases in most structures at seizure onset. 1 Hz was significantly increased in parietal cortex during spindles with differential increases at seizure onset. We conclude that gamma, 1 and 6-8 Hz frequencies do not appear to contribute to picrotoxin epileptogenesis but do play a role in generalised seizures. The distribution of these frequencies during discharges suggests that the spindles are thalamocortical events and that the seizure is a cortical event with downstream effects on other brain regions.


Phrenic nerve block with ultrasound-guidance for treatment of hiccups: a case report.
Persistent hiccups can be more than a simple and short-lived nuisance and therefore sometimes call for serious consideration. Hiccupping episodes that last only a few minutes may be annoying, but persistent hiccups may initiate many major complications. A 72-year-old Caucasian man with spinal stenosis presented for L4-5 laminectomy under spinal anesthesia. The surgery and anesthesia, as well as the perioperative period, passed without any incident, except for persistent postoperative hiccups not responding to conservative and pharmacological treatment. Hiccups resulted in a prolonged hospital stay as they lasted until the seventh postoperative day. On that day, a right-sided ultrasound-guided phrenic nerve block with 5 ml of bupivacaine 5 mg/ml with epinephrine was performed successfully with a single-injection technique. Ten minutes after the procedure the hiccups vanished and a partial sensomotoric block of his right shoulder developed. No adverse effect occurred; our patient could be discharged on the same day and the hiccups did not return. Ultrasound provides us with non-invasive information regarding anatomy and allows anesthesiologists to visualize needle insertion, to identify the exact location of the injected solution and to avoid such structures as arteries or veins. As such, this method should be actively utilized. In cases where both pharmacological and non-pharmacological treatments prove to be ineffective when treating persistent hiccups, a single-shot ultrasound-guided technique should be considered before the patient becomes exhausted.


Identification of strain diversity and phylogenetic analysis based on two major essential proteins of Orf viruses isolated from several clinical cases reported in Malaysia.
There is a little information on the characterization of Orf virus strains that are endemic in Malaysia. The relationship between the severity of disease and the molecular genetic profile of Orf virus strains has not been fully elucidated. This study documented the first confirmed report of contagious ecthyma causing by Orf virus in goats from a selected state of eastern peninsular Malaysia. The disease causes significant debilitation due to the inability of affected animals to suckle which brings a great economic loss to the farmers. A total of 504 animals were examined individually to recognize the affected animals with Orf lesion. Skin scrapping was used to collect the scab material from the infected animals. The presence of Orf virus was confirmed by combination of methods including virus isolation on vero cells, identification by Transmission Electron Microscopy (TEM) and molecular technique using PCR and Sanger sequencing. The results showed the successful isolation of four Orf virus strains with a typical cytopathic effects on the cultured vero cells line. The morphology was confirmed to be Orf virus with a distinctive ovoid and criss cross structure. The phylogenetic analysis revealed that these isolated strains were closely related to each other and to other previously isolated Malaysian orf viruses. In addition these Orf virus strains were closely related to Orf viruses from China and India. This study provides more valuable insight in terms of genotype of Orf virus circulating in Malaysia.


Analysis of Some Physiological and Biochemical Indices in Patients with Covid-19 Pneumonia Using Mathematical Methods.
The aim of the work was to conduct a retrospective analysis of the clinical data of patients with pneumonia caused by the SARS-CoV-2 virus, and to determine via mathematical methods the significance of some physiological and biochemical indices as predictive markers of an unfavorable outcome of the disease. A random cohort of patients with COVID-19 pneumonia numbered 209 people. Mathematical analysis addressed the physiological characteristics of patients recorded at the time of hospital admission, as well as blood coagulation parameters and those reflecting the development of an inflammatory reaction. The analyzed parameters were categorized relative to the reference ranges of physiologically normal values. Correlation analysis was carried out using categorical data on the disease outcome. The algorithms for calculating statistical characteristics, as well as results visualization, were programmed in Python. When comparing patient groups, the significance of differences between the determined parameters was assessed using the Pearson's χ2 test with Yates' correction. The study showed that the age over 50 and male sex can be considered risk factors for patients with COVID-19 pneumonia (p < 0.05). The disease outcome was found to be significantly affected by cardiovascular pathologies (p < 0.01) and to a lesser extent by diabetes mellitus (p < 0.10). There were revealed maximal correlation coefficients between the oxygen saturation level (-0.43), as well as the breathing rate (0.43), and a fatal outcome of the disease. For patients over 50 years of age, oxygen saturation below 80% at the time of hospital admission turned out to be a marker of mortality. It was shown that D-dimer blood levels above 625 ng/mL in patients over 80 years of age correlated with mortal outcomes. No correlation was found between the C-reactive protein (CRP) level and the disease outcome. The effect of corticosteroids on the disease outcome was analyzed in patients with different CRP levels. It was found that, while using corticosteroids, the mortality rate in patients with CRP ≤ 12.5 mg/L is 2.7 times higher than in those with CRP > 12.5 mg/L (p < 0.01). Thus, the use of adequate mathematical methods made it possible to define more precisely some mortality-associated physiological and biochemical indices in patients with COVID-19 pneumonia.


Calcium influx and calcium current in single synaptic terminals of goldfish retinal bipolar neurons.
1. The calcium influx pathway in large synaptic terminals of acutely isolated bipolar neurons from goldfish retina was characterized using Fura-2 measurements of intracellular calcium and patch-clamp recordings of whole-cell calcium current. 2. Depolarization of bipolar cells with high [K+]o resulted in a sustained, reversible increase in [Ca2+]i in both synaptic terminals and somata. Removal of external calcium abolished the response, as did the addition of 200 microM-cadmium to the bathing solution, indicating that the rise in [Ca2+]i was due to entry of external calcium. Dihydropyridine blockers of voltage-gated Ca2+ channels also blocked the influx, and the Ca2+ channel agonist Bay K 8644 potentiated influx, implicating voltage-activated, dihydropyridine-sensitive channels in the influx pathway. 3. Under voltage clamp, depolarization from a holding potential of -60 mV evoked a slowly inactivating inward current that began to activate at -50 to -40 mV and reached a maximal amplitude between -20 and -15 mV. This current was identified as a calcium current because it decreased when the extracellular calcium concentration was lowered, increased when barium was the charge carrier, and was blocked by 200 microM-external cadmium. The current was substantially blocked by 1 microM-nitrendipine and potentiated by 0.1 microM-Bay K 8644, as expected for L-type Ca2+ channels; it was unaffected by omega-conotoxin. No evidence for transient or rapidly inactivating Ca2+ current was found. 4. At a given level of potassium depolarization, both the amplitude and the speed of increase in [Ca2+]i were greater in synaptic terminals than in somata. For instance, depolarization by 32.6 mM-potassium caused an increase in intracellular calcium of 400 +/- 23 nM in terminals and 180 +/- 20 nM in somata (mean +/- S.E.M., n = 73 terminals, n = 30 somata), with maximal rates of change of 40 +/- 3 and 12 +/- 2 nM/s, respectively. 5. The contribution of terminal and somatic currents to the total whole-cell Ca2+ current was determined under voltage clamp by local application of calcium or of blocking agents. While there was no qualitative difference between currents in terminals and somata, synaptic terminals accounted for 64 +/- 3% (mean +/- S.E.M., n = 12) of the total whole-cell calcium current, and somata accounted for 39 +/- 2%. Thus, the density of Ca2+ current was higher in the terminal, accounting for the greater magnitude and speed of Ca2+ influx observed in terminals in Fura-2 experiments.(ABSTRACT TRUNCATED AT 400 WORDS)


A case report of acute testicular pain secondary to segmental testicular infarction.
Segmental testicular infarction is a rare condition that often occurs in the upper pole of the left testicle and usually presents with acute onset of scrotal pain. Contrast-enhanced ultrasound and MR are essential for diagnosing and differentiating segmental testicular infarction in clinical practice, and conservative treatment can only be adopted after a definitive diagnosis. In the present case, after conservative treatment, the infarct volume was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct. We performed a correlation analysis to investigate the causes of these changes. A 33-year-old male, without any specific disease history, was admitted to the hospital with a 5-day history of left testicular pain, and the imaging showed focal necrosis of the left testicle with hemorrhage. He was diagnosed with segmental testicular infarction after differentiating and excluding it from malignant tumors. Conservative medical treatment was given, and the symptoms of testicular pain were relieved after treatment. After discharge, regular reexamination at follow-ups showed that the infarct's size was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct. Conservative treatment has become the standard treatment currently adopted after confirming the diagnosis of segmental testicular infarction through contrast-enhanced ultrasound and MR. The blood flow changes in and around the focus of testicular infarction can be related to various factors. At present, relevant conclusions of the underlying mechanisms were mainly deduced from infarction studies of other related organs such as the heart and brain; thus, the specific pathological mechanism needs further experimental verification.


Improvement in medication education in a pediatric subspecialty practice.
The purpose of this study was to measure the impact of an educational intervention on parents of children taking methotrexate (MTX) for juvenile idiopathic arthritis (JIA). This study was conducted using a pre- and postsurvey design. The parents of 100 children with JIA taking MTX for at least 2 months were surveyed during a routine office visit. The parents completed an initial questionnaire regarding the safe use, adverse effects, and guidelines for monitoring the toxicity of MTX. An educational intervention was then administered, and an identical follow-up questionnaire was given during the next office visit. Statistical analysis using a paired t-test (critical P value < 0.05) was performed on individuals who answered both questionnaires. There were 100 responses to the initial questionnaire and 67 responses to the follow-up questionnaire. The mean length of time between surveys was 2.9 ± 0.9 months. In those who completed both questionnaires, the overall correct score increased significantly from 75.8% to 93.4%, respectively (P < 0.0001). Individuals scored the lowest (49%) on the question that addressed MTX's impact on pregnancy and fertility. MTX knowledge may be less than expected in the parents of children with JIA. Brief educational interventions in the pediatric subspecialty practice can significantly affect a family's understanding of their child's medications.


Automatic identification of novel bacteria using Raman spectroscopy and Gaussian processes.
Raman spectroscopy is successfully used for the reliable classification of complex biological samples. Much effort concentrates on the accurate prediction of known categories for highly relevant tasks in a wide area of applications such as cancer detection and bacteria recognition. However, the resulting recognition systems cannot always be directly used in practice since unseen samples might not belong to classes present in the training set. Our work aims to tackle this problem of novelty detection using a recently proposed approach based on Gaussian processes. By learning novelty scores for a large bacteria Raman dataset comprising 50 different strains, we analyze the behavior of this method on an independent dataset which includes known as well as unknown categories. Our experiment reveals that non-parametric methods such as Gaussian processes can be successfully applied to the task of finding unknown bacterial strains, leading to encouraging results motivating their further utilization in this area.


A 31P NMR study of the internal pH of yeast peroxisomes.
The internal pH of peroxisomes in the yeasts Hansenula polymorpha, Candida utilis and Trichosporon cutaneum X4 was estimated by 31P nuclear magnetic resonance (NMR) spectroscopy. 31P NMR spectra of suspensions of intact cells of these yeasts, grown under conditions of extensive peroxisomal proliferation, displayed two prominent Pi-peaks at different chemical shift positions. In control cells grown on glucose, which contain very few peroxisomes, only a single peak was observed. This latter peak, which was detected under all growth conditions, was assigned to cytosolic Pi at pH 7.1. The additional peak present in spectra of peroxisome-containing cells, reflected Pi at a considerably lower pH of approximately 5.8-6.0. Pi at a considerably lower pH of approximately 5.8-6.0. Experiments with the protonophore carbonyl cyanide m-chlorophenylhydrazon (CCCP) and the ionophores valinomycin and nigericin revealed that separation of the two Pi-peaks was caused by a pH-gradient across a membrane separating the two pools. Experiments with chloroquine confirmed the acidic nature of one of these pools. In a number of transfer experiments with the yeast H. polymorpha it was shown that the relative intensity of the Pi-signal at the low pH-position was correlated to the peroxisomal volume fraction. These results strongly suggest that this peak has to be assigned to Pi in peroxisomes, which therefore are acidic in nature. The presence of peroxisome-associated Pi was confirmed cytochemically.


Treatment of optic neuritis with intravenous megadose corticosteroids. A consecutive series.
Twelve consecutive patients with optic neuritis of unknown etiology treated with 250 to 500 mg methylprednisolone every 6 hours are described. All patients improved, some dramatically and rapidly. Patients with swollen discs and visual loss for less than 6 weeks improved uniformly, rapidly, and completely. In some patients, progressive visual deterioration was reversed rapidly. Serum serologies and cerebrospinal fluids findings were of limited use in determining etiology or prognosis with treatment. Side effects included exacerbation of a preexisting psychosis, elevated glucose levels, and oral candidiasis. None required cessation of treatment. Patients with optic neuritis may benefit from intravenous megadose corticosteroids.


Acute aquatic toxicity assessment of six anti-cancer drugs and one metabolite using biotest battery - Biological effects and stability under test conditions.
Available ecotoxicological data for anti-cancer drugs and their metabolites are incomplete, and only some studies have been accompanied by chemical analysis. Therefore, the main aim of this study was to evaluate the acute toxicity of the six most commonly used cytostatics, namely cyclophosphamide (CF), ifosfamide (IF), 5-fluorouracil (5-FU), imatinib (IMT), tamoxifen (TAM) and methotrexate (MET) and its metabolite - 7-hydroxymethotrexate (7-OH-MET), towards selected aquatic organisms, namely bacteria Vibrio fischeri, algae Raphidocelis subcapitata, crustaceans Daphnia magna and duckweed Lemna minor. All ecotoxicological tests were accompanied by chemical analysis to determine the differences between nominal and actual concentrations of investigated compounds and their stability under test conditions. For unstable compounds, tests were performed in static and semi-static conditions. It was observed that L. minor was the most sensitive organism. The compounds that were most toxic to aquatic organisms were 5-FU (highly toxic to algae, EC50 = 0.075 mg L-1), MET and TAM (very toxic to highly toxic to duckweed depending on the test conditions; EC50MET 0.08-0.16 mg L-1, EC50TAM 0.18-0.23 mg L-1). It is suspected that MET and 5-FU mainly affected algae and plants most probably because the exposure time was long enough for them to cause a specific effect (they inhibit DNA replication and act predominantly on actively dividing cells). Furthermore, the obtained results also suggest that the toxicity of the metabolites/potentially produced degradation products of MET towards duckweed is lower than that of the parent form, whereas the toxicity of TAM degradation products is in the same range as that of TAM.


National strategies for vaccination against COVID-19 in people living with HIV in Central and Eastern European region.
People living with HIV (PLWH) are at higher risk of poorer COVID-19 outcomes. Vaccination is a safe and effective method of prevention against many infectious diseases, including COVID-19. Here we investigate the strategies for national COVID-19 vaccination programmes across central and eastern Europe and the inclusion of PLWH in vaccination programmes. The Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of infectious diseases from 24 countries in the region. Between 1 November 2020 and 19 March 2021 the group proceeded an on-line survey consisting of 20 questions. Twenty-two countries (out of 24 invited) participated in the survey and 20/22 countries in the period between December 2020 and March 2021 had already started their COVID-19 vaccination programme. In total, seven different vaccines were used by participating countries. In 17/21 countries (81%), vaccinated persons were centralized within the national registry. In 8/21 countries (38%) PLWH were prioritized for vaccination (the Czech Republic, Greece, Hungary, Lithuania, Montenegro, Romania, Slovakia, Slovenia) and the Czech Republic, Greece and Serbia had put in place national guidelines for vaccination of PLWH. In 14/20 countries (70%) vaccination was only provided by designated centres. Eighteen respondents (18/21; 85.7%) reported that they planned to follow up HIV patients vaccinated against COVID-19, mainly by measuring antibody levels and checking COVID-19 incidence (11/21; 52.3%). This survey-based study suggests that there are significant differences in terms of prioritizing PLWH, the types of vaccines used, vaccination coverage, and the development and implementation of a vaccination programmes within the region. Regardless of heterogenicity and existing barriers within the region, systematic vaccination in PLWH should have the highest priority, especially in those with severe immunodeficiency, risk factors, and in the elderly, aiming for prompt and high vaccination coverage.


Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer.
The identification of the HER2 alteration as an actionable oncogenic driver in breast cancer has propelled the development of HER-targeting monoclonal antibodies (mAb) such as trastuzumab and pertuzumab, which led to dramatic improvements in survival outcomes. Lately, the great strides made toward developing antibody-conjugation methods have led to the development of a new class of compelling compounds, the antibody-drug conjugates (ADCs) targeting HER2 which have profoundly transformed the treatment landscape of breast cancer. HER2-targeting ADCs, trastuzumab-emtansine and trastuzumab-deruxtecan, have improved the overall survival in the second and third-line settings with manageable adverse events. Other HER2-targeting ADCs using novel technological advances in the antibody, linker and/or payload conception have shown promising activity in preclinical and clinical studies and some of them are now being evaluated in larger clinical trials. Multiple challenges still impede the success of ADCs in breast cancer namely the lack of a comprehensive understanding of resistance mechanisms as well as the mechanisms of action of ADCs in special subgroups of patients such as those with low or ultra-low HER2 expression and patients with brain or leptomeningeal metastases (BM). In this framework, we review the approved indications and ongoing trials for HER2-targeting ADCs, across patient subgroups, including those with BM and discuss the associated potential mechanisms of action and resistance. Last, we provide an overview of the future perspectives involving HER2-targeting ADCs in breast cancer.


Online social networking addiction and depression: The results from a large-scale prospective cohort study in Chinese adolescents.
The aim of this study is to estimate the longitudinal associations between online social networking addiction (OSNA) and depression, whether OSNA predicts development of depression, and reversely, whether depression predicts development of OSNA. A total of 5,365 students from nine secondary schools in Guangzhou, Southern China were surveyed at baseline in March 2014, and followed up 9 months later. Level of OSNA and depression were measured using the validated OSNA scale and CES-D, respectively. Multilevel logistic regression models were applied to estimate the longitudinal associations between OSNA and depression. Adolescents who were depressed but free of OSNA at baseline had 1.48 times more likely to develop OSNA at follow-up compared with those non-depressed at baseline [adjusted OR (AOR): 1.48, 95% confidence interval (CI): 1.14-1.93]. In addition, compared with those who were not depressed during the follow-up period, adolescents who were persistently depressed or emerging depressed during the follow-up period had increased risk of developing OSNA at follow-up (AOR: 3.45, 95% CI: 2.51-4.75 for persistent depression; AOR: 4.47, 95% CI: 3.33-5.99 for emerging depression). Reversely, among those without depression at baseline, adolescents who were classified as persistent OSNA or emerging OSNA had higher risk of developing depression compared with those who were no OSNA (AOR: 1.65, 95% CI: 1.01-2.69 for persistent OSNA; AOR: 4.29; 95% CI: 3.17-5.81 for emerging OSNA). The findings indicate a bidirectional association between OSNA and depression, meaning that addictive online social networking use is accompanied by increased level of depressive symptoms.


Protease-activated receptor 1 and 4 signal inhibition reduces preterm neonatal hemorrhagic brain injury.
This study examines the role of thrombin's protease-activated receptor (PAR)-1, PAR-4 in mediating cyclooxygenase-2 and mammalian target of rapamycin after germinal matrix hemorrhage. Germinal matrix hemorrhage was induced by intraparenchymal infusion of bacterial collagenase into the right ganglionic eminence of P7 rat pups. Animals were treated with PAR-1, PAR-4, cyclooxygenase-2, or mammalian target of rapamycin inhibitors by 1 hour, and ≤5 days. We found increased thrombin activity 6 to 24 hours after germinal matrix hemorrhage, and PAR-1, PAR-4, inhibition normalized cyclooxygenase-2, and mammalian target of rapamycin by 72 hours. Early treatment with NS398 or rapamycin substantially improved long-term outcomes in juvenile animals. Suppressing early PAR signal transduction, and postnatal NS398 or rapamycin treatment, may help reduce germinal matrix hemorrhage severity in susceptible preterm infants.


An alkaliphilic bacterium BKH4 of Bakreshwar hot spring pertinent to bioconcrete technology.
Hot springs have always drawn attention due to their unique chemical richness and the presence of different microbial communities. The use of hot spring bacteria in concrete technology is our primary focus; isolation of an alkaliphilic bacterium from the Bakreshwar hot springs having longer survival and better efficacy towards cementitious environment was the basis of our study's design. A novel facultative anaerobic and highly alkaliphilic bacterial strain (BKH4; GenBank accession no. KX622782) belonging to the family 'Bacillaceae' and homologous (99%) with Lysinibacillus fusiformis was isolated from Bakreshwar hot springs. The isolated coccoid-type Gram-positive bacterium grows well in a defined semi-synthetic medium (pH 12·0 and 65°C). This bacterium survives for more than a month and shows better efficacy in enhancing compressive strengths (>50%), ultrasonic pulse velocity (>25%) and durability of the cementitious mortar when incorporated at a concentration of 104 cells per ml of water used. The novel bacterium BKH4 is more effective for the enhancement of the bioconcrete properties. BKH4 bacterium will add a new dimension to future concrete technology for its usefulness in strength enhancement and durability due to its alkaliphilic nature and longer survival within a cementitious environment.


A20 overexpression exerts protective effects on podocyte injury in lupus nephritis by downregulating UCH-L1.
Lupus nephritis (LN), an autoimmune kidney disease caused by systemic lupus erythematosus (SLE), is the inflammation of the kidney. Although the treatment of LN is still a therapeutic challenge for many practitioners, the present study aims to provide a new insight for the treatment and management. The study aims to explore the effect of A20 on LN in relation to the nuclear factor-kappa B (NF-κB) signaling pathway. MRL/lpr mice were used as the LN mouse model. Next, A20, UCH-L1, and NF-κB expression in LN patients and MRL/lpr mice was determined. A20 was upregulated in podocytes to assess biological functions of A20 in LN. Furthermore, to further investigate the pivotal role of the NF-κB pathway in LN, the NF-κB pathway was blocked in podocytes. Next, UCH-L1 was downregulated in MRL/lpr mice to assess biological functions of UCH-L1 in LN. A20 was downregulated, whereas UCH-L1 was upregulated in LN. Overexpressed A20 declined NF-κB, UCH-L1 expression, and the extent of p65 phosphorylation. A20 overexpression or UCH-L1 inhibition increased expression of synaptoporin and nephrin but decreased desmin expression and ubiquitin accumulation level in podocytes. Moreover, A20 overexpression or UCH-L1 inhibition increased the podocyte number but decreased protein level of cleaved caspase-3, podocyte lesion improvement, decreased foot process width, glomerulus basement membrane, and foot process fusion rate. In addition, urine protein, blood urea nitrogen, serum creatinine, and ds-DNA antibody levels decreased with elevated A20 or depleted UCH-L1. Collectively, it could be concluded that A20 protects against podocyte injury in LN via UCH-L1 by inactivating the NF-κB signaling pathway.


Ocular findings in Japanese children with Down syndrome: the course of visual acuity and refraction, and systemic and ocular anomalies.
To investigate the age-related development of refractive errors and changes of visual acuity (VA), and the systemic and ocular anomalies in Japanese children and young adults with Down syndrome (DS). Retrospective cohort study. This study involved 222 Japanese children and young adults with DS (age range: 3 months to 19 years) seen at the Department of Ophthalmology, Shiga Medical Center for Children, Shiga, Japan. The subjects were divided into the following six age groups: 1) infant (age 0 to <4 years), 2) preschool (age 4 to <7 years), 3) lower primary-school grades (age 7 to <10 years), 4) upper primary-school grades (age 10 to <13 years), 5) junior high school (age 13 to <16 years), and 6) late teen/young adults (age 16 to <20 years). Through examination of the subjects' medical charts, we investigated the development and changes of refractive errors and VA, best-corrected VA (BCVA), and systemic and ocular anomalies. For vision testing, Teller Acuity Cards™ (Bernell Corporation) were used for the infants, and the Landolt ring was used for the school-age children. VA was found to develop with age. Mean BCVA was 0.19±0.17 logarithm of the minimum angle of resolution (mean age: 11.3±3.2 years). Mean of refractive errors was hyperopia in the infant (2.2±2.4 diopters [D] OD, 2.4±2.5D OS), yet became myopia to the junior high school (-0.3±4.4D OD, -0.2±4.4D OS). Our findings revealed that in children and in late-teen and young-adult subjects with DS, VA slowly develops and that refractive errors requiring correction exist and are difficult to examine.


[Structure-functional organization of the secretin molecule. I. Theoretical conformation analysis of the His1-Arg18 fragment].
Theoretical conformational analysis of the octadecapeptide His1-Arg18, corresponding to the entire amino acid sequence of porcine secretin was carried out for a solution of the "direct conformational problem" for this peptide molecule.


Enhanced degradation of azo dye in wastewater by pulsed discharge plasma coupled with MWCNTs-TiO2/γ-Al2O3 composite photocatalyst.
In order to improve the photocatalytic performance of TiO2 in pulsed discharge plasma systems, easily recycled multi-walled carbon nanotubes (MWCNTs)-TiO2 supported on γ-Al2O3 (MWCNTs-TiO2/γ-Al2O3) composite photocatalyst were prepared. The morphology and physicochemical properties of the prepared catalysts were investigated using XRD, SEM, FTIR and UV-vis spectroscopy. The photocatalytic activity was evaluated by degradation of azo dye acid orange II (AO7) in wastewater under pulsed discharge plasma. The results indicate that the MWCNTs-TiO2/γ-Al2O3 composite catalyst possesses enhanced photocatalytic activity facilitating the decomposition of AO7 compared with TiO2/γ-Al2O3 composite in pulsed discharge plasma systems. Under pulsed discharge plasma, almost 100% AO7 is degraded by the MWCNTs-TiO2/γ-Al2O3 composite after 60 min at optimal conditions. The degradation efficiency of AO7 is also affected by the dosage of the composite catalyst and pulsed discharge peak voltage. As the amount of MWCNTs-TiO2/γ-Al2O3 composite and pulsed discharge peak voltage increases, the degradation efficiency of AO7 increases. The photocatalyst was implemented for 6 cycles and the degradation efficiency of AO7 remains higher than 85% under pulsed discharge plasma. Results indicate that the catalyst displays easy separation and minimal deactivation after several uses. Possible decomposition mechanisms were also investigated. MWCNTs are capable of improving the photocatalytic activity of TiO2/γ-Al2O3 composite in pulsed discharge plasma systems primarily due to the photo-induced-electron absorption effect and the electron trap effect of MWCNTs. The results of this study establish the feasibility and potential implementation of MWCNTs-TiO2/γ-Al2O3 composites in pulsed discharge plasma systems for the degradation of dye wastewater.


Genetic and pharmacological models of cholinergic supersensitivity and affective disorders.
Increased muscarinic sensitivity has been associated with altered hormonal states (hypothyroidism and hyperadrenocorticism), chronic administration of muscarinic antagonists or antidepressants with muscarinic actions, selective breeding for anticholinesterase sensitivity, and certain inbred strains of rats and mice. Thus, both genetic and environmental factors may influence muscarinic receptor sensitivity. The reasonably detailed studies on the selectively-bred rats have revealed that the Flinders Sensitive Line (FSL) rats weigh less, are less active, are more sensitive to muscarinic agonists and to stressors, and have higher concentrations of hippocampal and striatal muscarinic receptors than 'normal', or the selectively-bred, Flinders Resistant Line (FRL) rats. Thus, there are a number of parallels between FSL rats and depressed humans. The FSL rats may be the first animal model of depression to mimic the actual trait of depression, and not just the state.


A molecular dynamics investigation for predicting the effect of various parameters on the mechanical properties of carbon nanotube-reinforced aluminum nanocomposites.
Carbon nanotube (CNT)-reinforced aluminum (Al) composites are being developed to replace the conventional materials due to the enhanced stiffness for more cost-effective engineering applications. In the present study, a qualitative analysis has been conducted on carbon nanotube aluminum (CNT-Al) composites to predict the effect of CNT volume fraction, diameter, and structure (zigzag, armchair) on elastic modulus, shear modulus, bulk modulus, and ultimate tensile strength (UTS) through molecular dynamics simulation. This study shows that the elastic modulus was improved by 105% compared with pure Al, for the CNT-Al composite reinforced with the (4, 4) armchair SWCNT at a volume fraction of 8.79%. The highest value of Young's modulus of 130.37 GPa occurred at the volume fraction of 11.75% for zigzag SWCNT. The CNT-Al composites showed better UTS for the Al matrix reinforced with larger diameter CNT. An enhancement of 31.65% was observed in the UTS of CNT-Al composite from 4.74 to 6.24 GPa with (6, 6) CNT at 0.51% volume fraction. Elastic and bulk moduli were found to improve with a higher volume fraction of CNTs. The CNT-Al composite reinforced with smaller diameter CNT's have better elastic modulus than those reinforced with larger diameter CNT for the same volume fraction. Graphical abstract Variation of Young's modulus with SWCNT volume fraction for a constant cell size of CNT-Al composite.


Erratum to: Changes in the pneumococcal disease-related hospitalisations in Spain after the replacement of 7-valent by 13-valent conjugate vaccine.
The original version of this article was published online with an incorrectly arranged Table 2. Also, Figs. 1 and 2 were missing the legends.


Involvement of purinergic signalling in central mechanisms of body temperature regulation in rats.
1. P2 purinoreceptors are present in hypothalamic and brainstem nuclei that are involved in the regulation of body temperature (T(b)). The role of ATP acting on these P2 receptors in thermoregulation was investigated by studying the effects of the stable ATP analogue alpha,beta-methyleneATP (alpha,beta-meATP) and P2 receptor antagonists suramin and pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) on T(b) when injected intracerebroventricularly (i.c.v.) via a pre-implanted cannula in conscious rats at various ambient temperatures and during lipopolysaccharide (LPS)-induced fever. 2. Depending on ambient temperature, alpha,beta-meATP (0.2 micromol, i.c.v.) induced a fall in T(b) (-3.3 degrees C, P<0.05), no changes in T(b) when compared to pre-injection levels, or an increase in T(b) ( approximately 1.0 degrees C, P<0.05) in rats maintained at 10 degrees C, 25 degrees C and 30 degrees C ambient temperature, respectively. 3. Suramin (7 nmol, i.c.v.) induced a lasting (up to 6 h) increase in T(b) (on average 1.2 degrees C, P<0.05) in rats kept at 25 degrees C or 30 degrees C, but failed to induce any rise in T(b) in rats at 10 degrees C ambient temperature. An increase in T(b) was also observed in rats (25 degrees C ambient temperature) treated with PPADS (0.2 micromol, i.c.v.). 4. alpha,beta-meATP (0.2 micromol) injected i.c.v. or directly into the anterior hypothalamus caused a profound fall in T(b) (by 0.9 degrees C and 1.0 degrees C, respectively; P<0.05) during LPS (E.coli; 50 microg kg(-1))-induced fever in rats at 25 degrees C ambient temperature. Fever was initiated more rapidly in rats treated with suramin (7 nmol) or PPADS (70 nmol), however its late phase was unaffected. Suramin (7 nmol) and PPADS (70 nmol) injected at the time when fever was already developed (2.5 h after LPS injections) did not alter febrile T(b). 5. These data indicate that purinergic signalling may play a significant role in central mechanisms of T(b) regulation at various ambient temperatures and during fever.


Specific non-histone protein fractions associated with 'active' chromatin in immunized rats.
Non-histone proteins of normal, non-immunized rats and rats immunized with mouse spleen cells were labelled with three different amino acids: [3H]tryptophan, [3H]methionine and [3H]leucine. Chromatin was fractionated at increasing salt concentrations into three fractions: 0.35 M NaCl-soluble, 2 M NaCl-soluble and residual. Non-histone protein fractions F (Mr 12 000) and H (Mr 3 000) highly labelled with [3H]tryptophan, lower with [3H]methionine but not with [3H]leucine, were present mainly in the residual fraction. After DNAse II treatment non-histone protein fractions F and H disappeared in chromatin fractions and were present in Mg2+ soluble fractions which suggests that, similar to the fractions I (Mr below 3 000) and B (Mr 120 000) described previously (5), these fractions may be associated with active transcribed genes.


Combination therapies for cancer: challenges and opportunities.
Gastrointestinal cancers represent a major challenge to public health. Pancreatic cancer is the most lethal cancer among all gastrointestinal cancers. Most patients cannot meet the criteria of resection at diagnosis, indicating these patients will have dismal prognosis. Neoadjuvant chemotherapy helps some patients regain the opportunity of radical resection. An optimal regimen of chemotherapy is one that maximizes the anti-tumor efficacy while maintaining a relatively manageable safety profile. The development of surgical procedures further improves the outcomes of these patients. Combination therapies in a multidisciplinary manner that involves modified chemotherapy regimen, radical resection, and intestine auto-transplantation may provide the currently best possible care to patients with locally advanced pancreatic cancer.


Super oblique tendon elongation with fascia lata.
Superior oblique lengthening with a silicone retinal band is used to treat superior oblique overaction (SOOA); however, secondary infection, implant extrusion, orbital cellulitis, and adhesion may occur. We present a method of superior oblique tendon elongation in which autogenous fascia lata is used to decrease the likelihood of these complications. Six patients (5 female, 1 male) aged 7-22 years (mean, 17 years) with 40-85(Delta) exotropia and SOOA (range, +2 to +4; mean, +3.5) underwent bilateral superior oblique lengthening with insertion of fascia lata. In the last 2 cases, the values of elongation were augmented by 2 mm. Fascia lata was harvested through a linear incision on the lateral aspect of the patient's thigh. Postoperatively, correction of A-pattern exotropia to within 10(Delta) was achieved in 66% of the cases as well as correction of SOOA to within +1 in 58% of the cases, with a follow-up of 9 months. All patients with +2 to +3 SOOA (3 cases) were fully corrected, whereas those with +4 SOOA (9 eyes) had residual overaction of +1 to +3. In the 4 eyes with augmented elongation, residual SOOA was between 0 and +2. No patient developed superior oblique palsy. Autogenous fascia lata may be used as an alternative to a silicone band for superior oblique lengthening. Our results were comparable with published results for the silicone band, with a lower rate of overcorrection. The improved biocompatibility makes it likely that autogenous fascia lata will have a lower complication rate than with a silicone band.


Advances and applications of fluids biomarkers in diagnosis and therapeutic targets of Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disease with challenging early diagnosis and effective treatments due to its complex pathogenesis. AD patients are often diagnosed after the appearance of the typical symptoms, thereby delaying the best opportunity for effective measures. Biomarkers could be the key to resolving the challenge. This review aims to provide an overview of application and potential value of AD biomarkers in fluids, including cerebrospinal fluid, blood, and saliva, in diagnosis and treatment. A comprehensive search of the relevant literature was conducted to summarize potential biomarkers for AD in fluids. The paper further explored the biomarkers' utility in disease diagnosis and drug target development. Research on biomarkers mainly focused on amyloid-β (Aβ) plaques, Tau protein abnormal phosphorylation, axon damage, synaptic dysfunction, inflammation, and related hypotheses associated with AD mechanisms. Aβ42 , total Tau (t-Tau), and phosphorylated Tau (p-Tau), have been endorsed for their diagnostic and predictive capability. However, other biomarkers remain controversial. Drugs targeting Aβ have shown some efficacy and those that target BACE1 and Tau are still undergoing development. Fluid biomarkers hold considerable potential in the diagnosis and drug development of AD. However, improvements in sensitivity and specificity, and approaches for managing sample impurities, need to be addressed for better diagnosis.


Enhancement of monoclonal antibodies against HLA-A2 is due to antibody bivalency.
Enhancement between two monoclonal antibodies directed against the same antigen is when binding of one antibody, the enhancing antibody, increases the measured binding of the other antibody. This phenomenon has been observed for monoclonal antibodies against a variety of molecules including histocompatibility antigens. The mechanism of enhancement for monoclonal antibodies against HLA-A2 has been studied with purified preparations of IgG, F(ab')2 and Fab. Enhancement was only observed between antibodies against different antigenic sites. It requires bivalency of both antibody species and involves formation of stable, cyclic, tetramolecular complexes consisting of two antigen molecules and one each of the two antibody molecules. Conformational changes of either antigen or antibody do not appear to be important in this system, nor is the formation of combinatorial determinants between antigen and enhancing antibody. The enhancing properties of the antibodies studied are adequately explained in terms of their affinities and association and dissociation constants.


The imminent role of protein engineering in synthetic biology.
Protein engineering has for decades been a powerful tool in biotechnology for generating vast numbers of useful enzymes for industrial applications. Today, protein engineering has a crucial role in advancing the emerging field of synthetic biology, where metabolic engineering efforts alone are insufficient to maximize the full potential of synthetic biology. This article reviews the advancements in protein engineering techniques for improving biocatalytic properties to optimize engineered pathways in host systems, which are instrumental to achieve high titer production of target molecules. We also discuss the specific means by which protein engineering has improved metabolic engineering efforts and provide our assessment on its potential to continue to advance biology engineering as a whole.


Rationally Designed Eco-Friendly Solvent System for High-Performance, Large-Area Perovskite Solar Cells and Modules.
The important but remained issue to be addressed to achieve the mass production of perovskite solar modules include a large-area fabrication of high-quality perovskite film with eco-friendly, viable production methods. Although several efforts are made to achieve large-area fabrication of perovskite, the development of eco-friendly solvent system, which is precisely designed to be fit to scale-up methods are still challenging. Herein, this work develops the eco-friendly solvent/co-solvent system to produce a high-quality perovskite layer with a bathing in eco-friendly antisolvent. The new co-solvent/additive, methylsulfonylmethane (MSM), efficiently improves the overall solubility and has a suitable binding strength to the perovskite precursor, resulting in a high-quality perovskite film with antisolvent bathing method in large area. The resultant perovskite solar cells showed high power conversion efficiency of over 24% (in reverse scan), with a good long-term stability under continuous light illumination or damp-heat condition. MSM is also beneficial to produce a perovskite layer at low-temperature or high-humidity. MSM-based solvent system is finally applied to large-area, resulting in highly efficiency perovskite solar modules with PCE of 19.9% (by aperture) or 21.2% (by active area) in reverse scan. These findings contribute to step forward to a mass production of perovskite solar modules with eco-friendly way.


Gastric cancer etiology: a biochemical hypothesis.
We have proposed a two-stage biochemical model for the etiology of "intestinal" gastric cancer. The model postulates that the gastric mucosal barrier is biochemically pierced as a result of chemical interactions between the mucoproteins and mucopolysaccharides of the barrier and ingested polysaccharrides (starches). This would allow the growth of gastric flora which could produce carcinogenic nitrosamines and/or nitrosamides. Observational and experimental evidence in favor of the model is provided. The model suggests various research initiatives, the results of which might provide the basis for biochemical and physiological methods for the prevention and/or treatment of gastric cancer. Various ways in which the model may be tested are also noted.


Prognostic value of lymph node status and number of removed nodes in patients with squamous cell carcinoma of the vulva treated with modified radical vulvectomy and inguinal-femoral lymphadenectomy.
To assess the outcome of patients with squamous cell vulvar carcinoma treated with deep partial or total vulvectomy and inguinal-femoral lymphadenectomy. The authors assessed 87 patients who underwent primary surgery. Tumor recurred in 34 patients, and the first relapse was local in 19, inguinal in ten, and distant in five. Five-year disease-free survival was 56.7% and was related to Stage (p < 0.0001), grade (p = 0.023), and node status (p < 0.0001). Groin failure occurred in 4.9% of node-negative patients compared with 29.6% of node-positive patients (p = 0.0096). Distant recurrences only developed in women with positive nodes. Among the 47 patients who underwent bilateral lymphadenectomy and who had negative nodes, groin recurrence occurred in 12% of those who had < or = 15 nodes removed and 0% of those who had > 15 nodes removed. Stage and node status were the most important prognostic variables. There was a trend favoring a better groin control in patients with node-negative disease who underwent extensive lymphadenectomy.


Effect of ibuprofen on proliferation, differentiation, antigenic expression, and phagocytic capacity of osteoblasts.
Ibuprofen is a nonselective nonsteroidal antiinflammatory drug commonly prescribed for acute postsurgical and posttraumatic pain. However, little known is about the effect of this drug on osteoblasts. In this study, we aimed to investigate the effect of ibuprofen on cell proliferation, differentiation, antigenic profile, and phagocytic activity, in a human MG-63 osteosarcoma cell line, as a model of osteoblasts. Flow cytometry was used to study proliferation, antigenic profile, and phagocytic activity, and radioimmunoassay was used to determine osteocalcin synthesis as a cell differentiation marker. Our results showed that therapeutic doses of ibuprofen (5 and 25 μM) did not modify cell proliferation and osteocalcin synthesis in the MG-63 cellular line. However, treatment with a higher dose (25 μM) increased the expression of antigens CD21, CD44, CD80, CD86, and HLA-DR and decreased phagocytic activity. The results indicate that a therapeutic dose of ibuprofen has no adverse effects on growth of the osteoblast-like cells. Treatment with ibuprofen alone may produce some cell activation, which would explain the increase in expression of membrane markers and decrease in phagocytic capacity.


A resistance monitor with power cut-off for automatic regulation of shadow and support film thickness in freeze-etching and related techniques.
A resistance monitor with sensors and automatic power cut-off has been developed to control the thickness of Pt-C shadow and C replica films in freeze-etching and related techniques. The monitor and sensors, in conjunction with newly modified evaporators, should considerably reduce the amount of C and Pt required and should prove useful in other applications employing vacuum evaporation of thin films of Pt, C, or other conducting materials.


Retracted: The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma.
[This retracts the article DOI: 10.1155/2022/2747799.].


Prevalence of and risk factors for aspirin resistance in elderly patients with coronary artery disease.
To assess the prevalence of and related risk factors for aspirin resistance in elderly patients with coronary artery disease (CAD). Two hundred and forty-six elderly patients (75.9 ± 7.4 years) with CAD who received daily aspirin therapy (≥ 75 mg) over one month were recruited. The effect of aspirin was assessed using light transmission aggregometry (LTA) and thrombelastography platelet mapping assay (TEG). Aspirin resistance was defined as ≥ 20% arachidonic acid (AA)-induced aggregation and ≥ 70% adenosine diphosphate (ADP)-induced aggregation in the LTA assay. An aspirin semi-responder was defined as meeting one (but not both) of the criteria described above. Based on the results of TEG, aspirin resistance was defined as ≥ 50% aggregation induced by AA. As determined by LTA, 23 (9.3%) of the elderly CAD patients were resistant to aspirin therapy; 91 (37.0%) were semi-responders. As determined by TEG, 61 patients (24.8%) were aspirin resistant. Of the 61 patients who were aspirin resistant by TEG, 19 were aspirin resistant according to LTA results. Twenty-four of 91 semi-responders by LTA were aspirin resistant by TEG. Multivariate logistic regression analysis revealed that elevated fasting serum glucose level (Odds ratio: 1.517; 95% CI: 1.176-1.957; P = 0.001) was a significant risk factor for aspirin resistance as determined by TEG. A significant number of elderly patients with CAD are resistant to aspirin therapy. Fasting blood glucose level is closely associated with aspirin resistance in elderly CAD patients.


Author Correction: 22q13 deletion syndrome: communication disorder or autism? Evidence from a specific clinical and neurophysiological phenotype.
Since the online publication of the above article, the authors have noted errors with the author list. The author names were listed as '(last name)(first name)' instead of '(first name)(last name)'.


Exploring the associations between coping patterns for everyday stressors and mental health in young schoolchildren.
The purposes of this study were to explore the structure of coping with everyday stressors in a young nonclinical population and examine the relationship between coping and mental health. A total of 1324 children from 91 second-grade classes in 35 schools participated. Mental health was assessed using the parent and teacher forms of the Strengths and Difficulties Questionnaire (Goodman, 1997), and coping was assessed by the Kidcope (Spirito et al., 1988) self-report checklist. Exploratory and confirmatory factor analyses suggested a three-factor structure of coping. Latent-variable regression analysis indicated that coping categories including both active and emotional strategies were associated with fewer mental health problems, whereas withdrawal and oppositional coping strategies were associated with greater mental health problems. With some important exceptions, the results replicated previous studies of adults and adolescents. The need for new, more comprehensive coping assessments is highlighted.


Does a new undergraduate curriculum based on Tomorrow's Doctors prepare house officers better for their first post? A qualitative study of the views of pre-registration house officers using critical incidents.
In 1994 Manchester University introduced an integrated undergraduate medical course using problem-based learning (PBL) throughout. The study reported here explored whether there were any differences between the new course graduates (NCGs) and the traditional course graduates (TCGs) in the types of scenarios they recalled as 'critical incidents', or challenging cases, while working as pre-registration house officers (PRHOs). The focus is on differences rather than causal links. We used semistructured interviews to generate our data. Twenty-four traditional course graduates and 23 new course graduates were interviewed approximately 3 months after starting their first PRHO placement. We identified 4 types of critical incidents relating to: clinical practice; limitations of competence; emotional involvement; and communication. Traditional course graduates reported difficulties in making patient management decisions, whereas the NCGs were better at dealing with uncertainty, knowing their limits and asserting their rights for support. Communication difficulties and coping with emotional involvement were common across both groups of graduates and hence remain problems in relation to being prepared for the role of a PRHO. Graduates of the new, integrated curriculum seemed to be much better at dealing with uncertainty, knowing their personal limits and asserting their rights for support when they felt these limits had been reached. Communication difficulties and emotional involvement remain major factors in the transition from student to PRHO.


Treatment Individualization in Colorectal Cancer.
Colorectal cancer has been characterized as a genetically heterogeneous disease, with a large diversity in molecular pathogenesis resulting in differential responses to therapy. However, the currently available validated biomarkers KRAS, BRAF, and microsatellite instability do not sufficiently cover this extensive heterogeneity and are therefore not suitable to successfully guide personalized treatment. Recent studies have focused on novel targets and rationally designed combination strategies. Furthermore, a more comprehensive analysis of the underlying biology of the disease revealed distinct phenotypic differences within subgroups of patients harboring the same genetic driver mutation with both prognostic and predictive relevance. Accordingly, patient stratification based on molecular intrinsic subtypes rather than on single gene aberrations holds promise to improve the clinical outcome of patients with colorectal cancer.