Expression analysis of sugarcane shaggy-like kinase (SuSK) gene identified through cDNA subtractive hybridization in sugarcane (Saccharum officinarum L.).
Identification of genes whose expression enables plants to adapt to any kind of stresses is integral to developing stress tolerance in crop plants. In this study, PCR-based cDNA suppression subtractive hybridization technique was used to construct sugarcane salt (NaCl) stress specific forward and reverse subtracted cDNA library. For this, mRNAs were pooled from the shoot and root tissues stressed with NaCl (200 mM) for various time intervals (0.5 to 18 h). Sequencing the clones from the forward subtracted cDNA library, we identified shaggy-like protein kinase (hereafter referred as sugarcane shaggy-like protein kinase, SuSK; NCBI GenBank EST database Acc: FG804674). The sequence analysis of the SuSK revealed homology to Arabidopsis thaliana shaggy-related protein kinase delta (E value, 1e(-108)), dzeta and iota. Alignment of the catalytic domain sequence of GSK-3/shaggy-like kinase with partial sequence of SuSK performed using ClustalW tool indicated kinase active-site signature sequence. Spatial and temporal transcript expression profiling of the SuSK gene based on Real-Time PCR revealed significant induction of transcript expression in response to short-term salt (NaCl 200 mM) or polyethylene glycol-8,000 (PEG; 20% w/v) induced osmotic stress in leaves and shoots of sugarcane plants. The transcript expression increased progressively under salt stress and reached to 1.5-fold of the control up to 8 h treatment. In response to PEG stress, the transcript expression increased by 1.5-fold over the control in 2-h treatment in leaf, whereas in shoots, the expression remained unchanged in response to the various treatments. Differences in growth parameters, relative water content, and membrane damage rate were statistically insignificant in the short-term salt or PEG-stressed plants as compared to the control, non-stressed plants. Expression analysis revealed the differential and temporal regulation of this gene under salt and PEG stress and that its early induction may indicate involvement in stress signaling.


Overexpression of DsEXLA2 gene from Dendrocalamus sinicus accelerates the plant growth rate of Arabidopsis.
Expansins play crucial roles in cell wall loosening and a range of life activities involving cell wall modification. Nevertheless, the biological functions of expansin genes during fast growth of bamboo remain unclear. In this study, Dendrocalamus sinicus, the largest and fastest growing bamboo species in the world, was used as the research material, and the full length of DsEXLA2 was cloned. Bioinformatics analysis revealed that DsEXLA2 contained expansin family typical domains (DPBB_1 and Pollen_allerg_1, CDRC motif) and amino acid sequence was highly conserved among different species. The expression level of DsEXLA2 increased from top section to basal section in different internodes. Subcellular localization verified that DsEXLA2 protein was located in the cell wall. Further genetic transformation studies in Arabidopsis indicated that compared with the wild type, DsEXLA2 overexpressed transgenic plants exhibited higher plant height, thicker stem, larger leaf, and less epidermal hair number and smaller stomatal aperture in the prophase and metaphase of growth. In addition, the cellulose content in the stem of transgenic plants was increased, and cell wall was thickened significantly. Moreover, a total of 1656 differentially expressed genes (DEGs) were identified by RNA-seq. The upregulated genes were predominantly enriched in the plant-pathogen interaction, MAPK signaling pathway-plant, plant hormone signal transduction, lipid metabolism and amino acid metabolism, while the downregulated genes were mainly enriched in energy metabolism, carbohydrate metabolism, plant hormone signal transduction and ribosome. These data implied that overexpression of DsEXLA2 gene accelerates the plant growth rate of Arabidopsis. This study is helpful to reveal the molecular mechanism of DsEXLA2 in culm growth and development of D. sinicus, and to understand the rapid growth of bamboos.


Assessment of genotoxicity in gonads, liver and gills of zebrafish (Danio rerio) by use of the comet assay and micronucleus test after in vivo exposure to methyl methanesulfonate.
Since generative tissues are a link between the generations, the detection of genetic damage in testis and ovary of fish is conductive to elucidating the relationship between genotoxicity and impairment of reproduction. In the current study, exposure of zebrafish to methyl methanesulfonate over two weeks caused concentration dependent genotoxic effects in gonads, liver and gills using the alkaline comet assay. Likewise, the micronucleus frequency was elevated in all of these organs. Thus, the comet assay and the micronucleus test proved appropriate for the detection of genotoxicity in primary male and female gonad cells and histological sections of the gonads from zebrafish, respectively.


Clinical-electroencephalographic correlations in measles: a long range study of 18 subjects.
EEGs of 18 cases of measles (uncomplicated, with seizures, with encephalitides) were obtained through an underground cable connection between the Infections Diseases Department and the EEG unit. The varions EEG features of the disease have been studied during the evolution of the illness. An occasional EEG does not offer specific information on either the severity or the evolution of the disease. Marked EEG abnormalities appeared in the encephalitic group. The Authors emphasize the importance of serial prolonged EEG follow-up of measles in order to define precisely the stage and the evolution of the disease.


Interaction of bilirubin with the synaptosomal plasma membrane.
The interaction of the neurotoxic pigment bilirubin with synaptosomal plasma membrane vesicles (SPMV) isolated from rat brain was investigated. The interaction seems to involve three steps: (a) a rapid formation of an electrostatic complex between bilirubin and polar lipid head groups; (b) a slow inclusion of the pigment into the hydrophobic core of the membrane; and (c) a SPMV-induced bilirubin aggregation, observed when membrane capacity for bilirubin is exceeded. The association constant of the initial complex increased markedly when pH was lowered below 7.4, particularly in SPMV isolated from newborn rats. A preferential binding of bilirubin to pure gangliosides and sphingomyelin was observed, thus suggesting a role for these lipids as first targets of the pigment in the synaptic membrane. The inclusion of bilirubin into the membranes was gradually enhanced when decreasing the pH or the age of the rats from which SPMV were isolated. In addition, membranes from 2-day-old rats have a higher capacity for bilirubin incorporation compared to those from adult rats. Experiments with reconstituted liposomes of varying protein and cholesterol contents suggest that the effect of age may be related to changes in synaptosomal membrane fluidity during development. Our results support the hypothesis that the interaction of bilirubin with the synaptic membrane plays an important role in the molecular mechanisms of bilirubin neurotoxicity.


Imaging the Dynamics of Cell Wall Polymer Deposition in the Unicellular Model Plant, Penium margaritaceum.
The unicellular green alga, Penium margaritaceum, represents a novel and valuable model organism for elucidating cell wall dynamics in plants. This organism's cell wall contains several polymers that are highly similar to those found in the primary cell walls of land plants. Penium is easily grown in laboratory culture and is effectively manipulated in various experimental protocols including microplate assays and correlative microscopy. Most importantly, Penium can be live labeled with cell wall-specific antibodies or other probes and returned to culture where specific cell wall developmental events can be monitored. Additionally, live cells can be rapidly cryo-fixed and cell wall surface microarchitecture can be observed with variable pressure scanning electron microscopy. Here, we describe the methodology for maintaining Penium for experimental cell wall enzyme studies.


Dermal toxicity of topical (-)epigallocatechin-3-gallate in BALB/c and SKH1 mice.
(-)Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, inhibits experimental chemical and physical carcinogenesis, yet little toxicological data has been reported. Therefore, we performed studies on the dermal toxicity of EGCG applied in an ointment formulation in mice. Female BALB/c mice were dehaired with a topical depilatory and administered 75 microl EGCG in hydrophilic Ointment U.S.P. at three concentrations (10, 3, and 1%, all w/w) daily for 30 days. At the 10% concentration, gross toxicity was manifested by the formation of erythema and papular lesions by day 5. A 7% reduction in weight was observed by day 15. No toxicity was observed at the two lower concentrations or in the vehicle control group. Also, no toxicity was observed when mice were dehaired by shaving. This study was repeated in female SKH1 mice, an outbred hairless strain that does not require depilation. No toxicity was observed in the SKH1 mice, indicating that daily topical EGCG appears non-toxic in normal skin. However, use of topical depilatories may potentiate dermal toxicity of EGCG.


More than a cultural experience: Assessing the impact of a medical-surgical international clinical on nursing students' academic performance.
A review of the extant literature suggests that there remains a dearth of evidence regarding the evaluation of well-defined outcomes related to international nursing clinical experiences. The purpose of this study was to explore the relationship between students' clinical experience (traditional versus international) and a number of academic outcomes including final medical-surgical course grades, performance on relevant Assessment Technologies Institute (ATI) proctored exams, and National Council Licensure Examination (NCLEX) pass rates. A non-experimental design was implemented using retrospective data obtained from a small university in the Midwest. Students complete a medical-surgical clinical in India during the interim of their third semester in the nursing program. Results of the t-tests show a statistically significant difference in final grades for Adult Health II theory when comparing students who completed a traditional clinical (M = 83.1, SD = 3.8) with those who completed an international clinical (M = 81.6, SD = 5.2); t(100) = 2.0, p = .043. The difference in mean scores for traditional clinical students (M = 70.3, SD = 6.6) versus international clinical students (M = 66.2, SD = 7.2) for the Adult Medical-Surgical proctored exam reached statistical significance, t(119) = 4.5, p ≤ .001. In contrast, there was no significant difference in means scores between the two groups with regard to scores on the Comprehensive Predictor proctored exam (traditional clinical, M = 76.1, SD = 5.9; international clinical, M = 75.2, SD = 6.4); t(121) = 1.0, p = .316. Finally, a chi square test of independence found that the relationship between clinical status and performance on NCLEX was not statistically significant, χ2 (1, N = 197) = 0.132, p = .716. Further research is needed to examine the impact of international clinicals on a broader range of outcomes including academic, cultural competency, and clinical performance measures.


Low potential detection of glutamate based on the electrocatalytic oxidation of NADH at thionine/single-walled carbon nanotubes composite modified electrode.
A glutamate biosensor based on the electrocatalytic oxidation of reduced nicotinamide adenine dinucleotide (NADH), which was generated by the enzymatic reaction, was developed via employing a single-walled carbon nanotubes/thionine (Th-SWNTs) nanocomposite as a mediator and an enzyme immobilization matrix. The biosensor, which was fabricated by immobilizing glutamate dehydrogenase (GlDH) on the surface of Th-SWNTs, exhibited a rapid response (ca. 5s), a low detection limit (0.1 microM), a wide and useful linear range (0.5-400 microM), high sensitivity (137.3+/-15.7) microA mM(-1)cm(-2), higher biological affinity, as well as good stability and repeatability. In addition, the common interfering species, such as ascorbic acid, uric acid, and 4-acetamidophenol, did not cause any interference due to the use of a low operating potential (190 mV vs. NHE). The biosensor can be used to quantify the concentration of glutamate in the physiological level. The Th-SWNTs system represents a simple and effective approach to the integration of dehydrogenase and electrodes, which can provide analytical access to a large group of enzymes for wide range of bioelectrochemical applications including biosensors and biofuel cells.


Diaphragmatic paralysis post COVID-19 treated with robot-assisted plication reinforced with acellular dermal matrix: a report of two cases.
Coronavirus disease 2019 (COVID-19) continues to be a disease of global importance, with an increasing array of sequelae attributed to infection by the severe acute respiratory syndrome coronavirus-2. One such complication that has been rarely documented thus far is diaphragmatic dysfunction. Here, we report the cases of 2 individuals who developed diaphragmatic paralysis post COVID-19, which failed to respond to conservative management. Both patients proceeded to undergo robot-assisted thoracoscopic plication of the diaphragm reinforced with a bovine acellular dermal matrix. In both cases, there was significant improvement in symptomatology, namely dyspnoea and fatigue. We conclude that robot-assisted diaphragmatic plication should be considered for the treatment of refractory diaphragmatic paralysis post COVID-19.


Hepatic tissue damage induced in Meriones ungliculatus due to infection with Babesia divergens-infected erythrocytes.
Babesia divergens is an intraerythrocytic parasite which is capable of infecting a wide range of vertebrates causing huge economic losses. Histopathological, hematological and biochemical changes during B. divergens infection in female Meriones ungliculatus were reported. Animals were challenged with 5 × 10(6) B. divergens-infected erythrocytes. Parasitemia were maximum at day 5 postinfection where all gerbils died. Infection of gerbils with Babesia induced a significant decrease in erythrocytic count as well as the hemoglobin concentration and hematocrit percentage but leucocytes were increased significantly when compared to uninfected gerbils. Liver enzymes aspartate aminotransferase (AST) and aniline aminotransferase (ALT) were significantly increased while albumin and total bilirubin were significantly decreased at day 5 postinfection with B. divergens-infected erythrocytes. Histopathological scores of inflammation after infection of gerbils were done using Ischak's activity index and indicated that the liver was severely affected. In conclusion, the study indicated that the course of infection by B. divergens-induced alternations in hematology, biochemistry and histopathology of the hepatic tissue.


In adults with coma after out-of-hospital cardiac arrest, hypothermia vs. normothermia did not reduce 6-mo mortality.
Dankiewicz J, Cronberg T, Lilja G, et al. Hypothermia versus normothermia after out-of-hospital cardiac arrest. N Engl J Med. 2021;384:2283-94. 34133859.


Tumor necrosis factor: recent advances.
Tumor necrosis factor is a protein secreted by activated monocytes. In addition to its known cytotoxic or cytostatic effect on some tumor cells, recently it was discovered to have multiple effects on normal cells. These effects include modulation of cell growth and function, production of growth factors, and induction of surface antigens. In this article we review some of the advances which were made since the gene for tumor necrosis factor was cloned.


In vitro characterization of a synthetic calcium phosphate bone graft on periodontal ligament cell and osteoblast behavior and its combination with an enamel matrix derivative.
Recent studies suggest that a combination of enamel matrix derivative (EMD) with grafting material may improve periodontal wound healing/regeneration. Newly developed calcium phosphate (CaP) ceramics have been demonstrated a viable synthetic replacement option for bone grafting filler materials. This study aims to test the ability for EMD to adsorb to the surface of CaP particles and to determine the effect of EMD on downstream cellular pathways such as adhesion, proliferation, and differentiation of primary human osteoblasts and periodontal ligament (PDL) cells. EMD was adsorbed onto CaP particles and analyzed for protein adsorption patterns via scanning electron microscopy and high-resolution immunocytochemistry with an anti-EMD antibody. Cell attachment and cell proliferation were quantified using CellTiter 96 One Solution Cell Assay (MTS). Cell differentiation was analyzed using real-time PCR for genes encoding Runx2, alkaline phosphatase, osteocalcin, and collagen1α1, and mineralization was assessed using alizarin red staining. Analysis of cell attachment revealed significantly higher number of cells attached to EMD-adsorbed CaP particles when compared to control and blood-adsorbed samples. EMD also significantly increased cell proliferation at 3 and 5 days post-seeding. Moreover, there were significantly higher mRNA levels of osteoblast differentiation markers including collagen1α1, alkaline phosphatase, and osteocalcin in osteoblasts and PDL cells cultured on EMD-adsorbed CaP particles at various time points. The present study suggests that the addition of EMD to CaP grafting particles may influence periodontal regeneration by stimulating PDL cell and osteoblast attachment, proliferation, and differentiation. Future in vivo and clinical studies are required to confirm these findings. The combination of EMD and CaP may represent an option for regenerative periodontal therapy in advanced intrabony defects.


Quantitative analysis of primaquine and its metabolites in human urine using liquid chromatography coupled with tandem mass spectrometry.
Primaquine (PQ), a prototype 8-aminoquinoline (8-AQ) drug used to treat malaria, is rapidly metabolized into different inactive and active metabolites. Due to the hemolytic toxicity, the uses of PQ have been confined. To understand its overall metabolism and its relation to drug efficacy and toxicity, profiling of urine for the parent drug and its metabolites is important. The current study presents a convenient and rapid method for simultaneously quantifying primaquine (PQ) and its metabolites in human urine. A simple liquid-liquid extraction followed by chromatographic separation and quantification through ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated to quantify PQ and its eleven metabolites in the urine of healthy human volunteers who received a single oral dose of PQ. The developed method separated fourteen analytes, including internal standards, within nine minutes of run time. The linearity of all analytes was suitable in the range of 1-500 ng/mL. The extraction recovery for all concentrations of analytes from urine was ranged from 90.1 to 112.9 %. The relative standard deviation for intra- and inter-day precision were < 9.8 and < 10.7 %, respectively. Along with PQ, its different metabolites were detected in urine. Primaquine-5,6-orthoquinone, the N-carbamoylglucuronide conjugate of PQ and carboxyprimaquine were the major metabolites found in urine. Significant enantiomeric differences in the urinary excretion profiles for PQ and metabolites were observed. This analytical method can be implemented in the pharmacokinetic analysis of PQ to explain its toxicity and clinical decision making.


Importance of functional performance and psychological readiness for return to preinjury level of sports 1 year after ACL reconstruction in competitive athletes.
This study aimed to identify independent predictive factors for return to sports (RTS) after anterior cruciate ligament (ACL) reconstruction in competitive-level athletes and to determine optimal cut-off values for these factors at 6 months after surgery. A total of 124 competitive athletes (50 males and 74 females; mean age, 17.0 years; preinjury Tegner activity scale > 7) who underwent primary ACL reconstruction were enrolled. Assessments at 6 months after surgery consisted of knee functional tests [quadriceps index, hamstrings index, and single-leg hop for distance (SLH)] and 2 self-report questionnaires [IKDC subjective score and ACL-Return to Sport after Injury scale (ACL-RSI)]. At 1 year after surgery, athletes were classified into the RTS group (n = 101) or non-RTS group (n = 23) based on self-reported sports activities. After screening possible predictive factors of RTS, multivariate logistic regression and receiver operating characteristic curve analyses were performed to identify independent factors. Multivariate logistic regression analysis identified SLH (odds ratio, 2.861 per 10 unit increase; P < 0.001) and ACL-RSI (odds ratio, 1.810 per 10 unit increase; P = 0.001) at 6 months as independent predictors of RTS at 1 year after surgery. Optimal cut-off values of SLH and ACL-RSI were 81.3% (sensitivity = 0.891; specificity = 0.609) and 55 points (sensitivity = 0.693; specificity = 0.826), respectively. In competitive athletes, SLH < 81% and ACL-RSI < 55 points at 6 months after surgery were associated with a greater risk of unsuccessful RTS at 1 year after surgery. SLH and ACL-RSI at 6 months could serve as screening tools to identify athletes who have difficulties with returning to sports after ACL reconstruction. III.


Dephenolization of stored olive-mill wastewater, using four different adsorbing matrices to attain a low-cost feedstock for hydrogen photo-production.
This investigation deals with the conversion of olive-mill wastewater (OMW) into several feedstocks suitable for hydrogen photo-production. The goal was reached by means of two sequential steps: (i) a pre-treatment process of stored-OMW for the removal of polyphenols, which made it possible to obtain several effluents, and (ii) a photo-fermentative process for hydrogen production by means of Rhodopseudomonas palustris sp. Four different adsorbent matrices (Azolla, granular active carbon, resin, and zeolite) were used to dephenolize stored-OMW. The four liquid fractions attained by using the above process created the same number of effluents, and these were diluted with water and then used for hydrogen photo-production. The maximum hydrogen production rate (14.31 mL/L/h) was attained with the photo-fermenter containing 25% of the effluent, which came from the pre-treatment of stored-OMW using granular active carbon. Using the carbon effluent as feedstock, the greatest light conversion efficiency of 2.29% was achieved.


A study of the compressive properties of lumbar vertebral trabeculae: effects of tissue characteristics.
The compressive material properties of human lumbar vertebral trabecular bone were examined and compared to in vivo and in vitro measures of bone density and to the degree of macroscopic disc degeneration. No significant differences in the material properties were found for segment level (L1-L4) or for degeneration grade (I-IV), although trabecular bone specimens from segments with slightly degenerated disks (I-II) were stronger (24%) and stiffer (16%) on the average than specimens from segments with severely degenerated discs. Significant positive logarithmic regressions were obtained, however, between the in vivo and in vitro measures of trabecular bone density and trabecular bone mechanical properties. The results indicate that in vivo mineral measurements can accurately estimate the compressive material properties of lumbar vertebral trabeculae.


Histological grade, elastosis, DNA ploidy and the response to chemotherapy of breast cancer.
The relationships between response to chemotherapy of advanced breast cancer and the histological type, grade, elastosis content and DNA ploidy of the primary tumours were examined using paraffin-embedded tissue derived from 125 patients. Higher response rates were seen amongst tumours with a high elastosis content and those that were diploid. However, selection of patients with advanced breast cancer for chemotherapy will not be assisted significantly by an assessment of these features in the primary tumour.


Long-term effects of early stress due to earthquake exposure on depression symptoms in adulthood: a cross-sectional study.
This study aimed to investigate the long-term effects of early stress by Tangshan earthquake on symptoms of depression in adulthood. A total of 1534 volunteers born and raised in Tangshan were investigated; finally, 1328 subjects were enrolled in the study. They were divided into three groups according to their birth dates: infant exposure, prenatal exposure, and non-exposure. The questionnaires and psychological evaluation of all subjects were completed using a one-on-one psychological test. The rate of depressive symptoms in the prenatal exposure group was the highest, and the lowest in the non-exposure group, with statistical differences among the three groups (P = 0.002). Moreover, the incidences of depressed mood, suicide ideation and work and loss of interest in the prenatal exposure group were significantly higher than those in the infant exposure group and the non-exposure group (P = 0.008, P = 0.001, P = 0.038, respectively). Multiple logistic regression analysis showed that male could be a protective factor for symptoms of depression in adulthood, and earthquake exposure was an important predictor of the incidence of depression symptoms. Fetal or infancy exposure to earthquake might correlate to depression symptoms in adulthood.


Platelet Activating Factor (PAF) biosynthesis is inhibited by phenolic compounds in U-937 cells under inflammatory conditions.
Interleukin 1 beta (IL-1β) induced platelet activating factor (PAF) synthesis in U-937 cells through stimulation of acetyl-CoA:lysoPAF-acetyltransferase (lyso PAF-AT) at 3 h and DTT-independentCDP-choline-1-alkyl-2-acetyl-sn-glycerol cholinophosphotransferase (PAF-CPT) at 0.5 h. The aim of this study was to investigate the effect of tyrosol (T), resveratrol (R) and their acetylated derivatives(AcDs) which exhibit enhanced bioavailability, on PAF synthesis in U-937 after IL-1β stimulation. The specific activity of PAF enzymes and intracellular levels were measured in cell homogenates. T and R concentration capable of inducing 50% inhibition in IL-1β effect on lyso PAF-AT was 48 μΜ ± 11 and 157 μΜ ± 77, for PAF-CPT 246 μΜ ± 61 and 294 μΜ ± 102, respectively. The same order of concentration was also observed on inhibiting PAF levels produced by IL-1β. T was more potent inhibitor than R (p<0.05). AcDs of T retain parent compound inhibitory activity, while in the case of R only two AcDs retain the activity. The observed inhibitory effect by T,R and their AcDs, may partly explain their already reported beneficial role.


Pneumatic retinopexy in 50 patients.
Pneumatic retinopexy was introduced in our clinic in 1986. This paper reports the results from the first 50 cases. Detachments with multiple breaks within 3 clock hours and proliferative vitreoretinopathy up to grade C1 were included. This technique compares favorably to buckling procedures in selected cases. The primary success rate was 83%, and the overall success rate was 90% (pneumatic retinopexy +/- scleral buckling +/- vitrectomy).


Highly sensitive determination of trace copper in food by adsorptive stripping voltammetry in the presence of 1,10-phenanthroline.
A highly sensitive, rapid, simple and selective adsorptive stripping assay for the determination of trace copper(II) is proposed. The methodology is based on the adsorptive accumulation of copper(II)-1,10-phenanthroline complexes onto a glassy carbon electrode, followed by oxidation of the adsorbed species by voltammetric scanning using square-wave voltammetry. The influences of experimental variables on the sensitivity of the proposed method, such as the effects of pH, ligand concentration, accumulation time, accumulation potential and interferences, were investigated. Under optimal conditions, the proposed method showed linearity from 0.1 ng mL(-1) to 50 ng mL(-1). The 3 S/N detection limits were 0.0185 ng mL(-1), and the relative standard deviations (n=10) were 0.09-4.71% for intra-day and 0.05-7.14% for inter-day analyses, respectively. The application of the proposed method to the direct analysis of food samples yielded results that agreed with those obtained from including inductively coupled plasma-optical emission spectrometry (ICP-OES) assays according to a paired t-test. The results are a step toward the development of an alternative and reliable analytical method for food research, which requires the direct determination of copper.


Expression patterns of miR-34a, miR-125b, miR-221 and antioxidant gene NRF2 in plasma samples of patients with atherosclerosis.
Atherosclerosis is one of the main reasons of cardiovascular diseases, the most common cause of death in the world. NRF2 is a critical transcriptional factor that regulates oxidative stress response and contributes to the pathogenesis of atherosclerosis. This study aims to compare the expression levels of miR-34a, miR-125b, miR- 221 and NRF2 in blood samples of patients with atherosclerosis and of controls to find a novel link between microRNAs, oxidative stress and atherosclerosis. miR-34a, miR-125b, miR-221 and NRF2 relative expressions were analysed in 26 atherosclerosis patients and 25 healthy controls by q-RT-PCR assay. The receiver operating characteristic curve (ROC) was used to assess the diagnostic values of miR-34a, miR-125b, miR-221 and NRF2 by comparing the area under the curves (AUC) to differentiate between atherosclerosis and control samples. miR-34a and NRF2 were significantly upregulated, whereas miR-125b and miR-221 were significantly downregulated in patients compared with healthy controls. The ROC curves suggested high diagnostic value of miR-221 (AUC: 0.7477), miR-125b (AUC: 0.8523) and NRF2 (AUC: 0.838) for detection of atherosclerosis. Our results suggest that circulating miR-34a, miR-125b and miR-221 levels can be used as novel biomarkers for detection of atherosclerosis by targeting NRF2.


A comparison of the effect of short-acting and long-acting cloxacillin-based dry-cow therapy on somatic cell counts after calving in cows also given internal teat sealants.
To compare, in cows treated with an internal teat sealant, the effect of short-acting and long-acting cloxacillin-based dry-cow therapy on somatic cell counts (SCC) after calving. Cows from a spring-calving, pasture-based dairy farm in the Manawatu-Whanganui region of New Zealand were randomly allocated to receive either a short-acting cloxacillin and ampicillin dry-cow therapy and internal teat sealant (n=291) or a long-acting cloxacillin and ampicillin dry-cow therapy and internal teat sealant (n=288) at the end of lactation. Cows were managed on-farm with routine husbandry procedures through the dry period and following calving. A multivariable logistic regression model was used to determine the association between length of action of dry-cow therapy and the proportion of cows with a SCC >150,000 cells/mL at the first herd test after calving. Age of cow, mean SCC for the preceding season and interval from calving to the first post-calving herd test were all associated with the proportion of cows with an individual SCC >150,000 cells/mL at the first herd test (p<0.001) Treatment with the short-acting dry-cow therapy was not associated with decreased odds of cows having a SCC >150,000 cells/mL at the first herd test compared with treatment with long-acting dry-cow therapy (OR=0.724; 95% CI=0.40-1.30). In this herd, which routinely used internal teat sealants, the use of short-acting cloxacillin-based dry-cow therapy did not result in an increased proportion of cows with elevated SSC post-calving. This was a single farm, single year study but indicates that in this herd, changing from a long-acting to a short-acting antimicrobial may have no impact on the prevalence of subclinical mastitis.


Effect of a single oral dose of milrinone on left ventricular diastolic performance in the failing human heart.
In 14 patients with severe congestive heart failure, left ventricular pressure (measured by tip manometer) and derived variables were measured before and every 10 minutes after administration of oral milrinone (10 mg) for 50 minutes along with measurements of coronary sinus blood flow and drug plasma levels. Arterial and coronary sinus catecholamines were measured only before and 50 minutes after milrinone. Left ventricular pressure, volume (as determined by angiography) and derived indexes were simultaneously assessed at matched atrial paced heart rate before and 60 minutes after milrinone. Three patients who did not achieve a therapeutic plasma level (less than 150 ng/ml) were excluded. Peak negative first derivative of left ventricular pressure (-dP/dt) progressively and significantly increased (10%) together with a decrease in the two exponential time constants of relaxation, namely, Tau 1 (19%) and Tau 2 (22%), which represent the fit for and after the first 40 ms, respectively. Coronary flow significantly increased by 43% within 30 minutes, whereas the decrease (-13%) in coronary vascular resistance failed to be statistically significant. No change occurred in catecholamine concentrations after milrinone. Peak filling rate significantly increased by 15%. Pressure-volume curves showed a leftward and, in four patients, a downward shift; a significant decrease in minimal left ventricular diastolic and end-diastolic pressures (by 55 and 38%, respectively) and in end-diastolic volume (18%) occurred. The constant of elastic chamber stiffness measured by the simple elastic model tended to decrease, but failed to achieve a statistically significant level. Thus, oral milrinone improved left ventricular early relaxation and filling as well as chamber distensibility. This global improvement of diastolic function makes milrinone a potentially useful drug in the oral treatment of heart failure.


[From Theory into Practice - Early Experiences with Home Treatment in Munich, Germany].
Stationsäquivalente Behandlung (StäB), a treatment for crisis-resolution and home-treatment has been established in the greater Munich area since 2018, after it was established by a federal law. Our aim was to characterise the patients treated and analyse how treatment was carried out, as well as determine future target groups. Quantitative data was gathered through examination of records from all patients included in StäB from 01.10.18-31.10.19. For analysis we used descriptive statistics. We report data from 164 treatment cases. 50 % of the patients were admitted to StäB directly from the community, the other 50 % were transferred from inpatient units. More than 75 % had affective or schizophrenic disorders, with many patients in the puerperium. There were few emergencies during StäB-treatment, and the therapy was usually ended on a regular basis. When discharged, most of the patients were in improved condition according to clinicians' judgement. Severity of illness was comparable to inpatients. Its successful implementation in Munich StäB offers an alternative and addition to inpatient treatment. There are certain needs which are specifically met such as mother-child treatment.


The role of the Patient-Generated Subjective Global Assessment (PG-SGA) and biochemical markers in predicting anemia patients with cancer.
The causes of anemia and the common side effects of cancer are multifactorial. Malnutrition is one of the alleged components of the aforementioned complications. This study planned to investigate the relationship among biochemical markers, Patient-Generated Subjective Global Assessment (PG-SGA), and anemia in cancer patients. This analysis consisted of 234 patients who were enlisted in the Department of Oncology of the First Hospital of Shanxi Medical University between December 2016 and October 2017. The groups were divided into anemic and non-anemic patients. The gathered data primarily discussed the patients' basic information, specifically the age, gender, smoking, alcohol consumption, and nutritional status based on levels of serum biochemical markers and PG-SGA scores. Among the participants, 31.2% of the cancer patients were diagnosed with anemia whereas, according to the scores of PG.SGA, 65.0% of patients experienced malnourishment. The anemia was significantly associated with biochemical markers, expecting a transferrin in univariable analyses. Binary logistic regression analysis between anemic cancer patients and non-anemic cancer patients suggested that high PG-SGA score (odds ratio 1.082; 95% CI 1.027-1.141) implied the risk factor for anemia, and high PG-SGA scores could potentially increase the risk of anemia. The multiple regression analysis showed that hemoglobin concentration (OR 0.575; 95% CI 0.450-0.736) and PG-SGA score (OR 1.231; 95% CI 1.013-1.496) were linked to anemia. However, total protein, albumin, prealbumin, serum iron, transferrin, and transferrin saturation lacked a strong relationship with anemia. Anemia prevailed in cancer patients, as nutritionally assessed by PG-SGA, while hemoglobin established a linkage with anemia as they could provide extra predictive information about anemia in patients diagnosed with cancer.


7-imidazolylalkanamido-1-carboxylalkylbenzo-diazepine, a novel series of farnesyltransferase inhibitors.
Design, synthesis and evaluation of a series of 7-imidazolylalkanamido-1-carboxylalkylbenzodiazepine farnesyltransferase (FTase) inhibitors. Coupling of imidazolylalkylcarboxylic acids and 1-substituted 7-aminobenzodiazepines (5a-5c) yielded 10 new compounds (6-12, 16-18) which were biologically tested against FTase using scintillation proximity assay method. Five target compounds were found to be potential farnesyltransferase inhibitors.


Fatty acid differences amongst leukemia cell types, with special reference to hairy cell leukemia: a preliminary report.
Fatty acid analyses of malignant cells from hairy cell leukemia patients revealed a profile which was rich in arachidonate and relatively low in linoleate and oleate. This profile was distinct from that of mononuclear cells derived from patients with other lymphoproliferative diseases or myeloproliferative disorders, and may reflect the unique membrane morphology of the hairy cell.


Major histocompatibility complex class II-restricted presentation of secreted and endoplasmic reticulum resident antigens requires the invariant chains and is sensitive to lysosomotropic agents.
We have tested the involvement of the invariant chains (Ii) p31 and p41 in the presentation of peptides derived from hen egg lysozyme (HEL) constructs targeted to different intracellular compartments within transfected fibroblasts. The endogenous HEL constructs were either present in the cytosol (HELc), secreted (HELs), or linked to the mammalian (KDEL C-terminal sequence that causes retention of HEL in the endoplasmic reticulum (ER)/pre-Golgi recycling compartment (HELr). Using Ii-negative antigen-presenting cells, the presentation of HELr to a HEL 46-61 specific T cell hybridoma was far less efficient than the presentation of the HELs. High levels of Ii expression enhanced drastically the presentation of the HEL 46-61 determinant derived from both HELr and HELs. HELr and HELs presentation was fully sensitive to lysosomotropic agents such as chloroquine, indicating that the formation of complexes between major histocompatibility complex (MHC) class II molecules and determinants derived from endogenous antigens entering the secretory pathway is taking place in an acidic compartment. The degradation and dissociation of Ii might be a prerequisite for the efficient presentation of endogenously derived determinants by MHC class II molecules, as for the presentation of most exogenous antigens. All our results are compatible with the notion that endogenous molecules being translocated into the lumen of the ER could be presented by class II molecules through a processing pathway involving an acidic compartment in which Ii chains dissociate from class II molecules.


Onto better TRAILs for cancer treatment.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. By cross-linking TRAIL-Receptor (TRAIL-R) 1 or TRAIL-R2, also known as death receptors 4 and 5 (DR4 and DR5), TRAIL has the capability to induce apoptosis in a wide variety of tumor cells while sparing vital normal cells. The discovery of this unique property among TNF superfamily members laid the foundation for testing the clinical potential of TRAIL-R-targeting therapies in the cancer clinic. To date, two of these therapeutic strategies have been tested clinically: (i) recombinant human TRAIL and (ii) antibodies directed against TRAIL-R1 or TRAIL-R2. Unfortunately, however, these TRAIL-R agonists have basically failed as most human tumors are resistant to apoptosis induction by them. It recently emerged that this is largely due to the poor agonistic activity of these agents. Consequently, novel TRAIL-R-targeting agents with increased bioactivity are currently being developed with the aim of rendering TRAIL-based therapies more active. This review summarizes these second-generation novel formulations of TRAIL and other TRAIL-R agonists, which exhibit enhanced cytotoxic capacity toward cancer cells, thereby providing the potential of being more effective when applied clinically than first-generation TRAIL-R agonists.


From a spin-off to the advantageous use in Diels-Alder reactions: a combined synthetic, spectroscopic and computational approach to N-(dienyl)acylamines.
The acid-catalyzed condensation of aldehydes and acetamide has been shown to provide a pool of diverse equilibrating species. For the first time, the synthesis of substituted 1-N-acylamino-1,3-butadienes has been accomplished directly in moderate yields upon telomerization of two molecules of aldehyde with one molecule of carboxamide. Detailed spectroscopic and computational investigations establish the favourable formation of all-trans aminodienes under the reaction conditions. Employment thereof as diene building blocks in Diels-Alder reactions allows for the synthesis of carbocyclic molecules with high stereocontrol.


Synthesis of lanthanide-doped NaYF₄@TiO₂ core-shell composites with highly crystalline and tunable TiO₂ shells under mild conditions and their upconversion-based photocatalysis.
NaYF4:Yb,Tm@TiO₂ core-shell composites were synthesized via a facile hydrothermal method. The highly crystalline TiO₂ shell can be uniformly coated onto lanthanide-doped NaYF₄ microrods and nanorods under mild conditions without calcination. The thickness of the TiO₂ shell can be tuned by varying the ratio of fluoride rods and Ti precursors. The microcomposite with a moderate TiO₂ shell shows excellent photocatalytic activity under near-infrared irradiation.


Rosiglitazone polarizes microglia and protects against pilocarpine-induced status epilepticus.
Activated microglia have been found in the forebrains and hippocampi of temporal lobe epilepsy (TLE) patients and status epileptic (SE) animal models. The peroxisome proliferator-activated receptor γ (PPAR γ) agonist rosiglitazone has been shown to prevent microglial activation. However, its role in pilocarpine-induced status epilepticus remains unknown. We aimed to examine the effect of the PPAR γ agonist rosiglitazone in protecting against pilocarpine-induced status epileptic resulting from over-activation and to explore phenotypic changes in microglia as the underlying mechanism. Male C57BL/6 mice were assigned to three groups: the control group, pilocarpine-induced (SE) group, and rosiglitazone-treated (SE+Rosi) group. Status epileptic mice were administered 300 mg/kg pilocarpine via intraperitoneal injection. SE+Rosi mice were administered rosiglitazone (0.1 mg/kg, i.p.) after SE. Flow cytometry, immunofluorescence staining, and quantitative real-time PCR were used to examine the activation of and phenotypic changes in microglia in the brain and to evaluate neuroinflammation. We found that the expression of proinflammatory CD86 and iNOS was increased and that the expression of antiinflammatory CD206 and Arg-1 was decreased in the brains of pilocarpine-induced SE mice compared to control mice. The mRNA levels of proinflammatory and antiinflammatory cytokines were not significantly changed in the brain. Rosiglitazone treatment significantly inhibited the proinflammatory polarization of microglia and rescued neuron loss in the temporal lobe and hippocampi of the brain after SE. Rosiglitazone reverses microglial polarization in the brains of SE mice and also affords neuroprotection against pilocarpine-induced status epilepticus without inducing significant changes in brain inflammation.


Imbalanced data preprocessing techniques for machine learning: a systematic mapping study.
Machine Learning (ML) algorithms have been increasingly replacing people in several application domains-in which the majority suffer from data imbalance. In order to solve this problem, published studies implement data preprocessing techniques, cost-sensitive and ensemble learning. These solutions reduce the naturally occurring bias towards the majority sample through ML. This study uses a systematic mapping methodology to assess 9927 papers related to sampling techniques for ML in imbalanced data applications from 7 digital libraries. A filtering process selected 35 representative papers from various domains, such as health, finance, and engineering. As a result of a thorough quantitative analysis of these papers, this study proposes two taxonomies-illustrating sampling techniques and ML models. The results indicate that oversampling and classical ML are the most common preprocessing techniques and models, respectively. However, solutions with neural networks and ensemble ML models have the best performance-with potentially better results through hybrid sampling techniques. Finally, none of the 35 works apply simulation-based synthetic oversampling, indicating a path for future preprocessing solutions.


Risk factors of post-operative malalignment in fixed-bearing medial unicompartmental knee arthroplasty.
The purpose of this study was to identify risk factors of post-operative malalignment in medial unicompartmental knee arthroplasty (UKA) using multivariate logistic regression. We retrospectively enrolled 92 patients who had 127 medial UKAs. According to post-operative limb mechanical axis (hip-knee-ankle [HKA] angle), 127 enrolled knees were sorted into acceptable alignment with HKA angle within the conventional ± 3 degree range from a neutral alignment (n = 73) and outlier with HKA angle outside ± 3 degree range (n = 54) groups. Multivariate logistic regression was used to analyse risk factors including age, gender, body mass index, thickness of polyethylene tibial insert, pre-operative HKA angle, distal femoral varus angle (DFVA), femoral bowing angle (FBA), tibial bone varus angle (TBVA), mechanical distal femoral and proximal tibial angles, varus and valgus stress angles, size of femoral and tibial osteophytes, and femoral and tibial component alignment angles. Pre-operative DFVA, TBVA and valgus stress angle were identified as significant risk factors. As DFVA increased by one degree, malalignment was about 45 times probable (adjusted OR 44.871, 95 % CI 2.608-771.904). Shift of TBVA and valgus stress angle to a more varus direction were also significant risk factors (adjusted OR 13.001, 95 % CI 1.754-96.376 and adjusted OR 2.669, 95 % CI 1.054-6.760). Attention should be given to the possibility of post-operative malalignment during medial UKA in patients with a greater varus angle in pre-operative DFVA, TBVA and valgus stress angle, especially with a greater varus DFVA, which was the strongest predictor for malalignment.


Artemisia campestris leaf extract alleviates early diabetic nephropathy in rats by inhibiting protein oxidation and nitric oxide end products.
Chronic hyperglycemia in diabetes leads to free radicals overproduction, which contributes to the development of diabetic nephropathy. The present study investigated the effects of Artemisia campestris (Ac), a plant of the Asteraceae family, on renal impairment and oxidative stress in alloxan-induced diabetic rats. Diabetes was induced by a single subcutaneous injection of alloxan (120 mg kg(-1)) in rats. Ac (200 mg kg(-1)) was administered to diabetic rats for 3 weeks. Diabetic renal injury was associated with hyperglycemia, increased serum creatinine, urea and uric acid levels. This nephropathophysiology was associated with a surproduction of nitric oxide (NO), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels and a decrease in glutathione (GSH) levels. In addition, hyperglycemia increased the activities of antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), in the kidney of diabetic rats. Treatment with Ac effectively ameliorated diabetic renal dysfunction by reducing oxidative and nitrosative stress. Histological studies also supported the experimental findings. The results suggested that Ac might act as a beneficial agent against renal dysfunctions developed in alloxan-induced diabetes.


Dopamine release and metabolism in nucleus accumbens and striatum of morphine-tolerant and nontolerant rats.
Morphine administered at high doses produces a biphasic locomotor effect, characterized by an initial locomotor depression, followed a short time later by hyperlocomotion. Prior exposure to morphine produces tolerance to the motor-depressive effects and sensitization to the motor-activating effects of morphine. Little is known of the neurochemical changes that occur to produce tolerance and sensitization to morphine. In the present study, we developed a morphine pretreatment regimen in rats that produced both tolerance and sensitization to a high (30 mg/kg) dose of morphine. Using in vivo microdialysis, we then measured dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) release in the nucleus accumbens (NAC) and striatum (STR) in morphine- and saline-pretreated rats after acute morphine administration. In morphine-tolerant/sensitized rats, basal DA concentrations in the NAC were higher and levels of DOPAC and HVA in the NAC after acute morphine injection were greater compared to controls. These results suggest that the NAC, but not the STR, may be important in mediating tolerance and sensitization to opiates.


A review of the biological role of miRNAs in prostate cancer suppression and progression.
Prostate cancer (PC) is the third-leading cause of cancer-related deaths worldwide. Although the current treatment strategies are progressing rapidly, PC is still representing a substantial medical problem for affected patients. Several factors are involved in PC initiation, progression, and treatments failure including microRNAs (miRNAs). The miRNAs are endogenous short non-coding RNA sequence negatively regulating target mRNA expression via degradation or translation repression. miRNAs play a pivotal role in PC pathogenesis through its ability to initiate the induction of cancer stem cells (CSCs) and proliferation, as well as sustained cell cycle, evading apoptosis, invasion, angiogenesis, and metastasis. Furthermore, miRNAs regulate major molecular pathways affecting PC such as the androgen receptor (AR) pathway, p53 pathway, PTEN/PI3K/AKT pathway, and Wnt/β-catenin pathway. Furthermore, miRNAs alter PC therapeutic response towards the androgen deprivation therapy (ADT), chemotherapy and radiation therapy (RT). Thus, the understanding and profiling of the altered miRNAs expression in PC could be utilized as a non-invasive biomarker for the early diagnosis as well as for patient sub-grouping with different prognoses for individualized treatment. Accordingly, in the current review, we summarized in updated form the roles of various oncogenic and tumor suppressor (TS) miRNAs in PC, revealing their underlying molecular mechanisms in PC initiation and progression.


Metabolic consequences of sleep and sleep loss.
Reduced sleep duration and quality appear to be endemic in modern society. Curtailment of the bedtime period to minimum tolerability is thought to be efficient and harmless by many. It has been known for several decades that sleep is a major modulator of hormonal release, glucose regulation and cardiovascular function. In particular, slow wave sleep (SWS), thought to be the most restorative sleep stage, is associated with decreased heart rate, blood pressure, sympathetic nervous activity and cerebral glucose utilization, compared with wakefulness. During SWS, the anabolic growth hormone is released while the stress hormone cortisol is inhibited. In recent years, laboratory and epidemiologic evidence have converged to indicate that sleep loss may be a novel risk factor for obesity and type 2 diabetes. The increased risk of obesity is possibly linked to the effect of sleep loss on hormones that play a major role in the central control of appetite and energy expenditure, such as leptin and ghrelin. Reduced leptin and increased ghrelin levels correlate with increases in subjective hunger when individuals are sleep restricted rather than well rested. Given the evidence, sleep curtailment appears to be an important, yet modifiable, risk factor for the metabolic syndrome, diabetes and obesity. The marked decrease in average sleep duration in the last 50 years coinciding with the increased prevalence of obesity, together with the observed adverse effects of recurrent partial sleep deprivation on metabolism and hormonal processes, may have important implications for public health.


Long-term outcomes in nondiabetic chronic kidney disease.
The Modification of Diet in Renal Disease (MDRD) Study examined the effects of strict blood pressure control and dietary protein restriction on the progression of kidney disease. Here, we retrospectively evaluated outcomes of nondiabetic participants with stages 2-4 chronic kidney disease (CKD) from randomized and nonrandomized cohorts of the MDRD Study. Kidney failure and survival status through December of 2000, were obtained from the US Renal Data System and the National Death Index. Event rates were calculated for kidney failure, death, and a composite outcome of death and kidney failure. In the 1666 patients, rates for kidney failure were four times higher than that for death. Kidney failure was a more likely event than death in subgroups based on baseline glomerular filtration rate, proteinuria, kidney disease etiology, gender, and race. It was only among those older than 65 that the rate for death approximated that for kidney failure. In contrast to other populations with CKD, our study of relatively young subjects with nondiabetic disease has found that the majority of the participants advanced to kidney failure with a low competing risk of death. In such patients, the primary emphasis should be on delaying progression of kidney disease.


Waitlist Trends in Heart-Liver Transplantation With Updated US Heart Allocation System.
In October 2018, the United States implemented a change in the donor heart allocation policy from a three-tiered to a six-tiered status system. The purpose of the current study was to examine changes in waitlist patterns among patients listed for concomitant heart-liver transplantation with implementation of the new allocation system. Patients listed for heart-liver transplantation between January 1, 2012, and June 30, 2021, were identified from the United Network for Organ Sharing database. Patients were grouped by era according to initial list date before or after October 18, 2018. Competing risks regression for mortality, transplantation, removal from waitlist due to illness was performed according to the method of Fine and Gray. Waitlist data were censored at 3 years from initial listing. Overall, 523 patients were identified, of whom 310 were listed before (era 1, 59%) and 213 after (era 2, 41%) allocation change. Patients in era 1 were older, had more restrictive cardiomyopathy, and more preoperative inotrope use (all P < .05). However, patients in era 2 has longer ischemic times (3.5 ± 1.1 vs 3.1 ± 1.1 hours, P < .01) and more intraaortic balloon pump use (8.9% vs 3.9%, P = .016). Era 2 was associated with lower subdistribution hazard for death (hazard ratio 0.37; 95% CI, 0.13-1.02; P = .054) and increased transplantation (hazard ratio 1.35; 95% CI, 1.06-1.72; P = .015). The implementation of the US donor heart allocation policy was associated with more preoperative intraaortic balloon pump use for patients listed for heart-liver transplantation. Despite that, the modern era was associated with lower waitlist mortality and more frequent transplantation, without increased risk of delisting due to illness.


Yeasts associated with an abandoned mining area in Pernek and their tolerance to different chemical elements.
Four plants, Cirsium arvense (creeping thistle), Equisetum arvense (field horsetail), Oxalis acetosella (wood sorrel) and Phragmites australis (common reed), which grew in an abandoned Sb-mining area in Pernek (Malé Karpaty Mts., Slovakia), were investigated for the yeast species. Yeasts were isolated from both the leaves of the plants and the soil adjacent to the plants. In total, 65 yeast cultures, belonging to 11 ascomycetous and 5 basidiomycetous yeast species, were isolated. The species most frequently isolated from both the soil and leaf samples were Trichosporon porosum, Galactomyces candidus and Candida solani, whereas Aureobasidium pullulans, Candida tsuchiyae and Sporidiobolus metaroseus were isolated exclusively from the plant leaves. All the yeast species isolated were tested for their tolerance to two heavy metals (Cd, Zn) and three metalloids (As, Sb and Si). The yeasts isolated from both the leaves and soils exhibited a high tolerance level to both As and Sb, present in elevated concentrations at the locality. Among the yeast species tested, Cryptococcus musci, a close relative to Cryptococcus humicola, was the species most tolerant to all the chemical elements tested, with the exception of Si. It grew in the presence of 200 mmol/L Zn, 200 mmol/L Cd, 60 mmol/L As and 50 mmol/L Sb, and therefore, it can be considered as a multi-tolerant species. Some of the yeast species were tolerant to the individual chemical elements. The yeast-like species Trichosporon laibachii exhibited the highest tolerance to Si of all yeasts tested, and Cryptococcus flavescens and Lindnera saturnus showed the same tolerance as Cryptococcus musci to Zn and As, respectively. The majority of the yeasts showed a notably low tolerance to Cd (not exceeded 0.5 mmol/L), which was present in small amounts in the soil. However, Candida solani, isolated from the soil, exhibited a higher tolerance to Cd (20 mmol/L) than to As (2 mmol/L).


Pheromone communication and the mushroom body of the ant, Camponotus obscuripes (Hymenoptera: Formicidae).
Communication by means of pheromones plays predominant roles in colony integration by social insects. However, almost nothing is known about pheromone processing in the brains of social insects. In this study, we successfully applied intracellular recording and staining techniques to anatomically and physiologically characterize brain neurons of the ant Camponotus obscuripes. We identified 42 protocerebral neurons that responded to undecane and/or formic acid, components of alarm pheromones that evoke attraction or evasive behavior, respectively. Notably, 30 (71%) of these neurons were efferent (output) or feedback neurons of the mushroom body, and many of these exhibited different responses to formic acid and undecane. Eight of the remaining 12 neurons had arborizations in the lateral and/or medial protocerebrum, which receive terminations of efferent neurons of the mushroom body and from which premotor descending neurons originate. The remaining four neurons were bilateral neurons that connect lateral accessory lobes or dorsal protocerebrums of both hemispheres. We suggest that the mushroom body of the ant participates in the processing of alarm pheromones. Seventeen (40%) of 42 neurons exhibited responses to nonpheromonal odors, indicating that the pheromonal and nonpheromonal signals are not fully segregated when they are processed in the protocerebrum. This may be related to modulatory functions of alarm pheromones, i.e., they change alertness of the ant and change responses to a variety of sensory stimuli.


[The control of tidal rhythm of emergence by an hourglass mechanism].
The arctic population of the intertidal midge Clunio marinus (location: Tromsö, Norway) shows a tidal rhythm of emergence (period: 12.4 hours) in midsummer. The emergence time exactly coincides with the initial exposure of the habitat during the ebb.When the animals were bred in a 24 hour light-dark cycle involving 16 hours of light, emergence occurred mainly 10-11 hours after light-on. When the animals were subsequently placed under constant light, no rhythm could be detected. When constant light was interrupted by a single period of 6 hours of darkness, only one peak of emergence was evoked, again 10-11 hours after light-on. Similar results were observed when in constant darkness a single period of 6 hours of lower temperature was offered.The mechanism of control differs from that of a southern population (location: St. Jean-de-Luz, France) which has a circadian clock mechanism and shows a free-running rhythm of emergence in constant light. It is postulated that the tidal rhythm of the Tromsö population is controlled by an hour-glass mechanism which starts its run of at least 10-11 hours during the preceding ebb.


Covalent binding of photosensitive 1-(12-azido-[9,10(-3)H2]oleoyl)glycero-3-phosphocholine (lysolecithin) to human serum high density apolipoproteins.
Human serum high density apoproteins were complexed with increasing concentrations of 1-(12-azido-[9,10(-3)H2]oleoyl)glycero-3-phosphocholine up to the saturation concentration (72 mol lysolecithin per mol apo HDL). Ultraviolet irradiation generated the nitrene which led to crosslinking with the two main apolipoproteins AI and AII. Methods are described for the removal of excess, unbound lipid and the column chromatographic separation of the lipopolypeptides AI and AII.


Influence of lifestyle on the FAIM2 promoter methylation between obese and lean children: a cohort study.
An obesity-related gene, Fas apoptotic inhibitory molecule 2 (FAIM2), is regulated by nutritional state and the methylation levels of the FAIM2 promoter are significantly associated with obesity. Lifestyle factors, such as sedentary behaviour and physical activity, might modify epigenetic patterns that have been related to obesity. Whether the molecular mechanisms by which FAIM2 affects obesity are involved in lifestyle is unclear. This study investigates the potential differences of the FAIM2 promoter methylation with sedentary behaviour and physical activity in obese and lean children. Cohort study. Institute of Pediatrics in China. 59 obese cases and 39 lean controls aged 8-18 years recruited from a cross-sectional survey of children from Beijing in 2013. The FAIM2 promoter methylation was quantified using the Sequenom MassARRAY platform. Sedentary behaviour and physical activity were investigated using a questionnaire. The influences of different lifestyles on methylation variations in obese and lean children were examined by multiple linear regression. The methylation levels at seven CpG sites of the FAIM2 promoter were significantly associated with sedentary behaviour, especially the methylation levels at site -975, site -413, sites -362 and -360, and sites -353 and -349 (p=0.00004, 0.00009, 0.0006 and 0.00005, respectively). There were significant differences between the methylation levels at four CpG sites in obese and lean participants with high or moderate physical activity level <150 min/week. This study provides the first evidence that there are significant differences in the associations of the FAIM2 promoter methylation with sedentary behaviour and physical activity between obese and lean children. Our results suggest that lifestyle may possibly be mediating the process of the FAIM2 involved in obesity.


Leadership behavior and employee effectiveness.
A research study shows how leaders can significantly impact employee productivity, job satisfaction and commitment. Five leadership skills basic to good management are developed and implemented to complement the nurse manager's own unique style. Employees, in turn, will respond to the manager's examples of high standards and values.


The Prognostic Value of Total Tumor Volume Response Compared With RECIST1.1 in Patients With Initially Unresectable Colorectal Liver Metastases Undergoing Systemic Treatment.
Compare total tumor volume (TTV) response after systemic treatment to Response Evaluation Criteria in Solid Tumors (RECIST1.1) and assess the prognostic value of TTV change and RECIST1.1 for recurrence-free survival (RFS) in patients with colorectal liver-only metastases (CRLM). RECIST1.1 provides unidimensional criteria to evaluate tumor response to systemic therapy. Those criteria are accepted worldwide but are limited by interobserver variability and ignore potentially valuable information about TTV. Patients with initially unresectable CRLM receiving systemic treatment from the randomized, controlled CAIRO5 trial (NCT02162563) were included. TTV response was assessed using software specifically developed together with SAS analytics. Baseline and follow-up computed tomography (CT) scans were used to calculate RECIST1.1 and TTV response to systemic therapy. Different thresholds (10%, 20%, 40%) were used to define response of TTV as no standard currently exists. RFS was assessed in a subgroup of patients with secondarily resectable CRLM after induction treatment. A total of 420 CT scans comprising 7820 CRLM in 210 patients were evaluated. In 30% to 50% (depending on chosen TTV threshold) of patients, discordance was observed between RECIST1.1 and TTV change. A TTV decrease of >40% was observed in 47 (22%) patients who had stable disease according to RECIST1.1. In 118 patients with secondarily resectable CRLM, RFS was shorter for patients with less than 10% TTV decrease compared with patients with more than 10% TTV decrease (P = 0.015), while RECIST1.1 was not prognostic (P = 0.821). TTV response assessment shows prognostic potential in the evaluation of systemic therapy response in patients with CRLM.


Primary pulmonary non-Hodgkin's lymphomas.
We report a retrospective study of the pathological features in 69 primary pulmonary non-Hodgkin's lymphomas which have previously been clinically reviewed. The tumours consisted of 61 (88%) low-grade and eight (12%) high-grade malignant lymphomas. Fifty-four of the low-grade malignant lymphomas were MALT lymphomas. Lymphoepithelial lesions were observed in bronchial, bronchiolar and alveolar lining. All tumours were composed of nodules, forming a lymphangitic pattern at the periphery and a confluent central mass. Invasion of pleura and vessels was often seen but this without any consequence on survival. Granulomas were found in 20% of cases. Six of the eight high-grade tumours were centroblastic and another two were B-cell lymphomas of undetermined type. In four cases, associated areas of low-grade malignant lymphoma with lympho-epithelial lesions indicated a preexisting MALT lymphoma. Clinical data suggest that limited surgery or non-aggressive chemotherapy can provide long-term survival in patients with such slowly developing neoplasms. However, non-invasive diagnostic methods need to be developed.


Hydatid disease: biology, pathology, imaging and classification.
Rupture and the sequellae of rupture are more important than the mass effect of hydatid cysts, except in the brain where the mass effect by itself has severe consequences. The biology of hydatid disease, including the complex interaction between primary and secondary hosts, is reviewed. The hydatid cyst always starts as a fluid-filled, cyst-like structure (Type I) which may proceed to a Type II lesion if daughter cysts and/or matrix develop. In some instances the Type II lesion becomes hypermature and due to starvation dies to become a mummified, inert calcified Type III lesion. Type I and II lesions may undergo three types of rupture: contained, communicating and direct. Contained rupture is clinically silent, but communicating rupture may cause biliary obstruction and evacuation or infection of the cyst. Direct rupture has the greatest clinical consequences which include anaphylaxis, dissemination of hydatid disease (secondary hydatosis) within the host, and bacterial infection of the pericyst cavity. The clinical implications of the hydatid disease at different stages are discussed. A plea is made for the development of an international medical hydatid registry employing uniform nomenclature and consistent reporting in order to allow more rational comparisons of different types of management.


Semitendinosus tendons are commonly contaminated with skin flora during graft harvest for anterior cruciate ligament reconstruction.
To investigate the rate of bacterial contamination of semitendinosus (ST) tendons during graft harvest in anterior cruciate ligament reconstruction (ACLR), in order to precisely specify the underlying pathogens and obtain data on their susceptibility to potential antibiotics. In a prospective study, a total of 59 consecutive patients undergoing primary ACLR were recruited from one centre. No patient had history of previous surgery to the knee or showed clinical signs of infection. Four tissue samples of harvested ST tendons for anterior cruciate ligament (ACL) autografts (case group; ST) were examined for evidence of bacterial colonisation and compared to four tissue samples of the native ACL as negative controls (control group; ACL). Three of the respective samples were subjected to cultural microbiological examination and one to 16S rRNA-PCR. Antibiotic susceptibility testing was performed for each pathogen that was identified. A total of 342 samples were analysed by culture. Significantly more patients showed a positive culture of the ST (33.9%; n = 20/59) compared to 3.4% of patients (n = 2/59) with positive culturing of the ACL (p < 0.0001). Including 16S rRNA-PCR, in a total of 42.4% (25/59) of patients, bacteria were detected in at least one ST sample either by PCR and/or culture. All species found (n = 33) belong to the typical skin flora with Staphylococcus epidermidis (39.4%; n = 13/33) being the most common species, followed by Staphylococcus capitis (24.2%; n = 8/33). All tested isolates (n = 29) were susceptible to vancomycin (29/29, 100%), 69% (n = 20/29) to oxacillin and 65.5% (n = 19/29) to clindamycin. ST autografts for ACLR were commonly contaminated with skin commensal bacteria during harvest. One-third of the isolates showed resistance to typical perioperative intravenous antibiotics, whereas all isolates were sensitive to vancomycin. Therefore, routine prophylactic decontamination of all hamstring autografts before implantation should be recommended, preferably with topical vancomycin. Level III.


Reliability of stroke volume or pulse pressure variation as dynamic predictors of fluid responsiveness in laparoscopic surgery: a systematic review.
The reliability of stroke volume variation (SVV) and pulse pressure variation (PPV) in predicting fluid responsiveness during laparoscopic surgery remains unclear. We conducted the present systematic review to summarize the current evidence. We reviewed studies that investigated the reliability of SVV and PPV in laparoscopic surgery. Seven studies were included in the final analysis. Two studies demonstrated that the area under the receiver operating characteristic curve (AUROC) for SVV was less than 0.8, and five studies reported that the AUROC was > 0.8. The pooled AUROC for SVV and PPV was more than 0.8 with high heterogeneities between the included studies. Most individual studies have suggested that SVV and PPV are sufficiently reliable for predicting fluid responsiveness during laparoscopic surgery. However, the limited number of patients, varied apparatus used to define fluid responsiveness, diverse definitions of fluid responsiveness, and different fluids used to perform fluid challenges in the included studies render firm conclusions about SVV's and PPV's reliability impossible.


Gastrointestinal symptoms related to autonomic dysfunction following spinal cord injury.
The impact of spinal cord injury on an individual's gastrointestinal tract function is often poorly understood by the general public and also by those involved with persons with spinal cord injury. This chapter reviews the anatomy, physiology and function of the gastrointestinal tract, with particular emphasis on neurological control mechanisms. In turn, it relates the effect that spinal cord injury has on the neurological control of the gastrointestinal tract. The symptoms that are encountered by patients in the acute phase following injury, and by individuals in the months/years after injury, with particular reference to the effect of altered autonomic nervous system control of the gastrointestinal tract, are discussed. Together with a following summary of current bowel management regimens and techniques, this chapter aims to provide an overall view of the effect that autonomic dysfunction due to spinal cord injury has on gastrointestinal function.


High EphA3 expressing ophthalmic trigeminal sensory axons are sensitive to ephrin-A5-Fc: implications for lobe specific axon guidance.
The ophthalmic, maxillary and mandibular axon branches of the trigeminal ganglion provide cutaneous sensory innervation to the vertebrate face. In the chick embryo, the trigeminal ganglion is bilobed, with ophthalmic axons projecting from the ophthalmic lobe, while maxillary and mandibular projections emerge from the maxillomandibular lobe. To date, target tissue specific guidance cues that discriminately guide the axon projections from the two trigeminal ganglion lobes are unknown. EphA receptor tyrosine kinases and ephrin-A ligands are excellent candidates for this process as they are known to mediate axon guidance in the developing nervous system. Accordingly, the expression of EphAs and ephrin-As was investigated at stages 13, 15, 20 of chick embryogenesis when peripheral axons from the trigeminal ganglion are pathfinding. EphA3 is expressed highly in the ophthalmic trigeminal ganglion lobe neurons in comparison to maxillomandibular trigeminal ganglion lobe neurons. Furthermore, from stages 13-20 ephrin-A2 and ephrin-A5 ligands are only localized to the mesenchyme of the first branchial arch (maxillary and mandibular processes), the target fields for maxillomandibular trigeminal ganglion axons. We found that ophthalmic and not maxillomandibular lobe axons were responsive to ephrin-A5-Fc utilizing a substratum choice assay. The implication of these results is that EphA3 forward signaling in ophthalmic sensory axons may be an important mechanism in vivo for lobe specific guidance of trigeminal ganglion ophthalmic projections.


The role of integrated F-18-FDG-PET scanning in the detection of M1 disease in oesophageal adenocarcinoma and impact on clinical management.
The aim of this study was to evaluate the efficacy of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) scanning in the staging of oesophageal adenocarcinoma. One hundred four patients with biopsy-proven adenocarcinoma underwent (18)F-FDG-PET scan. FDG avid lesions were further investigated to their diagnostic conclusion. Nineteen patients (18.26%) were found to have non-loco-regional FDG uptake. Of the patients, 3.84% were found to have M1 disease and 7.69% were found to have a second primary tumour. The sensitivity and specificity of FDG-PET scanning to detect metastatic disease in our series was 57.14% and 84.53%, respectively. The overall diagnostic accuracy was 82.69%. PET scanning improves staging and prevents unnecessary surgery in patients with M1 disease. It represents a good adjunct to computed tomography scanning and endoscopic ultrasound in the staging of oesophageal adenocarcinoma. The detection of asymptomatic coexisting synchronous cancers is an added benefit provided by PET scanning over similar diagnostic modalities.


New measures improve the accuracy of the directed-lie test when detecting deception using a mock crime.
The present study tested the accuracy of probable-lie and directed-lie polygraph tests. One hundred and twenty men and women were recruited from the general community and paid $30 to participate in a mock crime experiment. Equal numbers of males and females were assigned to either the guilty or innocent condition with equal numbers in each group receiving either a probable-lie or a directed-lie polygraph test resulting in a 2 x 2 design with two experimental factors (test type and deceptive condition). Half of the participants were guilty and half were innocent of committing a mock theft of $20 from a purse. All participants were paid a $50 bonus if they could convince the polygraph examiner that they were innocent. There were no significant differences in decision accuracy between probable-lie and directed-lie tests, but respiration measures were more diagnostic for the probable-lie test. New physiological measures, skin potential excursion and a new respiratory measure improved the accuracy of the directed-lie test such that 86% of the innocent participants and 93% of the guilty participants were correctly classified.


Freeze-dried nanocrystal dispersion of novel deuterated pyrazoloquinolinone ligand (DK-I-56-1): Process parameters and lyoprotectant selection through the stability study.
Recently, nanocrystal dispersions have been considered as a promising formulation strategy to improve the bioavailability of the deuterated pyrazoloquinolinone ligand DK-I-56-1 (7‑methoxy-2-(4‑methoxy-d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one). In the current study, the freeze-drying process (formulation and process parameters) was investigated to improve the storage stability of the previously developed formulation. Different combinations of lyoprotectant (sucrose or trehalose) and bulking agent (mannitol) were varied while formulations were freeze-dried under two conditions (primary drying at -10 or -45 °C). The obtained lyophilizates were characterized in terms of particle size, solid state properties and morphology, while the interactions within the samples were analyzed by Fourier transform infrared spectroscopy. In the preliminary study, three formulations were selected based on the high redispersibility index values (around 95%). The temperature of primary drying had no significant effect on particle size, but stability during storage was impaired for samples dried at -10 °C. Samples dried at lower temperature were more homogeneous and remained stable for three months. It was found that the optimal ratio of sucrose or trehalose to mannitol was 3:2 at a total concentration of 10% to achieve the best stability (particle size < 1.0 μm, polydispersity index < 0.250). The amorphous state of lyoprotectants probably provided a high degree of interaction with nanocrystals, while the crystalline mannitol provided an elegant cake structure. Sucrose was superior to trehalose in maintaining particle size during freeze-drying, while trehalose was more effective in keeping particle size within limits during storage. In conclusion, results demonstrated that the appropriate combination of sucrose/trehalose and mannitol together with the appropriate selection of lyophilization process parameters could yield nanocrystals with satisfactory stability.


A presynaptic locus of the action of Met-enkephalin demonstrated in mouse spinal cord cultures.
Monosynaptic excitatory post-synaptic potentials (EPSPs) evoked in spinal cord (SC) neurons by stimulation of dorsal root ganglion (DRG) neurons in cell cultures were reduced by perfusion application of the opiate peptide, Met-enkephalin (2-4 microM). In about 2/3 of cases examined, EPSPs evoked by stimulation of spinal cord cells were also reduced by Met-enkephalin. The effects were antagonized by concomitant perfusion with naloxone (1-2 microM) and recovered when perfusion with Met-enkephalin was stopped. Statistical analysis of synaptic responses indicated that the reduction of EPSP amplitude was due, at least to a major extent, to a decrease in presynaptic transmitter release.


A novel bacterial signalling system with a combination of a Ser/Thr kinase cascade and a His/Asp two-component system.
Prokaryotes and eukaryotes have long been thought to use very different types of kinases (the His kinases of the 'bacterial' two-component systems versus the 'eukaryotic' Ser/Thr/Tyr kinases) to carry out signal transduction. This paradigm no longer holds true, because both systems are now found together in an increasing number of prokaryotic organisms and 'two-component' His kinase are present in eukaryotes. Pioneering work on bacterial protein serine threonine kinases (PSTKs) has been performed in Myxococcus xanthus, a soil bacterium with a complex life cycle that possesses orthologues of signalling-related kinases 'typical' of both the prokaryotic and the eukaryotic kingdoms. In the work reported in this volume of Molecular Microbiology, Nariya and Inouye describe a PSTK cascade that modulates the biochemical activity of MrpC, a CRP-like transcriptional regulator for essential developmental signalling pathways in M. xanthus whose transcription is under the control of a two-component system. This is the first report of both a functional PSTK cascade in bacteria and the use of both PSTK and two-component systems to control a single complex bacterial signalling event.


Predictors of genitourinary malignancy in patients with asymptomatic microscopic hematuria.
To report the incidence of genitourinary malignancy and identify associated risk factors in patients undergoing urologic evaluation for asymptomatic microscopic hematuria (AMH) according to the 2012 American Urologic Association guidelines. A retrospective institutional review of patients who underwent evaluation for AMH between 2012 and 2015 was conducted. Covariates analyzed included age, sex, smoking status, history of other malignancy, history of pelvic irradiation, presence of irritative voiding symptoms, use of anticoagulation, number of red blood cells on microscopic urinalysis, and guideline adherence. Univariate analysis was performed to explore the association between these risk factors and the presence of genitourinary malignancy. Of the 1,049 patients analyzed with AMH, urologic malignancy was diagnosed in 12 patients (1.1%), including 1 upper-tract urothelial cancer, 5 renal tumors, and 6 bladder tumors. All patients with malignancy were over 50 years old. Older age, male sex, smoking history, and irritative voiding symptoms were associated with malignancy on univariate analysis. Our data adds to the growing evidence that the incidence of malignancy among patients with AMH is low. Risk factors associated with urinary tract cancer are male sex, age>50 years, smoking history, and irritative voiding symptoms. Further prospective, randomized trials would be useful for developing a more tailored screening protocol for low-risk patients.


In situ hybridization to the Crithidia fasciculata kinetoplast reveals two antipodal sites involved in kinetoplast DNA replication.
Kinetoplast DNA is a network of interlocked minicircles and maxicircles. In situ hybridization, using probes detected by digital fluorescence microscopy, has clarified the in vivo structure and replication mechanism of the network. The probe recognizes only nicked minicircles. Hybridization reveals prereplication kinetoplasts (with closed minicircles), donut-shaped replicating kinetoplasts (with nicked minicircles on the periphery and closed minicircles in the center), and postreplication kinetoplasts (with nicked minicircles). Replicating kinetoplasts are associated with two peripheral structures containing free minicircle replication intermediates and DNA polymerase. Replication may involve release of closed minicircles from the center of the kinetoplast and their migration to the peripheral structures, replication of the free minicircles therein, and then peripheral reattachment of the progeny minicircles to the kinetoplast.


Radiodiagnostic signs in pseudoxanthoma elasticum generalisatum (dysgenesis elastofibrillaris mineralisans).
The clinical symptomatology of patients suffering from pseudoxanthoma elasticum and the radiodiagnostic signs in four patients suffering from this disease have been reviewed. In these patients four groups of previously unpublished radiodiagnostic abnormalities were found. These are calcification of a number of ligaments; changes in the wall of brachiocephalic trunk, the right common, internal and external carotid arteries; fibro-osseous metaplasia of the long bones; dysplasia of the vertebrae. The authors believe that these changes are explicable by the general disorder of connective tissue and its derivatives which occurs in pseudoxanthoma elasticum.


Correction: Messele et al. Longitudinal Analysis of Antimicrobial Resistance among Enterococcus Species Isolated from Australian Beef Cattle Faeces at Feedlot Entry and Exit. Animals 2022, 12, 2690.
There was an error in the original publication [...].


Dipolar Waves as NMR maps of helices in proteins.
Dipolar Waves describe the periodic variation in the magnitudes of dipolar couplings in the backbone of a protein as a function of residue number. They provide a direct link between experimental measurements of dipolar couplings in aligned samples and the periodicity inherent in regular secondary structure elements. It is possible to identify the residues in a helix and the type of helix, deviations from ideality, and to orient the helices relative to an external axis in completely aligned samples and relative to each other in a common frame in weakly aligned samples with Dipolar Waves. They provide a tool for accurately describing helices and a step towards high throughput structure determination of proteins.


Adenocarcinoma of the stomach in association with Menetrier's disease.
Menetrier's disease is an uncommon lesion which may have malignant potential. This report documents a case of gastric malignancy arising in a patient with long-standing Menetrier's disease and emphasizes that close follow-up of patients with this condition is necessary because of the possible development of gastric malignancy.


Imaging palpable tumors in pediatrics.
Palpable tumors in children are a common reason for consulting a radiologist. The differential diagnosis is extensive and considerably different from that used in adults. Some of the etiologies of palpable tumors are little known outside of pediatrics. The most commonly used imaging test is ultrasonography, because in addition to being harmless and cost-effective, it is conclusive in most cases. Most palpable lesions in children are benign; it is estimated that only 1% are malignant. Knowing these lesions enables the correct diagnosis without the need to resort to unnecessary, sometimes invasive tests, thus avoiding delays in treatment when more severe disease is present. This article aims to review the clinical and radiological characteristics of the palpable lesions that are most common in pediatric patients, explaining the key features that enable accurate diagnosis.


Adverse infant outcomes following low-risk pregnancies in England: a retrospective cohort study.
There are limited data describing adverse infant outcomes in infants born to women with a low risk of complications during pregnancy, such as those who may be enrolled in maternal immunization trials. This retrospective study estimated incidence proportions of infant outcomes in different cohorts of liveborn infants in England between 2005 and 2017. The incidence proportions of 10 infant outcomes were calculated for liveborn infants from pregnancies represented in the Clinical Practice Research Datalink (CPRD) Mother-Baby Link (MBL) and linkage to Hospital Episode Statistics (HES). Three infant cohorts were designed: (1) the all pregnancies infants cohort (N = 185,119), (2) the all pregnancies with a gestational age (GA) ≥ 24 weeks infants cohort (N = 183,869), and (3) the low-risk pregnancies infants cohort (LR infants cohort, N = 121,871), which included pregnancies with a GA ≥ 24 weeks and no diagnosis of predefined high-risk medical conditions until 24 weeks GA. The most common adverse infant outcome in the three infant cohorts was macrosomia (e.g., 1,085.9/10,000 live births in the LR infants cohort), followed by minor congenital anomalies (e.g., 800.6/10,000 in the LR infants cohort), very low/low birth weight (e.g., 400.6/10,000 in the LR infants cohort), and major congenital anomalies (e.g., 270.4/10,000 in the LR infants cohort). The incidence proportions for early-onset sepsis, very low/low birth weight, and minor and major congenital anomalies were lower in the LR infants than in the other cohorts (non-overlapping confidence intervals [CIs]). The incidence proportions of neonatal death, infant death, late-onset sepsis, macrosomia, small for GA, and large for GA were similar between cohorts (overlapping CIs). This study generated background rates of adverse infant outcomes from liveborn infants of all and low-risk pregnancies represented in the CPRD Pregnancy Register MBL and linkage to HES. The results indicate lower incidence proportions of several adverse infant outcomes in infants from low-risk pregnancies compared to all pregnancies, illustrating the importance of considering maternal risk factors. These background rates may facilitate the interpretation of safety data from maternal immunization trials and of pharmacovigilance data from maternal vaccines. They may also be of interest for other interventions studied in pregnant women.


Protocol for genome editing in wild allotetraploid rice Oryza alta.
We present a protocol for Agrobacterium-mediated genetic transformation and genome editing in wild allotetraploid rice Oryza alta. We detail steps to induce embryogenic calli from mature seeds and co-cultivate with Agrobacterium after infection. We further describe how to select transformed cells that proliferated from infected calli based on hygromycin resistance, resulting in regeneration of transformed plantlets with multiple edited alleles. Edited lines produced via this protocol can be used for gene functions studies and de novo domestication of O. alta. For complete details on the use and execution of this protocol, please refer to Yu et al. (2021).


Neoadjuvant camrelizumab plus chemotherapy in locally advanced oesophageal squamous cell carcinoma: a retrospective cohort study.
Neoadjuvant therapy is recommended to improve the prognosis of oesophageal squamous cell carcinoma (ESCC). As a PD-1 inhibitor developed in China, camrelizumab is more accessible and available for Chinese ESCC patients. Camrelizumab plus neoadjuvant chemotherapy has shown promising efficacy with acceptable toxicity for resectable ESCC in the NIC-ESCC2019 trial. However, this was a single-arm trial, so we conducted a retrospective cohort study to compare neoadjuvant camrelizumab plus chemotherapy with neoadjuvant chemotherapy alone in terms of the safety and efficacy in patients with locally advanced ESCC. Between January 2017 and December 2021, patients with stage II-IVa ESCC who received neoadjuvant therapy at the First Affiliated Hospital of Chongqing Medical University and underwent radical oesophagectomy were enrolled in our study. These included 19 patients who received neoadjuvant chemotherapy plus camrelizumab (group 1) and 40 patients who only received neoadjuvant chemotherapy (group 2). The baseline characteristics of the patients were comparable between the two groups. The pathological complete response (pCR) rate in group 1 was significantly higher than that in group 2 (26.3% vs. 2.5%, P = 0.018). All patients in group 1 achieved complete resection (R0), compared with 39 (97.5%) patients in group 2. Adverse events occurred in 16 (84%) patients in group 1 versus 35 (87.5%) patients in group 2. No grade ≥ 4 adverse events occurred in either group. No significant difference was found in surgical outcomes or postoperative complications. The 90-day mortality rate was comparable between the two groups (1 patient died in group 1 versus 2 patients in group 2). Neoadjuvant camrelizumab plus chemotherapy followed by surgery was associated with a promising pCR rate and a manageable safety profile for patients with locally advanced ESCC.


Combined effects of rearing temperature regime (thermocycle vs. constant temperature) during early development and thermal treatment on Nile tilapia (Oreochromis niloticus) sex differentiation.
In nature, water temperature experiences daily variations known as thermocycles. Temperature is the main environmental factor that influences sex determination in most teleost fish. The purpose of this study was to examine the effects of rearing temperature (thermocycle (TC) vs. constant (CTE)) on development and a posterior thermal shock throughout the period of sex differentiation of Nile tilapia (Oreochromis niloticus). Embryos and larvae were kept under two temperature regimes: TC of 31 °C:25 °C day:night vs. CTE of 28 °C from 0 to 11 dpf. After this period, the larvae from each group were subjected to either heat treatment (HT, 36 °C for 12 days) or kept under the same rearing temperatures until 23 dpf (Control, C). Then all the groups remained at constant temperature until 270 dpf, when blood and gonads were collected. Larval samples were used to examine the expression of genes related to male (amh, ara, sox9a, dmrt1a) and female (cyp19a1a, foxl2, era) sexual differentiation. In juveniles, sex was characterized by histology, the gonadal expression of the genes involved in the sex steroid synthesis was analyzed by qPCR, and plasma testosterone (T) and estradiol (E2) levels were analyzed by ELISA. In larvae, daily TCs increased the survival rate against HT and up-regulated the expression of ovarian differentiation genes. In juveniles, TC + C induced a higher proportion of females and higher cyp19a1a expression compared to CTE + C. HT induced changes in the CTE group by up-regulating testicular differentiation genes and down-regulating female promoting genes, which did not occur in the TC group. Juveniles from TC + C group presented a higher proportion of females with higher E2 and cyp19a1a than CTE + HT. Fish from the CTE + HT group showed a higher percentage of males with highest T and amh. These findings indicate that daily TCs during larval development promote ovarian differentiation and diminish the masculinizing effects of HT.


Atrophy and decreased activation of fronto-parietal attention areas contribute to higher visual dysfunction in posterior cortical atrophy.
Voxel-based morphometry and functional magnetic resonance imaging demonstrated severe atrophy and decreased activation of visual attention areas and occipital lobes in a patient with early posterior cortical atrophy compared with healthy controls and patients with early Alzheimer's disease. Our complex approach indicates that structures responsible for attention can be damaged early in posterior cortical atrophy and may contribute to the characteristic decline in higher visual functions.


'Males second' strategy in the allocation of sexes by the parasitic wasp, Gryon japonicum.
Patterns of the sex ratio allocation of Gryon japonicum (Ashmead) (Hymenoptera: Scelionidae), a solitary egg parasitoid of Riptortus clavatus (Thunberg) (Heteroptera: Alydidae), were investigated in the laboratory, and the result was checked against the field data on the sex composition of the parasitoid. When five host eggs were presented simultaneously to each of the females of G. japonicum in a laboratory experiment, they had a strong tendency to lay a male egg in second host egg and female eggs in the others. However, when four host eggs were presented to each female more than 3 h after the completion of oviposition on a host egg, most of the females laid male eggs in the third oviposition, i.e. the second host eggs after the experimental interruption of oviposition. These results indicated that there was a mechanism for G. japonicum to produce a male egg in the second host egg in consecutive ovipositions, and that the mechanism was reset by more than 3 h intervals of oviposition. By this mechanism, G. japonicum is thought to produce the precise sex ratio in response to the size of a host egg batch. Field data on the size of a host egg batch and the sex composition of the parasitoid in a host egg batch supported this view.


Atenolol and sustained release nifedipine alone and in combination in hypertension. A randomised, double-blind, crossover study.
In this randomised, double-blind, crossover trial, the efficacy in hypertension of atenolol and nifedipine as single agents or in combination was compared. 81 patients with mild to moderate essential hypertension (sitting diastolic blood pressure 100-120 mm Hg, aged 20-70 years) from 6 outpatient clinics entered the study. By use of a Latin-square design, patients received, in randomised fashion, sustained release nifedipine 20mg twice daily, atenolol 50mg in the morning and then placebo in the evening, or sustained release nifedipine 20mg plus atenolol 50mg in the morning and then placebo in the evening. Each schedule was followed for 4 weeks. All treatments lowered systolic and diastolic blood pressure in the supine and standing positions compared with pretreatment values. The combination regimen significantly reduced supine and standing systolic (p less than 0.01 and p less than 0.001, respectively) and diastolic (p less than 0.001) blood pressure compared with nifedipine alone, and it also significantly reduced supine and standing systolic (p less than 0.01 and p less than 0.03, respectively) and diastolic (p less than 0.01) blood pressure compared with atenolol alone. Heart rate was significantly decreased by atenolol and the combination compared with nifedipine alone. 15 patients withdrew because of side effects: 9 during nifedipine treatment, 2 during atenolol treatment and 4 during combination treatment. Side effects were typical of those associated with nifedipine or atenolol. Flushes and hot sweats, which were frequent with nifedipine, were significantly less (p less than 0.001) with atenolol or the combination.(ABSTRACT TRUNCATED AT 250 WORDS)