Fasting affects more markedly neuropeptide Y than monoamines in the rat brain.
Monoamine turnover and neuropeptide Y (NPY) levels were evaluated in the CNS of 48- and 72-h-fasting adult, male rats in four brain areas: the hypothalamus, cortex, hippocampus, and striatum. In 48-h-fasted rats, NPY levels increased in the cortex and decreased in the striatum. The dopaminergic turnover increased in the hippocampus. The serotonergic turnover decreased in the hippocampus, striatum, and cortex and was still decreased after 72 h of fasting. In 72-h-fasted rats, an overall significant increase of NPY levels was observed except in the striatum, where it decreased significantly. No relationship appeared between NPY and monoamine levels, suggesting that NPY can act independently in feeding behavior and play, in different brain areas, an important role in its regulation.


The changing philosophy in the search for anti-rheumatic drugs: a personal overview.
A mini-review to mark the presentation of the Inwin Prize during the 3rd Interscience World Conference on Inflammation at Monte Carlo in March 1989 and to gratefully acknowledge my many co-authors. For this reason this article is devoted to some aspects of the work from this department over the past three decades.


Angiotensin-converting enzyme inhibition prevents myocardial infarction-induced increase in renal cortical cGMP and cAMP phosphodiesterase activities.
We investigated whether myocardial infarction (MI) enhances renal phosphodiesterases (PDE) activities, investigating particularly the relative contribution of PDE1-5 isozymes in total PDE activity involved in both cGMP and cAMP pathways, and whether angiotensin-converting enzyme inhibition (ACEi) decreases such renal PDE hyperactivities. We also investigated whether ACEi might thereby improve atrial natriuretic peptide (ANP) efficiency. We studied renal cortical PDE1-5 isozyme activities in sham (SH)-operated, MI rats and in MI rats treated with perindopril (ACEi) 1 month after coronary artery ligation. Circulating atrial natriuretic peptide (ANP), its second intracellular messenger cyclic guanosine monophosphate (cGMP) and cGMP/ANP ratio were also determined. Cortical cGMP-PDE2 (80.3 vs. 65.1 pmol/min/mg) and cGMP-PDE1 (50.7 vs. 30.1 pmol/min/mg), and cAMP-PDE2 (161 vs. 104.1 pmol/min/mg) and cAMP-PDE4 (307.5 vs. 197.2 pmol/min/mg) activities were higher in MI than in SH rats. Despite increased ANP plasma level, ANP efficiency tended to be decreased in MI compared to SH rats. Perindopril restored PDE activities and tended to improve ANP efficiency in MI rats. One month after coronary ligation, perindopril treatment of MI rats prevents the increase in renal cortical PDE activities. This may contribute to increase renal ANP efficiency in MI rats.


[Use of mannitol in neuroanesthesia and neurointensive care].
Mannitol, the osmotic diuretic used in neuroanaesthesia and neurointensive care, has, in addition to its osmotic properties, various effects upon haemodynamics, cerebral blood flow and cerebral blood volume. Three factors are proposed to contribute to mannitol's capacity to lower intracranial pressure and to improve cerebral compliance: cerebral dehydration, and two forms of autoregulation-mediated vasoconstriction. In the case of viscosity autoregulation, it is admitted that changes in blood viscosity after mannitol result in reflex vasoconstriction to maintain cerebral blood flow constant. It has also been proposed that when mannitol administration results in increased cerebral perfusion pressure, vasoconstriction may occur in vascular beds in which autoregulation to perfusion pressure is preserved. On the basis of its effects on cerebral blood flow and free radical scavenging properties, mannitol has recently been investigated as a cerebral protective agent, with the capacity to reduce or prevent damage due to cerebral ischaemia. Finally, mannitol may be injected into a carotid or a vertebral artery to produce blood-brain barrier breakdown, thus improving the brain penetration of chemotherapeutic agents.


Factor investing: A stock selection methodology for the European equity market.
This paper uses European high capitalization corporate data for the 1991-2019 period to demonstrate that a systematic active management portfolio based on the identification of value, profitability, and momentum factors can outperform competing benchmark strategies. Factor investment methodologies received significant attention in the literature in the U.S. market but their application to European corporates is more limited. The authors construct several systematic investment strategies combining different metrics measuring the three factors. Reported results show that a) combined (mixed/conditional) strategies deliver positive alphas and significantly outperform their pure strategy counterparts and b) while there exists a time changing performance of selected metrics the iterative combination of factors delivers the highest performance with average annualized compounded returns of up to about 17%. Three Key Takeaways: 1. This paper documents the existence of alpha-generating factor strategies based on a combination of value, profitability, and momentum metrics. Combined (mixed/conditional) portfolios significantly outperform their pure strategy counterparts. 2. The iterative combination of factors delivers the highest performance with annualized compounded returns of up to 17%. 3. In line with the recent literature, we find decaying returns to factor strategies.


First description of the gravid female of Philometra rubra (Leidy, 1856) (Nematoda: Philometridae), a parasite of the abdominal cavity of temperate basses Morone Spp. (Moronidae: Perciformes) in North America.
Gravid females of the little-known nematode species Philometra rubra ( Leidy, 1856 ) (Philometridae) are described from specimens from the abdominal cavity of the striped bass, Morone saxatilis (Walbaum), in South Carolina and Canada. The specimens were studied with the use of light and scanning electron microscopy. This species is mainly characterized by the distribution and different sizes of cephalic papillae from the external circle, which is a unique feature compared to other philometrids. Other characteristic features are the shape of the posterior end of body, size and location of caudal projections, and the presence of a well-developed anterior esophageal inflation. The morphology of the male of P. rubra and the life cycle of this nematode are still unknown.


[The value of low-dose segmental or total body irradiation in generalized disease of the lymphoreticular system: a case report (author's transl)].
The application of low-dose segmental or total body irradiation to patients with generalized malignant non-Hodgkin lymphoma is discussed. The indications and irradiation procedure are presented in the light of a case report of a patient with generalized intra-abdominal lymphosarcoma and no evidence of disease 5 years after treatment.


Adhesive functions of both chains of VLA-integrins are not fully conserved across the human-porcine species barrier: implications for xenotransplantation.
A possible solution to the shortage of organs for transplantation would be the use of swine as source animals. As current immunosuppressive protocols cannot prevent rejection of these organs, super-selective immunosuppression or the induction of donor-specific central tolerance represent two promising approaches. Central tolerance induction involves bone marrow transplantation, and depends on intrathymic deletion of donor reactive host cells by donor antigen-presenting cells. In super-selective immunosuppression, the aim would be to block specific adhesive interactions on one species side only, leaving the other species side unaffected. As both processes depend on the interaction of adhesion molecules with their ligands, we investigated whether the beta1-integrins, which play roles in hematopoiesis as well as in rejection, can successfully interact across the swine-to-human species barrier. We employed static cell-to-extracellular protein and cell-to-cell adhesion assays, using different cell types and monoclonal antibody as well as peptide-fragments to analyze conservation of cross-species adhesive interactions. We found that porcine and human cells interact differently with their cross-species ligands than their own and that the adhesive function of the beta1-chain does not seem to be fully conserved across the species barrier. Integrin functions are not fully conserved across the pig-to-human species barrier. While the development of multi-transgenic pigs, whose integrins interact with human ligands in a more ''human-like'' manner may be necessary to facilitate tolerance induction, these facts give rise to new possibilities concerning super-selective immunosuppression.


A new practical classification for spatial distribution and morphology of human hair: Ahmad's LGMA classification.
The human hair is a complex structure with a diversity within itself. There is a wide variation in distribution and spatial arrangement of hairs. The current classification was developed on the basis of high-resolution photographs of adult human scalp. On the observation, the new classification consisted of 4 categories. It will help the hair restoration surgeons and dermatologists to identify the various pattern and also to help in deciding the appropriate size of the punch in FUE.


[Cyclic nucleotide concentration changes in different tumors and therapeutic success through increasing the cAMP level].
Changes in the concentration of cyclic AMP as well as cyclic GMP were measured in different murine tumors and in human tumors of varying malignancy. The quotient of cAMP and cGMP seems to be an important parameter for the molecular-biological derangement. Because of the recently much discussed importance of cAMP and cGMP in the immune defence the changes in the concentration of both nucleotides were measured in the T-lymphocytes of tumor patients. Significant changes occurred in patients with malignant melanoma. Investigations of the stimulatibility of the cAMP and cGMP levels revealed a diminished activatibility of the cAMP level and a higher stimulatibility of the cGMP level in the T-lymphocytes of patients with malignant melanoma as compared with those of the controls. On the basis of the working hypothesis that there is a causal relationship between the deranged dualism of cAMP and cGMP in the T-lymphocytes and the failure of the immunological tumor cell defence, an increase in the cAMP level is offered as a possible therapy. Therapeutic results in tumor-bearing mice and first results in melanoma patients are discussed.


Vitamin D and the immune system.
The investigation of the potential influence of 1,25-(OH)2D3 on immune cells has expanded our understanding of hormone-cytokine interactions. 1,25-(OH)2D3 stimulates phenotypic and function changes in immature monocytes, alters protein synthesis, increases adherence, and augments interleukin-1 secretion. T lymphocyte proliferation and B cell immunoglobulin production are inhibited by the hormone. 1,25-(OH)2D3 decreases IL 2 and IFN-gamma synthesis by activated T lymphocytes in association with decreases in mRNA for these proteins. The step from the investigation of in vitro interactions to an understanding of in vivo effects of 1,25-(OH)2D3 on immune cells requires further study. On the basis of information at hand, such as the potential for macrophage conversion of 25-OH-D3 to 1,25-(OH)2D3, decreased or increased macrophage function in association with vitamin D3 status in vitro and in vivo, as well as altered T cell subset ratios and proliferative responses with administration of the hormone, it is tempting to speculate that 1,25-(OH)2D3 exerts an influence on immune cell function in concert with other recognized soluble mediators of monocyte and lymphocyte origin. The primary influence of 1,25-(OH)2D3 may vary with the tissue site. Systemic levels of hormone may aid in maintaining tonic immunosuppression and thus prevent trivial antigenic stimuli from initiating an immune response. Upon initiation of an immune response to a significant antigenic challenge 1,25-(OH)2D3 may, in concert with other suppressor mechanisms, limit the extent of the host response by inhibition of IL 2 and IFN-gamma production. At local sites of chronic inflammation concentrations of 1,25-(OH)2D3 may be elevated and may act in an autocrine or paracrine fashion to alter the immune response, for example, by increasing IL 1 production and antigen presentation by tissue monocyte/macrophages. The activation of T cells is associated with the synthesis of 1,25-(OH)2D3 receptors, thus potentially limiting T cell proliferation in the presence of the hormone. Other biological actions of IL 1, however, including effects on cells in bone, joint, and brain may be augmented. Thus, the end result of the opposing effects of 1,25-(OH)2D3 on immune cells and their secretory products may vary with the specific cells involved, their state of maturation and activation, and the local concentrations of the hormone. Studies to date support the concept of an expanded role for 1,25-(OH)2D3 in immune cell biology.


Brachytherapy focal dose escalation using ultrasound based tissue characterization by patients with non-metastatic prostate cancer: Five-year results from single-center phase 2 trial.
This prospective trial investigates side effects and efficacy of focal dose escalation with brachytherapy for patients with prostate cancer. In the Phase II, monocentric prospective trial 101 patients with low-/intermediate- and high-risk prostate cancer were enrolled between 2011 and 2013. Patients received either PDR-/HDR-brachytherapy alone with 86-90 Gy (EQD2, α/β = 3 Gy) or PDR-/HDR-brachytherapy as boost after external beam radiation therapy up to a total dose of 91-96 Gy (EQD2, α/β = 3 Gy). Taking place brachytherapy all patients received the simultaneous integrated focal boost to the intra-prostatic tumor lesions visible in computer-aided ultrasonography (HistoScanning™) - up to a total dose of 108-119 Gy (EQD2, α/β = 3 Gy). The primary endpoint was toxicity. Secondary endpoints were cumulative freedom from local recurrence, PSA-free survival, distant metastases-free survival, and overall survival. This trial is registered with ClinicalTrials.gov, number NCT01409876. Median follow-up was 65 months. Late toxicity was generally low with only four patients scoring urinary grade 3 toxicity (4/101, 4%). Occurrence of any grade of late rectal toxicities was very low. We did not register any grade ≥2 of late rectal toxicities. The cumulative 5 years local recurrence rate (LRR) for all patients was 1%. Five years- biochemical disease-free survival estimates according Kaplan-Meier were 98,1% and 81,3% for low-/intermediate-risk and high-risk patients, respectively. Five years metastases-free survival estimates according Kaplan-Meier were 98,0% and 83,3% for all patients, low-/intermediate-risk and high-risk patients, respectively. The 5 years-results from this Phase II Trial show that focal dose escalation with computer-aided ultrasonography and brachytherapy for patients with non-metastatic prostate cancer is safe and effective.


Integrated approach of migration prediction using numerical modelling associated to experimental determination of key parameters.
The principle of utilizing a computing program describing precisely the migration of additives from a polymer into a food simulant is presented. The model has been validated with a UV absorber in polypropylene migrating into glyceryl tripelargonate, a pure triglyceride whose behaviour and average molecular weight are similar to Myglyol (a synthetic mixture of C8-C12 triglycerides). Six parameters were used to fit the simulant sorption and additive extraction kinetics, and these were determined by independent experiments. The possibility of eliminating any of the parameters is also discussed. This work provides the first consistent set of experimental data that can be used to overestimate the diffusion coefficients of additives both in virgin (without contact with solvent) and in swollen (fat contact) polymer. The influence of mobility increase brought out by temperature or swelling are compared. The effects were more important for high molecular weight compounds.


Orexin-A protects against cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through OX1R-mediated MAPK/ERK/mTOR pathway.
Orexin A (OXA) is a neuroprotective peptide that exerts protective effects on multiple physiological and pathological processes. Activation of autophagy is linked to the occurrence of cerebral ischemia-reperfusion injury (CIRI); however, its function remains incompletely understood. In this study, OXA was sought to exert its neuroprotective role by regulating autophagy in oxygen and glucose deprivation and reoxygenation (OGD/R) model and middle cerebral artery occlusion (MCAO) model of rats, and to elucidate the underlying molecular mechanisms. Acridine orange (AO) staining was used to evaluate autophagic vacuoles. Cell viability was measured by CCK8. The levels of p-ERK1/2, t-ERK1/2, p-mTOR, LC3B, Beclin 1, and p62 were evaluated by western blotting. Apoptosis rate was detected by Hoechst 33342 staining and Terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL). OXA treatment alleviated neuronal apoptosis and significantly inhibited autophagy activity. Mechanistically, OXA exerted its neuroprotective effects in vivo and in vitro by suppressing over-activated autophagy by modulating OX1R-mediated MAPK/ERK/mTOR pathway. The results of this study elucidate the roles of autophagy in CIRI and the mechanisms underlying the neuroprotective action of OXA. Our findings could facilitate the development of novel therapeutics for ischemic stroke.


Early Failure in Medial Unicondylar Arthroplasty: Radiographic Analysis on the Importance of Joint Line Restoration.
Survivorship of unicondylar knee arthroplasty (UKA) remains a drawback, especially compared with the outcome of total knee arthroplasty. This could be improved by identifying and correcting failure mechanisms. To this purpose, this study aimed at exploring failure modalities of UKA, with particular focus on the role of joint line (JL) position and alignment as variable to be optimized for a successful outcome. This study explored modes of failure in 266 medial UKAs. Radiological comparison was performed between 24 failures and 24 matched controls, to determine the importance of UKA positioning in terms of femorotibial angle (FTA), tibial plateau angle, and posterior tibial slope (PTS). Radiographic comparative analysis showed statistically significant differences in the failure group compared with the control group in terms of variation in FTA (p = 0.0222), PTS (p = 0.0025), and JL height (p = 0.0022). Variations not only in FTA but also PTS and JL height were correlated with failures observed in this series. Thus, based on the results of this study, it emerges that JL position should be carefully controlled in all planes while implanting a UKA. This is a Level III, case-control study.


De-novo transcriptome analysis of the banana shrimp (Fenneropenaeus merguiensis) and identification of genes associated with reproduction and development.
The banana shrimp Fenneropenaeus merguiensis is a commercially important marine crustacean for world aquaculture and fisheries. Despite this, limited genetic information is available for it and many other penaeid shrimp species. Here we present the first in-depth analysis of the transcriptional content of 8 different tissues from the banana shrimp using RNA-Seq technologies. A total of over 1 million single-end and over 49 million paired-end reads were obtained from Roche 454FLX and illumina sequencing platforms, respectively, resulting in an assembly of 124,631 transcripts with an N50 of 1,332 and mean length of 514 nt. A total of 59,179 putative protein sequences obtained from the assembled transcripts were annotated using public protein sequence databases and assigned 20,430 BLAST hits, 16,866 GO terms and 13,304 KOG categories. Further analysis revealed a rich set of transcript sequences exhibiting homology with genes associated with reproduction, sex determination and development and distinguished the tissues responsible for this expression. This report adds a substantial contribution to the sequence data currently available for F. merguiensis, providing valuable resources for further research.


Bioremediation of Crude Oil by Rhizosphere Fungal Isolates in the Presence of Silver Nanoparticles.
This research work focuses on the utilization of indigenous fungi for in situ bioremediation of crude oil in the presence of silver nanoparticles. Two fungi belonging to two different genera showed promising crude oil-degrading abilities. Fungal isolates were identified based on internal transcribed spacer rDNA sequence analysis. Gas chromatography-mass spectrometry analysis of the crude oil remaining in the culture medium after seven days was performed. The response surface method (RSM) designed by Box-Behnken was used to establish a mathematical model. Inter-simple sequence repeat (ISSR) primers were used to examine the genetic variation of fungal isolates. Gas chromatography-mass spectrometry (GC-MS) analysis after seven days showed that the optimum biodegradation of crude oil was 57.8%. The crude oil degradation rate was significantly affected by a temperature of 30 °C, pH value of 7, crude oil concentration of 4 g/L, a 1:1 ratio between A. flavus AF15 and T. harzianum TH07, and an silver nanoparticle (AgNP) concentration of 0.05 g. Molecular characterization in fungal isolates is extremely valuable when using ISSR markers. Two fungal isolates showed promising crude oil-degrading abilities with positive effect of low concentrations of AgNPs on biodegradation. RSM is an efficient mathematical method to optimize the microbial biodegradation of crude oil.


Purification and characterization of a thermostable α-amylase produced by the fungus Paecilomyces variotii.
An α-amylase produced by Paecilomyces variotii was purified by DEAE-cellulose ion exchange chromatography, followed by Sephadex G-100 gel filtration and electroelution. The α-amylase showed a molecular mass of 75 kDa (SDS-PAGE) and pI value of 4.5. Temperature and pH optima were 60°C and 4.0, respectively. The enzyme was stable for 1 h at 55°C, showing a t₅₀ of 53 min at 60°C. Starch protected the enzyme against thermal inactivation. The α-amylase was more stable in alkaline pH. It was activated mainly by calcium and cobalt, and it presented as a glycoprotein with 23% carbohydrate content. The enzyme preferentially hydrolyzed starch and, to a lower extent, amylose and amylopectin. The K(m) of α-amylase on Reagen® and Sigma® starches were 4.3 and 6.2 mg/mL, respectively. The products of starch hydrolysis analyzed by TLC were oligosaccharides such as maltose and maltotriose. The partial amino acid sequence of the enzyme presented similarity to α-amylases from Bacillus sp. These results confirmed that the studied enzyme was an α-amylase ((1→4)-α-glucan glucanohydrolase).


Enhancing iPSC-CM Maturation Using a Matrigel-Coated Micropatterned PDMS Substrate.
Cardiac myocytes isolated from adult heart tissue have a rod-like shape with highly organized intracellular structures. Cardiomyocytes derived from human pluripotent stem cells (iPSC-CMs), on the other hand, exhibit disorganized structure and contractile mechanics, reflecting their pronounced immaturity. These characteristics hamper research using iPSC-CMs. The protocol described here enhances iPSC-CM maturity and function by controlling the cellular shape and environment of the cultured cells. Microstructured silicone membranes function as a cell culture substrate that promotes cellular alignment. iPSC-CMs cultured on micropatterned membranes display an in-vivo-like rod-shaped morphology. This physiological cellular morphology along with the soft biocompatible silicone substrate, which has similar stiffness to the native cardiac matrix, promotes maturation of contractile function, calcium handling, and electrophysiology. Incorporating this technique for enhanced iPSC-CM maturation will help bridge the gap between animal models and clinical care, and ultimately improve personalized medicine for cardiovascular diseases. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Cardiomyocyte differentiation of iPSCs Basic Protocol 2: Purification of differentiated iPSC-CMs using MACS negative selection Basic Protocol 3: Micropatterning on PDMS.


Morbidity of rectosigmoid resection and primary anastomosis in patients undergoing primary cytoreductive surgery for advanced epithelial ovarian cancer.
Studies from the colorectal literature have shown that factors associated with anastomotic leak after colorectal resection include long surgical time (>2 h), multiple blood transfusions, and short distance to the anal verge. The aim of this study was to assess the morbidity associated with en bloc resection of ovarian carcinoma with low anterior resection and anastomosis in patients undergoing primary cytoreductive surgery for advanced disease. We performed a retrospective chart review of all patients who had undergone primary cytoreduction for advanced epithelial ovarian cancer with rectosigmoid resection followed by low rectal anastomosis between January 1994 and June 2004. Patient characteristics, operative details, and postoperative complications were extracted from patients' charts. Seventy patients met the above criteria and form our study group. The median age was 59 years (range, 25-82). There were 52 stage IIIC (74%) and 18 stage IV (26%) cancers. The median operating time was 315 min (range, 120-750) and the median estimated blood loss was 1200 ml (range, 250-8000), with 53 (76%) patients requiring blood transfusion. Twenty-eight patients (40%) underwent major upper abdominal procedures other than omentectomy, and 14 patients (20%) underwent a second bowel resection. Twelve patients (17%) underwent a protective ileostomy while the remainder (83%) did not. Of the 58 patients with no ostomy, the only complications associated with the resection and anastomoses were a pelvic abscess in 3 patients (5%) and an anastomotic leak requiring diverting colostomy in 1 patient (1.7%). Of the 12 patients who had protective ileostomies, 3 (25%) had complications related to their ileostomy short-bowel syndrome requiring early reversal, incarceration of the prolapsed loop requiring surgical correction, and prolapse corrected electively at the time of second-look surgery. In women undergoing primary cytoreductive surgery, the morbidity associated with en bloc resection of ovarian carcinoma with low rectosigmoid resection and anastomosis without protective ileostomy was acceptably low, with an anastomotic leak rate of less than 2%. Protective ileostomy is not always necessary and should be used selectively.


The calcium-magnesium-deficient rat: a study on the distribution of calcium in the spinal cord using the electron probe microanalyser.
Using the scanning electron probe X-ray microanalysis technique, calcium distribution in the spinal cord of the calcium-magnesium-deficient rat was studied. Calcium accumulations were observed within and around the perikaryon of certain unspecified motoneurons in the spinal cord.


I Serve 2: Identifying and caring for military-connected children in civilian primary care settings.
Military children make tremendous sacrifices in support of a parent(s) military service. More than two million children have a parent who is serving or has served in the Armed Forces. Research shows that military-connected children are at higher risk of physical, psychological, and behavioral health issues. While "resilient" is the word used to describe most military children, it is important to recognize the stresses/stressors of military life- that military children serve too-to support and care for them.


[Medical jurisprudence problems raised by transsexualism in 1986. Apropos of 148 cases of gender dysphoria].
The authors review the classification of transsexualism and gender dysphoria with respect to a series of 148 patients followed up for 10 years by a multidisciplinary group of endocrinologists, surgeons and psychiatrists; transsexualism is a major problem of self-identity and not a sexual derivation. The principal features of the study population are presented with details of methodology, criteria for selection for sex change treatment, and results obtained. The two main medicolegal problems (changing civil identity and penal medical responsibility) posed by medico-surgical treatment in France are discussed.


Would the choice of multiplex platform impact the management of the allergic patient? A first approach focusing on LTPs.
In the Mediterranean area, patients with LTP syndrome who are sensitized to multiple allergens are often tested for sIgE using multiplex platforms. The results obtained from different commercial platforms are not interchangeable, so it is important to compare and validate the platform selected for use. The objective of this study is to compare and validate the performance of the ImmunoCAP ISAC E112i and the macroarray ALEX2 in our daily practice. From August 2021 to March 2022, we tested 20 random serum samples from polysensitized patients using the ALEX2 test (MADx) and ImmunoCAP tIgE and ISAC E112i (Thermo Fisher Scientific). We compared the total IgE (tIgE) and sIgE levels for shared allergens. The heatmap generally showed more intense results for ISAC. The overall correlation was good, but some exceptions were noted. The main discrepancies were found for Ole e 7, which was positive for 11 patients in ISAC but negative for all patients in ALEX2, and for nut LTPs, for which ISAC showed a threefold higher detection rate for Ara h 9 and a fivefold higher detection rate for Cor a 8 and Jug r 3 compared to ALEX2. The regression model showed no interchangeability of tIgE results. Despite our small sample size and the complexity of comparing a quantitative and a semi-quantitative platform, our results suggest that patient diagnosis and management can be influenced by the platform used. Therefore, our findings must be taken into consideration when choosing a platform to use for some profiles of LTP-polysensitized patients, even though more data is needed.


Role of cell-matrix contacts in cell migration and epithelial-mesenchymal transformation.
Epithelial cells make contact with extracellular matrix via receptors on the basal surface that interact with the basal actin cortex. In 3D matrix, the mesenchymal cell makes contact with matrix all around its circumference via similar receptors. When moving, the fibroblasts is constantly constructing a new front end. We postulate in a 'fixed cortex' theory of cell motility that the circumferential actin cortex is firmly attached to matrix and that the myosin-rich endoplasm slides past it into the continually forming new front end. During epithelial-mesenchymal transformation, the presumptive mesenchymal cell seems to turn on the new front end mechanism as a way of emigrating from the epithelium into the underlying matrix with which it makes 'fixed' contacts. Master genes may exist that regulate the expression of epithelial genes on the one hand, and mesenchymal genes on the other.


Large-scale comparative transcriptomic analysis of temperature-responsive genes in Arabidopsis thaliana.
Comparative transcriptomic analysis provides broad and detailed understandings of transcriptional responses to a wide range of temperatures in different plant tissues, and unique regulatory functions of temperature-mediating transcription factors. Climate change poses a great threat to plant diversity and food security. It is thus of necessity to understand the molecular mechanisms for perceiving and responding to adverse temperature changes, to develop the cultivars that are resilient to these environmental stresses. Making use of publicly available datasets, we gathered and re-analyzed 259 individual transcriptomic profiles from 139 unique experiments of Arabidopsis thaliana's shoot, root, and seedling tissues, subjected to a wide variety of temperature conditions, ranging from freezing, cold, low and high ambient temperatures, to heat shock. Despite the underlying differences in the overall transcriptomic profiles between the plant tissues, we were able to identify distinct sets of genes whose transcription patterns were highly responsive to different types of temperature conditions, some were common among the tissues and some were tissue-specific. Interestingly, we observed that the known temperature-responsive genes such as the heat-shock factor (HSF) family, were up-regulated not only in response to high temperatures, but some of its members were also likely involved in the cold response. By integrating the DNA-binding specificity information of the key temperature transcription factor (TF) HSFA1a, PIF4, and CBFs, we elucidated their distinct DNA-binding patterns to the target genes that showed different transcriptional responses. Taken together, we have comprehensively characterized the transcription patterns of temperature-responsive genes and provided directly testable hypotheses on the regulatory roles of key temperature TFs on the expression dynamics of their target genes.


Differential activation of yeast adenylate cyclase by wild-type and mutant RAS proteins.
In these experiments we demonstrate that purified RAS proteins, whether derived from the yeast RAS1 or RAS2 or the human H-ras genes, activate yeast adenylate cyclase in the presence of guanine nucleotides. These results confirm the prediction of earlier genetic and biochemical data and for the first time provide a complete biochemical assay for RAS protein function. Furthermore, we observe a biochemical difference between the RAS2 and RAS2val19 proteins in their ability to activate adenylate cyclase after preincubation with GTP.


Relationship between structure and P-glycoprotein inhibitory activity of dimeric peptides related to the Dmt-Tic pharmacophore.
To develop novel inhibitors of P-glycoprotein (P-gp), dimeric peptides related to an opioid peptide containing the Dmt-Tic pharmacophore were synthesized and their P-gp inhibitory activities were analyzed. Of the 30 analogs synthesized, N(α),N(ε)-[(CH(3))(2)Mle-Tic](2)Lys-NH(2) and its D-Lys analog were found to exhibit potent P-gp inhibitory activity, twice that of verapamil, in doxorubicin-resistant K562 cells. Structure-activity studies indicated that the correct hydrophobicity and spacer length between two aromatic rings are important structural elements in this series of analogs for inhibition of P-gp.


Efficient separation of phycocyanin of Nostoc commune by multistep diafiltration using ultra-filtration membrane modules.
Diafiltration (DF) is a separation method used to separate and concentrate macromolecules, such as polysaccharides and proteins. To obtain high-purity target molecules by DF, appropriate conditions should be used. In this study, a mathematical model was developed to suggest appropriate ultra-filtration (UF) membrane modules for the separation of phycocyanin (PC) by multistep DF. PC is a protein produced by microalgae. The contribution of each UF membrane module to PC productivity and purity at each stage of the multistep DF process was quantified by the proposed model. The parameters required as model inputs (k, Fα1, and Fα2) were experimentally determined by permeating PC-containing solution through UF membrane modules (150, 30, and 10 kDa cutoffs). The resulting analytical solutions and those predicted by the model were in close agreement. The PC purity increased from 0.20 to 0.30 when a 10 kDa UF membrane module was used in two-step DF. An orthogonal table was used to determine the combination of UF membrane modules needed to achieve higher purity of PC. The model predicted that the 30 kDa UF membrane module would have the highest contribution to PC productivity and purity at any position in a three-step DF. The developed model can help identify appropriate conditions for separating macromolecules by DF.


BMI among Timorese aged ≥ 40 years.
To determine the distribution and sociodemographic associations of BMI (kg/m2) among adults aged ≥40 years living in Timor-Leste. BMI was calculated for participants of a population-based cross-sectional survey. Urban and rural Timor-Leste. Adults aged ≥40 years living in Timor-Leste. Of those enumerated, 2014 participated (89·5 %). Male gender, rural domicile, older age, illiteracy and source of household income were associated with BMI < 18·5 kg/m2 on multivariate analysis. Female gender, urban domicile and literacy were associated with BMI ≥25·0 and ≥30·0 kg/m2. Adjusting for gender, age and domicile, and extrapolating to those aged ≥40 years across Timor-Leste, 9·9 %, 36·0 %, 6·6 % and 0·8 % had BMI <16·0, <18·5, ≥25·0 and ≥30·0 kg/m2, respectively. At this time, being 'underweight' or 'severely thin' is more prevalent in the Timorese adult population than being 'overweight' or 'obese'.


Protein post-translational modifications in the regulation of cancer hallmarks.
Posttranslational modifications (PTMs) of proteins, the major mechanism of protein function regulation, play important roles in regulating a variety of cellular physiological and pathological processes. Although the classical PTMs, such as phosphorylation, acetylation, ubiquitination and methylation, have been well studied, the emergence of many new modifications, such as succinylation, hydroxybutyrylation, and lactylation, introduces a new layer to protein regulation, leaving much more to be explored and wide application prospects. In this review, we will provide a broad overview of the significant roles of PTMs in regulating human cancer hallmarks through selecting a diverse set of examples, and update the current advances in the therapeutic implications of these PTMs in human cancer.


Growth and arrest of topological cycles in small physical networks.
The chordless cycle sizes of spatially embedded networks are demonstrated to follow an exponential growth law similar to random graphs if the number of nodes [Formula: see text] is below a critical value [Formula: see text] For covalent polymer networks, increasing the network size, as measured by the number of cross-link nodes, beyond [Formula: see text] results in a crossover to a new regime in which the characteristic size of the chordless cycles [Formula: see text] no longer increases. From this result, the onset and intensity of finite-size effects can be predicted from measurement of [Formula: see text] in large networks. Although such information is largely inaccessible with experiments, the agreement of simulation results from molecular dynamics, Metropolis Monte Carlo, and kinetic Monte Carlo suggests the crossover is a fundamental physical feature which is insensitive to the details of the network generation. These results show random graphs as a promising model to capture structural differences in confined physical networks.


Ionizing radiation induced degradation of diuron in dilute aqueous solution.
Cutting edge technologies based on Advanced Oxidation Processes (AOP) are under development for the elimination of highly persistent organic molecules (like pesticides) from water matrices. Among them, ionizing radiation treatment represents a promising technology that requires no additives and can be easily adapted to an industrial scale. In these processes several reactive species are produced, mainly powerful oxidizing radicals inducing the degradation. This paper investigates the reactions taking place in dilute aqueous solutions of a hazardous pollutant (diuron) during irradiation. Irradiation of aqueous diuron solutions resulted in effective degradation of the solute mainly due to the reactions of hydroxyl radicals formed in water radiolysis. Hydroxyl radical reacts with diuron with a second order rate constant of (5.8 ± 0.3) × 10(9) mol(-1) dm(3) s(-1). The main reaction is addition to the ring forming hydroxycyclohexadienyl radical. 30 - 50% of hydroxyl radical reactions induce dechlorination. Reactions with the methyl groups or with the α-amino group have low contribution to the transformation. The presence of dissolved oxygen enhances the rate of degradation; one hydroxyl radical on average induces five-electron oxidations. The high oxidation rate is attributed to the reaction of some of the primarily formed organic radicals with dissolved O2 and the subsequent reactions of the peroxy radicals. The presence of dissolved oxygen is highly important to achieve efficient ionizing radiation induced degradation of diuron in dilute aqueous solution.


[Mechanisms of inhibition of synaptic transmission in the sympathetic ganglia of rats with alloxan diabetes].
In experiments on the isolated superior cervical sympathetic ganglia of rats with alloxan diabetes rhythmic stimulation of preganglionic nerves was effected; summation presynaptic spikes and EPSPs of ganglionic neurons were registered. In rats with moderately severe alloxan diabetes progressive depression of rhythmic ganglion potentials was connected with suppression of the mediator emission to the impulse due to rapid exhaustion of its operational fraction. Rats with severe diabetes displayed also postsynaptic suppression of the ganglionic neurons. Dynamic characteristics of the transmitter turnover assessed on the basis of consideration of the successive patterns of posttetanic potentiation showed insignificant changes in the mediator output and a significant (by 38%) suppression of the mediator reserve per sec in comparison with control.


Hepatocyte growth factor receptor signaling mediates the anti-fibrotic action of 9-cis-retinoic acid in glomerular mesangial cells.
Retinoic acid (RA), an active metabolite of vitamin A, plays a critical role in the regulation of cell proliferation, survival, and differentiation. RA action is primarily mediated through its receptors, ligand-dependent transcription factors of the steroid/thyroid/vitamin D nuclear receptor superfamily. Recent studies indicate that administration of RA mitigates progressive kidney disease, underscoring its renoprotective potential. In this study, we investigated the effects of 9-cis-RA on glomerular mesangial cell activation induced by transforming growth factor (TGF)-beta1 using an in vitro cell culture system. In human mesangial cells 9-cis-RA suppressed TGF-beta1-induced alpha-smooth muscle actin, fibronectin, and plasminogen activator inhibitor-1 expression, but it did not significantly affect cell proliferation and survival. Interestingly, 9-cis-RA induced hepatocyte growth factor (HGF) mRNA expression and protein secretion, stimulated HGF promoter activity, and activated c-met receptor phosphorylation. Similar to HGF, 9-cis-RA induced expression of the Smad transcriptional co-repressor TGIF in mesangial cells. Overexpression of exogenous TGIF by transfection or 9-cis-RA treatment suppressed trans-activation of the TGF-beta-responsive promoter. Moreover, conditional ablation of the c-met receptor completely abolished the anti-fibrotic effect of 9-cis-RA and abrogated TGIF induction. Collectively, these results indicate that 9-cis-RA possesses anti-fibrotic ability by antagonizing TGF-beta1 in mesangial cells and that 9-cis-RA activity is likely mediated through a mechanism dependent on HGF/c-met receptor signaling.


Detection of right atrial myxoma by Fourier phase analysis.
The usefulness of radionuclide imaging in the detection of cardiac tumors has been demonstrated previously in left atrial myxomas. We report a case of right sided myxoma successfully diagnosed by radionuclide imaging and evaluated by cine display, Fourier phase analysis and paradox image. These three techniques are now available in many computer programs for gated cardiac blood pool imaging and provide an additional tool for assessing cardiac tumors. Particularly, functional paradox and Fourier phase analysis seem promising tools in the detection of both left and right sided tumors.


A highly conservative, cyclically permuted, non-homologous exchange among three unrelated DNA sequences in bleomycin-treated CHO cells.
Molecular analysis of a bleomycin-induced rearrangement of the aprt gene in CHO cells revealed that it consisted of a nearly perfect three-way exchange among non-homologous sequences, consistent with a mechanism involving cyclically permuted misjoining of the six ends of three double-strand breaks.


Artificial Light at Night (ALAN) causes size-dependent effects on intertidal fish decision-making.
Artificial Light at Night (ALAN) alters cycles of day and night, potentially modifying species' behavior. We assessed whether exposure to ALAN influences decision-making (directional swimming) in an intertidal rockfish (Girella laevisifrons) from the Southeastern Pacific. Using a Y-maze, we examined if exposure to ALAN or natural day/night conditions for one week affected the number of visits and time spent in three Y-maze compartments: dark and lit arms ("safe" and "risky" conditions, respectively) and a neutral "non-decision" area. The results showed that fish maintained in natural day/night conditions visited and spent more time in the dark arm, regardless of size. Instead, fish exposed to ALAN visited and spent more time in the non-decision area and their response was size-dependent. Hence, prior ALAN exposure seemed to disorient or reduce the ability of rock fish to choose dark conditions, deemed the safest for small fish facing predators or other potential threats.


Spinal cord malformations.
Malformations of the spinal cord are one of the most frequent malformations. They should be clearly divided into two completely different families of malformations: open dysraphisms and occult dysraphisms. Open dysraphism mostly consists in myelomeningocele (MMC). Its incidence is 1/1000 live births with a wide variation. Folic acid supplementation has been shown to reduce its risk. In most cases, the diagnosis is done prenatally by serum screening and ultrasound and may lead to termination of pregnancy. In case of decision to continue pregnancy, surgical treatment must be achieved during the first days of life, and in 50 to 90% of cases, a ventricular shunt must be installed. The follow-up of these children must be continued throughout life looking for late complications (Chiari II and syringomyelia, vertebral problems, neuropathic bladder, tethered cord). Occult dysraphisms are a heterogeneous group of malformations. Lipomas (filum and conus) are the most frequent and their treatment remains controversial. Diastematomyelia, neurenteric cysts, dermal sinus, and more complex forms (Currarino syndrome) belong to this group. Most of them can and must be diagnosed prenatally or at birth by careful examination of the lower back for the cutaneous stigmata of the disease to decrease the risk of neurological, urological, or orthopedic permanent handicap.


Comparison of the effect of 360° versus two-dimensional virtual reality video on history taking and physical examination skills learning among undergraduate medical students: a randomized controlled trial.
Before caring for patients, video instruction is commonly used for undergraduate medical students, and 360° virtual reality (VR) videos have gained increasing interest in clinical medical education. Therefore, the effect of immersive 360° VR video learning compared with two-dimensional (2D) VR video learning in clinical skills acquisition should be evaluated. This randomized, intervention-controlled clinical trial was aimed to assess whether immersive 360° VR video improves undergraduate medical students' learning effectiveness and reduces the cognitive load in history taking and physical examination (H&P) training. From May 1 2018 to October 30 2018, 64 senior undergraduate medical students in a tertiary academic hospital were randomized to receive a 10-min immersive 360° (360° VR video group; n = 32) or 2D VR instructional video (2D VR video group; n = 32), including essential knowledge and competency of H&P. The demographic characteristics of the two groups were comparable for age, sex, and cognitive style. The total procedure skill score, physical examination score, learner's satisfaction score, and total cognitive load in the 360° VR video group were significantly higher than those in the 2D VR video group (effect sizes [95% confidence interval]: 0.72 [0.21-1.22], 0.63 [0.12-1.13], 0.56 [0.06-1.06], and 0.53 [0.03-1.03], respectively). This study suggested that a10-minute 360° VR video instruction helped undergraduate medical students perform fundamental H&P skills as effectively as 2D VR video. Furthermore, the 360° VR video might result in significantly better procedural metrics of physical examinations with higher learner satisfaction despite the higher cognitive load. The online version contains supplementary material available at 10.1007/s10055-022-00664-0.


Trabecular bone structure and spatial differences in articular cartilage MR relaxation times in individuals with posterior horn medial meniscal tears.
To analyze knee trabecular bone structure and spatial cartilage T(1ρ) and T(2) relaxation times using 3-T magnetic resonance imaging (MRI) in subjects with and without tears of posterior horn of the medial meniscus (PHMM). 3-T MRI from 59 subjects (>18 years), were used to evaluate PHMM tears based on modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring; and to calculate apparent trabecular bone-volume over total bone volume fraction (app. BV/TV), apparent trabecular number (app. Tb.N), apparent trabecular separation (app. Tb.Sp) and apparent trabecular thickness (app. Tb.Th) for overall femur/tibia and medial/lateral femur/tibia; and relaxation times for deep and superficial layers of articular cartilage. A repeated measures analysis using Generalized Estimating Equation (GEE) was performed to compare trabecular bone and cartilage relaxation time parameters between people with (n = 35) and without (n = 24) PHMM tears, while adjusting for age and knee OA presence. Subjects with PHMM tears had lower app. BV/TV and app. Tb.N, and greater app. Tb.Th, and app. Tb.Sp. They also had higher T(1ρ) times in the deep cartilage layer for lateral tibia and medial femur and higher T(2) relaxation times for the deep cartilage layer across all compartments. PHMM tears are associated with differences in underlying trabecular bone and deep layer of cartilage. Over-load of subchondral bone can lead to its sclerosis and stress shielding of trabecular bone leading to the resorptive changes observed in this study. The results underline the importance of interactions of trabecular bone and cartilage in the pathogenesis of knee OA in people with PHMM tears.


Performance and mechanism of synchronous nitrate and phosphorus removal in constructed pyrite-based mixotrophic denitrification system from secondary effluent.
The performance and process of the constructed pyrite-based mixotrophic denitrification (POMD) system using pyrite and residual organic matters as the co-electron donors were investigated for simultaneous removal of N and P from secondary effluent. After the batch experiments, 61.80 ± 3.26% of phosphate and 99.99 ± 0.01% of nitrate were removed, and the obtained nitrate removal rate constant can reach 2.09 days-1 in POMD system, which was significantly superior to that reported (0.95 day-1) in pyrite-based autotrophic denitrification (PAD) system. PO43--P removal was mainly achieved via chemical precipitation as FePO4 with iron, and it was irrelevant with the initial nitrate and ammonium concentrations. High-throughput 16S rRNA gene sequencing analysis showed the coexistence of heterotrophic and autotrophic denitrifiers in the mixotrophic environment. The denitrification process could be divided into two stages according to the carbon balance and calculation of sulfate accumulation: (a) nitrate was mainly reduced heterotrophically during 12-36 h and (b) nitrate was reduced autotrophically after 36 h. The calculated proportion of heterotrophic denitrification was 58.17 ± 3.78%, which was promoted by a higher ammonium concentration. These findings are likely to be useful in understanding the mixotrophic denitrification process and developing a cost-effective technology to simultaneously remove N and P from secondary effluent. Graphical abstract.


The Urogenital Epithelium and Corporal Tissues Are the Primary Targets of Rejection in Penile Vascularized Composite Allotransplantation: A New Real-Time Tissue-Based Monitoring System.
Although significant surgical advances have been made in the form of microvascular surgery and autologous free tissue transfer, penile reconstruction still poses several difficult challenges. Although interest in penile vascularized composite allotransplantation has grown since the first attempted transplant in 2006, little is known regarding the kinetics of rejection and subsequent function of penile allografts. The penis contains multiple tissue types that are not qualified by the Banff 2007 vascularized composite allotransplantation classification system, including urogenital mucosal epithelium and erectile tissues. In this study, the authors investigate the propagation of rejection and the resultant function following rejection in rat and human penile tissues. Rejected human and rat penile tissues were examined using an ex vivo real-time tissue-based derivative of the classic mixed lymphocyte reaction assay to determine the interactions occurring between en bloc penile tissues and peripheral blood mononuclear cells (autologous and allogeneic). Correlative in vivo heterotopic rat penile vascularized composite allotransplantation was used to correlate ex vivo findings. In both human and rat ex vivo systems and in vivo rat vascularized composite allotransplantation, the urethral mucosa was the first to undergo rejection-associated apoptosis. The urethral mucosa was the most immunogenic and led to the highest level of peripheral blood mononuclear cell proliferative generations in all systems, whereas the neural tissues of the penis remained immune privileged. These findings are the first to describe the kinetics of rejection in both human and rat penile vascularized composite allotransplantation and that the urethral mucosa is the most antigenic, suffering the highest level of rejection-associated apoptosis and peripheral blood mononuclear cell proliferative aggregation.


Differences reported in the lifespan and aging of male Wistar rats maintained on diets containing fat with different fatty acid profiles (virgin olive, sunflower or fish oils) are not reflected by histopathological lesions found at death in central nervous and endocrine systems.
The present study was designed to examine if dietary fat sources that have shown differences in lifespan and if some aging-related aspects can modulate the range of histopathologic changes in central nervous and endocrine systems that occur during the lifespan of Wistar rats. Moreover, it was attempted to gain insight into the relationship between longevity and the development of the different pathological changes, as well as possible interaction with diet. In order to achieve this, male Wistar rats were randomly assigned to three experimental groups fed semisynthetic and isoenergetic diets from weaning until death with different dietary fat sources, namely virgin olive, sunflower, or fish oil. An individual follow-up until death of each animal was performed. Incidence, severity, and burden of specific or group (i.e., neoplastic or non-neoplastic proliferative and non-proliferative) of lesions was calculated along with individual's disease and individual organ lesion burden. Most of the histopathological lesions found have been described in previous studies. Neoplasms, and in particular pituitary adenomas followed by brain tumors, were the most prevalent lesions found in the rats and the main cause of death involving both systems. Incidence of brain lesions was associated with age-at-death. Assayed dietary fats did not present differential effects on pathological changes occurring in endocrine and central nervous systems throughout rat lifespan.


Livestock associated MRSA (LA-MRSA) and its relevance for humans in Germany.
Livestock-associated Staphylococcus aureus (LA-MRSA) are mainly associated with the clonal complex (CC) 398. Although having its main reservoir as MRSA in livestock such as pigs, poultry or cattle LA-MRSA CC398 has no pronounced host specificity and can colonize or infect other animals such as horses and dogs and also humans. In German conventional farming systems nasal colonization of the animals and of humans occupationally exposed to them (up to 86%) are frequent. Further human-to-human dissemination in households occurs more rarely in general (∼4% of humans living on farms but without occupational exposition). Nasal colonization with LA-MRSA of humans at hospital admission is found in 0.08-0.2% for Germany in general. However, this proportion is higher in areas with a high density of livestock production such as in northwestern North Rhine-Westphalia or Lower Saxony. LA-MRSA CC398 is not less pathogenic for humans than S. aureus in general. Hence, LA-MRSA accounts for ∼15% of all MRSA isolates from deep-seated skin and soft-tissue infections in the community and for about 0.8-2% of all MRSA isolated from clinical specimens obtained in hospital settings. When introduced into the hospital it can cause postoperative wound infections and even septicemia. Differently from hospital-associated MRSA clones, LA-MRSA CC398 has obviously limited capacity to spread in the nosocomial setting so far (proportion of ∼1.8% among MRSA from nosocomial infections, the proportion among MRSA from blood cultures is ∼1%).


[Cooperation in wearing orthodontic appliances].
In orthodontics the degree of treatment outcome largely depends on patient cooperation. In this article factors related to cooperation with removable appliance wear are discussed.


Formation of tight junctions in epithelial cells. I. Induction by proteases in a human colon carcinoma cell line.
The experimental modulation of tight junctions (TJ) was studied in the human adenocarcinoma cell line HT 29 by freeze-fracture electron microscopy. The cell line has virtually no TJ when grown in culture. TJ could be induced by mild treatment with a variety of endopeptidases (trypsin, chymotrypsin, collagenase, elastase, plasmin, thrombin, papain, and pronase). Pronase induced the formation of TJ at low (but not at high) concentrations. All exopeptidases studied were unable to induce the formation of TJ. At 0 degree C the trypsin-induced formation of TJ was greatly slowed down although not entirely inhibited. However, when cells were briefly treated with trypsin at 0 degree C and subsequently transferred to 37 degrees C in the presence of protease inhibitors, TJ were rapidly assembled. Thus an induction phase at low temperature and an assembly phase at high temperature could be experimentally separated. When cells were briefly trypsinized at 0 degrees and subsequently kept at 0 degree C without trypsin for several hours, TJ still formed abundantly upon incubation at 37 degrees C. It appears therefore that the effect produced by the protease is retained for long periods in the cold.


Effect of the analgesic butorphanol on activity behaviour in turkeys (Meleagris gallopavo).
During fattening, the bodyweight of modern broad-breasted turkeys increases considerably within a very short space of time. In particular, the breast muscles increase disproportionately. This leads to a disadvantageous distribution in weight, and as a consequence, to a disturbed leg position and skeletal deformations like antitrochanteric degeneration, tibial dyschondroplasia, bending, twisting and rotation of the tibia, osteochondrosis, osteomyelitis, rickets, and epiphyseolysis of the femoral head increases. This cases of degenerative joint disease cause severe pain in humans and there are indications that this is also true for turkeys. The purpose of this study was to determine if behaviour indicative of such pain in turkeys of the B.U.T. Big 6 breeding line could be attenuated by administering a quick-acting analgesic, butorphanol. Twelve pairs of turkeys were tested at the ages of 7 and 12 weeks. One bird in each pair received an analgesic opioid injection, while the other one received a control injection of physiologically balanced saline solution. The time the birds spent putting weight on their legs, i.e., 'walking' and 'standing' and the distance covered by the birds were recorded during the 30 min periods before and after the application of the drug. At week seven the treated birds spent significantly more time putting weight on their legs than control birds. At week 12, the same tendency was observed. No significant differences were found in the distances covered by the animals. It is concluded that fattening turkeys reduce the time they are putting weight on their legs because these behaviours may be associated with pain.


IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy.
Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in 'early tendinopathy' compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders.


Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study.
Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools. We aimed to develop tissue- and blood-based diagnostic platforms for EG. Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels. Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P = .0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r = -0.83, P < .0001), periglandular circumferential collars (r = -0.73, P < .0001), and endoscopic nodularity (r = -0.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P = .0002; serum: r = 0.54, P = .0015), and (3) inversely correlated with EGDP18 scores (plasma: r = -0.64, P = .0015; serum: r = -0.46, P = .0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P < .0001). We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.


Soluble PD-1 aggravates progression of collagen-induced arthritis through Th1 and Th17 pathways.
The programmed cell death 1 (PD-1) protein is a critical regulator of T-cell activation and is also an important therapeutic target for autoimmune diseases. Little is known about the regulation and functional properties of the soluble PD-1 (sPD-1) variant. The aim of this study was to examine the role of sPD-1 in the regulation of human and murine rheumatoid arthritis (RA). Expression of cytokines and sPD-1 in sera, synovial fluid, and peripheral blood (PB) mononuclear cells of patients with RA were analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. PD-1 function was assessed in PB T cells after stimulation of the cells with anti-CD3 and PD-L1-Fc to crosslink PD-1. Recombinant PD-1-Fc was injected intraperitoneally into DBA/1 mice with collagen-induced arthritis (CIA) to analyze the function of sPD-1 in vivo. High concentrations of sPD-1 were found in sera and synovial fluid of patients with RA. The levels of serum sPD-1 were significantly correlated with titers of rheumatoid factor (RF) (r = 0.306, p = 0.005) and 28-joint Disease Activity Score (r = 0.545, p < 0.001). Further characterization of sPD-1 revealed that it functionally blocked the inhibitory effect of membrane-bound PD-1 on T-cell activation. Interferon γ, tumor necrosis factor α, and interleukin 17A were identified as inducers of sPD-1 in vitro. Moreover, PD-1-Fc enhanced proinflammatory cytokine expression, generation of Th1 cells and Th17 cells, and joint pathology in a CIA model. sPD-1 regulates peripheral T-cell responses in both human and murine RA. Thus, sPD-1 may represent an additional biomarker or target in immunomodulatory therapy for RA.


Sorption-desorption behavior of polycyclic aromatic hydrocarbons in upstream and downstream river sediments.
Sorption and desorption behaviors of phenanthrene and naphthalene were studied with the whole sediment, humic acid (HA) and humin samples from downstream and upstream sites along the Kishon River, Israel. The 13C nuclear magnetic resonance spectra and the sorption coefficients suggest that sorption occurs to both aromatic and aliphatic moieties of the sedimentary organic matter and that rigid paraffinic domains probably contribute to the sorption non-linearity. The carbon-normalized Freundlich affinity values for the two sorbates were significantly higher for the whole sediment and humin samples from the downstream region of the river than for the upstream sediment samples. On the basis of the measured affinity values, the sorbents can be arranged in the following order: humin>HA>whole sediment. Phenanthrene exhibited the lowest desorption from the whole sediment samples compared with the other sorbents. For naphthalene, the desorption hysteresis obtained with the whole sediment and humin samples were similar: both exhibited a decrease in desorption with decreasing solute concentration. The higher sorption affinities observed for all the organic fractions from the downstream sediment are suggested to be related to the low levels of polar domains and humin content. It is concluded that in bulk sediment samples, the overall contribution of the HA fraction to short-term sorption is of high importance, but the sorption non-linearity is controlled mainly by the humin complexes. The low desorption potential recorded for the whole sediment samples could affect the natural attenuation of the sorbed hydrophobic organic compounds.


The prospective clinical and scintigraphic assessment of patients with preserved left ventricular systolic function after transmyocardial laser revascularisation.
To analyse the clinical outcome and myocardial perfusion and function after transmyocardial revascularisation (TMR) in patients with normal left ventricular function and multivessel coronary artery disease non-amenable for standard revascularisation. Twenty three severely symptomatic patients (CCS score median 4) with normal left ventricular systolic function but coronaries non-amenable for either PTCA or CABG were subjected to TMR. The angina score, left ventricular systolic and diastolic function in radionuclide ventriculography at rest, exercise tolerance and myocardial perfusion--Thallium-201 SPECT (adenosine stress 74 and 37 MBq under nitrate cover) were evaluated before and 3, 6, 12 months post-operatively. After an average of 40 +/- 12 (range 14-56) TMR channels angina score decreased significantly (p< 0.0001) and the exercise tolerance increased (from 6.0 +/- 4.5 to 9.1 +/- 4.6 after 6 months, p< 0.05) in 21 patients. During the follow up period two patients had a myocardial infarction and one committed suicide after 6 months. Ejection fraction dropped significantly only after 1 year post-TMR from 70 +/- 13 to 63 +/- 0.13%, p < 0.05. The overall perfusion improved initially in 14 patients with subsequent deterioration in time. The changes in segmental perfusion were not associated with the symptomatic improvement. Transmyocardial revascularisation in patients with normal ejection fraction may improve the angina class, exercise tolerance and overall but not segmental perfusion and does not show any immediate effect on left ventricular function.


Technical management of traumatic arteriovenous fistula: Tips and tricks.
Traumatic Arteriovenous Fistulas (AVFs) are a rare complication of vascular injuries and pose a problem of topographic diagnosis and therapeutic management. Delayed treatment may cause cardiac and trophic complications. We describe 4 cases of AVFs complicating stab wounds of the lower limb, associated in 2 cases with pseudoaneurysms. In two cases we performed a surgical repair, whereas in the other 2 patients we choose an endovascular treatment with wall graft stent placement. All traumatic AVFs must be treated to avoid vascular, local and general complications. Using both techniques, we had great results with no complications.


Dataset of acute repeated sessions of bifrontal transcranial direct current stimulation for treatment of intractable tinnitus: A randomized controlled trial.
Transcranial direct current stimulation (tDCS) has reportedly shown promising therapeutic effects for tinnitus (Forogh et al., 2016; Joos et al., 2014) [1], [2]. Studies are ongoing to determine optimum treatment protocol and the site of stimulation. Findings of the early studies are heterogeneous and most studies have focused on single session tDCS and short follow-up periods. There is no study on repeated sessions of tDCS with long term follow-up. This study presents the results of a randomized clinical trial investigating the therapeutic effects of acute multi-session tDCS over dorsolateral prefrontal cortex (DLPFC) on tinnitus symptoms and comorbid depression and anxiety in patients with chronic intractable tinnitus. The dataset includes the demographic information, audiometric assessments, tinnitus specific characteristics, and the response variables of the study. The response variables included the scores of tinnitus handicap inventory (THI), tinnitus loudness and tinnitus related distress based on 0-10 numerical visual analogue scale (VAS) scores, beck depression inventory (BDI-II) and beck anxiety inventory (BAI) scores. The dataset included the scores of THI pre and immediately post intervention, and at one month follow-up; the tinnitus loudness and distress scores prior to intervention, and immediately, one hour, one week, and at one month after the last stimulation session. In addition, the BDI-II, and BAI scores pre and post intervention are included. The data of the real (n=25) and sham tDCS (n=17) groups are reported. The main manuscript of this dataset is "Acute repeated sessions of bifrontal transcranial direct current stimulation for treatment of intractable tinnitus: a randomized controlled trial" (Bayat et al., submitted for publication) [3].


Infestation of the coccid, Icerya seychellarum (Westw.), on the mangrove Avicennia marina (forsk.) vierh. on Aldabra Atoll, with special reference to tree age.
The level of infestation by the coccid Icerya seychellarum on the mangrove tree Avicennia marina was measured on a stand of ca. 670 trees on Aldabra Atoll in 1978. Trees varied in basal trunk diameter (btd) between 3 and 30 cm. Leaf infestation increased significantly with increasing btd-class and young trees (btd 3.0-4.5 cm) had a mean infestation of 0.3 mg coccids g-1 leaf whilst the heaviest infested trees (btd 13.0-14.5 cm) supported 7.6 mg g-1. Leaf and shoot growth were not correlated with coccid infestation but shoot vigour (leaf to green shoot ratio) declined significantly with increasing btd-class (or age). Leaves of older, heavily infested trees did not differ from those of young uninfested trees in the concentration of soluble or total nitrogen of in four other leaf elements, indicating that nutrient status was not an important factor in infestation. Field observations showed that many of the older trees were subjected to poor drainage which may have increased their susceptibility to attack and also that on the leaves of young trees salt secretion presented an effective barrier to the establishment of coccids. re19800212.


Quantitative analysis of unconjugated and total bisphenol A in human urine using solid-phase extraction and UPLC-MS/MS: method implementation, method qualification and troubleshooting.
The aim of the presented investigation was to document challenges encountered during implementation and qualification of a method for bisphenol A (BPA) analysis and to develop and discuss precautions taken to avoid and to monitor contamination with BPA during sample handling and analysis. Previously developed and published HPLC-MS/MS methods for the determination of unconjugated BPA (Markham et al. Journal of Analytical Toxicology, 34 (2010) 293-303) [17] and total BPA (Markham et al. Journal of Analytical Toxicology, 38 (2014) 194-203) [20] in human urine were combined and transferred into another laboratory. The initial method for unconjugated BPA was developed and evaluated in two independent laboratories simultaneously. The second method for total BPA was developed and evaluated in one of these laboratories to conserve resources. Accurate analysis of BPA at sub-ppb levels is a challenging task as BPA is a widely used material and is ubiquitous in the environment at trace concentrations. Propensity for contamination of biological samples with BPA is reported in the literature during sample collection, storage, and/or analysis. Contamination by trace levels of BPA is so pervasive that even with extraordinary care, it is difficult to completely exclude the introduction of BPA into biological samples and, consequently, contamination might have an impact on BPA biomonitoring data. The applied UPLC-MS/MS method was calibrated from 0.05 to 25ng/ml. The limit of quantification was 0.1ng/ml for unconjugated BPA and 0.2ng/ml for total BPA, respectively, in human urine. Finally, the method was applied to urine samples derived from 20 volunteers. Overall, BPA can be analyzed in human urine with acceptable recovery and repeatability if sufficient measures are taken to avoid contamination throughout the procedure from sample collection until UPLC-MS/MS analysis.


Acute Calcium Pyrophosphate Crystal Arthritis Flare Rate and Risk Factors for Recurrence.
Little is known about acute calcium pyrophosphate (CPP) crystal arthritis flare rates and risk factors for recurrence. We characterized flares and determined the rate and predictors of acute CPP crystal arthritis flares in an academic medical center cohort. We performed a retrospective cohort study among a random sample of patients with acute CPP crystal arthritis identified in the Partners HealthCare electronic medical record, 1991-2017. Flare was defined as self-limited, acute-onset synovitis with synovial fluid CPP crystals and/or chondrocalcinosis, not better explained by another cause. We calculated incidence rates (IR) for acute CPP crystal arthritis flare among all subjects and by sex. We estimated HR for recurrent flare using univariate Cox models that accounted for within-person correlated data. We identified 70 patients with acute CPP crystal arthritis with a total of 111 flares. Recurrent flares occurred in 24% of patients; half of flares occurred in a previously unaffected joint. The acute CPP crystal arthritis flare rate was 11.4 per 100 person-years overall (95% CI 8.2-15.4), 14.2 in women (95% CI 9.6-0.1), and 7.1 in men (95% CI 3.4-13.0). Cancer (HR 2.98, 95% CI 1.33-6.68) and chronic kidney disease (HR 2.92, 95% CI 1.10-7.76) were associated with a higher rate for recurrent flare. Recurrent flares occurred in about one-fourth of patients with acute CPP crystal arthritis and often occurred in previously unaffected joints. The acute CPP crystal arthritis flare rate was twice as high in women as in men.


Solid-phase extraction of vinblastine and vincristine from plasma and urine: variable drug recoveries due to non-reproducible column packings.
A sensitive and selective high-performance liquid chromatographic (HPLC) method for the determination of vinblastine and vincristine in plasma and urine is described. The drugs are isolated from 1.0 ml of the biological fluid with a solid-phase extraction column (Bond-Elut Diol). The HPLC method was combined with electrochemical detection at +850 mV versus an Ag/AgCl reference electrode. The detection limit is 100 pg for vinblastine and 250 pg for vincristine with a signal-to-noise ratio of 3, which permits the determination of these compounds in biological fluids at the nanogram level. Evaluation of the isolation method revealed that the drug recoveries and the reproducibility of the extraction procedure depend on the batch number of the solid-phase extraction column used.


[Effect of lipid hydroperoxides on the yield of chromosome aberrations in irradiated cells].
The combined effect of linoleic acid hydroperoxide and gamma-radiation on Ehrlich ascites tumor cells was not additive with regard to the formation of chromosome aberrations. When cells were preincubated in the presence of a subliminal hydroperoxide dose of 2.10(-5) M the number of aberrant cells increased after irradiation.


Hormone sensitivity of gynecological tumor cells in tissue culture.
Proliferating tumor cells obtained from ovarian, mammary, and endometrial tumors in tissue culture were tested for the influence of proteohormones and steroid hormones on cellular DNA synthesis and cell growth. The gonadotropic hormones stimulated DNA synthesis of ovarian tumor cells by single administration, or in combination with cortisol, up to the 11-fold of the comparable controls. The hormone sensitivity of the cell lines was variable, resulting in individual reaction patterns. There was no correlation to the histological diagnosis of the primary tumors with respect to the grade of differentiation. The results suggest that ovarian tumor cells in tissue culture can maintain sensitivity to organotropic hormones. Compared to the ovarian carcinoma lines, mammary or endometrial tumor cells did not respond to a similar extent. Progesterone decreased DNA synthesis of endometrial carcinoma cells.


Correlating MRI and clinical disease activity in multiple sclerosis: relevance of hypointense lesions on short-TR/short-TE (T1-weighted) spin-echo images.
Magnetic resonance imaging (MRI) is being used as an outcome criterion in therapeutic trials in multiple sclerosis (MS) on the assumption that it, as a sensitive marker of biologic disease activity, could serve as a surrogate marker of disability. We evaluated the relation between MRI findings and disability in a quantitative follow-up study of 48 MS patients. Median duration of follow-up was 24 months (range, 10 to 42 months). Computer-assisted volume measurements employing a seed-growing technique yielded a standard error of measurement of 0.275 cm2. The median total area of the hyperintense lesions on the initial T2-weighted images was 8.4 cm2. The median increase was 0.76 cm2/yr (9%). In a subgroup (n = 19) with short-TR/short-TE spin-echo (SE) images, we measured the hypointense lesion load. The median total area of the lesions at entry was 0.70 cm2, with a median increase of 0.28 cm2/yr (40%). The total area of the hyperintense lesions on the initial T2-weighted images showed a weak correlation with the Expanded Disability Status Scale score at entry (Spearman rank correlation coefficient [SRCC] = 0.30; 0.02 < p < 0.05). The increase in disability showed a positive correlation (SRCC = 0.19) with the increase in hyperintense lesion load on the T2-weighted SE images, but this correlation did not reach statistical significance (p = 0.09), probably because of lack of clinical progression.(ABSTRACT TRUNCATED AT 250 WORDS)


Increased interleukin-6 levels associated with malaria infection and disease severity: a systematic review and meta-analysis.
Interleukin-6 (IL-6) is generated by immune cells during infection with malaria parasites and they are associated with the immunopathogenesis of malaria. The present systematic review and meta-analysis aimed to compare the differences in IL-6 levels between several groups of patients with malaria and healthy control groups. The systematic review was registered at PROSPERO with a registration number: CRD42021290753. Systematic literature searches were conducted in PubMed, Web of Science, and Scopus until November 7, 2021 to obtain studies that documented IL-6 levels in patients with malaria. The quality of the included studies was assessed using critical appraisal tools from the Joanna Briggs Institute. Differences in the mean IL-6 levels among patients with: (1) severe and non-severe malaria, (2) uncomplicated malaria and controls, (3) uncomplicated and asymptomatic malaria, (4) asymptomatic malaria and healthy controls, and (5) those that died or survived were estimated using a random-effects model. Forty-three of 1,969 studies were included in the systematic review. Results of the meta-analysis showed that patients with severe malaria had higher mean IL-6 levels than those with non-severe malaria [P = 0.04, weight mean difference (WMD) = 96.63 pg/mL, 95% confidence interval (CI) = 0.88 - 19.38 pg/mL, I2 = 99.9%, 13 studies]. Patients with uncomplicated malaria had higher mean IL-6 levels than the controls (P < 0.001, WMD = 42.86 pg/mL, 95% CI = 30.17 - 55.56 pg/mL, I2 = 100%, 17 studies). No differences in the mean levels of IL-6 were found between patients with uncomplicated malaria and those with asymptomatic malaria (P = 0.063, WMD = 42.07 pg/mL, 95% CI = - 2.23 pg/mL to - 86.37 pg/mL, I2 = 99.1%, 8 studies), or between patients with asymptomatic malaria and healthy controls (P = 0.45, WMD = 1.67 pg/mL, 95% CI = - 2.73 pg/mL to - 6.07 pg/mL, I2 = 98.1%, 2 studies). A higher mean level of IL-6 was observed in patients who died compared with the levels of those who survived (P = 0.007, WMD = 1,399.19 pg/mL, 95% CI = 384.16 - 2,414.2 pg/mL, I2 = 93.1%, 4 studies). Our meta-analysis of the pooled evidence can be used to guide future studies in which IL-6 levels are measured during malaria outbreaks to monitor malaria severity. Heterogeneity of the effect estimate among the included studies was the main limitation of this analysis. In conclusion, significantly increased levels of IL-6 were observed in patients with severe malaria compared with those in patients with non-severe malaria, which indicates that IL-6 is a candidate marker for severe malaria. Future studies should investigate the sensitivity and specificity of increased IL-6 levels to determine the effectiveness of assessments of IL-6 levels monitoring of malaria infection and severity.


A mark-release-recapture study on dispersal and flight distance of Culex pipiens pallens in an urban area of Japan.
A mark-release-recapture of Culex pipiens pallens was conducted in an urban area of Japan during June 26-29, 2007. Larvae naturally occurring in rain gutters were collected and reared to adults in a laboratory. A total of 10,183 emerging female Cx. pipiens pallens of 4-8 days old were marked with fluorescent dye and released from one site. Recapture was made on 4 consecutive days using 41 Centers for Disease Control and Prevention traps with 1 kg of dry ice and human landing collection, and 121 marked females were recaptured. The overall recapture rate was 0.01. The mean distance traveled by the recaptured females was estimated as 470, 287, 326, and 517 m on days 1-4, respectively. The maximum flight distance of host-seeking Cx. pipiens pallens was estimated as 1,217 m based on the relationship between distance from the release site to the collection site and the total number of recaptures/traps. The population size of female Cx. pipiens pallens in the study area was estimated as 100,904 +/- 8,509. The size of operational area for the control of Cx. pipiens pallens in urban area is discussed.


Outcomes of psychological support skills training for cancer care staff: Skill acquisition, work engagement, mental wellbeing and burnout.
Psychological support skills training has the potential to improve both the ability of cancer staff to help their patients, and staff wellbeing. However, few recent studies have assessed both these outcomes or incorporated current developments in psychological skills training, such as deliberate practice, which includes the use of iterative, corrective feedback to identify and improve individualised skill deficits. No studies have evaluated the contribution that psychological skills training could make to cancer care staff wellbeing and expertise in the wake of the COVID-19 pandemic. This study aimed to evaluate staff skill acquisition and work-related wellbeing following psychological support skills training that applied deliberate practice principles. A 2-day training and monthly supervision was offered to 145 cancer care staff that focused on brief assessment and intervention skills for patients experiencing mental health problems after cancer diagnosis and treatment. Deliberate practice principles were used to focus training on skills practice and feedback, over technique description. Self-reported ability to perform key skills taught, staff mental wellbeing, work engagement, and burnout were assessed at baseline, 3-month and 8-month follow-up. Significant improvements in skills, mental wellbeing, burnout and work engagement were reported at 8-month follow-up. Full engagement in both training sessions was predicted by poorer baseline mental wellbeing, more positive evaluation of initial training, supervision attendance, and shorter follow-up. A 2-day psychological support skills training using deliberate practice principles may support improvement in staff skill, mental wellbeing, burnout and work engagement.


OsSPL13 controls grain size in cultivated rice.
Although genetic diversity has a cardinal role in domestication, abundant natural allelic variations across the rice genome that cause agronomically important differences between diverse varieties have not been fully explored. Here we implement an approach integrating genome-wide association testing with functional analysis on grain size in a diverse rice population. We report that a major quantitative trait locus, GLW7, encoding the plant-specific transcription factor OsSPL13, positively regulates cell size in the grain hull, resulting in enhanced rice grain length and yield. We determine that a tandem-repeat sequence in the 5' UTR of OsSPL13 alters its expression by affecting transcription and translation and that high expression of OsSPL13 is associated with large grains in tropical japonica rice. Further analysis indicates that the large-grain allele of GLW7 in tropical japonica rice was introgressed from indica varieties under artificial selection. Our study demonstrates that new genes can be effectively identified on the basis of genome-wide association data.


Household air pollution and childhood stunting in China: A prospective cohort study.
Exposure to air pollution, especially indoor air pollution, was associated with an increased risk of childhood stunting. However, few longitudinal studies have explored the long-term impacts of indoor air pollution from household solid fuel use on child growth. We aimed to investigate the association between household air pollution (HAP) from solid fuel use and childhood stunting in Chinese children. The longitudinal data from the Chinese Family Panel Study over 2010-2018 were included in this study with a total of 6,013 children aged 0-15 years enrolled at baseline. Exposure to HAP was measured as solid fuel use for cooking, while solid fuel was defined as coal and firewood/straw according to the questionnaire survey. Stunting was defined as-2SD below the height-for-age z-score (HAZ) of the reference children. Logistic regression and Cox proportional hazards models with time-varying exposures were employed to estimate the association between childhood stunting and HAP exposure. At baseline, children with exposure to HAP from combusting solid fuels had a relatively higher risk of stunting [OR (95%CI): 1.42 (1.24-1.63)]. Among children without stunning at baseline, those living in households with solid fuel use had a higher stunting risk over an 8-year follow-up [HR (95%CI): 2.05 (1.64-2.57)]. The risk of childhood stunting was increased for those with HAP exposure from firewood/straw combustion or with longer exposure duration [HR (95%CI): 2.21 (1.74-2.79) and 3.01 (2.23-4.08), respectively]. Meanwhile, this risk was significantly decreased among children from households switching from solid fuels to clean fuels [HR (95%CI): 0.53 (0.39-0.70)]. Solid fuel use was suggested to be a mediator of the relationship between poor socioeconomic factors (i.e., household income and parental education level) and childhood stunning, with a mediation effect ranging from 11.25 to 14.26%. HAP exposure from solid fuel use was associated with childhood stunting. Poor parental education and low household income might be socioeconomic factors contributing to solid fuel use. Therefore, household energy policies to facilitate access to clean fuels are urgently needed, especially for low-income and low-educated households.


Proximity ligation initiated DNAzyme-powered catalytic hairpin assembly for sensitive and accurate microRNA analysis.
MicroRNAs (miRNAs) play a significant role in regulating diverse physiological processes, and are regarded as novel diagnostic biomarkers. However, the sensitive and reliable miRNA detection remains a huge challenge. Herein, we propose a proximity ligated initiated magnesium ion (Mg2+)-dependent DNAzyme-powered signal cascade for sensitive, accurate and reliable detection of miRNAs. Three signal amplification processes are involved in this approach, including the target miRNA recycle, DNAzyme powered substrate cleavage, and catalytic hairpin reaction (CHA). Based on this, the approach shows a low limit of detection of 523 aM and a wide detection range of 7 orders of magnitudes, which is comparable or superior to most of the former miRNA detection methods. In addition, the approach also possesses a high selectivity to target miRNA, suggesting a potential promising future of the approach for rapid detection of miRNAs in the application of developing novel tools for skin cancer diagnosis, and recovery evaluation.


Endoscopic full-thickness resection of gastric ectopic splenic nodules.
Ectopic spleen is extremely rare. Most cases are congenital, acquired ectopic spleen may be a consequence of surgery or trauma to the spleen. The ectopic spleen in the gastric wall we reported is even rarer. We report a 41-year-old female patient, with a past history of splenectomy, who presented with heartburn. Gastroscopy revealed a swelling in the fundus in the stomach. Ultrasonography and computed tomographic examination suggested the possibility of gastrointestinal stromal tumor. We performed endoscopic resection of the mass. Pathological examination of the resected mass showed ectopic spleen. When a patient with a history of splenectomy presents with a gastric submucosal tumor, ectopic spleen should also be considered in the differential diagnoses. And minimally invasive endoscopic treatment can achieve the purpose of diagnosis and treatment for unobvious submucosal tumors.


Aspects of tissue water relations and seasonal changes of leaf water potential components of evergreen and deciduous species coexisting in tropical dry forests.
This study compared the tissue water relations and seasonal changes in leaf water potential components of an evergreen tree,Morisonia americana, and two evergreen shrubs,Capparis verrucosa andC. aristiquetae, with two deciduous trees,Humboltiella arborea andLonchocarpus dipteroneurus, and the deciduous vineMansoa verrucifera. All these species coexist in a tropical dry forest in Venezuela. Leaves of the evergreen species are sclerophyllous, while those of the deciduous species are mesophytic. Leaf area to leaf weight ratios of fully mature leaves were about 75 and 170 cm2 g-1 in evergreen and deciduous species, respectively. Seasonal fluctuations of leaf water content per unit of dry weight, water potential, and turgor pressure were smaller in evergreen than in deciduous species. The analysis of tissue water relations using pressurevolume curves showed that evergreen species could develop a higher leaf turgor and lose turgor at lower leaf water potentials than deciduous species. This was related to a lower osmotic potential at full turgor in evergreen (≃-3.0 MPa)_than in deciduous (≃-2.0 MPa) species, rather than to the elastic properties of leaf tissue. The volumetric modulus of elasticity was 14 MPa in evergreen compared with 7-10 MPa in deciduous species. Thus, leaf characteristics are important in determining the drought resistance of evergreen species of this tropical dry forest.


Contaminant assimilation within the water column of two newly created prairie wetlands.
This research examined the influence of abiotic factors on contaminant assimilation within the water column of two wetlands (RMA3 and RMA4) located on Rocky Mountain Arsenal National Wildlife Area, north of Denver, Colorado, USA. We define contaminant assimilation as the ability of a wetland system to reduce negative impacts of contaminants on aquatic organisms. To examine the influence of abiotic factors (i.e., alkalinity, suspended solids), chronic toxicity tests were performed from February 1992 through November 1993. Ceriodaphnia dubia were exposed to water from the wetlands, which was spiked with Zn. These tests indicated higher assimilative capacity in wetland RMA4 relative to RMA3. Dissolved organic carbon (DOC) was significantly greater in RMA4 than in RMA3, suggesting that it may have influenced differences in bioavailability of Zn in wetland water. Suspended solids were also consistently higher in RMA4 than in RMA3. To test the influence of suspended solids on contaminant assimilation, C. dubia were exposed to filtered and unfiltered Zn-spiked water from RMA4. The greater toxicity of Zn to C. dubia in filtered water indicated that suspended solids were important in ameliorating impacts of Zn in RMA4. Results from this study suggest that from the suite of variables assessed, DOC and suspended solids were the most important physiochemical influences on Zn toxicity within the water column of these two wetlands. Differences in habitat characteristics of RMA3 and RMA4 demonstrated the importance of site-selection toward functional design of wetlands.


Tardive dyskinesia: clinical presentation and treatment.
Tardive dyskinesia (TD) is a common and potentially irreversible side effect of dopamine blocking agents, most often antipsychotics. It is often socially and sometimes also physically disabling. The clinical picture can be divided into orofacial, limb-truncal, and respiratory dyskinesia. The clinical options to prevent or mitigate TD include psychoeducation, systematic screening, and evaluation of the need for antipsychotics and/or dosages, managementof known risk factors, and switching to an antipsychotic with a lower risk of TD. There is no evidence-based approach for treating existing TD but several clinical interventions can be effective including discontinuing the antipsychotics or reducing the dosage, switching to clozapine, adding an antidyskinetic agent, or applying deep brain stimulation.


Scheduled and unscheduled DNA synthesis in epidermal cells of hairless mice treated with immunosuppressive drugs and UVB-UVA irradiation.
The effects of the immunosuppressive drugs azathioprine, prednisolone and cyclosporin A, and UV irradiation on scheduled DNA synthesis, representing mitotic activity, and unscheduled DNA synthesis, representing DNA repair activity, in the skin of hairless mice were determined autoradiographically following intradermal administration of [3H]-thymidine. Azathioprine and prednisolone, and, to a lesser extent, cyclosporin A, were found to impair normal repair of UVR-induced DNA lesions in epidermal keratinocytes. Prednisolone, but not the other two drugs, further suppressed the normal delayed mitotic response in the skin following UVR. The depressive effects of these drugs, particularly the combined azathioprine/prednisolone regime, on scheduled and unscheduled DNA synthesis are considered likely to predispose skin to mutagenic and carcinogenic processes.