Viability of a circular economy for space debris.
The orbital debris population is rapidly growing, increasing the chance of a Kessler-style collision event. We report a novel method for the production of estimates for the total monetary value of all debris objects and total mass of all objects currently in orbit. The method was devised using debris object data from the European Space Agency's DISCOS dataset, classified via a decision tree. 'Reuse' and 'scrap material' scenarios were developed. A high-end estimate for reuse shows a net value of $1.2 trillion. Median and low-end net value estimates of $600 billion and $570 billion, respectively, are probably judicious. A scrap material scenario produced a high mass estimate of 19,124 tonnes, a median of 6,978 tonnes and a low estimate of 5,312 tonnes. Development of in-orbit services will be crucial to solve the orbital debris problem. A future circular economy for space may be financially viable, with potentially beneficial consequences for risk reduction; resource efficiency; additional high-value employment; and climate-change knowledge, science, monitoring and early warning data.


Convertibility of a saponifiable lipoidal derivative of 18-hydroxycorticosterone.
Metabolic properties and subcellular localization of the biosynthesis of SM, a saponifiable 18-OH-B (18-Hydroxycorticosterone) derivative, were investigated. Homogenates biosynthesized SM at a nearly constant rate of 463 pmol/50 mg tissue during 30 min. This biosynthesis was more efficient at pH 7.4 than at pH 4.8. Not only 18-OH-B but also its less polar anhydride 18-DAL (18-Deoxyaldosterone) were good precursors. SM was reverted to these precursors both enzymatically and spontaneously, 4.8 being a more suitable pH for this reversion than 7.4. Trapping experiments demonstrated a sequence comprising, in this order, the following echelons: SM, 18-OH-B, 18-DAL, Aldosterone. The first two steps are reversible and the last two ones depend on proton concentrations. It is postulated that SM could be on a dead-end to which 18-OH-B could be deviated if Aldosterone biosynthesis became temporarily unnecessary. Also, that 18-OH-B may convert to either 18-DAL or SM for selective membrane transports, according to homeostatic requirements.


Evaluation of cell penetrating peptides fused to elastin-like polypeptide for drug delivery.
Translocation through the plasma membrane is a major limiting step for the cellular delivery of macromolecules. Several cell penetrating peptides (CPP) have been demonstrated to efficiently internalize various molecular cargo to targets inside eukaryotic cells. In this study, the efficiency and mechanism of cellular uptake of the CPPs penetratin, Tat, and MTS fused to elastin-like polypeptides (CPP-ELP) were evaluated. Elastin-like polypeptides are biopolymers with features that make them useful as polymeric carriers for the delivery of therapeutics. Therefore, improving efficiency of cellular uptake by fusing ELPs to CPPs and understanding the mechanism of their cellular internalization could contribute to development of new therapeutic approaches. Flow cytometry and confocal fluorescence microscopy were used to elucidate the mechanism of CPP-ELP uptake. The internalization of all CPP-ELPs was impaired dramatically at 4 degrees C, under ATP depletion conditions, and with hyperosmolar sucrose, implicating involvement of an endocytic pathway for CPP-ELP internalization. Penetratin was identified as the most effective CPP for delivering ELP. Finally, in order to demonstrate the potential of CPP-ELP for drug delivery, a fusion polypeptide was made containing penetratin, ELP, and a peptide derived from the cyclin-dependent kinase inhibitor p21. This polypeptide was shown to inhibit proliferation of SKOV-3 and HeLa cells by slowing their growth rate.


LY339434, a GluR5 kainate receptor agonist.
The activity of a gamma-substituted glutamate analogue, (2S, 4R, 6E)-2-amino-4-carboxy-7-(2-naphthyl)hept-6-enoic acid (LY339434) and (2S,4R)-4-methylglutamic acid at ionotropic glutamate receptors has been examined. Ligand binding studies were performed using [3H] AMPA binding to membranes expressing either homomeric recombinant GluR1, GluR2, GluR4 receptors, and [3H] kainate binding to GluR5 and GluR6 kainate receptors. LY339434 and (2S,4R)-4-methylglutamic acid showed selectivity in ligand binding studies for kainate receptors over AMPA receptors. Within the kainate class of glutamate receptors, LY339434 showed selectivity for GluR5 over GluR6 whereas (2S,4R)-4-methylglutamic acid showed high affinity for both GluR5 and GluR6 kainate receptors. Examination of the functional activity of LY339434 and (2S,4R)-4-methylglutamic acid showed that both compounds evoked inward currents in dorsal root ganglion neurons (DRG) with estimated EC50 values of 0.8 +/- 0.2 microM and 0.17 +/- 0.04 microM, respectively. In GluR5 expressing HEK 293 cells, LY339434 evoked inward currents with an estimated EC50 value of 2.5 +/- 0.9 microM but had little effect on GluR6 expressing cells at concentrations less than 100 microM. LY339434 was a weak AMPA receptor agonist (EC50 values > 300 microM) as determined by activity in acutely isolated cerebellar Purkinje neurons. LY339434 and (2S,4R)-4-methylglutamic acid had agonist activity at NMDA receptors studied in cultured hippocampal neurons with EC50s of 2.5 microM and 11.7 microM, respectively. These results indicate that both LY339434 and (2S,4R)-4-methyl glutamic acid may be useful pharmacological tools for the examination of kainate receptors.


Application of artificial neural network in food classification.
Artificial neural network (ANN) classifiers have been successfully implemented for various quality inspection and grading tasks of diverse food products. ANN are very good pattern classifiers because of their ability to learn patterns that are not linearly separable and concepts dealing with uncertainty, noise and random events. In this research, the ANN was used to build the classification model based on the relevant features of beer. Samples of the same brand of beer but with varying manufacturing dates, originating from miscellaneous manufacturing lots, have been represented in the multidimensional space by data vectors, which was an assembly of 12 features (% of alcohol, pH, % of CO(2) etc.). The classification has been performed for two subsets, the first that included samples of good quality beer and the other containing samples of unsatisfactory quality. ANN techniques allowed the discrimination between qualities of beer samples with up to 100% of correct classifications.


The puzzling distribution of Heteromurus (Verhoeffiella) absoloni Kseneman, 1938 (Collembola: Entomobryidae: Heteromurinae) resolved: detailed redescription of the nominal species and description of a new species from Catalonia (Spain).
The species Heteromurus (Verhoeffiella) absoloni Kseneman, 1938 is redescribed in detail and characterized by its barcode, based on specimens from its type locality in Montenegro. A neotype is designated. Dorsal S-chaetotaxy is given for the first time in the subgenus Verhoeffiella. Chaeta morphology and distribution are thoroughly analyzed, in particular on antennae where 12 chaetal types are recognized. Several morphological features are newly described for the genus and for Heteromurinae. The widely disjunct distribution of the species is approached through morphological and molecular comparison of specimens from the type locality in Montenegro and from the Catalan population. We established that this last record is a new species described here as Heteromurus (Verhoeffiella) gamae sp. nov. New combination is proposed Heteromurus (Verhoeffiella) constantinellus (Ćurčić & Lučić in Lučić, Ćurčić & Mitić 2007) comb. nov. A table of all species of the subgenus is provided. The taxonomic status of Verhoeffiella and the problems of species discriminations in the subgenus are discussed.


In situ phytoremediation of dyes from textile wastewater using garden ornamental plants, effect on soil quality and plant growth.
In situ phytoremediation of dyes from textile wastewater was carried out in a high rate transpiration system ridges (91.4 m × 1.0 m) cultivated independently with Tagetes patula, Aster amellus, Portulaca grandiflora and Gaillardia grandiflora which reduced American Dye Manufacturers Institute color value by 59, 50, 46 and 73%, respectively within 30 d compared to dye accumulated in unplanted ridges. Significant increase in microbial count and electric conductivity of soil was observed during phytoremediation. Reduction in the contents of macro (N, P, K and C), micro (B, Cu, Fe and Mn) elements and heavy metals (Cd, As, Pb and Cr) was observed in the soil from planted ridges due to phyto-treatment. Root tissues of these plants showed significant increase in the specific activities of oxido-reductive enzymes such as lignin peroxidase, laccase, veratryl alcohol oxidase, tyrosinase and azo reductase during decolorization of textile dyes from soil. Anatomical studies of plants roots revealed the occurrence of textile dyes in tissues and subsequent degradation. A minor decrease in plant growth was also observed. Overall surveillance suggests that the use of garden ornamental plants on the ridges of constructed wetland for the treatment of dyes from wastewater along with the consortia of soil microbial flora is a wise and aesthetically pleasant strategy.


Infrared Thermography as a Diagnostic Tool for Peripheral Artery Disease.
The prevalence of peripheral arterial disease (PAD) is increasing worldwide. The ankle-brachial index (ABI) is considered the criterion standard of noninvasive screening, but it does have limitations. The present study aimed to clarify the clinical diagnostic potential of infrared thermography (IRT) compared with conventional noninvasive measurements for PAD. Patients were divided into two groups: the healthy control group (n = 93) and the PAD group (n = 164). Control participants had an ABI 0.9 to 1.4 and no former PAD diagnosis. The PAD group was divided into three subgroups based on ABI classifications and two subgroups based on toe pressure measurements. Investigators performed IRT using a standardized protocol with temperature measurements at five different foot sites. Differences in skin temperatures between feet were greater (P < .001) in the PAD group than in healthy controls. In general, mean foot temperatures were lower in the PAD group than in controls but did not differ significantly among PAD subgroups based on ABI classifications or toe pressure measurements. Infrared thermography effectively distinguished temperature differences between feet and thus might be diagnostically useful. However, because normal skin surface temperature varies among individuals, IRT alone cannot be recommended for evaluating PAD. However, it does have potential to provide additional information about circulation, subclinical infections, and the severity of vascular disease.


Effect of statil on kidney structure, function and polyol accumulation in diabetes mellitus.
We examined the effects of an aldose-reductase inhibitor, statil, which blocks the conversion of glucose to sorbitol, in rats rendered diabetic with streptozotocin in order to determine whether the anticipated changes in sorbitol content was associated with beneficial lack of changes in renal morphology and function. Groups of diabetic, insulin-treated and untreated rats were fed statil daily for a period of five months; each group was paired with a non-drug-treatment control group. At the conclusion of the study period, statil was not found to affect renal sorbitol concentrations nor did it effect functional or structural changes seen in the kidney. We conclude that further study, using other doses of statil and longer duration over which data is collected, must be undertaken in order to implicate the polyol pathway in the renal complications of diabetes mellitus.


Point mutations of c-ras genes in human bladder cancer and kidney cancer.
Point mutations of c-ras genes at codons 12, 13 and 61 were analyzed in 26 cases of bladder cancer and 16 cases of kidney cancer. DNA prepared from either frozen tissues or 10% formalin-fixed, paraffin-embedded tissues were amplified by means of polymerase chain reaction methods, and mutations were analyzed by dot blot hybridization assays with oligonucleotide probes. In three cases of bladder cancer c-ras mutations were found, at codons 13 and 61 of c-Ha-ras and at codon 61 of c-Ki-ras, while no mutation was found in kidney cancer. No mutation was found in normal bladder epithelial tissues from the same patients. Our findings, taken together, may indicate relative scarcity of c-ras mutations in these types of human cancer. The results of dot blot hybridization assays and DNA sequencing showed a G-to-C transition of the first nucleotide at codon 13 c-Ha-ras. This is the first time that such a point mutation has been detected in human cancer tissues.


A critical evaluation of benthic phase shift studies on coral reefs.
Coral reef decline has accelerated in the last two decades resulting in substantial research into the phenomenon of 'phase shifts' or 'regime shifts'. However, the conclusions drawn from this research have been varied. Some of this variability may stem from methodological approaches, although the extent to which these factors have shaped our understanding remain largely unexplored. To examine this, we conducted a systematic review of the literature. In doing so, we revealed marked variability in the approaches used for studying phase shifts. Notably, very few studies clearly defined what they meant by phase shifts. Therefore, we developed a clarified definition of phase shifts, which specifically defined persistence and dominance. The applicability of this definition was tested on multi-decadal benthic composition data on the Great Barrier Reef. The number of shifts depended critically on the definition selected, suggesting that this may be a primary reason underpinning the variability in past results.


Inverse Regulation of DHT Synthesis Enzymes 5α-Reductase Types 1 and 2 by the Androgen Receptor in Prostate Cancer.
5α-Reductase types 1 and 2, encoded by SRD5A1 and SRD5A2, are the two enzymes that can catalyze the conversion of testosterone to dihydrotestosterone, the most potent androgen receptor (AR) agonist in prostate cells. 5α-Reductase type 2 is the predominant isoform expressed in the normal prostate. However, its expression decreases during prostate cancer (PCa) progression, whereas SRD5A1 increases, and the mechanism underlying this transcriptional regulatory switch is still unknown. Interrogation of SRD5A messenger RNA expression in three publicly available data sets confirmed that SRD5A1 is increased in primary and metastatic PCa compared with nontumoral prostate tissues, whereas SRD5A2 is decreased. Activation of AR, a major oncogenic driver of PCa, induced the expression of SRD5A1 from twofold to fourfold in three androgen-responsive PCa cell lines. In contrast, AR repressed SRD5A2 expression in this context. Chromatin-immunoprecipitation studies established that AR is recruited to both SRD5A1 and SRD5A2 genes following androgen stimulation but initiates transcriptional activation only at SRD5A1 as monitored by recruitment of RNA polymerase II and the presence of the H3K27Ac histone mark. Furthermore, we showed that the antiandrogens bicalutamide and enzalutamide block the AR-mediated regulation of both SRD5A1 and SRD5A2, highlighting an additional mechanism explaining their beneficial effects in patients. In summary, we identified an AR-dependent transcriptional regulation that explains the differential expression of 5α-reductase types 1 and 2 during PCa progression. Our work thus defines a mechanism by which androgens control their own synthesis via differential regulatory control of the expression of SRD5A1 and SRD5A2.


Role of benzylsuccinate in the induction of the tutE tutFDGH gene complex of T. aromatica strain T1.
Expression of the tutE tutFDGH gene cluster of Thauera aromatica strain T1 was examined by Northern and Western analysis in a wild-type strain and chromosomally deleted strains with or without in-frame deletion plasmids. While expression was observed when the wild-type strain was induced with toluene, various chromosomally deleted strains exhibited little or no expression of the tut genes. In contrast, both wild-type and chromosomally deleted strains expressed the tut genes when induced with benzylsuccinate. We conclude that benzylsuccinate is required for the full induction of the tutE tutFDGH gene cluster of T. aromatica strain T1.


Decision Making in Surgery for Nonsaccular Posterior Inferior Cerebellar Artery Aneurysms With Special Reference to Intraoperative Assessment of Collateral Blood Flow and Neurophysiological Function.
Posterior inferior cerebellar artery (PICA) aneurysms represent a challenging pathology. PICA sacrifice is often necessary, due to the high proportion of nonsaccular aneurysms that can be found in this location. Several treatments are available, but the infrequency of these aneurysms and the increasing number of endovascular techniques have limited the development of a standardized algorithm for cases in which open surgery is indicated. We present our series of nonsaccular PICA aneurysms, in the attempt to define an algorithm for their surgical management. We retrospectively reviewed the operation database, identifying patients harboring nonsaccular PICA aneurysms who were surgically treated at our institution from 2007 to 2016. During a 9-yr period, 17 patients harboring 18 nonsaccular PICA aneurysms were surgically treated at our institution. Fourteen (7.7%) aneurysms were located within the proximal PICA (including those located at the vertebral artery-PICA junction), and 4 were located distally. We performed PICA revascularization in 8 (57.1%) cases of proximal aneurysms (n = 4, PICA-PICA bypass; n = 4, occipital artery-PICA bypass). We based our decision whether to perform bypass on intraoperative test occlusion with indocyanine green (ICG) videoangiography and neurophysiological monitoring. In no cases, bypass was necessary for distal aneurysms. For nonsaccular PICA aneurysms, in which vessel occlusion is often necessary, it is possible to adopt a selective use of revascularization techniques. Intraoperative occlusion test with ICG videoangiography and neurophysiological monitoring provides reliable indications, allowing real-time assessment of collateral circulation.


Ectopic breast cancer: case report and review of the literature.
Ectopic breast tissue comes in two forms: supernumerary and aberrant. Despite morphologic differences, ectopic breast tissue presents characteristics analogous to orthotopic breast tissue in terms of function and, most importantly, pathologic degeneration. Data in the literature concerning its precise incidence, the probability of malignant degeneration, and its standardized management are scarce and controversial. This study selected more than 100 years of literature, and this report discusses a case of ectopic breast cancer treatment, suggesting novel therapeutic advice that could bring considerable clinical advantages, improve cosmetic results, and reduce the psychological impact on patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Adult characteristics of survivors of early life malnutrition in an impoverished population.
To determine the characteristics of adults who survived early life malnutrition (ELM) and the possible associated factors. The setting is an impoverished community in Kenya. The coastal region of Kenya has a high prevalence of acute protein-energy-malnutrition and stunting. Observational cross-sectional survey where 872 skeletally mature adults of African origin, were surveyed in a period of three months. A discrimination tool to detect ELM survivors was created. Personal, historical and family data were collected in a semi-structured questionnaire. Various observations and body measurements were done. The subjects were grouped into two, those with ELM (Group1), and those without (Group2). Group1 had 242 participants, 49.8% males, mean age of 49.1 ± 8.7 years. Group2 had 630 participants, 48.3% males, mean age 41.0 ± 9.7 years. The phenotypic characteristics included height, BMI, and head circumference (P < 0.05). Developmental characteristics were duration of schooling, occupation and income (P < 0.001). Factors associated with malnutrition were County of origin, parental education, parental occupation, and family size (P < 0.001). There are discernible phenotypic and developmental characteristics associated with adult survivors of ELM. The predisposing factors for ELM are location of birth, parental education and occupation, and family size.


Multiecho magnetic resonance angiography.
Several pulse sequences which generate projected MR angiograms are presented. These pulse sequences exploit multiple-gradient refocused echoes to obtain several independent angiograms, which can be combined or separately analyzed to provide more information than an individual angiogram. For example, a series of angiograms, each with a different projection axis, can be obtained in the time required to obtain a single angiogram using a single-echo method. If the view angle of each echo is the same, then the acquired angiograms can be added to enhance the signal-to-noise ratio. Another pulse sequence simultaneously obtains two or more angiograms, sensitive to orthogonal flow components of the overall blood flow. These angiograms are then added to give an angiogram which is sensitive to flow in all directions.


Ethical Considerations for Mechanical Support.
Extracorporeal life support can support patients with severe forms of cardiac and respiratory failure. Uncertainty remains about its optimal use owing in large part to its resource-intensive nature and the high acuity illness in supported patients. Specific issues include the identification of patients most likely to benefit, the appropriate duration of support when prognosis is uncertain, and what to do when patients become dependent on extracorporeal life support but no longer have hope for recovery or transplantation. Careful deliberation of ethical principles and potential dilemmas should be made when considering the use of extracorporeal life support in advanced cardiopulmonary failure.


Perinatal steroid exposure and respiratory control during early postnatal life.
Numerous factors involved in general homeostasis are able to modulate respiratory motor output. These include placental-derived steroids, which are necessary for maternal physiological adjustments during gestation, including respiratory stimulation. Despite the fact that these hormones exert potent effects on neural development in the fetus, the hypothesis of a developmental control of the neural respiratory network by placental-derived steroids has been approached experimentally only recently. The objective of this review is to summarize the role and mode of action of placental steroids on respiratory control in adult mammals and highlight the potential pathways by which such steroids are supplied to the developing fetus. Additionally, we present recent results showing that the beta estradiol and progesterone receptors are expressed in the carotid body of newborn male rats, thus supporting the hypothesis of receptor-mediated effect of estradiol and progesterone on carotid bodies.


Spin Labeling and Characterization of Tau Fibrils Using Electron Paramagnetic Resonance (EPR).
Template-assisted propagation of Tau fibrils is essential for the spreading of Tau pathology in Alzheimer's disease. In this process, small seeds of fibrils recruit Tau monomers onto their ends. The physical properties of the fibrils play an important role in their propagation. Here, we describe two different electron paramagnetic resonance (EPR) techniques that have provided crucial insights into the structure of Tau fibrils. Both techniques rely on the site-directed introduction of one or two spin labels into the protein monomer. Continuous-wave (CW) EPR provides information on which amino acid residues are contained in the fibril core and how they are stacked along the long fibril axis. Double electron-electron resonance (DEER) determines distances between two spin labels within a single protein and hence provides insights into their spatial arrangement in the fibril cross section. Because of the long distance range accessible to DEER (~2-5 nm) populations of distinct fibril conformers can be differentiated.


A limited-capacity response process in absolute identification.
In two absolute identification experiments, the dependency of the current response, Rn, on the immediately preceding stimulus, Sn-1, and response, Rn-1, was measured by means of multivariate information transmission (see McGill, 1954). In these experiments, the amount of stimulus information available to subjects, measured as the amount of information transmission from a current stimulus, Sn, to Rn, was manipulated. The magnitude of the dependency of Rn on Sn-1 and Rn-1 was inversely proportional to that of information transmission from Sn to Rn, supporting the argument of Ward and Lockhead (1971) that the less stimulus information the subjects get, the more their responses will be likely to depend on previous stimuli and responses. Interestingly, the sum of information transmission from Sn, Sn-1, and Rn-1 to Rn was always about 2.5 bits, without respect to the variance of each term. This result could have arisen from the operation of a limited-capacity response process.


Effect of maternal ketorolac administration of platelet function in the newborn.
Ketorolac is a potent analgesic agent with antiplatelet properties which is known to cross the placenta. The aim of this study was to determine whether maternal administration of ketorolac in labour had any effect on neonatal platelet function as compared with maternal administration of pethidine and prochlorperazine. Eighteen parous women were studied in labour, twelve received pethidine (control) and six received ketorolac for analgesia. Immediately after delivery, blood was taken from the umbilical vein and anticoagulated with citrate. Platelet aggregation in whole blood was studied. Ketorolac significantly inhibited aggregation in response to arachidonic acid and collagen but not ADP. These findings confirm that ketorolac crosses the placenta. The antiplatelet effects are likely to be related to ketorolac's inhibitory effect on TxA2 production which is required for arachidonic acid and collagen-induced aggregation, but not the primary aggregation response induced by ADP. These effects suggest that ketorolac should be used with caution in patients whose neonates are at risk of haemostatic problems.


Relationship Between Crown to Root Ratio and Alveolar Bone Support in Patients With Unilateral Cleft Lip and Alveolus.
To evaluate the tooth lengths, crown to root ratios (CRRs), and alveolar bone support (ABS) around cleft-adjacent maxillary central incisors (U1s) in patients with unilateral cleft lip and alveolus (UCLA) and to investigate the relationships between CRR and ABS. This is a retrospective study. Cleft Lip and Palate Care Center of Shanghai Ninth People's Hospital, Shanghai, China. Fifty-eight Chinese patients with UCLA. Cone beam computed tomography data from 58 nonsyndromic patients with UCLA (36 males, 22 females; mean age = 12.65 ± 3.64 years) were evaluated. Crown length and root length, alveolar bone thickness (ABT), and the distances between the cementoenamel junction and alveolar bone crest on 4 surfaces of cleft-adjacent U1 were measured and compared with those of noncleft side in the same patients. Crown to root ratio and frequency of dehiscence were calculated and comparisons were also made between cleft and noncleft sides. Regression analysis was performed to explore the association between CRR and ABS. The CRR of cleft-adjacent U1 and alveolar bone crest heights (ACHs) on the 4 surfaces were significantly greater than those of noncleft side (P < .01). A 3 mm labial, all lingual, and apico-distal ABTs decreased on the cleft side (P < .01). A positive correlation was found between lingual ACH and CRR (R = 0.316, P < .05), between the 3 mm (R = 0.417, P < .05) and 6 mm labial (R = 0.448, P < .05) ABT and CRR. A negative correlation was found between the 3 mm and 6 mm labial ABTs and the root length. It can be suggested that the CRR is related to ACH and ABT. The lingual ACH, the 3 mm, and 6 mm labial ABTs tend to increase with the increasing CRR.


The Influence of Insulin Therapy on the Course of Acute Exacerbation of Bronchial Asthma.
Large doses of systemic corticosteroids are the basis of treatment of acute exacerbation of bronchial asthma. The hyperglycemic activity of systemic corticosteroids often leads to the loss of control of diabetes diagnosed earlier or to its first diagnosis during treatment of the exacerbation of asthma. We conducted a prospective, randomized study in a group of 24 adult patients treated for asthma exacerbation, with the blood glucose level at admission above 8.4 mmol/l. The patients were randomly divided into a group treated with intravenous insulin infusion by an electric syringe pump in doses controlling glycemia at 4.5-7.2 mmol/l (Group A) and a group of patients treated with insulin administered subcutaneously in three doses controlling glycemia at 7.2-10.0 mmol/l (Group B). A control group (Group C) consisted of patients without any disturbances in carbohydrate metabolism, treated for exacerbation of asthma. Asthma exacerbation was treated in all groups in a uniform way. We found that the average hospitalization time was 8.2 ± 2.4 days in Group A, 10.2 ± 5.2 days in Group B, and 5.8 ± 1.9 days in Group C; the last being significantly shorter than those in Groups A and B. We conclude that hyperglycemia is a significant factor increasing the risk of extending hospitalization time due to asthma exacerbation, regardless of the way of insulin therapy.


Myasthenia gravis after glioblastoma resection: paraneoplastic syndrome or coincidence? A unique case report and review of the literature.
Paraneoplastic neurological syndromes (PNS) can manifest with every type of malignancy. A well-known syndrome is myasthenia gravis (MG) in combination with thymomas. No association between primary brain tumors and neuromuscular disorders has been described. Here, we present a case of a 65-year-old patient who developed MG, following an uncomplicated, gross-total resection of a glioblastoma. To our knowledge, this is the first case describing the onset of MG during the early postoperative phase after glioblastoma resection. Current criteria of PNS are insufficient when the neurological syndrome is diagnosed at the time of a malignancy or shortly thereafter and should be revisited.


Cyclosporin A inhibits protein kinase C activity: a contributing mechanism in the development of nephrotoxicity?
Cyclosporin A modifies many intracellular functions in a variety of different cells. This study investigated the potential interaction between cyclosporin A and protein kinase C, as a possible mechanism for the development of nephrotoxicity. The activity of protein kinase C, in the cytosol of renal epithelial cells, was shown to be significantly inhibited in a dose-dependent manner by CSA. Activation of protein kinase C by 12-O-tetradecanoylphorbol-13-acetate (phorbol ester) in rat mesangial cells in culture leads to an increase in PGE2 release. Phorbol ester stimulated PGE2 release was significantly inhibited by cyclosporin A. These results would suggest that intracellular site of action of cyclosporin A, in producing alterations in intracellular function and toxicity, may be at the level of protein kinase C.


Biologically inspired robotic perception-action for soft fruit harvesting in vertical growing environments.
Multiple interlinked factors like demographics, migration patterns, and economics are presently leading to the critical shortage of labour available for low-skilled, physically demanding tasks like soft fruit harvesting. This paper presents a biomimetic robotic solution covering the full 'Perception-Action' loop targeting harvesting of strawberries in a state-of-the-art vertical growing environment. The novelty emerges from both dealing with crop/environment variance as well as configuring the robot action system to deal with a range of runtime task constraints. Unlike the commonly used deep neural networks, the proposed perception system uses conditional Generative Adversarial Networks to identify the ripe fruit using synthetic data. The network can effectively train the synthetic data using the image-to-image translation concept, thereby avoiding the tedious work of collecting and labelling the real dataset. Once the harvest-ready fruit is localised using point cloud data generated by a stereo camera, our platform's action system can coordinate the arm to reach/cut the stem using the Passive Motion Paradigm framework inspired by studies on neural control of movement in the brain. Results from field trials for strawberry detection, reaching/cutting the stem of the fruit, and extension to analysing complex canopy structures/bimanual coordination (searching/picking) are presented. While this article focuses on strawberry harvesting, ongoing research towards adaptation of the architecture to other crops such as tomatoes and sweet peppers is briefly described. The online version contains supplementary material available at 10.1007/s11119-023-10000-4.


Ca2+ release from mitochondria induced by prooxidants.
A variety of chemically different prooxidants causes Ca2+ release from mitochondria. The prooxidant-induced Ca2+ release occurs from intact mitochondria via a route which is physiologically relevant and may be regulated by protein ADP-ribosylation. When the released Ca2+ is excessively cycled by mitochondria they are damaged. This leads to uncoupling, a decreased ATP supply, and a decreased ability of mitochondria to retain Ca2+. Excessive Ca2+ cycling by mitochondria will deprive cells of ATP. As a result, Ca2+ ATPases of the endoplasmic (sarcoplasmic) reticulum and the plasma membrane are stopped. The rising cytosolic Ca2+ level cannot be counterbalanced due to damage of mitochondria which, under normoxic conditions, act as safety device against increased cytosolic Ca2+. It is proposed that prooxidants are toxic because they impair the ability of mitochondria to retain Ca2+.


[Oral combined contraception: is there any difference between ethinyl-estradiol and estradiol?].
Estradiol 17-β, which is the natural estrogen in women, offers an alternative to ethinyl-estradiol to be used in combined oral contraceptives. Thanks to its biochemical structure, estradiol has a far lesser impact on the synthesis of hepatic proteins than ethinyl-estradiol, which is likely to result in a better metabolic and vascular profile. However and until lately, the different clinical trials that had investigated estradiol-containing oral contraceptives were limited by bleeding disturbances, with breakthrough and irregular bleeding and higher rates of discontinuation. Development of anti-gonadotropic progestins with a potent endometrial activity is likely to make possible their combination with estradiol in oral contraceptives. The objective of this current review is to provide an overview of the development of combined oral contraceptives containing natural estrogen from the respective biochemical and pharmacological characteristics of ethinyl-estradiol and estradiol.


Kidney transplantation from hepatitis B (HB)-positive donors to HB negative recipients: anti-HB Core immunoglobulin G became positive in all recipients after the transplantation.
Hepatitis B surface antigen (HBsAg)-positive donors are not accepted by many transplant centers as a kidney source owing to risk of transmission of hepatitis B; however, some reports show that these donors can be used under a special protocol. Herein, we report our cases of kidney transplantation from HBsAg(+) donors to HbsAg(-) recipients. In the years 2010-2012, we transplanted 4 kidneys from 4 HBsAg(+) donors to HBsAg(-) recipients. They were all living related. All antiHBs(-) recipients were vaccinated before transplantation and became HBsAg(-), anti-HB core immunoglobulin G antibody negative [antiHBcIg(-)], and antiHBs(+). Pretransplantation antiHBs titers were targeted to be >100 IU. If lower, hepatitis B Ig was used at the time of transplantation. One patient received hepatitis B Ig at the time of transplantation (owing to titer of 62 IU/L antiHBs). Lamivudine was prescribed for all kidney allograft recipients after transplantation. Two patients had special induction treatment including rituximab, intravenous immunoglobulin, and plasmapheresis owing to the presence of donor-specific antibody. All patients became antiHBcIgG(+) at 1-6 months after the transplantation, despite the presence of antiHBs positivity, which might be explained by transmission of hepatitis B virus through the graft.


Prevalence and patterns of polysubstance use in a nationally representative sample of 10th graders in the United States.
The current study examines the prevalence and demographic correlates of self-reported substance use and identifies subgroups of polysubstance users among a cohort of United States 10th-grade students. A nationally representative school-based cohort of United States 10th-grade students completed the NEXT Generation Health Study baseline survey in spring 2010 (N = 2,524). Past-year use of marijuana was most common among illicit drugs (26%), followed by misuse of medication (9%) and use of other illicit drugs (8%). During the past month, alcohol use was reported by more than one third (35%), binge drinking by 27%, and cigarette smoking by 19%. Results further show that substance use varied somewhat by demographic characteristics. Results from the latent class analysis of polysubstance use indicated a four-class solution as the best-fitting model; class 1 (59%) included the nonuser group; class 2 (23%) comprised the predominant alcohol user group; class 3 (11%) formed the predominant marijuana user group; and class 4 (8%) was characterized as the predominant polysubstance user group. Somatic and depressive symptoms varied significantly by class membership, with predominant polysubstance users reporting elevated levels of somatic and depressive symptoms. The findings from this national study of 10th-grade students indicate high rates of substance and polysubstance use. The high level of depressive and somatic symptoms among polysubstance users indicates the need for mental health screening and referral.


Multiple cerebral cavernous malformations associated with extracranial mesenchymal anomalies.
Cerebral cavernous malformations (CCM) are common hamartous dysplasias characterized by abnormally dilated vascular channels. CCM mostly occur sporadically, and multiple occurrence of CCM is highly suggestive of a genetic origin of the disorder. Typical clinical symptoms are seizures, hemorrhages, focal neurological deficits, and headaches. Three genes have so far been described that are responsible for most cases of familial CCM and more than half of the sporadic cases with multiple CCM (CCM1-3). The coincidence of CCM and other vascular anomalies has been described before. The present review discusses the association of CCM with mesenchymal anomalies, with special emphasis on the possible common pathogenetic pathway for CCM and atrial myxomas. An illustrative case is presented in which CCM occurred together with different dysplasias (multiple CCM, liver cavernoma, and cardiac atrial myxoma), which are all thought to arise from abnormal mesenchymal cell differentiation processes.


A new species in the leafhopper genus Processina (Hemiptera: Cicadellidae: Mileewinae: Mileewini) from China.
A new species in the Mileewinae genus Processina Yang, Deitz Li, 2005, P. hunanensis sp. nov., from China is described. A checklist and a key to all known species of Processina are provided.


Development of high-throughput screening system by single-cell reaction using microchamber array chip.
To demonstrate the practical use of a novel high-throughput screening system by a single cell reaction for the rapid screening of combinatorially mutated beta-glucosidase 1 from Aspergillus oryzae, a yeast cell chip microchamber array in combination with yeast cell surface engineering was successfully developed.


Adult case of tetralogy of Fallot associated with atrioventricular septal defect.
The patient was a 28-year-old woman who was misdiagnosed with tetralogy of Fallot and straddling mitral valve after birth. She underwent a left modified Blalock-Taussig shunt at the age of 1 year. At age 28, she presented with fatigue and progressive cyanosis. Finally, she was diagnosed with tetralogy of Fallot and complete atrioventricular septal defect. To measure the exact biventricular volumes, we performed cardiac magnetic resonance imaging in addition to cardiac angiography and ensured adequate volume capacity. We eventually decided to perform biventricular repair. Her postoperative course was uneventful, and she returned to full-time work.


The influence of calcitriol and methylprednisolone on podocytes function in minimal change disease in vitro model.
Minimal change disease (MCD), considered one of the major causes of nephrotic syndrome, is a complex pathological condition with disturbances in podocytes' foot processes. Numerous studies suggested the essential role of vitamin D3 in maintaining proper glomerulus function. However, the data on direct potential of that compound in reference to podocytes are scarce. Thus, here we assessed the influence of calcitriol (active vitamin D3) on podocyte function, apart from commonly used steroids (methylprednisolone). CIHP-1 podocyte cell line was used to implement the LPS-PAN-induced MCD in vitro model. Viability, podocyte-related slit diaphragm proteins, morphology, function as a barrier was evaluated using flow cytometry, RT-PCR, confocal microscopy, and TEER analysis. Calcitriol or methylprednisolone did not affect cell viability. Podocyte-related proteins demonstrated different responses to in vitro treatment compared to previously reported changes in total glomeruli. Podocyte morphology was partially restored in the presence of the tested compounds. In addition, TEER analysis revealed improvement of LPS-PAN-induced cells' function as a barrier when vitamin D3 or steroid was used. In conclusion, a significant potential for modulation of MCD in vitro model podocytes with calcitriol or selected steroids was reported. Further studies on vitamin D3 in context of podocyte-related phenomenon accompanying MCD are of great importance.


Revision of total shoulder arthroplasty to hemiarthroplasty: results at mean 5-year follow-up.
Although there is a trend to manage failed anatomic total shoulder arthroplasties (aTSA) with revision to a reverse total shoulder arthroplasty, such revisions can be complicated by difficulties in baseplate fixation, instability, and acromial stress fractures. Some cases of failed aTSA may be safely revised to a hemiarthroplasty (HA). The objectives of this study were to report patient-reported outcomes after conversion from aTSA to HA and assess patient and shoulder characteristics associated with a successful outcome. Patients who underwent revision from aTSA to HA between 2009 and 2018 were contacted. Patient demographics, surgical history, intraoperative findings, and microbiology results were collected. Patient-reported outcomes were collected with minimum 2-year follow-up. Preoperative radiographic characteristics were reviewed for component positioning and component loosening. Patients with a clinically significant improvement exceeding the minimal clinically important difference (MCID) of the Simple Shoulder Test (SST) were compared with those patients who did not improve past the MCID. Twenty-nine patients underwent conversion from aTSA to HA with a mean follow-up of 4.5 ± 1.8 years. Intraoperative glenoid or humeral component loosening was found in all 29 patients. Pain improved in 25 of 30 patients (87%), and mean pain scores improved from 6.2 ± 2.3 to 3.1 ± 2.4 (P < .001). SST scores improved from 4.1 ± 3.1 to 7.3 ± 3.2 (P < .001), and 18 of 29 patients (62%) had improvement above the SST MCID threshold of 2.4. The mean American Shoulder and Elbow Surgeons score at the latest follow-up was 64 ± 19, and the Single Assessment Numeric Evaluation score was 65 ± 23. Twenty-two of 29 (76%) patients were satisfied with the procedure. Four patients (14%) required conversion to total shoulder arthroplasty-2 to anatomic and 2 to reverse. An additional 3 patients (10%) had a revision HA performed. No significant differences in patient or shoulder characteristics were found in those patients who improved greater than the MCID of the SST compared patients who improved less than the MCID of the SST. Fifty-nine percent of patients had ≥2 positive cultures with the same bacteria, and 82% of these were with Cutibacterium. Seven of 8 patients (88%) with a loose humeral component had ≥2 positive cultures with the same bacteria. Component loosening is a common failure mode after aTSA. Revision to HA can improve pain and patient-reported outcomes in most patients.


Gate-tunable quantum pathways of high harmonic generation in graphene.
Under strong laser fields, electrons in solids radiate high-harmonic fields by travelling through quantum pathways in Bloch bands in the sub-laser-cycle timescales. Understanding these pathways in the momentum space through the high-harmonic radiation can enable an all-optical ultrafast probe to observe coherent lightwave-driven processes and measure electronic structures as recently demonstrated for semiconductors. However, such demonstration has been largely limited for semimetals because the absence of the bandgap hinders an experimental characterization of the exact pathways. In this study, by combining electrostatic control of chemical potentials with HHG measurement, we resolve quantum pathways of massless Dirac fermions in graphene under strong laser fields. Electrical modulation of HHG reveals quantum interference between the multi-photon interband excitation channels. As the light-matter interaction deviates beyond the perturbative regime, elliptically polarized laser fields efficiently drive massless Dirac fermions via an intricate coupling between the interband and intraband transitions, which is corroborated by our theoretical calculations. Our findings pave the way for strong-laser-field tomography of Dirac electrons in various quantum semimetals and their ultrafast electronics with a gate control.


Is Emtricitabine-Tenofovir Disoproxil Fumarate Pre-exposure Prophylaxis for the Prevention of Human Immunodeficiency Virus Infection Safer Than Aspirin?
Background. The safety and effectiveness studies of emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for human immunodeficiency virus (HIV) infection pre-exposure prophylaxis (PrEP) in men and women showed that daily use reduced the risk of HIV acquisition, but there still may concerns about safety. Methods. A narrative review was done in September 2015 comparing the 5 major studies on PrEP for HIV infection-Preexposure Prophylaxis Initiative (N = 2499; 3324 person-years), Partners Preexposure Prophylaxis (N = 4747; 7830 person-years), TDF2 (N = 1219; 1563 person-years), Preexposure Prophylaxis Trial for HIV Prevention among African Women (N = 2056; 1407 person-years), and Vaginal and Oral Interventions to Control the Epidemic (N = 4969; 5509 person-years)-and the 2 major studies on aspirin safety-Physicians' Health Study (N = 22 071; over 110 000 person-years) and the Women's Health Study (N = 39 876; approximately 400 000 person-years). The numbers needed to harm (NNH) were calculated for FTC-TDF for HIV infection PrEP and aspirin. Results. The NNH for FTC-TDF in men who have sex with men and transgender women was 114 for nausea and 96 for unintentional weight loss; in heterosexual couples, the NNH was 68 for moderate decreased absolute neutrophil count. For aspirin, the NNH was 909 for major gastrointestinal bleeding, 123 for any gastrointestinal bleeding, and 15 for any bleeding problems in men. In women, the NNH for easy bruising was 10. Conclusions. We conclude that FTC-TDF for PrEP for HIV infection favorably compares with aspirin in terms of user safety. Although long-term studies are needed, providers should feel reassured about the safety of short- and medium-term PrEP for HIV infection with FTC-TDF.


Ellipsometry of human tears.
The outer surface layer of tears is presumably composed of lipid. The thickness of this layer is considered critical to retard evaporation. Prior thickness measurements differ widely. Advances in ellipsometry have availed more precise and accurate measurements for thin films. The range in thickness of the surface layer of tears was studied by ellipsometry to uncover the source of prior discrepancies. Tear surface layers of normal and dry eye subjects were measured by in-vitro ellipsometry. Lateral and Z resolutions of ∼1 μm and 0.1 nm, were achieved respectively. Thicknesses were derived from matrices and a Levenberg-Marquardt multivariate regression algorithm to Fresnel equations for multi-layered films. Ellipsometric measurements of pooled and individual human tears in-vitro revealed a larger overall range (0-500 nm) of surface film thicknesses than previously reported by any one study. Each sample showed thin areas (0-2.6 nm) with interspersed thicker regions (∼200-500 nm). Repeat measurements of a single donor collected at weekly intervals showed a broad range of surface thicknesses within and between samples. Thickness measurements from a dry eye subject overlapped that of normal subjects. The data show that published disparity in surface film thickness may be attributable to limitations of prior methodologies. The range and overlap of surface film thicknesses challenge less rigorous methodologies that claim to segregate normal and dry eye.


Highly diastereoselective synthesis of decalin skeletons with quaternary carbon centers via the tandem oxy-Cope/ene/Claisen reaction.
The highly diastereoselective cascade sequence of three successive thermal pericyclic reactions of 1,2-divinylcyclohexanol allyl and propargyl ethers is described. This novel tandem process provides an efficient synthesis of sesqui- and diterpenoid skeletons having a quaternary carbon at C9. [reaction: see text]


Prescribing and sales of intramammary antimicrobials in Ireland in 2019 and 2020: the role of milk purchasers.
In Ireland between 2008 and 2022, intramammary antimicrobial (AM) products could be prescribed by a veterinary practitioner under what was known as Schedule 8 (or remote) prescribing. Under this prescribing route, an annual herd visit was not required when criteria were met as outlined in Animal Remedies Regulation 2007 to 2017 (statutory instruments No. 786/2007 and 558/2017). Under this prescribing route, the responsibilities of the milk purchaser, the farmer and the veterinary practitioner were each outlined, and a written mastitis control programme (MCP) was required. Milk purchasers implemented MCPs on participating farms (so-called MCP herds) with support from veterinary practitioner(s) who undertook Schedule 8 prescribing of intramammary AM tubes. This study seeks a clearer understanding of the role of milk purchasers in the prescribing and sale of intramammary AM products in Ireland during 2019 and 2020, whilst this Regulation was in force. Specifically, the study sought insights into the role of milk purchasers in the prescribing and sale of intramammary AM products in the Irish dairy industry during 2019 and 2020, using anonymised and highly aggregated milk purchaser data. The study also provided insights into milk quality among supplying herds during this period. For this study, we had access to anonymised, highly aggregated data from all milk purchasers that operated a MCP on at least some of their supplying herds during 2019 or 2020. Data collection was undertaken by the Department of Agriculture, Food and Marine. Data analysis was primarily descriptive. Data were available on 11 milk purchasers (64.7% of all) and 13,251 supplying herds. Of these, 52% were MCP herds. The quality of milk from supplying herds varied significantly by month, year and milk purchaser. During 2019 and 2020, there was a single Schedule 8 prescriber (a private veterinary practitioner prescribing intramammary AMs as part of a MCP), on average, for 549.3 herds. The sale of intramammary AM products through milk purchasers represented 15.2% and 26.9% of national sales in in-lactation and dry cow tubes, respectively. There was an overall 2% increase in sales through milk purchasers between 2019 and 2020. Few European Medicines Agency (EMA) category B ('Restrict') intramammary AM products were sold by milk purchasers. For both in-lactation and dry cow tubes, there was a statistically significant association between EMA classification and route of sale (through milk purchasers or otherwise). The study findings provide important insights into mastitis control and intramammary AM stewardship in the Irish dairy industry. Significant differences between milk purchasers were observed in the quality of milk, as measured through somatic cell count (SCC) values, from supplying herds. This warrants further research. In the context of intramammary AM prescribing, veterinary oversight under the Animal Remedies Regulation 2007 to 2017 was very limited during 2019 and 2020. There were also significant associations between EMA classification and route of sale during 2019 and 2020, reinforcing the need for Irish veterinary practitioners to move away from EMA category B intramammary AMs. Higher quality data are needed to address important industry questions. Specifically it is recommended that national bulk tank SCC data are made available for public good research. Past experiences with Schedule 8 prescribing (no longer permitted from 28 January 2022) may influence current efforts towards improved intramammary AM stewardship.


The Use of Contrast Agents in Clinical and Preclinical PET-MR Imaging.
PET-MR imaging is an exciting field of research for imaging chemists that allows for innovative approaches such as the use of cocktails of agents or bimodal contrast. In this review, we provide an overview of some of the work in the in preclinical and clinical PET-MR imaging to date, and discuss limitations in the design and applications of these materials.


Immunosuppressive effect of small extracellular vesicle PD-L1 is restricted by co-expression of CD80.
The PD-L1 on tumor cell-derived small extracellular vesicles (sEVs) can suppress the proliferation and cytokine production of T cells. However, PD-L1 can also be expressed by non-tumor cells. The present study is designed to test whether immunocytes release immunosuppressive PD-L1-positive sEVs. sEVs were isolated from different clinical samples of head and neck squamous cell carcinoma (HNSCC) patients, the level and cellular origins of PD-L1-positive sEVs were assessed. Co-expression of CD80 on PD-L1-positive sEVs was examined to evaluate the immunosuppressive and tumor-promotive effects. PD-L1-positive sEVs in HNSCC patients had various cellular origins, including tumor cell, T cell, B cell, dendritic cell and monocyte/macrophage. However, PD-L1-positive sEVs derived from immune cells did not exert immunosuppressive functions due to the co-expression of CD80. It was verified that co-expression of CD80 disrupted the binding of sEV PD-L1 to its receptor PD-1 on T cells and attenuated the immunosuppression mediated by sEV PD-L1 both in vitro and in vivo. The study suggests that PD-L1-positive sEVs have the cellular origin and functional heterogeneity. Co-expression of CD80 could restrict the immunosuppressive effect of sEV PD-L1. A greater understanding of PD-L1-positive sEV subsets is required to further improve their clinical application.


Microbial community networks across body sites are associated with susceptibility to respiratory infections in infants.
Respiratory tract infections are a major cause of morbidity and mortality worldwide in young children. Concepts such as the gut-lung axis have highlighted the impact of microbial communities at distal sites in mediating disease locally. However, little is known about the extent to which microbial communities from multiple body sites are linked, and how this relates to disease susceptibility. Here, we combine 16S-based rRNA sequencing data from 112 healthy, term born infants, spanning three body sites (oral cavity, nasopharynx, gut) and the first six months of life. Using a cross-niche microbial network approach, we show that, already from the first week of life on, there is a strong association between both network structure and species essential to these structures (hub species), and consecutive susceptibility to respiratory tract infections in this cohort. Our findings underline the crucial role of cross-niche microbial connections in respiratory health.


Educational attainment and adult mortality in the United States: a systematic analysis of functional form.
A vast literature has documented the inverse association between educational attainment and U.S. adult mortality risk but given little attention to identifying the optimal functional form of the association. A theoretical explanation of the association hinges on our ability to describe it empirically. Using the 1979-1998 National Longitudinal Mortality Study for non-Hispanic white and black adults aged 25-100 years during the mortality follow-up period (N = 1,008,215), we evaluated 13 functional forms across race-gender-age subgroups to determine which form(s) best captured the association. Results revealed that the preferred functional form includes a linear decline in mortality risk from 0 to 11 years of education, followed by a step-change reduction in mortality risk upon attainment of a high school diploma, at which point mortality risk resumes a linear decline but with a steeper slope than that prior to a high school diploma. The findings provide important clues for theoretical development of explanatory mechanisms: an explanation for the selected functional form may require integrating a credentialist perspective to explain the step-change reduction in mortality risk upon attainment of a high school diploma, with a human capital perspective to explain the linear declines before and after a high school diploma.


Equestrian-Related Musculoskeletal Injuries Presenting to a Chiropractic Practice: A Retrospective Chart Review of 19 Patients.
The purpose of this study was to describe the types of equestrian-related musculoskeletal injuries and their management. We retrospectively reviewed the charts of 19 patients who presented with injuries from equestrian activities at a chiropractic practice from December 2000 to December 2020. Deidentified data were extracted from the charts and summarized. Of the 19 patients, 42.3% presented with acute trauma, 38.5% had overuse injuries, and 19.2% had chronic injuries as a result of previous trauma. We found that 90% of overuse injuries and 18.2% of acute injuries led to chronic conditions that needed ongoing management. From this sample of patients, there was a high percentage of overuse and chronic injuries for patients who participated in equestrian activities.


Physiology of B cells in mice with X-linked immunodeficiency. I. Size, migratory properties, and turnover of the B cell pool.
In terms of certain immune functions and density of surface IgM, B cells from xid mice are often viewed as the equivalent of the immature (Lyb-5-) B cell subset of normal adult mice. In this paper we examine xid B cells with regard to certain physiologic functions, including homing to the lymphoid tissues, recirculation, and turnover. Xid mice were found to possess about one-third of the total number of B cells found in normal mice. This applied irrespective of whether one examined the spleen, lymph nodes, or outputs of B cells in thoracic duct lymph. In terms of migration to spleen, lymph nodes, and Peyer's patches, capacity to recirculate from blood to thoracic duct lymph, and turnover, xid B cells proved to be indistinguishable from normal spleen or thoracic duct B cells. Within these parameters, most xid B cells closely resemble the normal mature long-lived population of B cells residing in the recirculating pool of normal mice. Because xid B cells are functionally quite different from normal mature B cells, it seems reasonable to view xid B cells as an abnormal population not represented in normal mice.


Possible steroid withdrawal syndrome following short Synacthen test--a personal report.
Symptoms not attributable either to disease rebound or to adrenal suppression have been reported both in patients receiving steroids when long-term therapy has been stopped and in normal volunteers after single oral doses of prednisolone or intravenous equivalents. This so-called steroid withdrawal syndrome remains poorly understood. It has not previously been reported following exposure to increased levels of endogenous steroids after diagnostic administration of synthetic adrenocorticotrophic hormone (ACTH). The author's personal experience of an apparent steroid withdrawal reaction following a short Synacthen test is described. It is suggested that as yet unidentified individual factors must play a role in determining whether steroid withdrawal symptoms occur. Closer observation of other subjects after the Synacthen test might reveal other instances of steroid withdrawal symptomatology following this common diagnostic procedure.


Monoclonal antibodies to bovine serum albumin: affinity and specificity determinations.
A panel of 12 monoclonal antibodies (MAb) to bovine serum albumin (BSA) was developed and characterized as to their physiochemical and immunological properties. Affinity constants of the MAb varied over a wide range from 10(5) to 10(8) M-1. MAb were assembled into several groups of non- or minimally interacting antibodies by analysis of competitive binding experiments, and BSA domain and subdomain specificities of the MAb were assigned by analysis of results of MAb binding to purified BSA fragments. Further fine specificity delineation was accomplished by examination of cross-reactivity patterns to several mammalian albumins. The data suggest that some of the low affinity MAb recognize sites on different portions of the BSA molecule, indicating that similar epitopes exist on different domains of the BSA molecule.


Novel peptides prevent alcohol-induced spatial learning deficits and proinflammatory cytokine release in a mouse model of fetal alcohol syndrome.
Previously, the novel peptides NAPVSIPQ and SALLRSIPA were shown to prevent alcohol-induced fetal death and growth abnormalities in a mouse model of fetal alcohol syndrome. This study evaluated whether these peptides could prevent long-term alcohol-induced learning abnormalities. In addition, because specific cytokines are known to effect long-term potentiation, a model of learning at the molecular level, we studied the effect of these novel peptides on tumor necrosis factor-alpha, interleukin-6, and interferon-gamma levels. We used a well-characterized mouse model of fetal alcohol syndrome. Pregnant mice were injected on day 8 with alcohol (0.03 mL/kg) or placebo. Pretreatment with NAPVSIPQ+SALLRSIPA (20 mug) or placebo was given 30 minutes before alcohol. Embryos were removed after 6 hours, at which time cytokine, tumor necrosis factor-alpha, interleukin-6, and interferon-gamma levels were measured with enzyme-linked immunoassays. To test spatial learning, adult offspring from litters that were treated with alcohol, control, NAPVSIPQ+SALLRSIPA then alcohol, or NAPVSIPQ+SALLRSIPA alone were evaluated for latency to find a hidden platform in the Morris water maze. Alcohol treatment increased tumor necrosis factor-alpha levels versus control levels (50.0 +/- 3.5 pg/mL vs 32.7 +/- 2.4 pg/mL; P < .001). NAPVSIPQ+SALLRSIPA pretreatment prevented this increase (39.9 9 +/- 2.8 pg/mL; P </= .01), with levels similar to control (P=.1). Similarly, alcohol increased interleukin-6 levels versus control levels (22.6 +/- 1.4 pg/mL vs 17.3 +/- 0.6 pg/mL; P < .001), and NAPVSIPQ+SALLRSIPA prevented this increase (19.1 +/- 1.0 pg/mL; P </= .02), with levels similar to control levels (P=.2). Interferon-gamma levels were not different among the 3 groups (alcohol, 14.6 +/- 4.9 pg/mL; control, 17.9 +/- 6.6 pg/mL; alcohol+NAPVSIPQ+SALLRSIPA, 13.6 +/- 4.9 pg/mL; P=.2). In the Morris water maze, alcohol-treated groups did not learn over the 7-day trial compared with the control group (P=.001). Groups that were pretreated with NAPVSIPQ+SALLRSIPA then alcohol learned significantly, which was similar to the control group. Groups that were treated with only NAPVSIPQ+SALLRSIPA learned significantly earlier, with the shortest latency once learning commenced. The peptides, NAPVSIPQ+SALLRSIPA, prevented the alcohol-induced spatial learning deficits and attenuated alcohol-induced proinflammatory cytokine increase in a model of fetal alcohol syndrome. This study demonstrates the peptides' significant in vivo efficacy with long-lasting effects obtained after prenatal administration.


Temporal lobe hemorrhage as a complication of HSV encephalitis: a case report.
This case underlined the importance of having high suspicion for lobar hemorrhage as a rare but deadly complication of herpes simplex virus encephalitis and shone light upon the added complexity it poses on management on an already deadly disease. Herpes simplex virus (HSV) encephalitis is the most common type of sporadic encephalitis that inflicts high rates of morbidity and mortality. Differentiating a progressing encephalitis syndrome from a lobar hemorrhage as a complication presents a challenge and requires great vigilance and insight on part of the treating physician.


[Transfusion in haematology].
In the field of oncohematology, the rationale for the use of blood transfusion relies both on the proliferative advantage of the transformed clone over the others and on hematologic toxicity of chemotherapy. In France, transfusion thresholds are established by a consensus conference organized by the Agence française de sécurité sanitaire des produits de santé (Afssaps), the French health products safety agency: 80g/l for PRC and 10G/l for platelets concentrates in patients without additional hemorragic risk factors. For FFP especially in TTP, thresholds are more patient-related. Transfusion for sickle cell patients remains a scientific challenge.


In vitro anthelmintic and cytotoxicity activities the Digitaria insularis (Poaceae).
This study aimed to evaluate the in vitro activity of D. insularis extracts and fractions against gastrointestinal nematodes of goats and its cytotoxicity on Vero cells. The egg hatch (EHT) and larval motility (LMT) tests were conducted to investigate the anthelmintic effects of the crude hydroethanolic (CH), ethyl acetate (EA), butanolic (BT) and residual hydroethanolic (RH) extracts. The elution of the active extract (EA) on column chromatography (SiO2) using organic solvents furnished six fractions (FR1 to FR6), which were also tested. Cytotoxicity was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Trypan Blue exclusion assays. All extracts, FR2 and FR3, inhibited egg hatching in a concentration-dependent manner. The EHT led to EC50 values (effective concentration 50%) of 0.64; 0.69; 0.77; 0.96; 0.27 and 0.65mg/mL for CH, EA, BT, RH, FR2 and FR3, respectively. However, the extracts exhibited low effect on the motility of L3. In the cytotoxicity evaluation (MTT assay), the IC50 (inhibitory concentration 50%) was 1.18 (EA), 1.65 (FR2) and 1.59mg/mL (FR3), which was relatively high (low toxicity) in comparison to the EC50 values in EHT, mainly for FR2. The chemical analyses of most active fractions (FR2) by Liquid Chromatography coupled to Mass Spectrometry (LC-MS) led the characterization of the flavones tricin and diosmetin. These results showed the high anthelmintic effect and low cytotoxicity of D. insularis and also that the flavones can be probably responsible for the nematocidal activity of this plant.


Human neutrophil antigen-3a antibodies induce neutrophil stiffening and conformational activation of CD11b without shedding of L-selectin.
HNA-3a antibodies induce severe transfusion-related acute lung injury (TRALI) in which neutrophils play a major role. As neutrophil passage through the pulmonary microvasculature is a critical step in the pathogenesis of TRALI, we investigated the impact of HNA-3a antibodies on two important factors that could impair granulocyte passage through lung capillaries: the elasticity of neutrophils and the expression and activation of adhesion molecules. The impact of HNA-3a antibodies on the elasticity of neutrophils was investigated using atomic force microscopy (AFM). Neutrophils were settled on poly-2-hydroxyethyl-methacrylate-coated glass slides before treatment with anti-HNA-3a plasma samples, control plasma, or control plasma containing formyl-methionyl-leucyl-phenylalanine (fMLP). Elasticity measurements were carried out in a temperature-controlled perfusion chamber using an atomic force microscopy (AFM) device. The impact of HNA-3a antibodies on the surface expression of total CD11b, activation of CD11b, and L-selectin (CD62L) shedding was investigated by flow cytometry. The functional impact of HNA-3a antibodies on neutrophil adhesion was assessed using fibrinogen-coated plates. HNA-3a antibodies induced stiffening of neutrophils (+24%-40%; p < 0.05) to a similar extent as fMLP. This effect was blocked by treatment of neutrophils with cytochalasin D. While total surface expression of CD11b and L-selectin on neutrophils was largely unaffected, HNA-3a antibodies induced alloantigen-specific activation of CD11b (+72%-107%; p < 0.05) and increased adhesion of neutrophils to fibrinogen. Accumulation of neutrophils in the pulmonary microvasculature during severe TRALI is likely mediated by increased rigidity and CD11b-mediated adhesion of neutrophils leading to retention of neutrophils.


[Oxycodone, piritramide and tramadol for the management of postoperative pain : A registry study on use and effectiveness in clinical routine].
In the context of improving perioperative pain management and shortening hospital stays, potent oral analgesics, such as slow release opioids, are gaining increasingly in importance. The aim of this study was to compare the use and effectiveness of different opioids in postoperative pain treatment in Germany. Using data from the QUIPS database, the records of 5249 patients were evaluated. The total study population was divided into four groups: group 1 (10 mg oxycodone with or without naloxone 5 mg), group 2 (20 mg oxycodone with or without naloxone 10 mg), group 3 (piritramide) and group 4 (tramadol). Maximum pain intensity, pain-related interference with sleep and respiration, vomiting, postoperative fatigue, desire for more pain treatment and satisfaction with pain management were evaluated. The differences in pain intensity were statistically significant between groups. Patients with piritramide reported more pain, more interference with sleep and respiration and more fatigue compared to those from the other groups. In the group with 10 mg oxycodone, the desire for additional pain medication was the lowest. Postoperative vomiting and satisfaction with pain management differed significantly between the four groups. Procedure-specific analysis has shown that differences between sub-groups were also significant following cholecystectomy and total knee arthroplasty. In summary, our findings suggest that postoperative pain treatment with slow release oral oxycodone does not show disadvantages compared to tramadol or piritramide with regard to pain-related impairments and opioid-induced side effects. This hypothesis needs to be further analyzed in controlled studies.


Reproductive biomass allocation in three Sargassum species.
Allocation of biomass to sexual reproductive (receptacle) tissue and vegetative (holdfast) tissue differed absolutely and relatively in three Sargassum species that form the bulk of the intertidal algal canopy in the northern Gulf of California. Sargassum herporhizum devoted a greater proportion of its thallus mass into its rhizoidal holdfast than did S. sinicola var. camouii or S. johnstonii, whose holdfasts are solid, more compact, and composed of a lower percentage of water. Conversely, more sexual receptacle tissue was produced by these two species with small holdfasts during the spring reproductive period. Sargassum sinicola var. camouii, which is the only species of the three that becomes fertile in the fall, produces a comparable amount of sexual tissue during this second period of reproduction. Removal of Sargassum from single-species patches showed that canopy regrowth by S. herporhizum with its encroaching rhizoidal holdfast was more rapid and complete than that of the other two species, which invest most of their reproductive efforts into sexual propagules that can disperse long distances. Sargassum herporhizum also displayed a more rapid and complete recovery of canopy cover in patches cleared of thalli and in control patches following the annual summer dieback. These two divergent modes of reproductive biomass allocation suggest that ability to encroach upon nearby open sites and ability to colonize distant discrete islands of suitable habitat represent two distinct reproductive strategies requiring different patterns of biomass allocation. Moreover, for energetic reasons, a species may not be able to excel at both modes of reproduction.


Between Education and Opinion-Making: Dialogue between Didactic/Didaktik Models from Science Education and Science Communication in the Times of a Pandemic.
The fields of science education and science communication are said to have developed as disparate fields of research and practice, operating based on somewhat different logics and premises about their audiences. As the two fields share many of the same goals, arguments have been made for a rapprochement between the two. Drawing inspiration from a historical debate between the scholars John Dewey and Walter Lippmann, the present article is a case-oriented theoretical contribution applying models from science education and science communication in relation to a current socio-scientific issue (SSI), the COVID-19 pandemic. The main question of interest is how selected didactic (didaktik) models from science education and science communication can contribute to shed light on the present situation of an ongoing pandemic specifically and socio-scientific issues in general. Three models are synthesised to give a new composite model that may help communicators and educators understand, discuss, and analyse complex socio-scientific issues. The model is subsequently applied on the apparently contradictory issue of Norwegian and Swedish governments' very different responses to the pandemic, despite grounding their decisions on largely the same scientific evidence and advice. Contrast is made by comparison with another SSI, anthropogenic global warming (AGW). It is argued that the exchange and combination of didactic models from the two fields may open new spaces for cross-pollination and cross-fertilisation to the mutual benefit of both science education and science communication.


Therapeutic effect of quercetin polymeric nanoparticles on ischemia/reperfusion-induced acute kidney injury in mice.
Acute kidney injury (AKI) is known as a sudden episode of kidney injury, which happens suddenly within a few hours or a few days. Quercetin (3,3',4',5,7-pentahydroxyflavone) is a flavonoid found in plants. Quercetin is known to have several biological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic effects. However, low water solubility and bioavailability are the limitations of quercetin for its clinical applications. Moreover, ischemia/reperfusion (I/R) injury is a common cause of AKI. There are no satisfactory strategies for I/R-induced AKI. Developing suitable preventive or therapeutic intervention for AKI is an important and urgent issue. We investigated the benefit effect of synthesized polyethylene glycol (PEG) conjugated polyethyleneimine (PEI) nanoparticles for targeted delivery of quercetin on AKI in a mouse model. An I/R-induced AKI mouse model was used to evaluate the therapeutic effect of quercetin polymeric nanoparticles by intravenous injection. Biochemical changes for renal function in blood samples were analyzed. Histological and immunohistochemical changes were also analyzed. The biochemical changes of blood urea nitrogen (BUN), creatinine, and cystatin C were significantly increased in I/R-induced AKI mice, which could be significantly reversed by quercetin polymeric nanoparticles. Quercetin polymeric nanoparticles could also significantly decrease the histological lesions, positive staining for 3-nitrotyrosine and cyclooxygenase-2, and lipid peroxidation in the kidneys of I/R-induced AKI mice. These results demonstrate for the first time that quercetin polymeric nanoparticles possess therapeutic potential for the treatment of I/R-induced AKI in vivo.


Risk groups and predictors of short-term abstinence from smoking in patients with coronary heart disease.
We sought to identify risk groups among smoking cardiac patients from their social cognitive profiles, and to assess predictors of smoking abstinence shortly after discharge. Smoking cardiac patients (n = 133) completed questionnaires at hospital admission and 1 month after discharge. Hierarchical cluster analysis was used to detect risk groups of smokers, based on baseline scores for smoking-related social cognitions. Regression analyses were used to identify predictors of the intention to abstain from smoking and smoking abstinence 1 month after discharge. Three groups of smokers were distinguished that differed significantly on the pros of nonsmoking, self-efficacy expectancies toward nonsmoking, social support, social modeling, and smoking behavior. Abstinence from smoking 1 month after discharge was predicted by group membership and a stronger intention to quit. A previous hospital admission because of a cardiac event significantly decreased the likelihood of abstinence. One third of cardiac patients are at high risk of continuing smoking after hospital discharge because of an unfavorable smoking and disease history and a poor social cognitive profile. Interventions for cardiac patients should address risk profiles to achieve long-term abstinence. The implications of nursing practices in smoking cessation treatments are discussed.


Knowledge, attitudes, and barriers related to medication adherence of older patients with coronary heart disease in China.
To investigate the knowledge, attitudes, and barriers related to medication adherence in older patients with coronary heart disease (CHD). A total of 272 older patients with CHD were investigated by the Chinese version of the Medication Adherence Scale. The score ranges for the knowledge, attitudes, and barrier subscales were 0-30, 0-30, and 0-110, respectively. Higher scores indicate more knowledge, positive attitudes, and more barriers related to medication adherence. The median scores of knowledge, attitudes and barriers were 25.5, 28, and 8, respectively. Having stents, living alone, good financial status and fewer chronic diseases were related to more knowledge. Younger age, having no stent, and more chronic diseases were associated with more barriers. Patients with good financial status and higher age had more positive attitudes. Understanding older patients' knowledge, attitudes, and barriers related to medication adherence and their associated factors can help develop tailored interventions in medication adherence studies.


The Effects of Boat Docks on Eelgrass Beds in Coastal Waters of Massachusetts.
/ The effects of docks on eelgrass beds were measured using plant population characteristics (shoot density, canopy height, and growth rates), light levels, and an assessment of eelgrass bed quality in Massachusetts estuaries. Eelgrass populations were impacted under and directly adjacent to docks, as shown by depressed shoot density and canopy structure. Severe impacts can cause fragmentation of eelgrass beds, thus contributing to large-scale declines in estuaries such as Waquoit Bay. Impacts were fewer under docks supported by piers than under floating docks, and taller piers resulted in fewer impacts. Based on this investigation, we conclude that docks should be greater than 3 m in height above the bottom in areas with tidal ranges less than 1 m to allow enough light to sustain eelgrass beds under the docks. In addition to dock height, orientation and width were also found to be important factors affecting eelgrass. Narrow docks with a north-south orientation can best ensure the long-term survival of eelgrass under and near the dock. KEY WORDS: Docks; Shade; Eelgrass beds; Zostera marina; Seagrass


Syntheses and biological evaluation of C-3'-N-acyl modified taxane analogues from 1-deoxybaccatin-VI.
A series of side-chain modified taxane analogues were synthesized and their in vitro anticancer activities against four human cancer cell lines: MDA-MB-231 (human breast cancer), PC-3 (human prostatic cancer), HepG2 and H460 (human hepatoma) were studied. The three hydroxyl groups at C-7, C-9 and C-10 enable the behavior of these compounds to be evidently distinct from other similar compounds. The strong cytotoxicity in the four cell lines showed by the newly synthesized taxane analogues 13a and 13d indicated them as potential lead compounds for anticancer drug design.


Response of neurons in primary somatosensory cortex of cat following prolonged exposure to strong sinusoidal mechanical stimuli.
Psychophysical studies in humans have demonstrated adaptation of the mechanoreceptive submodalities of flutter and vibration after prolonged presentation of a strong adapting, or conditioning, stimulus. In our studies we recorded from single neurons in cat primary somatosensory cortex, and followed a paradigm in which the response of a single unit was measured before and after the presentation of a strong conditioning stimulus. Our findings show no adaptive response in the 30 sec period immediately after cessation of the conditioning stimulus, and suggest that other parallel ascending pathways or somatosensory cortical areas other than SI account for these psychophysical observations.


Toxaphene detoxification and acclimation in Daphnia magna: do cytochrome P-450 enzymes play a role?
Toxaphene is a persistent environmental contaminant that has been shown to alter male production in Daphnia magna and to induce P-450 activity in mammals. Cytochrome P-450-mediated metabolism may lead to xenobiotic detoxification resulting in acclimation. To determine if D. magna acclimate to toxaphene via P-450 pathways, chronic and acute toxicity tests were conducted with D. magna exposed to toxaphene in the presence and absence of piperonyl butoxide (PBO), an inhibitor of cytochrome P-450 enzymes. Toxaphene exposure increased male production in acute but not chronic assays, indicating that D. magna may acclimate to chronic toxaphene exposure. Upon co-administration of toxaphene and PBO in chronic tests, D. magna exhibited a decline in growth rate, fecundity and survival. The observed toxaphene acclimation in chronic tests, along with its increased toxicity in the presence of a P-450 suppressor, suggests that P-450 enzymes may contribute to detoxification and subsequent acclimation of D. magna to chronic toxaphene exposure. Additional chronic toxicity tests indicated that toxaphene acclimation occurs between 7 and 12 days following initial exposure, at which time sex determination is no longer affected. Thus, sublethal toxaphene toxicity effects such as reproductive impairments may be detectable with acute but not chronic tests, potentially due to the upregulation of P-450 isozymes.


Tuning the DNA conformational perturbations induced by cytotoxic platinum-acridine bisintercalators: effect of metal cis/trans isomerism and DNA threading groups.
Four highly charged, water soluble platinum-acridine bisintercalating agents have been synthesized. Depending on the cis/trans isomerism of the metal and the nature of the acridine side chains, bisintercalation induces/stabilizes the classical Watson-Crick B-form or a non-B-form. Circular dichroism spectra and chemical footprinting experiments suggest that 4, the most active derivative in HL-60 cells, produces a structurally severely perturbed DNA with features of a Hoogsteen base-paired biopolymer.


Karyometric investigation on circadian rhythmic changes in the periportal and perivenous zones of the acinus of the rat liver.
In untreated adult male albino rats changes in nuclear volume within the periportal and the perivenous zones of the liver acinus were measured during a full day and night cycle. Only the perivenous zone displayed circadian rhythmic changes as expressed in the sinus-like course of the nuclear volume-distribution graph (polynomial) with a maximum between 16.00 h and 18.00 h and a minimum at 8.00 h. In all groups studied zonal heterogeneity of the means of nuclear volume and the percent-distribution graphs of nuclear volume classes were retained during the full cycle. Within each zone, however, distribution curves of nuclear volume classes were homogeneous indicating an equally directed trend in time-dependent changes in nuclear volume.


Use of random and saturation mutageneses to improve the properties of Thermus aquaticus amylomaltase for efficient production of cycloamyloses.
Amylomaltase from Thermus aquaticus catalyzes intramolecular transglycosylation of alpha-1,4 glucans to produce cyclic alpha-1,4 glucans (cycloamyloses) with degrees of polymerization of 22 and higher. Although the amylomaltase mainly catalyzes the transglycosylation reaction, it also has weak hydrolytic activity, which results in a reduction in the yield of the cycloamyloses. In order to obtain amylomaltase with less hydrolytic activity, random mutagenesis was perfromed for the enzyme gene. Tyr54 (Y54) was identified as the amino acid involved in the hydrolytic activity of the enzyme. When Y54 was replaced with all other amino acids by site-directed mutagenesis, the hydrolytic activities of the mutated enzymes were drastically altered. The hydrolytic activities of the Y54G, Y54P, Y54T, and Y54W mutated enzymes were remarkably reduced compared with that of the wild-type enzyme, while those of the Y54F and Y54K mutated enzymes were similar to that of the wild-type enzyme. Introducing an amino acid replacement at Y54 also significantly affected the cyclization activity of the amylomaltase. The Y54A, Y54L, Y54R, and Y54S mutated enzymes exhibited cyclization activity that was approximately twofold higher than that of the wild-type enzyme. When the Y54G mutated enzyme was employed for cycloamylose production, the yield of cycloamyloses was more than 90%, and there was no decrease until the end of the reaction.


Gambling Research and Industry Funding.
This paper discusses the relationship between investigative credibility and the sources of funding associated with gambling research. Some researchers argue against accepting funding from gambling industry sources; similarly, they decline to participate in activities directly or indirectly sponsored by gambling industry sources. In contrast, these anti-industry investigators evidence less resistance toward accepting funds from sources other than industry, for example, governments, because they believe that they have greater independence, reliability, and validity, and less undue influence and/or interference. We organize this article, around six primary issues: (1) researchers making a priori judgments that restrict positions towards industry associated research; (2) the potential negative impacts of holding such a position; (3) a description of the different sources of funding available to support gambling-related research; (4) an examination of the extant empirical support associated with the sources of funding and whether such support evidences bias; (5) a description of six cases illustrating how refusing to participate in any project funded by the industry can adversely influence the advancement of science and, at times, be itself unethical; and finally, (6) we suggest some remedies to advance solutions to this problem by stimulating the participation of reluctant researchers to work towards a greater harmony, keeping in mind that the pivotal goal of our work is to increase our knowledge in different area of science and to harness it to public goods.


MRI confirms loss of blood-brain barrier integrity in a mouse model of disseminated candidiasis.
Disseminated candidiasis primarily targets the kidneys and brain in mice and humans. Damage to these critical organs leads to the high mortality associated with such infections, and invasion across the blood-brain barrier can result in fungal meningoencephalitis. Candida albicans can penetrate a brain endothelial cell barrier in vitro through transcellular migration, but this mechanism has not been confirmed in vivo. MRI using the extracellular vascular contrast agent gadolinium diethylenetriaminepentaacetic acid demonstrated that integrity of the blood-brain barrier is lost during C. albicans invasion. Intravital two-photon laser scanning microscopy was used to provide the first real-time demonstration of C. albicans colonizing the living brain, where both yeast and filamentous forms of the pathogen were found. Furthermore, we adapted a previously described method utilizing MRI to monitor inflammatory cell recruitment into infected tissues in mice. Macrophages and other phagocytes were visualized in kidney and brain by the administration of ultrasmall iron oxide particles. In addition to obtaining new insights into the passage of C. albicans across the brain microvasculature, these imaging methods provide useful tools to study further the pathogenesis of C. albicans infections, to define the roles of Candida virulence genes in kidney versus brain infection and to assess new therapeutic measures for drug development.


Epidermal growth factor receptor mutations are associated with gefitinib sensitivity in non-small cell lung cancer in Japanese.
The protein-kinase family is the most frequently mutated gene family found in human cancer. Gefitinib, an ATP-competitive inhibitor of epidermal growth factor receptor (EGFR), also appears to be particularly effective in adenocarcinoma of the lung and in patients without smoking history. To determine whether lung tumors sensitive to gefitinib contained mutations within the tyrosine kinase (TK) domain of EGFR, we screened exons 18-23 of EGFR of tumors in 20 patients with non-small cell lung cancer (NSCLC) who had been treated with gefitinib. Nine (45%) tumors had TK domain mutations. All mutations were observed in adenocarcinoma. Seven (77.8%) of 9 cases with mutated types showed sensitivity to gefitinib, while no cases of 11 with wild type showed gefitinib sensitivity. Such mutations were more frequently observed in patients who had never smoked (5/8 or 62.5%) than in smokers (4/12 or 33.3%). The patients with mutations of EGFR to have a more favorable prognosis than those with wild type (p=0.033). These data show that adenocarcinomas from patients who had never smoked comprise a specific subset of patients with NSCLC sensitive to gefitinib treatment.


Cerebrospinal fluid measures of neurotransmitter changes associated with pharmacological alteration of the despair response to social separation in rhesus monkeys.
Social separation is a risk factor for major depressions that can be modeled in nonhuman primates. Changes in central monoamine neurotransmission are also likely to be involved in major depression. This study examined the relationship between separation-induced depressive-like behavior and central monoamine neurotransmitter changes in rhesus monkeys. Measures of cerebrospinal fluid (CSF) norepinephrine (NE), 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were used to assess the neurobiological impact of social separation and drug treatments alone or in combination. alpha-Methyl-p-tyrosine exacerbated, and fusaric acid ameliorated, the depressive-like response to separation. Probenecid-induced accumulations of HVA and 5HIAA reflected changes in behavior, but were not consistently affected by drug treatment. In contrast, pretreatment CSF NE was comparatively stable across repeated sampling, and drug-induced changes in this measure were correlated with changes in behavior. Low CSF NE, whether drug-induced or naturally occurring, was associated with a more severe depressive-like response to separation.


Investigation of the organisation of the major proteins in bovine myelin membranes. Use of chemical probes and bifunctional crosslinking reagents.
Bovine myelin was incubated with a variety of bifunctional reagents and chemical probes. The use of a photosensitive hydrophobic compound, 1-azido-[125I]iodobenzene, led to the suggestion that the proteolipid protein is deeply intercalated into the hydrophobic milieu of the membrane, but did not support the contention that regions of the basic protein behave in a similar fashion. Crosslinking studies indicated that both polypeptides may be present in the membrane as homodimers and these dimers may be part of much larger assemblies. These results give rise to a somewhat different model for the structural organisation of myelin to that proposed earlier.


Immunization with streptozotocin-treated NOD mouse islets inhibits the onset of autoimmune diabetes in NOD mice.
In this study, we determined whether a single intraperitoneal injection of NOD islets exposed to streptozotocin (STZ; 5 mmol/l) in vitro could prevent onset of diabetes in female NOD mice. Pre-diabetic female NOD mice were injected with saline or islets exposed to either STZ or citrate buffer alone. Single injection of STZ-exposed islets significantly (P<0.03) decreased the incidence of diabetes in pre-diabetic NOD mice compared to control groups. At 40 weeks of age, the onset of diabetes in NOD mice injected with STZ-treated islets was 16% (3/19) compared to 88% (14/16) in mice that received islets exposed to citrate buffer and 84% (26/31) in those mice injected with saline. Histological examination of the pancreases from normoglycemic mice given STZ-treated islets revealed numerous intact islets devoid of mononuclear cell infiltration while pancreases from control groups contained few intact islets infiltrated with mononuclear cells. This study demonstrates that immunization of pre-diabetic female NOD mice with syngeneic islets exposed to STZ prevents insulitis and onset of autoimmune diabetes. Our data suggest that exposure of islets to STZ may possibly induce the release of soluble antigens and/or cause an antigenic change in pancreatic beta cells that subsequently results in immunization of pre-diabetic NOD mice.


Climatic conditions and prevalence of melanistic snakes-contrasting effects of warm springs and mild winters.
Climate change is one of the greatest challenges that wildlife is facing. Rapid shifts in climatic conditions may accelerate evolutionary changes in populations as a result of strong selective pressure. Most studies focus on the impact of climatic conditions on phenologies and annual cycles, whereas there are fewer reports of empirical support for climate-driven changes in the phenotypic variability of free-living populations. We investigated whether climatic variables explain the prevalence of colour polymorphism in a population of the grass snake (Natrix natrix) with two morphotypes, the melanistic and non-melanistic ones, in the period 1981-2013. We found that the prevalence of the black phenotype was negatively related to spring temperature and winter harshness, expressed as the number of snow days. According to the thermal melanism hypothesis, a high predation rate during warmer springs may override relaxed thermal benefits and vice versa, i.e. black individuals may perform better than typical ones when thermal conditions in spring are unfavourable. In turn, because they are smaller, melanistic individuals may be exposed to a higher risk of winter mortality, particularly during longer winters. We highlight the need for more studies on the effects of climatic conditions on temporal variation in melanism prevalence in other populations and species as well as in various geographic regions.


Ascorbic acid levels in aqueous and vitreous humors of the rabbit: effects of inflammation and ceruloplasmin.
A HPLC method for determination of ascorbic acid and dehydroascorbic acid in plasma and aqueous and vitreous humors of rabbits is described. Values for total ascorbic acid concentration found in this study are in agreement with those of previous investigators. Endotoxin-induced ocular inflammation caused a decrease in the concentration of ascorbic acid in the aqueous humor and an increase in the vitreous humor. The additional lack of correlation between levels of ascorbic acid in normal aqueous and vitreous humors from the same uninflamed eye indicates that the aqueous humor is not the source of vitreal ascorbic acid. The copper concentration of the aqueous humor is increased during ocular inflammation, most likely due to the influx of ceruloplasmin from plasma when the blood-aqueous barrier is disrupted. Ceruloplasmin caused a decrease in the amount of ascorbic acid in the aqueous humor in vitro and the vitreous humor in vivo. The presence of ceruloplasmin in the aqueous humor during inflammation thus may contribute to the decreased concentration of ascorbic acid in this fluid.