Myoglobin in rat hind limb muscles after denervation and during reinnervation.
Radioimmunoassay of myoglobin (Mb) was performed in rat hind limb muscles after surgical denervation and during reinnervation following cryolesion of the sciatic nerve. Muscles of the contralateral leg served as controls. After resection of the sciatic nerve, decreased Mb concentrations were noted on the fourth day in the tibialis anterior, peroneus longus, and extensor digitorum longus (EDL) muscles. Thereafter, the levels increased up to the last observation on day 32. The increases in Mb levels in the tibialis anterior and EDL muscles were considerably more pronounced (305% and 324%, respectively) than in the peroneus longus and soleus muscles (148% and 137%, respectively). After cryolesion of the sciatic nerve, the Mb concentrations in the tibialis anterior, peroneus longus, and EDL muscles increased, reaching maximal values on days 16-21. The levels then decreased and normal values were observed 2 months postoperatively. The normalization of the Mb levels during reinnervation corresponded fairly well in time with the clinical recovery and neurophysiological findings observed in a previous study.


Robotic Appendicectomy: A review of feasibility.
Acute appendicitis is one of the most common abdominal emergencies. There has been an increasing use of robotic abdominal surgery. However, it remains underutilised in emergency settings. This study aimed to systematically review robotic appendicectomy (RA) feasibility. A 20-year systematic review was performed, along with quality assessment. The research protocol was registered with PROSPERO. The search yielded 1,242 citations, including 9 articles. The mean quality score was 10.72 ± 2.56. The endpoints across the studies were rate of conversion to open surgery, length of hospital stay, blood loss and operative time. RA is a safe, feasible technique that can be performed in elective and emergency settings with minimal blood loss. The operative time and hospital stay were within acceptable limits. Robotic surgery's major drawback is its high cost and limited availability. Future studies evaluating RA with a focus on its application during emergencies and its cost-effectiveness are recommended.


Rheumatoid nodulosis: an unusual variant of rheumatoid disease.
A middle-aged man developed multiple subcutaneous nodules associated with palindromic rheumatism. There was little evidence of synovitis; however multiple cyst-like intraosseous radiolucencies were noted. Nodules from two sites were histologically typical rheumatoid nodules. Subjective and objective improvement occurred during penicillamine therapy. This clincial presentation seems sufficiently distinctive to warrant characterization as a variant of rheumatoid disease termed by us: rheumatoid nodulosis.


Glypican-3 distinguishes aggressive from non-aggressive odontogenic tumors: a preliminary study.
Glypican-3 is a cell surface proteoglycan that is found in embrionary tissues, and there are no studies investigating this protein in odontogenic tumor. Thus, the aim of this study was to investigate glypican-3 in a series of aggressive and non-aggressive odontogenic tumors. Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, four unicystic ameloblastoma, 28 KOTs including five associated with Gorlin-Goltz syndrome) and non-aggressive odontogenic tumors (five adenomatoid odontogenic tumors and two calcifying cystic odontogenic tumors) and analyzed for glypican-3 using immunohistochemistry. Glypican-3 was observed in seven solid ameloblastoma and eighteen keratocystic odontogenic tumors including three of the five syndromic cases, but there was no significant difference between syndromic and sporadic cases (P > 0.05; Fisher's exact Test). All cases of unicystic ameloblastoma (n = 4), adenomatoid odontogenic tumor (n = 5), and calcifying cystic odontogenic tumor (n = 2) were negative. This provided insights into the presence of glypican-3 in odontogenic tumors. This protein distinguished aggressive from non-aggressive odontogenic tumors.


Mind the gap: Concordance between perceptions regarding vaccination as declared by patients and their evaluation by their general practitioner.
The high level of vaccine hesitancy reported in the French population may lead general practitioners to anticipate difficult discussions on this topic. We aimed to assess the extent to which general practitioners' evaluation of their patients' vaccine hesitancy was correlated with the real vaccine hesitancy expressed by these patients. The study was based on two brief paper questionnaires completed in private by the general practitioner and the patient at the beginning of a medical appointment: one for the physician to evaluate on three quantitative and non-graduated visual scales (then analysed as a 0-100 scale) their patients' perceptions regarding vaccine safety, vaccine efficacy and 'being in favour of vaccination'; and one for the patient to express their perceptions for the same three axes using the same scales. Overall, 31 physicians participated in the study, with 540 physician-patient pairs being included. The physicians' evaluation of patient perceptions was more positive when the physician was male (vs female), when the patient was male (vs female) and when both were males (vs both females). The median differences (in absolute values) between the physician evaluations and the patient perceptions were between 9 and 11 (on the 0-100 scale) for the three axes (vaccine safety, vaccine efficacy and 'being in favour'). A correlation was observed between the physicians' evaluation and the patients' declaration (Kendall test: vaccine efficacy: tau = 0.199, p < 0.001; vaccine safety: tau = 0.234, p < 0.001; being in favour of vaccination: tau = 0.365, p < 0.001). Physicians correctly classified 83.4 % of the patients with high perceptions of vaccine safety and efficacy (>75/100 for both scales) but only 54.5 % of those with low perceptions (<75/100 for both scales). Physicians tend to correctly identify patients with the most favourable perceptions about vaccination but not those with the least favourable perceptions.


Cognitive predictors of mortality in elderly retirees: results from the Freedom House study.
The objective of this longitudinal cohort study was to study the cognitive domains associated with five-year longitudinal survival among healthy, well-educated, noninstitutionalized elderly. Survival curves were generated as a function of cross-sectional baseline cognitive test performance. Nonverbal tests were significantly associated with survival. This finding was markedly consistent. Several nonverbal tasks were each significantly associated with survival independently of age, gender, baseline level of care, and healthcare utilization. In a multivariate model, copying a clock made the strongest, independent contribution to survival. Right hemisphere integrity in general and nonverbal drawing tasks in particular have been associated with survival in conditions as diverse as Alzheimer disease, stroke, and epilepsy. This study extends this association to "normal" aging. The mechanism by which nonverbal cognitive function is related to mortality remains unclear but may be mediated by changes in right hemisphere cortical control of autonomic function. Nondemented older persons may be at risk. Clock drawing may provide a simple means of identifying them.


Response of a submerged macrophyte (Vallisneria natans) to water depth gradients and sediment nutrient concentrations.
Submerged plants constitute a vital component of shallow lake ecosystems, where water depth and sediment nitrogen‑phosphorus content are two key factors influencing their growth. This study focuses on Vallisneria natans and investigates the morphological and physiological changes of V. natans under the interaction of three water depth gradients and two different sediment nutrient levels. It explores the mechanisms through which varying sediment nutrient conditions under different water depths affect the growth of V. natans. The results indicate that both independent and interactive effects of water depth and sediment nutrient status significantly impact the morphology, antioxidant enzyme activity, and photosynthetic pigment content of V. natans, with water depth having a greater influence. To adapt to increased water depth-induced light stress, V. natans responds morphologically by increasing leaf length, leaf width, and decreasing maximum root length. Physiologically, it enhances its antioxidant regulation capacity and photosynthetic efficiency by increasing antioxidant enzyme activity, root vitality, and photosynthetic pigment content to counter weak light stress. However, these adaptations are insufficient to cope with excessively deep waters (200 cm). Sediment nutrient levels primarily control the growth of V. natans by affecting its root system. When sediment nitrogen and phosphorus content is lower, V. natans exhibits greater total root volume and surface area to enhance nutrient absorption efficiency. Water depth not only directly influences the growth of submerged plants but may also impact the migration and transformation of phosphorus in sediments, further exacerbating its effects on the growth of these plants, thus accelerating the regime shift of shallow lakes. Therefore, this study reveals V. natans' response strategies to varying water depths and sediment nutrient levels, determining suitable water levels and sediment nutrient conditions for its growth. These research findings provide a scientific basis for water level management and ecological restoration of submerged aquatic plants in shallow lakes.


Importance of locally derived birth weight nomograms.
Significant differences exist between the published nomograms of birth weight for gestational age. Differences in demographics, altitude above sea level and study methodology have all been implicated. A three-year experience of uncomplicated singleton gestations (N = 14,766) was analyzed for birth weight and gestational age. The mean, 10th percentile and their 95% confidence intervals were compared to Brenner's data and a pooled sample from other studies in this country. The mean birth weights were significantly higher than Brenner's after 32 weeks' gestation and higher than the pooled mean after 35. The 10th percentiles were significantly greater than Brenner's after 36 weeks' gestation. Approximately 66% of neonates at risk, below our 10th percentile, would not be identified with Brenner's criteria. We agree with Goldenberg that uniform criteria for the definition of the normal population are important in identifying aberrant growth. However, birth weight standards should be developed for the specific population in question.


Plasmapheresis for Pembrolizumab-Induced Hepatitis in a Patient with Squamous Cell Carcinoma and Prior Orthotopic Liver Transplantation.
Checkpoint inhibitor therapy with monoclonal antibodies against programmed cell death protein 1 (PD1) has been implemented in the treatment of numerous malignancies. Pembrolizumab is one such medication. While severe toxicities are very rare, mild immune-mediated reactions with a variety of end organ injuries are among the most commonly encountered adverse events attributed to these medications. Acute liver injury manifesting as biochemical abnormalities with or without synthetic dysfunction is one such potential adverse reaction. Rarely, a relatively severe hepatitis can occur. While such severe adverse events are often successfully managed with systemic corticosteroids and drug discontinuation, our patient was refractory to standard management. We present a case of pembrolizumab-induced hepatitis in a patient with squamous cell carcinoma and prior orthotopic liver transplantation. Through a combination of serial plasmapheresis and intravenous immunoglobulin(IVIG) infusion, the patient's hepatitis resolved as evidenced by virtual normalization of his liver indices. This illustrates the effectiveness of a relatively novel treatment strategy for this rare side effect of checkpoint inhibitor antineoplastic therapy.


Seasonal abundance and control of Culex spp. in catch basins in Illinois.
Street catch basins in western Cook County, IL, were examined regularly June through August of 1987 to determine their seasonal larval production, adult mosquito harborage and the influence of abiotic factors on the associated mosquito population. Only larvae of Culex pipiens (63% of total) and Cx. restuans (37% of total) were recovered. These 2 species and Cx. erraticus were the most frequently collected adults. The abundance of mosquito larvae within catch basins was not correlated with water pH and only showed a weak, positive correlation with water temperature. Only a partial flushing of larvae (22-34% reduction) from catch basins by normal rainfall (less than 25 mm) was generally recorded. Treatments with larvicide oil (mineral seal oil/kerosene 175/tergitol) at a rate of 60-90 ml/catch basin resulted in a mean larval reduction of 97%. Adult females showed a mean reduction of 87%.


CT analysis of the Stafne's bone defects of the mandible.
To investigate the aetiology of Stafne's bone defects by analysing the CT findings of two types of defects, which appeared differently on panoramic radiographs. 32 lesions with suspicion of the Stafne's bone defect on a panoramic radiograph were categorised into two groups: typical "Stafne type", which showed the connection to the base of the mandible, and non-typical "Cyst type", which showed no connection. Age, sex, the existence of hypertension and the following CT findings: location, size and inner content of the defect, existence of expansion of the buccal cortical bone, and location of submandibular glands, were analysed. There were 14 "Stafne type" and 17 "Cyst type" on the panoramic radiographs. One lesion in the "Cyst type" was a true cystic lesion and was excluded from further review. The "Stafne type" was seen primarily in the posterior and inferior locations, while the "Cyst type" was seen in the anterior and superior locations on the CT. The size of the defect was significantly larger in the "Stafne type". Buccal cortical expansion was observed only in three lesions in the "Stafne type". While the "Cyst type" contained mainly fatty tissue, the "Stafne type" contained other soft tissues. Though the submandibular glands on the defect side were located anteriorly in both types compared with those on the contralateral side and on the control patients, they spread mainly outwards in the "Stafne type". The Stafne's bone defects are thought to be caused by the dislocated submandibular gland. The differences between the two types might occur as a result of a different location of the submandibular gland.


Why the Discretion Mix Matters: Understanding the Transformation of Long-term Care Services.
This study aims to extend the concept of discretion, ie, a certain degree of freedom in crucial decisions left to specific actors, to understand and examine the transformation of social care services in the era of aging and austerity. Although previous studies have reviewed and analyzed changes in care provision, they have been less concerned with who has the authority to make care decisions in the implementation process. We propose a new theoretical concept, the discretion mix, to understand the realignment of social care services beyond simply tracking institutional changes. Using a case study approach, this research investigates how the discretion mix of the Korean long-term care system has changed and the consequences of these changes; in addition, it discusses why the discretion mix can be a useful concept for analyzing the changing landscape of social care services.


Nicotiana tabacum seed endophytic communities share a common core structure and genotype-specific signatures in diverging cultivars.
Seed endophytes of crop plants have recently received increased attention due to their implications in plant health and the potential to be included in agro-biotechnological applications. While previous studies indicated that plants from the Solanaceae family harbor a highly diverse seed microbiome, genotype-specific effects on the community composition and structure remained largely unexplored. The present study revealed Enterobacteriaceae-dominated seed-endophytic communities in four Nicotiana tabacum L. cultivars originating from Brazil, China, and the USA. When the dissimilarity of bacterial communities was assessed, none of the cultivars showed significant differences in microbial community composition. Various unusual endophyte signatures were represented by Spirochaetaceae family members and the genera Mycobacterium, Clostridium, and Staphylococcus. The bacterial fraction shared by all cultivars was dominated by members of the phyla Proteobacteria and Firmicutes. In total, 29 OTUs were present in all investigated cultivars and accounted for 65.5% of the combined core microbiome reads. Cultivars from the same breeding line were shown to share a higher number of common OTUs than more distant lines. Moreover, the Chinese cultivar Yunyan 87 contained the highest number (33 taxa) of unique signatures. Our results indicate that a distinct proportion of the seed microbiome of N. tabacum remained unaffected by breeding approaches of the last century, while a substantial proportion co-diverged with the plant genotype. Moreover, they provide the basis to identify plant-specific endophytes that could be addressed for upcoming biotechnological approaches in agriculture.


Temperature- and pressure-dependent lattice behaviour of RbFe(MoO4)2.
Trigonal RbFe(MoO(4))(2) is a quasi-two-dimensional antiferromagnet on a triangular lattice below T(N) = 3.8 K, The crystal exhibits also a structural phase transition at T(c) = 190 K related to symmetry change from P3m1 to P3. We present the temperature- and pressure-dependent characteristics of this material in the context of ambiguous opinions on the symmetry and crystal properties below T(c). A single-crystal x-ray diffraction shows that the temperature-dependent evolution of the unit cell in the range 100-300 K is strongly anisotropic with markedly discontinuous changes at T(c). The transition is connected with a spontaneous strain developing in effect of the volume decrease. The structure releases the strain by rotation of corner-sharing rigid MoO(4) and FeO(6) polyhedra in the (a,b) basal plane. The temperature dependence of the IR vibrational wavenumbers exhibits weak changes near T(c), which are consistent with the symmetry transformation from P3m1 to P3. High-pressure x-ray powder diffraction indicates that the material is extremely soft but with some stiffening at high pressure. The zero-pressure bulk modulus is B(0) = 7.9(6) GPa and the pressure derivative is B(0)' = 10(1). The compression curve can be described by a single equation of state, corresponding to the trigonal cell, up to 5 GPa. An amorphization appearing above 5 GPa and increasing gradually on further pressure increase suggests the thermodynamic instability of the high-pressure structure.


Nature-Guided Synthesis of Advanced Bio-Lubricants.
Design of environmentally friendly lubricants derived from renewable resources is highly desirable for many practical applications. Here, Orychophragmus violaceus (Ov) seed oil is found to have superior lubrication properties, and this is based on the unusual structural features of the major lipid species-triacylglycerol (TAG) estolides. Ov TAG estolides contain two non-hydroxylated, glycerol-bound fatty acids (FAs) and one dihydroxylated FA with an estolide branch. Estolide branch chains vary in composition and length, leading to their thermal stability and functional properties. Using this concept, nature-guided estolides of castor oil were synthesized. As predicted, they showed improved lubrication properties similar to Ov seed oil. Our results demonstrate a structure-based design of novel lubricants inspired by natural materials.


IBS-catalyzed regioselective oxidation of phenols to 1,2-quinones with Oxone®.
We have developed the first example of hypervalent iodine(V)-catalyzed regioselective oxidation of phenols to o-quinones. Various phenols could be oxidized to the corresponding o-quinones in good to excellent yields using catalytic amounts of sodium salts of 2-iodobenzenesulfonic acids (pre-IBSes) and stoichiometric amounts of Oxone® as a co-oxidant under mild conditions. The reaction rate of IBS-catalyzed oxidation under nonaqueous conditions was further accelerated in the presence of an inorganic base such as potassium carbonate (K₂CO₃), a phase transfer catalyst such as tetrabutylammonium hydrogen sulfate (nBu₄NHSO₄), and a dehydrating agent such as anhydrous sodium sulfate (Na₂SO₄).


Tachykininergic mediation of viscerosensitive responses to acute inflammation in rats: role of CGRP.
Tachykinins, colocalized with calcitonin gene-related peptides (CGRP) in sensory afferents, are involved in viscerosensitive responses. We investigated the role of tachykinins and CGRP in both nociceptive and visceromotor responses to inflammation. Visceral pain was assessed by abdominal muscle contractions. Gastric emptying was evaluated after gavage with reconstituted milk containing 51Cr-labeled sodium chromate. Acetic acid or 9% NaCl was injected intraperitoneally before the meal. RP-67580, SR-48968, human CGRP [hCGRP-(8-37)], or their vehicles were injected before acetic acid or saline. RP-67580, SR-48968, or their vehicles were injected before CGRP and the meal. GR-73632 or GR-76349 was injected before the meal. Acetic acids inhibited gastric emptying and increased the number of abdominal contractions. RP-67580 reduced the inhibition of gastric emptying without affecting the abdominal response. SR-48968 only reduced the acetic acid-induced increase of abdominal contractions. hCGRP-(8-37) reduced both responses induced by acetic acid. CGRP mimicked the effects of acetic acid. RP-67580 abolished CGRP-induced gastric emptying inhibition, whereas SR-48968 only diminished visceral pain. GR-73632 reduced gastric emptying, and GR-64349 increased abdominal response. In inflammation, neurokinin receptors (NK1 and NK2) mediate the gastric emptying inhibition and visceral pain, respectively. These responses involve a release of CGRP.


Multidisciplinary approach to chronic pain from myofascial pain dysfunction syndrome: a four-year experience at a Brazilian center.
Chronic pain is the major complaint of myofascial pain dysfunction syndrome (MPDS) and is a complex problem which involves physical, psychological and social aspects. The etiology of MPDS is multifactorial and the multidisciplinary approach is essential for differential diagnosis and for comprehensive treatment planning. In 1993, the Dental School of Piracicaba-UNICAMP, Brazil, opened a Center for Pain Studies (CPS), staffed by health care providers including, dentists, psychologists, physicians, physiotherapists and phonoaudiologists. The major aims of the CPS are to provide clinical care and to develop basic and applied research. Sixty-two MPDS patients had been admitted to the CPS by 1997. There were 60 females and 2 males, mean age-32.5 years. The mean duration of chronic pain was 48 months. Pain intensity and unpleasantness were measured employing the Visual Analogue Scale. The tendency to develop stress-related diseases was assessed by the Social Readjustment Scale. There was a mean reduction of chronic pain of 69.89% and 71.78% relative to intensity and unpleasantness, respectively. The experience of clinical attendance at a multidisciplinary center showed the relevance of a team consisting of health care providers from different specialties with well-established aims, completely integrated and sensitive enough to understand the painful complaints of MPDS patients.


Expression of MHC class Ia and class Ib during ontogeny: high expression in epithelia and coregulation of class Ia and lmp7 genes.
The amphibian Xenopus permits the examination of immune responses in a species that progresses through two distinct lives, tadpole and adult, in which animals are free-living and immunocompetent. MHC gene expression as well as general features of the immune system change profoundly at metamorphosis. In this study gene expression of class Ia, class Ib, and the immune proteasome component lmp7 was investigated by Northern blotting at all stages of development. Class Ia genes are expressed in most adult tissues, with highest levels in intestine. Class Ib genes are expressed at lower levels, and their tissue distribution is somewhat more restricted than that of class Ia. Consistent with the idea that particular class Ib isotypes can perform distinct functions, preferential expression of class Ib genes is found in some tissues, with one family being expressed exclusively in epithelia. The onset of MHC expression is not simultaneous in all tissues: class Ia transcripts are first present in tadpole lung, gill, and intestine, organs with epithelial surfaces in contact with the environment. In every tissue except colon and muscle, class Ia expression increases markedly after metamorphosis. Interestingly, expression of the MHC-linked proteasome component lmp7 mirrored class Ia expression, while the constitutive lmp7 homologue X was expressed ubiquitously at all stages. Class Ib transcripts were never detected before metamorphosis, suggesting that the Xenopus class Ib proteins identified to date do not subserve class Ia functions in tadpole life.


Backward stimulated radiation from filaments in nitrogen gas and air pumped by circularly polarized 800 nm femtosecond laser pulses.
We report on strong backward stimulated emission at 337 nm in nitrogen gas pumped by circularly polarized femtosecond laser pulses at 800 nm. A distinct dependence of the backward UV spectrum on pump laser polarization and intensity is observed, pointing to the occurrence of backward amplified spontaneous emission inside filaments. We attribute the population inversion to inelastic collision between the free electrons produced by the pump laser and neutral N2 molecules. The addition of oxygen molecules is detrimental for the gain, reducing it to near threshold at atmospheric concentration.


Limited protection of TAT-Bcl-X(L) against pneumolysin-induced neuronal cell death.
Severe brain damage in patients with pneumococcal meningitis is in part caused by the cytosolic pneumococcal protein pneumolysin. The devastating effect of this neurotoxin might be alleviated by interfering with the cell death pathways that it sets in motion. An important player in these pathways is Bcl-X(L), an antiapoptotic protein of the Bcl-2 family, which is neuroprotective in various in vitro and in vivo models of cell death. We investigated whether its membrane-permeable form, the TAT-Bcl-X(L) fusion protein, is capable of protecting human SH-SY5Y neuroblastoma cells against pneumolysin-induced cell death. Under mild pneumolysin-induced neuronal injury, TAT-Bcl-X(L) increased cell viability significantly by approximately 40% (82.7 +/- 16.1% versus 70.0+/-8.2%; p = 0.04). When the cells were exposed to a more rigorous pneumolysin treatment, TAT-Bcl-X(L) had no protective effects. This suggests the involvement of additional neuronal death pathways in pneumolysin-induced cell death, which are not controlled by Bcl-X(L). Therefore, Bcl-X(L), a promising therapeutic candidate for ischemia and neurodegenerative diseases, is only of partial efficacy in preventing the direct neurotoxicity of pneumolysin.


How I determine if and when to recommend stopping tyrosine kinase inhibitor treatment for chronic myeloid leukaemia.
Treatment-free remission (TFR) has recently emerged as a goal of treatment in chronic myeloid leukaemia (CML). Molecular remission is sustained in around 30% of imatinib-treated patients who stop treatment after ≥2 years with undetectable minimal residual disease (UMRD) by conventional real-time reverse transcription polymerase chain reaction. An additional 20-30% of patients will lose UMRD, but remain in stable major molecular remission off treatment. Most patients with molecular recurrence have a significant increase in BCR-ABL1 within the first 6 months off treatment, but there are also rare late relapses. As re-treatment with imatinib restores control, a trial of TFR is safe so long as careful molecular monitoring is provided to enable prompt re-treatment. The minimum eligibility criteria for a trial of TFR are not yet defined, but the available data support a MRD level of around a molecular response of 4.5 log for at least 2 years. Factors associated with a higher probability of TFR include low risk Sokal score, prior interferon treatment, longer total duration of imatinib treatment and higher numbers of natural killer cells at the time of imatinib discontinuation. Preliminary data suggest that the rate of TFR in patients treated with more potent tyrosine kinase inhibitors will probably be higher. The biology that underlies TFR is an area of active investigation.


TRDMT1-mediated RNA C-5 methylation as a novel target in anticancer therapy.
Affected landscape of RNA modifications is frequently observed in different cancer cells that can be associated with the development of cancer cell phenotypic traits such as sustained proliferation, migration and invasion, apoptosis resistance and metabolic reprograming. DNMT2/TRDMT1 5-methylcytosine methyltransferase, initially classified as DNA methyltransferase, can methylate both tRNA and mRNA promoting tRNA stability and proper protein synthesis, and orchestrating DNA damage response (DDR) and DNA stability, respectively. TRDMT1 is associated with cancer progression as its levels can be elevated and its mutations can be observed in a number of cancer types. TRDMT1 gene knockout (KO) can sensitize cancer cells of different origin to radiotherapy and chemotherapy. In the present review paper, based on literature data, the physiological and pathophysiological roles of TRDMT1 in different biological systems are described with the emphasis on human normal and cancer cells. Potential TRDMT1 substrates, inhibitors and regulatory mechanisms of catalytic activity and cellular localization are also presented and evaluated. TRDMT1 as a novel promising target in anticancer therapy is proposed and discussed.


Distribution of genes for virulence and ecological fitness among diverse Vibrio cholerae population in a cholera endemic area: tracking the evolution of pathogenic strains.
The pathogenic strains of Vibrio cholerae that cause acute enteric infections in humans are derived from environmental nonpathogenic strains. To track the evolution of pathogenic V. cholerae and identify potential precursors of new pathogenic strains, we analyzed 324 environmental or clinical V. cholerae isolates for the presence of diverse genes involved in virulence or ecological fitness. Of 251 environmental non-O1, non-O139 strains tested, 10 (3.9%) carried the toxin coregulated pilus (TCP) pathogenicity island encoding TCPs, and the CTX prophage encoding cholera toxin, whereas another 10 isolates carried the TCP island alone, and were susceptible to transduction with CTX phage. Most V. cholerae O1 and O139 strains carried these two major virulence determinants, as well as the Vibrio seventh pandemic islands (VSP-1 and VSP-2), whereas 23 (9.1%) non-O1, non-O139 strains carried several VSP island genes, but none carried a complete VSP island. Conversely, 30 (11.9%) non-O1, non-O139 strains carried type III secretion system (TTSS) genes, but none of 63 V. cholerae O1 or O139 strains tested were positive for TTSS. Thus, the distribution of major virulence genes in the non-O1, non-O139 serogroups of V. cholerae is largely different from that of the O1 or O139 serogroups. However, the prevalence of putative accessory virulence genes (mshA, hlyA, and RTX) was similar in all strains, with the mshA being most prevalent (98.8%) followed by RTX genes (96.2%) and hlyA (94.6%), supporting more recent assumptions that these genes imparts increased environmental fitness. Since all pathogenic strains retain these genes, the epidemiological success of the strains presumably depends on their environmental persistence in addition to the ability to produce major virulence factors. Potential precursors of new pathogenic strains would thus require to assemble a combination of genes for both ecological fitness and virulence to attain epidemiological predominance.


Effects of VEGF + Mesenchymal Stem Cells and Platelet-Rich Plasma on Inbred Rat Ovarian Functions in Cyclophosphamide-Induced Premature Ovarian Insufficiency Model.
Premature ovarian insufficiency (POI), a fertility disorder affecting women under 40 years of age, is characterized by early loss of ovarian function. This study was aimed to maintain ovarian function in POI animal models by mesenchymal stem cells (MSCs) transplantation with/without the supplementation of platelet-rich plasma (PRP). Adipose tissue-derived MSCs were isolated from inbred rats (Fisher-344), and constitutive expression of both VEGF and GFP were maintained by transfection with plasmids, pVEGF and pGFP-N. PRP was derived from the blood of healthy untreated rats. A total of 60 rats were divided into 5 groups of 12 rats in each. First group was kept as untreated-control (Control), and POI model was induced in Fisher-344 rats by cyclophosphamide in the next four groups. Second group was kept as sham-operated-control (Sham). MSC, PRP and MSC+ PRP-treated groups were transplanted following the validation of POI model in rats. After 2 months following the transplantation, anti-mullerian-hormone (AMH) and oestradiol (E2) blood levels were measured. Follicles were evaluated after hematoxylin-eosin staining, and the immunofluorescence staining and gene expression analyses were performed to show the ovarian regeneration. The follicular count was improved after MSC- and MSC + PRP-treatment to 63% of Control-group and significantly higher than that in Sham-group, but a significant increase was not observed in PRP-group. Higher AMH and E2 levels were measured in MSC + PRP than in Sham-group, and CXCL12, BMP-4, TGF-β and IGF-1 expressions were also increased. This study showed MSCs +/-PRP transplantation after POI supports recovery of the follicular count and function. For ovarian recovery, a single administration of PRP was found not sufficient. Although MSC treatment increased follicular regeneration, better results were obtained in the co-transplantation of MSCs and PRP. These results might be promising for follicular regeneration in POI patients.


E2F1 controls alternative splicing pattern of genes involved in apoptosis through upregulation of the splicing factor SC35.
The transcription factor E2F1 has a key function during S phase progression and apoptosis. It has been well-demonstrated that the apoptotic function of E2F1 involves its ability to transactivate pro-apoptotic target genes. Alternative splicing of pre-mRNAs also has an important function in the regulation of apoptosis. In this study, we identify the splicing factor SC35, a member of the Ser-Rich Arg (SR) proteins family, as a new transcriptional target of E2F1. We demonstrate that E2F1 requires SC35 to switch the alternative splicing profile of various apoptotic genes such as c-flip, caspases-8 and -9 and Bcl-x, towards the expression of pro-apoptotic splice variants. Finally, we provide evidence that E2F1 upregulates SC35 in response to DNA-damaging agents and show that SC35 is required for apoptosis in response to these drugs. Taken together, these results demonstrate that E2F1 controls pre-mRNA processing events to induce apoptosis and identify the SC35 SR protein as a key direct E2F1-target in this setting.


Common gastroenterological problems. The irritable bowel syndrome.
The irritable bowel syndrome is one of the commonest conditions seen in gastroenterology clinics. The diagnosis is suggested by the presence of longstanding colonic symptoms without any deterioration in the patient's general condition but depends essentially on the exclusion of any underlying organic disease. Particular care is required before attaching this label to middle-aged and elderly patients presenting with bowel symptoms for the first time. The most important aspects of treatment are firm reassurance, a simple explanation of symptom production and sympathetic follow-up. Drug therapy plays a comparatively minor role although a variety of preparations are helpful in individual cases. Reinvestigation is rarely indicated unless the symptom complex changes or the patient loses weight.


Global Networking of Cancer and NCD professionals using internet technologies: the Supercourse and mHealth applications.
Cancer is a leading cause of death around the world. Education is at the core of cancer prevention activities, especially programs targeting empowering existing public health workforce. In the past 10 years, researchers at the University of Pittsburgh have been building the Global Health Network Supercourse project, a library of over 4500 online lectures and a network of nearly 50000 public health professionals in 174 countries. As of November, 2010, the overall number of Supercourse participants from Asia exceeds 7000 participants. The Supercourse network has been investigating methods for Internet based recruitment of cancer prevention professionals in order to network cancer experts locally and globally, including the use of mHealth technologies for cancer research education and for NCD registries. Supercourse is a tool that can offer a solution to the challenges of information sharing, especially in the field of NCDs and cancer. In this paper, we highlight the need for the development of Cancer Supercourse with Satellite in Asia and encourage faculty members from Asia to join the network.


Actions of peptide YY and neuropeptide Y on chief cells from guinea pig stomach.
Peptide YY (PYY), found in intestinal endocrine cells, and neuropeptide Y (NPY), a structural analogue of PYY found in neurons, inhibit gastric, pancreatic, and intestinal fluid and electrolyte secretion. We examined the effects of these peptides on dispersed chief cells from guinea pig stomach. PYY and NPY, but not pancreatic polypeptide, starting at nanomolar concentrations, caused a 40-50% inhibition of secretin-, vasoactive intestinal polypeptide-, prostaglandin E2-, and forskolin-induced increases in chief cell adenosine 3',5'-cyclic monophosphate (cAMP) content and pepsinogen secretion. These inhibitory peptides did not alter pepsinogen secretion caused by cholecystokinin, carbamylcholine, A23187, 8-bromo-cAMP, or a phorbol ester. The inhibitory effects of PYY on chief cell cAMP production occurred within 30 s, were independent of phosphodiesterase activity, and did not affect the actions of cholera toxin. However, the inhibitory effects of PYY were abolished when chief cells were preincubated with pertussis toxin, an agent that uncouples inhibitory guanine nucleotide binding (G) proteins from their receptors. In gastric chief cells, PYY and NPY attenuate the stimulatory effects of secretagogues whose actions are mediated by changes in cellular levels of cAMP. PYY-induced attenuation of chief cell adenylate cyclase activity appears to involve activation of inhibitory G proteins.


Nonlinear electronic line shape determination in Yb3+-doped phosphate glass.
Nonlinear refraction spectroscopy has been performed in Yb3+-doped phosphate glass to determinate the line shape of real and imaginary parts of n2 (n2' and n2"). The n2' spectrum presented an asymmetric feature due to the interference of resonant and nonresonant contributions, where the nonresonant term arises from the polarizability difference between excited and ground states (delta alpha). The measurements were performed in the transient regime to determine population dynamics and the pump saturation intensity at 975 nm (peak of the absorption spectrum). Because of the small quantum defect of Yb3+, we estimated that the magnitude of the thermal lens effect is approximately 20 times smaller than the population lens effect, caused by n2.


(11)C-Labeling of a potent hydroxyethylamine BACE-1 inhibitor and evaluation in vitro and in vivo.
The enzyme β-secretase 1 (BACE-1) is associated with the catalytic cleavage of amyloid precursor protein (APP) which leads to the production of amyloid-β, an amyloidogenic peptide that forms insoluble fibrils and is linked to neurodegeneration and Alzheimer's disease (AD). A PET-radioligand for the quantification of BACE-1 would be useful for the understanding of AD. In this report, we describe the synthesis and carbon-11 radiolabeling of a potent hydroxyethylamine BACE-1 enzyme inhibitor (BSI-IV) and its evaluation in vitro and in vivo. (11)[C]-N(1)-((2S,3R)-4-(cyclopropylamino)-3-hydroxy-1-phenylbutan-2-yl)-5-(N-methylmethyl-sulfonamido)-N(3)-((R)-1-phenylethyl)isophthalamide, a β-secretase inhibitor, denoted here as [(11)C]BSI-IV was synthesized through a palladium-mediated aminocarbonylation with an aryl halide precursor (I or Br) and [(11)C]CO. The effect of different palladium/ligand-complexes on radiochemical yield in the carbonylative reaction was investigated. The binding of the labeled compound to BACE-1 enzyme was studied in vitro by frozen section autoradiography from brains of healthy rats. Dynamic small animal PET-CT studies and ex vivo biodistribution were performed in male rats. The halide precursors were synthesized in six steps starting from methyl-3-nitrobenzoate with an overall yield of 21-26%. [(11)C]BSI-IV was obtained in 29±12% decay corrected radiochemical yield (n=12) with a specific activity of 790±155GBq/μmol at the end of synthesis with a radiochemical purity of >99%. The preclinical studies showed that [(11)C]BSI-IV has a rapid metabolism in rat with excretion to the small intestines. (11)[C]BSI-IV was obtained in sufficient amount and purity to enable preclinical investigation. The preclinical studies showed low specific binding in vitro and fast clearance in vivo and a low uptake in the brain. These findings suggests that [(11)C]BSI-IV has limited use as a PET-ligand for the study of BACE-1 or AD.


Developing a Communication Curriculum and Workshop for an Internal Medicine Residency Program.
Learning effective communication is essential for physicians. Effective communication has been shown to affect healthcare outcomes, including patient safety, adherence rates, patient satisfaction, and enhanced teamwork. The importance of these skills has become even more apparent in recent years, with value-based purchasing programs and federal measures of patient satisfaction in the form of Hospital Consumer Assessment of Healthcare Providers and Systems scores becoming an important part of measuring the performance of a healthcare facility. We conducted a communication workshop for internal medicine residents at the University of Texas. Topics covered included the Acknowledge, Introduce, Duration, Explanation, Thank You framework; managing up; resolving conflicts; error disclosure; new medication and discharge counseling; intercultural communication; understanding Hospital Consumer Assessment of Healthcare Providers and Systems scores; and avoiding burnout. Because it would have been logistically difficult to block whole days for the workshop, the various topics were offered to residents during their regular noon conference hour for several consecutive days. After the workshop, the residents completed an anonymous questionnaire regarding their perception of the importance of various aspects of communication in patient care. The majority of the participating residents perceived the various communication skills explored during the workshop to be highly important in patient care. Concurrently, however, most residents believed that they had initially overestimated their knowledge about these various communication issues. Some demographic differences in the responses also were noted. Our findings demonstrate a needs gap and an area of potential improvement in medical education. We anticipate that with the growing understanding of the importance of communication skills in the healthcare setting, there will be an enhanced role for teaching these skills at all levels of medical education. More studies are needed to further elucidate the specific areas of communication in health care where additional training is necessary.


The Olfactory System Revealed: Non-Invasive Mapping by using Constrained Spherical Deconvolution Tractography in Healthy Humans.
Although the olfactory sense has always been considered with less interest than the visual, auditive or somatic senses, it does plays a major role in our ordinary life, with important implication in dangerous situations or in social and emotional behaviors. Traditional Diffusion Tensor signal model and related tractography have been used in the past years to reconstruct the cranial nerves, including the olfactory nerve (ON). However, no supplementary information with regard to the pathways of the olfactory network have been provided. Here, by using the more advanced Constrained Spherical Deconvolution (CSD) diffusion model, we show for the first time in vivo and non-invasively that, in healthy humans, the olfactory system has a widely distributed anatomical network to several cortical regions as well as to many subcortical structures. Although the present study focuses on an healthy sample size, a similar approach could be applied in the near future to gain important insights with regard to the early involvement of olfaction in several neurodegenerative disorders.


Further insight into the genetic diversity of Entamoeba coli and Entamoeba hartmanni.
Despite the species' wide distribution, studies of the genetic diversity within Entamoeba coli and Entamoeba hartmanni remain limited. In the present study, we provide further insight into the genetic diversity of both species based on analysis of partial nuclear small subunit ribosomal DNA sequences generated from human fecal DNAs from samples collected in Africa, South America, and Europe. Reinforcing the previous recognition that E. coli is a species complex, our data confirm the existence of the two subtypes, ST1 and ST2, previously identified plus, potentially, a new subtype, ST3. While ST1 appears to be genetically quite homogenous, ST2 shows a substantial degree of intrasubtype diversity. ST2 was more common in samples collected outside Europe, whereas ST1 showed no geographical restriction. The potentially novel subtype is represented to date exclusively by sequences from South American and African samples. In contrast to previous reports, our new data also indicate substantial variation in E. hartmanni that could also support the establishment of subtypes within this species. Here, however, no links were identified between subtype and geographical origin.


Social Security reform: evaluating current proposals. Latest results of the EBRI-SSASIM2 policy simulation model.
The present Social Security program has been shown to be financially unsustainable in the future without modification to the current program. The purpose of this Issue Brief, EBRI's fourth in a series on Social Security reform, is threefold: to illustrate new features of the EBRI-SSASIM2 policy simulation model not available in earlier EBRI publications, to expand quantitative analysis to specific proposals, and to evaluate the uncertainty involved in proposals that rely on equity investment. This analysis compares the Gregg/Breaux-Kolbe/Stenholm (GB-KS) and Moynihan/Kerrey proposals with three generic or "traditional" reforms: increasing taxes, reducing benefits, and/or increasing the retirement age. Both proposals would create individual accounts by "carving out" funds from current Social Security payroll taxes. This analysis also examines other proposed changes that would "add on" to existing Social Security funds through the use of general revenue transfers and/or investment in the equities market. President Clinton has proposed a general revenue transfer and the collective investment of some of the OASDI trust fund assets in equities. Reps. Archer and Shaw have proposed a general revenue tax credit to establish individual accounts that would be invested partially in the equities markets. When comparing Social Security reform proposals that would specifically alter benefit levels, the Moynihan/Kerrey bill compares quite favorably with the other proposals in both benefit levels and payback ratios, when individuals elect to use the individual account option. In contrast, the GB-KS bills do not compare quite as favorably for their benefit levels, but do compare favorably in terms of payback ratios. An important comparison in these bills is the administrative costs of managing the individual accounts, since benefits can be lowered by up to 23 percent when going from the assumed low to high administrative costs. Moreover, allowing individuals to decide whether to save the 2 percent of their OASDI taxable income or to receive higher takehome pay, as would be allowed in Moynihan/Kerrey, could lead to substantial differences in ultimate retirement income. Allowing for individual investment choices and using actual 401(k) participant allocation data, as opposed to an assumed average allocation for everyone, results in substantial differences in account balances. The Archer/Shaw approach mandates a 60 percent/40 percent equity/bond split specifically to avoid the variations in returns that arise from individual investment allocation decisions. Although there are greater chances for higher returns for equity investment in the president's proposal, there are also greater chances for worse outcomes. This is also true for other reforms that would invest Social Security assets in equities.


Effects of exercise on anxiety and depression disorders: review of meta- analyses and neurobiological mechanisms.
Anxiety and depression are the most frequently diagnosed psychological diseases showing a high co-morbidity. They have a severe impact on the lives of the persons concerned. Many meta-analytical studies suggested a positive anxiolytic and depression-reducing effect of exercise programs. The aim of the present article is to synthesize metaanalyses on the effects of exercise on anxiety and depression and to describe average effect sizes. For this purpose 37 meta-analyses were included reporting 50 effect sizes for anxiety scores of 42,264 participants and depression scores of 48,207 persons. The average documented anxiolytic effect of exercise in these reviews was small, 0.34. In contrast, the effect of exercise on depression was significantly higher and at a moderate level, 0.56. Data of randomized controlled trials suggest higher sizes for the effect of exercise on anxiety and depression leading to increases up to moderate and large effects, respectively. Additionally, exercise seems to be more beneficial for patients compared to participants within a non-clinical, normal range of psychological disease. Especially for the effect of exercise on anxiety, more high quality meta-analyses of randomized controlled trials are needed. Finally, possible neurobiological explanations are suggested for the positive effect of exercise on psychological disorders like anxiety and depression.


Protein profile of Beta vulgaris leaf apoplastic fluid and changes induced by Fe deficiency and Fe resupply.
The fluid collected by direct leaf centrifugation has been used to study the proteome of the sugar beet apoplastic fluid as well as the changes induced by Fe deficiency and Fe resupply to Fe-deficient plants in the protein profile. Plants were grown in Fe-sufficient and Fe-deficient conditions, and Fe resupply was carried out with 45 μM Fe(III)-EDTA for 24 h. Protein extracts of leaf apoplastic fluid were analyzed by two-dimensional isoelectric focusing-SDS-PAGE electrophoresis. Gel image analysis revealed 203 consistent spots, and proteins in 81% of them (164) were identified by nLC-MS/MS using a custom made reference repository of beet protein sequences. When redundant UniProt entries were deleted, a non-redundant leaf apoplastic proteome consisting of 109 proteins was obtained. TargetP and SecretomeP algorithms predicted that 63% of them were secretory proteins. Functional classification of the non-redundant proteins indicated that stress and defense, protein metabolism, cell wall and C metabolism accounted for approximately 75% of the identified proteome. The effects of Fe-deficiency on the leaf apoplast proteome were limited, with only five spots (2.5%) changing in relative abundance, thus suggesting that protein homeostasis in the leaf apoplast fluid is well-maintained upon Fe shortage. The identification of three chitinase isoforms among proteins increasing in relative abundance with Fe-deficiency suggests that one of the few effects of Fe deficiency in the leaf apoplast proteome includes cell wall modifications. Iron resupply to Fe deficient plants changed the relative abundance of 16 spots when compared to either Fe-sufficient or Fe-deficient samples. Proteins identified in these spots can be broadly classified as those responding to Fe-resupply, which included defense and cell wall related proteins, and non-responsive, which are mainly protein metabolism related proteins and whose changes in relative abundance followed the same trend as with Fe-deficiency.


Partial oxidation as a rational approach to kinetic control in bioinspired magnetite synthesis.
Biological systems show impressive control over the shape, size and organization of mineral structures, which often leads to advanced physical properties that are tuned to the function of these materials. Such control is also found in magnetotactic bacteria, which produce-in aqueous medium and at room temperature-magnetite nanoparticles with precisely controlled morphologies and sizes that are generally only accessible in synthetic systems with the use of organic solvents and/or the use of high-temperature methods. The synthesis of magnetite under biomimetic conditions, that is, in water and at room temperature and using polymeric additives as control agents, is of interest as a green production method for magnetic nanoparticles. Inspired by the process of magnetite biomineralization, a rational approach is taken by the use of a solid precursor for the synthesis of magnetite nanoparticles. The conversion of a ferrous hydroxide precursor, which we demonstrate with cryo-TEM and low-dose electron diffraction, is used to achieve control over the solution supersaturation such that crystal growth can be regulated through the interaction with poly-(α,β)-dl-aspartic acid, a soluble, negatively charged polymer. In this way, stable suspensions of nanocrystals are achieved that show remanence and coercivity at the size limit of superparamagnetism, and which are able to align their magnetic moments forming strings in solution as is demonstrated by cryo-electron tomography.


Validity of peptic ulcer disease and upper gastrointestinal bleeding diagnoses in administrative databases: a systematic review protocol.
Administrative healthcare databases are useful to investigate the epidemiology, health outcomes, quality indicators and healthcare utilisation concerning peptic ulcers and gastrointestinal bleeding, but the databases need to be validated in order to be a reliable source for research. The aim of this protocol is to perform the first systematic review of studies reporting the validation of International Classification of Diseases, 9th Revision and 10th version (ICD-9 and ICD-10) codes for peptic ulcer and upper gastrointestinal bleeding diagnoses. MEDLINE, EMBASE, Web of Science and the Cochrane Library databases will be searched, using appropriate search strategies. We will include validation studies that used administrative data to identify peptic ulcer disease and upper gastrointestinal bleeding diagnoses or studies that evaluated the validity of peptic ulcer and upper gastrointestinal bleeding codes in administrative data. The following inclusion criteria will be used: (a) the presence of a reference standard case definition for the diseases of interest; (b) the presence of at least one test measure (eg, sensitivity, etc) and (c) the use of an administrative database as a source of data. Pairs of reviewers will independently abstract data using standardised forms and will evaluate quality using the checklist of the Standards for Reporting of Diagnostic Accuracy (STARD) criteria. This systematic review protocol has been produced in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) 2015 statement. Ethics approval is not required given that this is a protocol for a systematic review. We will submit results of this study to a peer-reviewed journal for publication. The results will serve as a guide for researchers validating administrative healthcare databases to determine appropriate case definitions for peptic ulcer disease and upper gastrointestinal bleeding, as well as to perform outcome research using administrative healthcare databases of these conditions. CRD42015029216.


Fluctuations in intracellular calcium concentration and their effect on tonic tension in canine cardiac Purkinje fibres.
Ca2+-activated aequorin luminescence and tension were measured in dog Purkinje fibres during twitches and during the increase in resting force produced by exposure of the fibres to a low-Na+ solution after 3 min without external K+. Over the restricted range which could be examined, the relation between tension and 'mean' aequorin luminescence (luminescence filtered at 0.2 Hz) was approximately linear during the development and maintenance of contracture. For a given level of force, the mean aequorin luminescence during contracture was up to 20 times greater than the peak luminescence during the twitch. Noise analysis of aequorin luminescence and tension during contracture indicated the presence of periodic fluctuations, with a predominant frequency in the range 1-4 Hz. Ryanodine (1 microM) or caffeine (10 mM) abolished the fluctuations in luminescence and tension and made the relation between tension and mean aequorin luminescence much steeper. A mathematical model, the key feature of which is periodicity in the asynchronous occurrence of spatially localized regions of relatively high [Ca2+], reproduces the experimental data derived from contractures. From the model analysis, we infer that tonic tension is produced by recruitment of increasing numbers of regions of high [Ca2+], rather than by homogeneous graded activation. These results indicate that during contracture or 'tonic tension', intracellular [Ca2+] is not at steady state, but rather undergoes large, asynchronous spatio-temporal fluctuations. Thus the assumptions that intracellular [Ca2+] is at steady state or homogeneous during tonic tension are not valid.


Vascular endothelial growth factor induces MEF2C and MEF2-dependent activity in endothelial cells.
Vascular endothelial growth factor is a key regulator of physiological and pathologic angiogenesis. Although much is known about the major upstream signaling pathways of VEGF in endothelial cells, less is known about key transcription factors involved in VEGF action. The transcription factor myocyte enhancer factor (MEF)-2C is thought to play an important role in vasculogenesis and angiogenesis during vascular development. The purpose of this study was to investigate the regulation of MEF2C expression and MEF2-dependent activity in endothelial cells by VEGF. Expression of MEF2C in human retinal endothelial cells and human umbilical vein endothelial cells was assayed by real-time PCR and Western blot. VEGF regulation of MEF2-dependent transcription was studied using an MEF2-luciferase reporter construct containing three copies of a high-affinity MEF2 binding site. The effect of MEF2 on endothelial cell migration was evaluated using a dominant-negative MEF2C mutant. VEGF induced MEF2C expression in a dose- and time-dependent fashion. This induction was completely abrogated by the inhibition of protein kinase C and was partially blocked by the inhibition of PKC-beta and PKC-delta. In addition to regulating MEF2C expression, VEGF stimulated transcription from an MEF2-dependent promoter. VEGF stimulation of transcription was significantly reduced by the inhibition of calcineurin, CaMKII, p38 MAPK, and PKC, but not by the inhibition of ERK1/2 or BMK1/ERK5. Transfection of a dominant-negative mutant of MEF2C significantly inhibited VEGF-stimulated endothelial cell migration. These results implicate VEGF as a key regulator of MEF2C and suggest that MEF2 may be an important mediator of VEGF in endothelial cells.


Prevalence of Cervical Artery Abnormalities on CTA in Patients with Spontaneous Coronary Artery Dissection: Fibromuscular Dysplasia, Dissection, Aneurysm, and Tortuosity.
Little is known about associations between spontaneous coronary artery dissection and cervical artery abnormalities. This study sought to assess the prevalence of cervical artery abnormalities among patients with spontaneous coronary artery dissection. A retrospective analysis was completed of patients who underwent CTA neck imaging as part of arterial assessment following the diagnosis of spontaneous coronary artery dissection. The internal carotid and vertebral arteries were evaluated for the presence of fibromuscular dysplasia, dissection and/or pseudoaneurysm, ectasia and/or aneurysmal dilation, atherosclerosis, and webs. Carotid tortuosity was categorized into kinks, loops, coils, and retrojugular and/or retropharyngeal carotid courses; vertebral tortuosity was classified by subjective analysis of severity. Two hundred fourteen patients were included in the final cohort, of whom 205 (95.8%) were women; the average age was 54.4 years. Fibromuscular dysplasia was the most frequently observed abnormality (83 patients; 38.8%), followed by dissections and/or pseudoaneurysms (n = 28; 13.1%), ectasia and/or aneurysmal dilation (n = 22; 10.3%), and carotid webs (n = 10; 4.7%). At least 1 type of carotid tortuosity was present in 99 patients (46.3%). The majority (n = 185; 86.4%) of patients had no carotid atherosclerosis; and 26 (12.2%) had mild; 3 (1.4%), moderate; and 0, severe carotid atherosclerosis. The most common abnormality in the cervical artery vasculature of patients with spontaneous coronary artery dissection is fibromuscular dysplasia. Cervical dissections were higher than previously reported but were not observed in most patients.


A critical mathematics perspective on reading data visualizations: reimagining through reformatting, reframing, and renarrating.
Data visualizations have proliferated throughout the COVID-19 pandemic to communicate information about the crisis and influence policy development and individual decision-making. In invoking exponential growth, mathematical modelling, statistical analysis, and the like, these data visualizations invite opportunities for mathematics teaching and learning. Yet data visualizations are social texts, authored from specific points of view, that narrate particular, and often consequential, stories. Their fundamental reliance on quantification and mathematics cements their social positioning as supposedly objective, reliable, and neutral. The reading of any data visualization demands unpacking the role of mathematics, including how data and variables have been formatted and how relationships are framed to narrate stories from particular points of view. We present an approach to a critical reading of data visualizations for the context of mathematics education that draws on three interrelated concepts: mathematical formatting (what gets quantified, measured, and how), framing (how variables are related and through what kind of data visualization), and narrating (which stories the data visualization tells, its potential impacts and limits). This approach to reading data visualisations includes a process of reimagining through reformatting, reframing and renarrating. We illustrate this approach and these three concepts using data visualizations published in the New York Times in 2020 about COVID-19. We offer a set of possible questions to guide a critical reading of data visualizations, beyond this set of examples.


Pdx1 protein induces human embryonic stem cells into the pancreatic endocrine lineage.
Success in generating insulin-producing cells (IPCs) from human embryonic stem (hES) cells by genetic manipulation has recently revealed a new therapeutic potential for diabetes. However, clinical application has been hampered by the viral genome integration and the risk of insertion mutagenesis that are entailed. Herein, we report the induction of hEC into IPCs by direct delivery of human Pdx1 proteins per se. Recombinant human Pdx1 proteins (hPdx1), which have an Antennapedia-like protein transduction domain sequence in their structure, can be efficiently translocated into hES cells and function as pancreatic transcription factor. hPdx1 protein activates a group of genes related to pancreatic beta-cell lineage development in hES cells, including NeuroD1, Nkx2.2, Pax4, Pax6, Nkx6.1 and Isl-1. hPdx1-treated hES cells synthesise and release insulin in response to glucose challenge. Therefore, this study constitutes a proof-of-concept demonstration of protein-mediated pancreatic specific differentiation of the hES cells by exploiting specific intrinsic properties of the hPdx1 protein.


NKG2D-directed cytokine-activated killer lymphocyte therapy combined with gemcitabine for patients with chemoresistant metastatic solid tumors.
Natural-killer group 2, member D (NKG2D) is an activating receptor found on activated natural killer cells and on activated T-cells, here termed cytokine-activated killer (CAK) cells. NKG2D ligands are expressed on various human cancer types. Gemcitabine is an anticancer drug which is a less immune-destructive agent than others. Herein, we investigated the clinical efficacy and the underlying mechanisms of a combination of CAK cell infusion therapy and gemcitabine. Twenty-three patients with disseminated carcinomas were treated with chemo-immunotherapy consisting of CAK cell infusion therapy following gemcitabine treatment. To investigate the underlying mechanisms by which CAK cells synergize with gemcitabine, we used enzyme-linked immunosorbent assay, Real-time reverse transcription polymerase chain reaction assay, calcein-release assay, and adherent target detachment assay. Using these assays we determined the NKG2D ligands such as major histocompatibility complex-class I-related chain (MIC)A/B expression in carcinoma cells and the level of cellular cytotoxicity generated by treatment with gemcitabine with/without CAK cells. The tumor responses differed among the patients (n=23). In vitro experiments revealed that MICA/B protein and mRNA expression were up-regulated in several carcinoma cell lines after gemcitabine treatment. Pre-treatment with gemcitabine and subsequent exposure to CAK cells induced greater cytotoxicity than either treatment alone. Inclusion of soluble MICB in CAK cell-mediated cytotoxicity assay significantly reduced cytotoxicity. Our clinical results of gemcitabine-CAK combinatorial therapy demonstrated long-term stable disease despite chemoresistance. In conclusion, the combination of gemcitabine and CAK cells may have clinical therapeutic significance for pancreatic, hepato-biliary tract, and urothelial tract cancer. Our study shows that combining CAK therapy with gemcitabine can lead to successful treatment of metastatic cancer.


Prevalence of monochloroacetate degrading genotypes among soil isolates of Pseudomonas sp.
This study reports the isolation of Pseudomonas sp. strains with monochloroacetate (MCA) degradation function, from uncontaminated soil, and the use of Southern blot hybridization technique to detect MCA degrading catabolic genes and their divergence. Based on their capacity to remove Cl- from MCA in a minimal medium containing 185 ppm Cl-, the strains were classified into three groups: poor degraders (Cl- release between 0-15 ppm), medium degraders (Cl- release between 16-30 ppm), and high degraders (Cl- release between 31-45 ppm). We have applied a gene probe assay for determining the diversity of MCA degradative genotypes of 61 strains. Two different gene probes, dehCI and dehCII were used in Southern blot hybridization assays. Majority of the DNA samples that produced signals on the membrane blots (18 out of 24) hybridized with only dehCI DNA probe, while 6 strains hybridized with only dehCII probe. On the other hand, 37 isolates did not hybridize to either of the gene probes used. The results indicated the high specificity of the DNA hybridization method and the divergence of metabolic functions and/or genotypes among the native MCA-degrading Pseudomonas sp. populations in the soil.


[Molecular arrangement of protochlorophyll aggregated forms in solid films].
The conditions were found for the successive self-assembly of two protochlorophyll aggregated forms in solid films with absorption maxima at 647 (+/-1) nm (PChl 647) and 651 (+/-1) nm (PChl 651) and fluorescence maxima at 653-655 nm and 654-657 nm, respectively. These forms model the native photochemically active form of the precursor of chlorophyll (chlorophyllide) in plants (P650). The investigation of infrared spectra (in the region 1800-1600 cm-1), CD-spectra and fluorescence, carried out in this study, permitted in between the indicated forms to distinguish the type of the molecular arrangement of aggregated structures, PChl 647 is supposed to consist of unstable dimers formed without the participation of keto groups of the cyclopentanone rings, while the structure of PChl 651 includes the dimers to bind more firmly by the intermolecular bonds formed at the expense of keto groups and a central magnesium atom.


Ecosystem response to solar ultraviolet-B radiation: influence of trophic-level interactions.
Solar ultraviolet radiation (UVR) can reduce the photosynthesis and growth of benthic diatom communities in shallow freshwater. Nevertheless, greater amounts of algae accumulate in UVR-exposed habitats than in UVR-protected environments. Near-ultraviolet (UVA wavelengths of 320 to 400 nanometers) and mid-ultraviolet (UVB, wavelengths of 280 to 320 nanometers) radiation also inhibit algal consumers (Diptera: Chironomidae). Larval chironomids are more sensitive to UVB than sympatric algae. Differential sensitivity to UVB between algae and herbivores contributes to counterintuitive increases in algae in habitats exposed to UVB. These mesocosm experiments illustrate that predictions of the response of entire ecosystems to elevated UVB cannot be made on single trophic-level assessments.


Investigating antiarthritic potential of polyherbal emulgel.
Rheumatoid arthritis (RA) is an inflammation of joints with increased cellularity of synovial tissue. Allopathic drugs possess several adverse effects, which have led to increase in the utilization of herbal medicines. Polyherbal emulgel resolves the bioavailability issue associated with hydrophobic drugs and can be used effectively in the treatment of RA. The present study aimed at the formulation of polyherbal emulgel, and evaluation of in vitro anti-inflammatory activity and in vivo antiarthritic activity. Seven emulgels F-1 to F-7 were optimally formulated. In vitro anti-inflammatory activity was determined using protein denaturation method employing Diclofenac sodium as the standard. In antiarthritic study Complete Freund's Adjuvant (CFA) model was used. The various parameters were assessed, like paw volume, body weight, hematological parameters, antioxidant parameters, Rheumatic factor (RF), and histopathological study of ankle joint. F-4 and F-7 were found to be optimized formulations as compared to other formulations. The in vitro anti-inflammatory activity was found to be highest in F-4 with IC50 7.74 and F-7 with IC50 8.87 in comparison with Diclofenac sodium having IC50 57.0. Both formulations F-7 and F-4 showed a significant reduction in paw volume and normalization of body weights. The formulation F-7 even showed more potent antiarthritic activity than F-4 by decreasing white blood cells (WBC), lymphocytes, increasing packed cell volume (PCV), neutrophils, superoxide dismutase (SOD), catalase and decreasing malondialdehyde (MDA) levels in serum. This was further confirmed by histopathological study. As an anti-inflammatory agent, this newly developed emulgel was found to possess more therapeutic efficacy than commercially available diclofenac sodium.


Research and development of phamaceutical dosage forms.
The development of a suitable formulation and a freeze-dry cycle for a pharmaceutical dosage form requires knowledge of some basic properties such as (1) eutectic temperature, if one exists, (2) temperature effect on solubility, (3) degree of supercooling, (4) heat transfer properties of the frozen product and (5) equipment design and equipment capability. Basic work with several inorganic and organic salts shows that eutectic temperature is a function of the melting point and the differential heat of solution of a drug. From a knowledge of these parameters, a mathematical expression can be used to estimate eutectic temperature. The desired characteristics which can be achieved by proper formulation of the solution to be freeze-dried and by employing optimum freeze-drying cycles include an intact cake, sufficient strength, uniform color and rapid reconstitution. By utilizing resistivity measurements to determine eutectic temperature and supercooling properties it is possible to reformulate products, increase batch sizes and reduce overall times for freeze-drying cycles.


[Structural polymorphism of the provirus integrated in the genome of mammalian cells transformed by Rous sarcoma virus].
The structural organization of integrated Rous sarcoma virus (RSV) genome in 8 different mammalian tumour cell lines has been studied. The different types of provirus rearrangements were found, e.g.: breakpoint mutations, deletions of RSV structural genes, elimination of the entire viral genome. The structural changes of proviruses appeared during long-term cultivation of tumour cell lines in vitro. The ability of transformed cells to produce complete infectious RSV correlate with the structural peculiarities of proviruses, although the tumorigenic properties of these cells are retained in all cases.


Fellows identify key issues affecting surgery.
All changes in our health care delivery system during the past three years have had an effect on reimbursement rates, net income, and practice satisfaction among surgeons. Implementation of the Medicare fee schedule and increasing penetration of the health care market by managed care firms have clearly had the most profound influence. Sixty percent of practicing surgeons have experienced a decrease in net practice income since 1992. Of referrals from required gatekeeper physicians, 15 percent of such episodes are viewed by surgeons to result in decreased quality of care. Finally, there was a surprisingly high (40%) enthusiasm for implementation of a federalized single-payor health care system.


[Effect of thiamine deficiency and excess on activity of NA+, K+, Mg2+-ATPase in plasma membranes of rat liver].
The activity of Na+, K+, Mg2+-ATPase in plasma membranes of the rat liver was studied as affected by thiamine, oxythiamine and food B1-avitaminosis. It is shown that the ATPase activity of the liver plasma membranes is inhibited only in case of modelling the alimentary thiamine deficiency.


Mechanisms of extraocular muscle injury in orbital fractures.
The gross and microscopic events that occur after orbital blowout fractures were evaluated to assess the mechanisms of diplopia and muscle injury. Intramuscular and intraorbital pressures were evaluated in experimental animals, in cadavers, and at the time of orbital fracture explorations for repair of orbital fractures in humans. Histologic and circulatory changes, muscle pressure recordings, and operative observations were evaluated. Creation of a compartment syndrome was evaluated to include a histologic evaluation of the orbital fibrous sheath network for the extraocular muscles and the intramuscular vasculature. These experiments and observations do not support the role of a compartment syndrome in ocular motility disturbances because (1) intramuscular pressures were subcritical in both humans and animals; (2) no limiting fascial compartment could be demonstrated; and (3) microangiograms and histologic evaluations did not confirm areas of compartmental ischemic necrosis. Muscle contusion, scarring within and around the orbital fibrous sheath network, nerve contusion, and incarceration within fractures remain the probable causes of diplopia, with the most likely explanations being muscle contusion and fibrosis or incarceration involving the muscular fascial network.


[Analgesics use in patients with chronic musculoskeletal complaints].
Chronic musculoskeletal complaints are common in the clinical setting and a therapeutic challenge. Little is known about the extent and type of pain-relieving drugs used by these patients in Norway. 500 patients were referred for specialist evaluation because of chronic musculoskeletal pain, most of them from the National Insurance Administration. The diagnoses were grouped into four main categories. 95% of the patients had non-specific myofascial pain syndromes and about 5% had some form of osteoarthritis. In the majority the pain was chronic. All patients were asked which pain-relieving drugs they had taken during the previous week, prescribed drugs as well as over-the-counter drugs. Those taking non-steroidal anti-inflammatory drugs (NSAIDs) were also asked if these had been prescribed under the National Health Insurance scheme. 40% had completely abstained from analgesics. 32% had taken an NSAID; 20% a codeine-paracetamol compound; 15% paracetamol; 8% muscle-relaxants, while 26 patients had taken some other type of medication. About two thirds of the patients reported having received reimbursable NSAID-prescriptions, of which only about 9% were judged to qualify for this. Even though a substantial number of patients had not taken pain-relieving drugs during the previous week, the number of patients having taken either NSAIDs, opioids or muscle relaxants was relatively high, both with regard to actual or potential side effects and to existing recommendations. The study also suggests that stricter application of the rules for reimbursement of drugs seems justified.


Lack of Associations Between Dietary Intake and Gastrointestinal Symptoms in Autism Spectrum Disorder.
Background: Many individuals with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but their etiology is currently unknown. Dietary interventions are common in children and adolescents with ASD, including diets with increased omega-3 fatty acids or diets free of gluten and/or casein, which may also impact GI symptoms and nutrition. However, little is known about the relationship between nutritional intake and GI symptomatology in ASD. The objective of this study was to assess the relationships between GI symptoms, omega-3 intake, micronutrients, and macronutrients in children with ASD. Methods: A total of 120 children diagnosed with ASD participated in this multisite study. A food frequency questionnaire was completed by the patient's caretaker. The USDA Food Composition Database was utilized to provide nutritional data for the food items consumed by each participant. GI symptomatology was assessed using a validated questionnaire on pediatric gastrointestinal symptoms. Results: There were no significant associations between GI symptoms and the amount of omega-3 fatty acids and/or other micro- and macronutrients contained in the diet. Conclusions: This study suggests that dietary variations do not appear to drive GI symptoms, nor do GI symptoms drive dietary variations in those with ASD, although causation cannot be determined with this observational assessment. Furthermore, there may be other factors associated with lower GI tract symptoms in ASD, such as increased stress response.


Melanoma differentiation-associated gene 5 (MDA5) is involved in the innate immune response to Paramyxoviridae infection in vivo.
The early host response to pathogens is mediated by several distinct pattern recognition receptors. Cytoplasmic RNA helicases including RIG-I and MDA5 have been shown to respond to viral RNA by inducing interferon (IFN) production. Previous in vitro studies have demonstrated a direct role for MDA5 in the response to members of the Picornaviridae, Flaviviridae and Caliciviridae virus families ((+) ssRNA viruses) but not to Paramyxoviridae or Orthomyxoviridae ((-) ssRNA viruses). Contrary to these findings, we now show that MDA5 responds critically to infections caused by Paramyxoviridae in vivo. Using an established model of natural Sendai virus (SeV) infection, we demonstrate that MDA5(-/-) mice exhibit increased morbidity and mortality as well as severe histopathological changes in the lower airways in response to SeV. Moreover, analysis of viral propagation in the lungs of MDA5(-/-) mice reveals enhanced replication and a distinct distribution involving the interstitium. Though the levels of antiviral cytokines were comparable early during SeV infection, type I, II, and III IFN mRNA expression profiles were significantly decreased in MDA5(-/-) mice by day 5 post infection. Taken together, these findings indicate that MDA5 is indispensable for sustained expression of IFN in response to paramyxovirus infection and provide the first evidence of MDA5-dependent containment of in vivo infections caused by (-) sense RNA viruses.


Characterization of the substituted N-triazole oxindole TROX-1, a small-molecule, state-dependent inhibitor of Ca(V)2 calcium channels.
Biological, genetic, and clinical evidence provide validation for N-type calcium channels (Ca(V)2.2) as therapeutic targets for chronic pain. A state-dependent Ca(V)2.2 inhibitor may provide an improved therapeutic window over ziconotide, the peptidyl Ca(V)2.2 inhibitor used clinically. Supporting this notion, we recently reported that in preclinical models, the state-dependent Ca(V)2 inhibitor (3R)-5-(3-chloro-4-fluorophenyl)-3-methyl-3-(pyrimidin-5-ylmethyl)-1-(1H-1,2,4-triazol-3-yl)-1,3-dihydro-2H-indol-2-one (TROX-1) has an improved therapeutic window compared with ziconotide. Here we characterize TROX-1 inhibition of Cav2.2 channels in more detail. When channels are biased toward open/inactivated states by depolarizing the membrane potential under voltage-clamp electrophysiology, TROX-1 inhibits Ca(V)2.2 channels with an IC(50) of 0.11 μM. The voltage dependence of Ca(V)2.2 inhibition was examined using automated electrophysiology. TROX-1 IC(50) values were 4.2, 0.90, and 0.36 μM at -110, -90, and -70 mV, respectively. TROX-1 displayed use-dependent inhibition of Ca(V)2.2 with a 10-fold IC(50) separation between first (27 μM) and last (2.7 μM) pulses in a train. In a fluorescence-based calcium influx assay, TROX-1 inhibited Ca(V)2.2 channels with an IC(50) of 9.5 μM under hyperpolarized conditions and 0.69 μM under depolarized conditions. Finally, TROX-1 potency was examined across the Ca(V)2 subfamily. Depolarized IC(50) values were 0.29, 0.19, and 0.28 μM by manual electrophysiology using matched conditions and 1.8, 0.69, and 1.1 μM by calcium influx for Ca(V)2.1, Ca(V)2.2, and Ca(V)2.3, respectively. Together, these in vitro data support the idea that a state-dependent, non-subtype-selective Ca(V)2 channel inhibitor can achieve an improved therapeutic window over the relatively state-independent Ca(V)2.2-selective inhibitor ziconotide in preclinical models of chronic pain.


Influenza 101: what you need to know.
Each year, 5% to 20% of the U.S. population is infected with the influenza virus. The influenza season occurs annually between the months of October and May, with 3,000 to 49,000 influenza-related deaths each year. Since complications delay recuperation, those in high-risk groups need to be monitored carefully. High-risk groups are more vulnerable to severe illness and complications of the disease and include: people older than 65 years of age, children under 2 years of age, pregnant women, obese patients, and patients with other serious comorbid conditions. This article provides home healthcare clinicians with important information on influenza, how it is transmitted, influenza virus types and changes in the virus, signs and symptoms of complications, and measures to prevent the occurrence and transmission of influenza.


Urinary excretion of ginkgolide terpene lactones following acute consumption of Ginkgo biloba extract.
Urinary biomarkers of plant food supplement (PFS) exposure/intake represent an accurate, objective tool for determining PFS consumption in humans with applications ranging from epidemiology to subject compliance in clinical trials. Ginkgo biloba remains one of the worlds most popular PFS, yet few studies have investigated the uptake and metabolism of its primary unique bioactives: the terpene lactones. To this end, we conducted a dual-dose, acute crossover intervention using G. biloba supplements in healthy participants (n = 12). Pooled 24-H urine samples were analyzed by triple quadrupole LC-MS-MS. We observed that bilobalide and ginkgolides A and B were passed into urine intact and in a dose-dependent manner. Low levels of intact ginkgolides C and J were also excreted. To our knowledge, this is the first study to report intact ginkgolide J in urine following oral consumption of ginkgo supplements and is also the first to account for excreted terpene lactones as a proportion of dose.


Do all fair-skinned Caucasians consider themselves fair?
Fair skin color is a risk factor for skin cancer. We aimed to determine whether Caucasians have an accurate perception of their skin color. A convenience sample of 341 Caucasian adults in Townsville, Queensland, Australia was asked to categorize the color of their unexposed skin as fair, medium, or olive. Reflectance was measured on the inner upper arm (400-700 nm) for each subject to provide an objective measure of inherent skin pigmentation. The median skin reflectances at 685 nm for the olive (68.7%), medium (68.9%), and fair (71.9%) perception groups were very similar and were within the reflectance range generally associated with a fair/light complexion (>/=67%). Of those with a skin reflectance >/=67%, 46.6% considered their skin medium or olive. Agreement between perceived and measured skin color was poor (kappa = 0.113), with 36.4% over-estimating and 16.4% under-estimating their skin's natural pigmentation. Some Caucasians over-estimate their skin pigmentation and possibly the level of protection from sunlight this affords them. Skin cancer prevention campaigns that attempt to target those at greater risk of skin cancer, on the basis of fair/light skin color, are likely to fail, as many of these individuals don't consider themselves fair.


The potential accuracy of dual-energy computed tomography for the determination of hepatic iron.
Physical experiments are described which simulated the main practical and technical problems encountered in estimating iron concentrations in liver by dual-energy computed tomography. In aqueous solutions located in an oval water phantom, the presence of Fe at concentrations of 1 and 2 mg/ml was detected and estimated with good accuracy and reproducibility. The main physical problem was that water showed a non-zero dual-energy difference reading whose magnitude varied with location, but this potential error was largely eliminated by measuring the location-specific water values using a technique readily adapted to patient studies. Experiments with pieces of bovine tissue in the same system suggested that the dual-energy response shown by liver tissue may include an Fe-independent contribution, reflecting its organic composition (including fat content): if attributed to Fe, this would correspond to an error less than +/- 1 mg/g wet weight in the evaluation.


Unscreened water-diversion pipes pose an entrainment risk to the threatened green sturgeon, Acipenser medirostris.
Over 3,300 unscreened agricultural water diversion pipes line the levees and riverbanks of the Sacramento River (California) watershed, where the threatened Southern Distinct Population Segment of green sturgeon, Acipenser medirostris, spawn. The number of sturgeon drawn into (entrained) and killed by these pipes is greatly unknown. We examined avoidance behaviors and entrainment susceptibility of juvenile green sturgeon (35±0.6 cm mean fork length) to entrainment in a large (>500-kl) outdoor flume with a 0.46-m-diameter water-diversion pipe. Fish entrainment was generally high (range: 26-61%), likely due to a lack of avoidance behavior prior to entering inescapable inflow conditions. We estimated that up to 52% of green sturgeon could be entrained after passing within 1.5 m of an active water-diversion pipe three times. These data suggest that green sturgeon are vulnerable to unscreened water-diversion pipes, and that additional research is needed to determine the potential impacts of entrainment mortality on declining sturgeon populations. Data under various hydraulic conditions also suggest that entrainment-related mortality could be decreased by extracting water at lower diversion rates over longer periods of time, balancing agricultural needs with green sturgeon conservation.


[Formation of a unified system of mental regulation of activities and functional state of the flyer during effects of piloting strain].
The article describes the method of improving professional dependability of pilot impacted by aerobat g-loads through formation of a unified system for psychic regulation of his activity and status of the psychological function in the process of training on flight simulator. To this end, the simulator was retrofitted with an adaptive training circuit to establish functional and correction feedback by changing the intensity of display brightness proportionally to the degree of "g-load" and effectiveness of countermeasures applied to simulate visual disorders due to hypergravity. Data from real flights with high aerobat g-loads proved effectiveness of the proposed training scenarios as judged by increased probability of administration of breathing (0.9 vs. 0.4) and muscular (1.0 vs. 0.8) countermeasures by members of the experimental group against their controls. Besides, the trained pilots had no visual disorders, whereas this was the case in 28% of their controls. Possible mechanisms of how to form a unified system for psychic regulation in which implementation of a task is kept under permanent conscious control and self-control of the psychological function is essentially accomplished on the level of automated habits are the subject of the authors' discussion.


Primary amebic meningoencephalitis: a silent killer.
One week after swimming in a man-made lake, a 9-year-old boy presented to the emergency department with headache, vomiting and lethargy. He had neck pain upon flexion and was unable to stand or walk. Cerebrospinal fluid examination revealed trophozoite and diflagellate forms consistent with Naegleria fowleri, an ameba species known to cause primary amebic meningoencephalitis. Despite aggressive management with amphotericin B and rifampin, he died 2 days later. This case report describes the clinical presentation, diagnostic findings and management of this uncommon but lethal entity.


Short communication: Factors affecting hair cortisol concentrations in lactating dairy cows.
Cortisol has long been used as a marker of the stress response in animals. Cortisol can be analyzed from different media, most notably from the blood, saliva, and feces; however, the collection of cortisol from some of these media requires invasive procedures or excessive handling of the animals. Furthermore, it is not possible to capture long-term increases in circulating concentrations of cortisol from the blood, saliva, or feces. Hair cortisol has been found to be a reliable alternative for measuring chronic stress. With this emerging measure, appropriate sampling methodology must be developed and validated. The aim of this study was to determine the effects of hair color, sampling location, and processing method on cortisol concentrations in hair from lactating black and white Holstein cows (n=18). Furthermore, we aimed to measure the hair growth rates at different body locations (n=12) and test hair cortisol levels when resampled over short intervals (n=37). Both black- and white-colored hair was collected from the shoulder, top line, hip, and tail switch of Holsteins; due to breed characteristics only white hair was harvested from the tail switch. All samples were cleaned with water and isopropanol, and then ground in a ball mill or finely cut with scissors once dry. Cortisol was extracted with methanol before being measured using a commercially available ELISA kit. Concentrations of cortisol were greater in white than in black hair (7.8 ± 1.1 vs. 3.8 ± 1.1 pg/mg). When only white samples were analyzed, hair from the tail switch had more cortisol than hair from the shoulder (11.0 ± 1.2 vs. 6.2 ± 1.2 pg/mg), whereas no difference was found when compared with the hip and top line. Samples ground with a ball mill had greater concentrations of cortisol extracted than those minced with scissors (10.4 ± 1.2 vs. 4.7 ± 1.2 pg/mg). The growth rate of hair was significantly greater at the tail switch compared with the hip and shoulder (0.51 ± 0.05 vs. 0.04 ± 0.05 vs. 0.03 ± 0.05 mm/d). When hair was collected every 3 wk after calving, a tendency was detected for multiparous cows to have greater concentrations of hair cortisol and significantly greater concentrations of cortisol on d 0 and 21 after calving compared with d 42, 84, and 126. In Holsteins, the hair on the tail switch is always white, grows more rapidly than other sites, and is sensitive enough to capture changes in cortisol over intervals as short as 3 wk, making it the ideal location for measuring hair cortisol.


Galactomannan detection for invasive aspergillosis in immunocompromised patients.
Invasive aspergillosis is the most common life-threatening opportunistic invasive mycosis in immunocompromised patients. A test for invasive aspergillosis should neither be too invasive nor too great a burden for the already weakened patient. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) seems to have the potential to meet both requirements. To obtain summary estimates of the diagnostic accuracy of galactomannan detection in serum for the diagnosis of invasive aspergillosis. We searched MEDLINE, EMBASE and Web of Science with both MeSH terms and text words for both aspergillosis and the sandwich ELISA. We checked the reference lists of included studies and review articles for additional studies. We conducted the searches in February 2014. We included cross-sectional studies, case-control designs and consecutive series of patients assessing the diagnostic accuracy of galactomannan detection for the diagnosis of invasive aspergillosis in patients with neutropenia or patients whose neutrophils are functionally compromised. The reference standard was composed of the criteria given by the European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG). Two review authors independently assessed quality and extracted data. We carried out meta-analysis using the bivariate method. We investigated sources of heterogeneity by adding potential sources of heterogeneity to the model as covariates. We included 54 studies in the review (50 in the meta-analyses), containing 5660 patients, of whom 586 had proven or probable invasive aspergillosis. When using an optical density index (ODI) of 0.5 as a cut-off value, the sensitivity of the test was 82% (73% to 90%) and the specificity was 81% (72% to 90%). At a cut-off value of 1.0 ODI, the sensitivity was 72% (65% to 80%) and the specificity was 88% (84% to 92%). At a cut-off value of 1.5 ODI, the sensitivity was 61% (47% to 75%) and the specificity was 93% (89% to 97%). None of the potential sources of heterogeneity had a statistically significant effect on either sensitivity or specificity. If we used the test at a cut-off value of 0.5 ODI in a population of 100 patients with a disease prevalence of 9% (overall median prevalence), two patients who have invasive aspergillosis would be missed (sensitivity 82%, 18% false negatives), and 17 patients would be treated unnecessarily or referred unnecessarily for further testing (specificity 81%, 19% false negatives). If we used the test at a cut-off value of 1.5 in the same population, that would mean that four invasive aspergillosis patients would be missed (sensitivity 61%, 39% false negatives), and six patients would be treated or referred for further testing unnecessarily (specificity 93%, 7% false negatives). These numbers should, however, be interpreted with caution because the results were very heterogeneous.


Bovine serum albumin chronic serum sickness nephropathy in rats.
We administered bovine serum albumin (BSA) 1 or 3 mg i.v. into hyper-immune Sprague-Dawley rats weekly for up to 6 months. Animals with free circulating antibody 1 h after BSA developed mesangial deposits of IgG and C-3 without proteinuria. Rats without free antibody at 1 h developed either mesangial or mesangial and glomerular basement membrane (GBM) deposits. Rats given 3 mg BSA tended to have GBM deposits, proteinuria and undetectable antibody at 1 h. By electronmicroscopy, all rats had mesangial and subendothelial dense deposits, while those with GBM lesions had intramembranous and subepithelial deposits with foot process obliteration. Light microscopic evaluation of kidney tissue revealed only mild histological changes similar to those in age-matched control rats. The present studies demonstrate that prolonged i.v. administration of BSA into rats results in the development of a chronic non-inflammatory nephropathy. Despite certain parallels to chronic serum sickness nephropathy in rabbits, species differences appear to modify the nephropathy in rats.