Highly enantioselective hydrogenation of N-aryl imines derived from acetophenones by using Ru-pybox complexes under hydrogenation or transfer hydrogenation conditions in isopropanol.
The asymmetric reduction of N-aryl imines derived from acetophenones by using Ru complexes bearing both a pybox (2,6-bis(oxazoline)pyridine) and a monodentate phosphite ligand has been described. The catalysts show good activity with a diverse range of substrates, and deliver the amine products in very high levels of enantioselectivity (up to 99 %) under both hydrogenation and transfer hydrogenation conditions in isopropanol. From deuteration studies, a very different labeling is observed under hydrogenation and transfer hydrogenation conditions, which demonstrates the different nature of the hydrogen source in both reactions.


Construction of eight mixed-valence pentanuclear CuI4CuII clusters using ligands with inhomogeneous electron density distribution: synthesis, characterization and photothermal properties.
To enhance light absorption in the visible region for the utilization of sunlight, eight mixed-valence polynuclear CuI/CuII clusters have been synthesized for evaluating their photothermal conversion performance. They are fabricated considering the ligand's electron density distribution inhomogeneity using 1,2,3-triazole (3N) or tetrazole (4N) and different mono-phosphine ligands. We report here the synthesis, crystal structure, characterization, optical properties, and photothermal conversion performance of these clusters. X-ray crystal structures reveal that those pentanuclear clusters are neutral clusters with octahedrally-coordinated copper(II) ion being surrounded by four tetrahedrally coordinated copper(I) ions. Interestingly, with the introduction of the mixed-valence centers, these compounds show additional light absorption centers in 350-600 nm via the IVCT transition mechanism, compared with our previously reported Cu(II) compounds. These clusters show excellent photothermal conversion performance, with an average equilibrium temperature (∼60 °C) and a temperature increment (∼40 °C), which are also superior to Cu(II) complexes (the average equilibrium temperature ∼55 °C). This work proves that it is possible to design and prepare new polynuclear mixed-valence CuI/CuII clusters for achieving high-performance photothermal conversion materials.


EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production.
The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 (histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide (NO) concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.


Preliminary results of hyperthermic intraperitoneal intraoperative chemotherapy as an adjuvant in resectable pancreatic cancer.
Background and Aims. 5-year survival in patients with pancreatic cancer is poor. Surgical resection is the only potentially curative resection. The results of adjuvant treatment either with chemotherapy or with radiotherapy have been contradictory and the incidence of local-regional recurrence remains high. If local-regional recurrence is controlled survival may be expected to increase. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) may be used in order to control local-regional recurrences. The purpose of the study is to identify the effect of HIPEC in patients with pancreatic cancer undergoing potentially resection. Patients and Methods. From 2007-2011, 21 patients, mean age 69.4 ± 9.5 (50-86) years, underwent tumor resection, and HIPEC with gemcitabine. The hospital mortality and morbidity rate was 9.5% and 33.3%, respectively. 5-year and median survival was 23% and 11 months, respectively. The recurrence rate was 50% but no patient developed local-regional recurrence. No patient was recorded with gemcitabine-induced toxicity. Conclusions. This clinical study of 21 patients is the first to combine an R(0) pancreas cancer resection with HIPEC. Increased morbidity and mortality from intraoperative gemcitabine was not apparent. Patients with pancreatic cancer undergoing potentially curative resection in combination with HIPEC may be offered a survival benefit. Data suggested that local-regional recurrences may be greatly reduced. Further studies with greater number of patients are required to confirm these findings.


Advanced Cognitive Algorithm for Biomedical Data Processing: COVID-19 Pattern Recognition as a Case Study.
Automated disease prediction has now become a key concern in medical research due to exponential population growth. The automated disease identification framework aids physicians in diagnosing disease, which delivers accurate disease prediction that provides rapid outcomes and decreases the mortality rate. The spread of Coronavirus disease 2019 (COVID-19) has a significant effect on public health and the everyday lives of individuals currently residing in more than 100 nations. Despite effective attempts to reach an appropriate trend to forecast COVID-19, the origin and mutation of the virus is a crucial obstacle in the diagnosis of the detected cases. Even so, the development of a model to forecast COVID-19 from chest X-ray (CXR) and computerized tomography (CT) images with the correct decision is critical to assist with intelligent detection. In this paper, a proposed hybrid model of the artificial neural network (ANN) with parameters optimization by the butterfly optimization algorithm has been introduced. The proposed model was compared with the pretrained AlexNet, GoogLeNet, and the SVM to identify the publicly accessible COVID-19 chest X-ray and CT images. There were six datasets for the examinations: three datasets with X-ray pictures and three with CT images. The experimental results approved the superiority of the proposed model for cognitive COVID-19 pattern recognition with average accuracy 90.48, 81.09, 86.76, and 84.97% for the proposed model, support vector machine (SVM), AlexNet, and GoogLeNet, respectively.


Management of magnesium depletion.
In addition to the well-known complexities inherent in the recognition of hypomagnesemia and/or magnesium depletion, the management of magnesium deficiency oftentimes is not straightforward and requires the understanding of several important principles. Among these is that the avoidance of ineffective undertreatment of patients with symptomatic severe depletion may require parenteral administration of quite large amounts of magnesium for several days. This point is evident in the included case example describing a patient in whom the small amounts of magnesium given initially were entirely ineffective. The use of the various protocols to provide a patient with magnesium by the parenteral route requires consideration of several factors. The purpose of this paper is to provide the practitioner with a comprehensive, clinically useful review of the oral and parenteral therapy of patients with magnesium depletion.


Hypercalcemia in patients with bipolar disorder treated with lithium: a cross-sectional study.
Lithium-induced hyperparathyroidism (LIH) is a relative underrecognized complication of long-term lithium treatment. Hypercalcemia may be the first, but often overlooked, sign of LIH. Symptoms of LIH can be similar to the underlying psychiatric illness, which may cause a significant doctor's delay in diagnosing LIH. The aim of this study was to determine the prevalence of hypercalcemia in a cohort of psychiatric patients. In this cross-sectional study, we collected data from 314 patients treated with lithium in an outpatient clinic for bipolar disorder. Patients with bipolar disorder from the same clinics, who had never been treated with lithium and of whom serum calcium levels were available, were included as controls (n = 15). Patient characteristics and laboratory results were collected during the period of June 2010 till June 2011. The mean serum calcium level was 2.49 (SD 0.11) mmol/l. The point prevalence of hypercalcemia (>2.60 mmol/l) was 15.6%. In a comparable group of psychiatric patients not using lithium, the mean serum calcium level was 2.37 mmol/l, and none of these patients had hypercalcemia (p = 0.001). The duration of lithium treatment was the only significant predictor for the development of hypercalcemia (p = 0.002). The prevalence of hypercalcemia in lithium-treated patients was significantly higher than that in non-lithium treated controls and correlated to the cumulative time lithium was used in this cross-sectional study. We recommend that serum calcium levels should be routinely tested in patients using lithium for timely detection of LIH or hypercalcemia due to other causes.


Targeting Antigens to Different Receptors on Conventional Type 1 Dendritic Cells Impacts the Immune Response.
Targeting Ag to surface receptors on conventional type 1 dendritic cells can enhance induction of Ab and T cell responses. However, it is unclear to what extent the targeted receptor influences the resulting responses. In this study, we target Ag to Xcr1, Clec9A, or DEC-205, surface receptors that are expressed on conventional type 1 dendritic cells, and compare immune responses in BALB/c and C57BL/6 mice in vitro and in vivo after intradermal DNA vaccination. Targeting hemagglutinin from influenza A to Clec9A induced Ab responses with higher avidity that more efficiently neutralized influenza virus compared with Xcr1 and DEC-205 targeting. In contrast, targeting Xcr1 resulted in higher IFN-γ+CD8+ T cell responses in spleen and lung and stronger cytotoxicity. Both Clec9A and Xcr1 targeting induced Th1-polarized Ab responses, although the Th1 polarization of CD4+ T cells was more pronounced after Xcr1 targeting. Targeting DEC-205 resulted in poor Ab responses in BALB/c mice and a more mixed Th response. In an influenza challenge model, targeting either Xcr1 or Clec9A induced full and long-term protection against influenza infection, whereas only partial short-term protection was obtained when targeting DEC-205. In summary, the choice of targeting receptor, even on the same dendritic cell subpopulation, may strongly influence the resulting immune response, suggesting that different targeting strategies should be considered depending on the pathogen.


A Pharmacological Examination of the Cardiovascular Effects of Malayan Krait (Bungarus candidus) Venoms.
Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension) are often clinical outcomes of snake envenoming. Malayan krait (Bungarus candidus) envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this effect has yet to be determined. In the present study, we investigated the in vivo and in vitro cardiovascular effects of B. candidus venoms from Southern (BC-S) and Northeastern (BC-NE) Thailand. SDS-PAGE analysis of venoms showed some differences in the protein profile of the venoms. B. candidus venoms (50 µg/kg-100 µg/kg, i.v.) caused dose-dependent hypotension in anaesthetised rats. The highest dose caused sudden hypotension (phase I) followed by a return of mean arterial pressure to baseline levels and a decrease in heart rate with transient hypertension (phase II) prior to a small decrease in blood pressure (phase III). Prior administration of monovalent antivenom significantly attenuated the hypotension induced by venoms (100 µg/kg, i.v.). The sudden hypotensive effect of BC-NE venom was abolished by prior administration of hexamethonium (10 mg/kg, i.v.) or atropine (5 mg/kg, i.v.). BC-S and BC-NE venoms (0.1 µg/kg-100 µg/ml) induced concentration-dependent relaxation (EC50 = 8 ± 1 and 13 ± 3 µg/mL, respectively) in endothelium-intact aorta. The concentration-response curves were markedly shifted to the right by pre-incubation with L-NAME (0.2 mM), or removal of the endothelium, suggesting that endothelium-derived nitric oxide (NO) is likely to be responsible for venom-induced aortic relaxation. Our data indicate that the cardiovascular effects caused by B. candidus venoms may be due to a combination of vascular mediators (i.e., NO) and autonomic adaptation via nicotinic and muscarinic acetylcholine receptors.


Large-cell neuroendocrine carcinoma arising in the endometrium: A case report.
Large-cell neuroendocrine carcinoma (LCNEC) of the endometrium is an extremely rare, high-grade malignant tumor. We herein report a case of a rapidly growing LCNEC arising in the endometrium. A 52-year-old woman was referred to Toyooka Hospital (Tooyoka, Japan) due to genital bleeding in February 2016. There had been no abnormalities on a regular gynecological and physical examination 3 months prior to the consultation. Imaging (computed tomography and magnetic resonance imaging) and a pelvic examination revealed a tumor sized 16.9×8.4×7.8 mm occupying the intrauterine cavity and extending into the vaginal cavity. Multiple metastatic pelvic and paraaortic lymph nodes were also identified. Continuous bleeding from the tumor was observed, and a blood examination revealed anemia, which was likely due to that bleeding. Biopsy of the tumor was performed, and large atypical cells were identified. The tumor cells were negative for cytokeratin AE1/AE3 and chromogranin A, but positive for CD56 and synaptophysin. There was also an abundance of Ki-67-positive cells in the tumor, altogether suggesting that the tumor was an LCNEC. The patient succumbed to the disease 36 days after the first consultation. Based on the findings of the present case and previously published cases, LCNECs arising in the endometrium may progress rapidly and are associated with an unfavourable outcome. LCNEC should be included in the differential diagnosis in cases of rapidly growing tumors of the uterine corpus.


Patterned regeneration of internal femoral structures in the cockroach, Periplaneta americana L.
The morphology of the nerve and tracheal supply to the extensor tibiae muscle in normal legs was compared to that in regenerate legs. In normal femurs, the extensor nerve and trachea extend along the posterior surface of the extensor muscle. The nerve and trachea are closely associated and branch coincidently at regular intervals. In regenerate femurs, the nerve and trachea are not closely associated with each other, and both structures differ from normals in their branching patterns. The results suggest that tissue level interactions during regeneration differ from those during embryogenesis.


An Ultrafast Air Self-Charging Zinc Battery.
Air self-charging power systems possess the capability of energy harvesting, conversion, and storage simultaneously. However, in general, their self-charging rate is slow and the batteries cannot be oxidized to the fully charged state due to the weak oxidizability of O2 . Herein, an ultrafast air self-charging aqueous zinc battery is designed by constructing a polyaniline@Pt/C (PANI@Pt/C) composite cathode. The introduction of Pt/C catalyst endows the redox reaction between PANI and O2 with fast reaction kinetics and extended redox potential difference. Therefore, the self-charging rate of the Zn/PANI@Pt/C batteries is effectively accelerated and they can be self-charged to fully charged state. Furthermore, the PANI can be recharged by O2 simultaneously during discharging process to compensate the consumed electrical energy, achieving prolonged energy supply. In addition, the PANI@Pt/C cathodes can be directly used as the cathodes of flexible self-charging zinc batteries due to their excellent mechanical properties. As a proof of concept, flexible soft-packaged Zn/PANI@Pt/C batteries are fabricated and displayed stable electrochemical performance and self-rechargeability even at different bending states. A route is provided here to design ultrafast chemical self-charging energy storage devices and the horizons of flexible energy storage devices are broadened.


Overexpression of NAC1 confers drug resistance via HOXA9 in colorectal carcinoma cells.
Colorectal carcinoma (CRC) is one of the most common types of malignancy worldwide. Recently, neoadjuvant chemotherapy has become an important treatment strategy for CRC. However, treatment frequently fails due to the development of chemoresistance, which is a major obstacle for positive prognosis. However, the underlying mechanisms of chemoresistance remain unclear. The present study assessed the functions of nucleus accumbens‑associated protein 1 (NAC1), an important transcriptional regulator, in CRC progression. Reverse transcription‑quantitative polymerase chain reaction, western blot analysis and immunohistochemistry were performed to detect the expression levels of NAC1. It was identified that NAC1 was significantly overexpressed in CRC compared with non‑tumorous tissues, indicating an oncogenic role. Following this, gain and loss of function analyses were performed in vitro to further investigate the function of NAC1. Cell viability and caspase‑3/7 activity assays were used to assess chemotherapy‑induced apoptosis. These results indicated that overexpression of NAC1 in CRC cells increased resistance to chemotherapy and inhibited apoptosis. Additionally, RNA interference‑mediated knockdown of NAC1 restored the chemosensitivity of CRC cells. Furthermore, mechanistic investigation revealed that NAC1 increased drug resistance via inducing homeobox A9 (HOXA9) expression, and that knockdown of HOXA9 abrogated NAC1‑induced drug resistance. In conclusion, the results of the present study demonstrated that NAC1 may be a critical factor in the develo-pment of chemoresistance, offering a potential novel target for the treatment of CRC.


Knowledge, Attitudes and Practices of Dental Hygienists Regarding Diabetes Risk Assessments and Screenings.
Purpose: Untreated and poorly controlled diabetes causes increased levels of blood glucose associated with poor periodontal disease outcomes. Dental hygienists can play a significant role in screening patients for diabetes mellitus, leading to referral and early diagnosis. The purpose of this study was to determine the knowledge, attitudes, practices, and barriers faced by clinical dental hygienists regarding diabetes risk assessment and screenings.Methods: A mixed method design was used with a convenience sample of dental hygienists in clinical practice (n=316). A 32 item, electronic survey was validated at item-level, and participants were recruited through multiple dental hygiene Facebook groups. Descriptive statistics were used to analyze the data. The survey also included two open-ended attitude questions that were interpreted using thematic analysis to pinpoint common patterns within the data.Results: Dental hygienists had high knowledge scores regarding diabetes and oral health, although many were unaware of their states' specific statutes and regulations for screening practices. Nearly all (95.9%), were likely to educate and refer patients (82%), although fewer than half (40.9%), were likely to perform chairside screening for diabetes. Emergent themes for barriers to screening were time, money, patient acceptance/willingness, lack of education, not having the proper tools, and states' rules and regulations.Conclusion: Despite high knowledge scores regarding diabetes and oral health, there is a gap in regards to dental hygienists' willingness to perform diabetes screenings in a clinical setting. Dental hygienists should be capable of integrating chairside diabetes screening practices into the process of care with proper training.


Postpartum quality improvement strategy for increasing long-acting contraception uptake at a University Hospital in Haiti.
To address the gap in the uptake of long-acting contraception (LAC) methods among high-risk postpartum women who fail to return for a family planning method at HôpitalUniversitaire de Mirebalais in the Central Plateau Department of Haiti, contraceptive implant trainings were held for providers on the Labour and Delivery, Post-Partum and Internal Medicine inpatient wards. A very high maternal mortality rate affects large numbers of women in Haiti; however, contraceptive use can reduce maternal mortality significantly. A quality improvement strategy to offer LAC methods to immediate postpartum women at a University Hospital in rural Haiti was initiated in March 2016. This new strategy produced an average improvement from 5% to 32% of women delivering at the hospital, accepting a long-acting method (including bilateral tubal ligations) by the end of the project and which has proved sustainable at an average of 20% to date.


Transforming growth factor-beta inhibits Leydig cell steroidogenesis in primary culture.
The effects of transforming growth factor (TGF) on Leydig cell steroidogenesis in primary culture were investigated. Basal testosterone levels were 3.7 +/- 0.54 ng/ml (mean +/- SE, N = 7). In the presence of hCG (10 ng/ml), testosterone levels increased to 22.77 +/- 3.05 ng/ml. TGF-beta caused a dose dependent inhibition of hCG-stimulated testosterone formation but without effects on basal levels. TGF-beta also inhibited 8-bromo cyclic AMP-induced testosterone formation and hCG-stimulated cyclic AMP formation. In contrast, TGF-alpha had no effect on either basal or hCG-stimulated testosterone formation and did not modify the inhibitory effect of TGF-beta. Present study indicates that TGF-beta can modulate Leydig cell steroidogenesis.


Lignification in trees: indication of exclusive peroxidase participation.
Syringaldazine did not turn purple on cross sections of tree branches or saplings or on cambial tissue cultures unless hydrogen peroxide was added; this indicated the absence of laccase but presence of peroxidase in lignifying cells. Peroxidase, therefore, apparently is the only en enzyme that polymerizes p-coumaryl alcohols to lignin in trees.


Neurobrucellosis Presenting with Unilateral Abducens Nerve Palsy.
One of the rare complications of brucellosis is neurobrucellosis. There have been numerous reports showing clinical forms of brucellosis affecting CNS, such as cranial nerve involvement, myelitis, vascular disease, radiculoneuritis, meningitis, meningoencephalitis, and demyelinating disease. In this case report, we introduce a 2.5 yr old girl with unilateral abducens nerve palsy referred to Baghiyatallah Hospital Outpatient Clinic, Tehran, Iran in June 2015.


Pilot study of the implementation of G8 screening tool, Cognitive screening assessment and Chemotherapy Toxicity assessment in older adults with cancer in a Tertiary University Hospital in Ireland.
Comprehensive geriatric assessment (CGA) is recommended by international guidelines prior to initiation of systemic anti-cancer treatment (SACT). In practice, CGA is limited by time constraints, lack of resources and expert interpretation. The primary objective of this pilot study was to establish the prevalence of frailty (assessed by G8), cognitive impairment (assessed by Mini-Cog), and risk of chemotherapy toxicity (assessed by CARG Chemo-Toxicity Calculator) among patients (pts) ≥65 years commencing SACT. We selected these three screening tools due to the ease of conducting them in a busy outpatient setting. In addition, they have been validated to predict frailty and risk of toxicity from SACT among older adults with cancer. Eligible participants were identified from medical oncology clinics. Assessments were conducted in an outpatient setting by treating physicians. Pt records were reviewed to gather demographic and cancer details. Statistical analyses were conducted using SPSS statistical software. Sixty-three participants were enrolled. The mean age of participants was 73yrs (range=65-88). Thirty-three (52.4%) were female and 30 (47.6%) were male. The majority (n=38, 60.3%) had metastatic cancer. The mean G8 score was 11.9 (range=6-19). Eighty-three percent had a G8 score ≤14. Mini-Cog was positive in 13 pts (21%). The mean CARG score was 7.5 (range=0-16), and 80% had a risk of at least 50% grade ≥3 toxicity. Of these, 48 (76.2%) received chemotherapy and 15 (23.8%) received non-cytotoxic SACT. In multi-variate analyses, age, cancer type, treatment type, and disease stage did not impact G8, Mini-Cog, or CARG scores. Our study has several limitations but suggests that the majority of older adults with cancer would qualify for formal CGA assessment. The risk of high-grade toxicity from SACT is substantial in this cohort. Chronological age was not found to negatively impact pts' frailty, cognition, or risk of toxicity.


Functionalized cyclobutenes via multicomponent thermal [2 + 2] cycloaddition reactions.
[reaction: see text] Enamine [2 + 2] cycloadditions can be achieved in useful yields simply by stirring a mixture of an aldehyde, diethylamine, a dialkyl fumarate, and potassium carbonate in acetonitrile at 25 degrees C, conditions that are compatible with the presence of a potential leaving group on the beta-position of the intermediate enamine. Methylation and elimination of the product cyclobutanes completes a mild nonphotochemical route to functionalized cyclobutenes.


Danish Breast Cancer Cooperative Group (DBCG). A description of the register of the nation-wide programme for primary breast cancer.
An account of the criteria for protocol allocation and of the various treatments in the DBCG programme is given together with some numerical representations. Furthermore the article explains how the DBCG programme has been run, including its randomization. Finally there is a description of the calculation of recurrence-free survival and survival. It is concluded that in the nation-wide programme there are only minor methodological errors, and that the conclusions based on the therapeutic outcome of the different therapies are reliable.


Collagen degradation by inflammatory phagocytes.
Inflammatory phagocytes are frequently found in the osteoarthritic joint. Current models of the pathogenesis of osteoarthritis (OA) would indicate that proteolytic modification of the cartilage extracellular matrix is important in the development of irreversible joint destruction. Neutrophils and macrophages contain collagenolytic proteinases with different substrate specificity and which are capable of degrading native collagens which are present in articular cartilage. The biochemical nature of these proteinases is discussed. Inflammatory phagocytes may contribute to the process of joint destruction in OA.


Time-resolved fluoroimmunoassay compared with virus isolation for rapid detection of respiratory syncytial virus in nasopharyngeal aspirates.
Two monoclonal antibodies against two distinct conserved epitopes of the respiratory syncytial virus (RSV) nucleocapsid protein were used in a direct time-resolved fluoroimmunoassay (TR-FIA) for the detection of RSV antigens in nasopharyngeal aspirates. The capture antibody was adsorbed to the solid phase of microdilution strip wells, and the indicator antibody was labeled with a europium chelate. Specimens and label were incubated simultaneously for 1 h at 37 degrees C in the coated wells. After the test samples were washed, fluorescence enhancement solution was added, strips were shaken, and the time-resolved fluorescence was measured. The test procedure took only 75 min, and the total time for 20 specimens, with pretreatment by sonication, was 2 to 3 h. We prospectively evaluated the detection of RSV in nasopharyngeal aspirates of pediatric patients by TR-FIA and by virus isolation in human diploid fibroblasts. TR-FIA detected 40 of 42 isolation-positive specimens. Nine additional isolation-negative specimens were positive by TR-FIA; all proved to be true positives by a blocking-type confirmatory assay. The sensitivity, specificity, positive predictive value, and negative predictive value for TR-FIA were 95, 96, 82, and 99%, respectively, of the values obtained by virus isolation and 96, 100, 100, and 99%, respectively, of the values obtained by virus isolation and the confirmatory assay.


[The diagnosis of morbus maculosus in horses].
This is a review on Morbus maculosus equorum (purpura haemorrhagica) on the base of literature data and of a case report on 13 own patients. It is shown, that the clinical picture of this disease has not changed within the last 150 years. Clinical main symptoms are haemorrhagic diathesis (petechiae, ecchymosis, suggillations) as well as peripheral edema and fever. The main haematological findings are neutrophilia, mostly going along with shift to the left and lymphopenia. In the last few years thrombocytopenia was also described in some cases. Basic therapeutics are glucocorticoids and penicillins. Problems of differential diagnosis and of nomenclature are discussed.


Function, target-cell preference and cell-surface characteristics of herpes-simplex virus type-2-induced non-antigen-specific killer cells.
Wild-type and congenitally athymic nude mice injected with herpes-simplex virus type 2 (HSV 2) responded with a local outburst of non-antigen-specific killer cells masking any virus-specific response. Cytolytic activity could be assayed on mouse-tumor cell lines and on syngeneic or allogeneic non-transformed cells from various sources. Some of the tumor cell lines and proteose-peptone-induced peritoneal exudate cells were lysed more efficiently after infection with either HSV 2, vaccinia or influenza A virus. Preference for virus-infected target cells was already expressed 24 hours after HSV-2 injection. Killing activity was not H-2-restricted, not complement- or immunoglobulin-dependent and did not involve Fc receptors. The cytotoxic cells were non-adherent and could be shown to express Thy1, Quat4, and Quat4 cell-surface antigens. They lacked immunoglobulin and Lyt1: Lyt2,3 determinants. The functional and serological characteristics identify the HSV-2-induced cytolytic cells as natural killer (NK) cells. The potential importance of this cell population for natural resistance will be discussed.


Identification of activated matrix metalloproteinase-2 (MMP-2) as the main gelatinolytic enzyme in malignant melanoma by in situ zymography.
The involvement of extracellular matrix-degrading enzymes, such as matrix metalloproteinases and serine proteases, during tumour progression and metastasis is well established. In particular, the activation of pro-matrix metalloproteinase (MMP)-2 on the surface of malignant cells by membrane-bound MT1-MMP has been shown to contribute to the invasive abilities of various tumours. This study presents evidence that in tissue of malignant melanomas, increased effective gelatinolytic activity is mainly located at sites where melanoma cells interact with the surrounding extracellular matrix. Forty-one primary melanomas (30 superficial spreading and 11 nodular type) and six lymph node metastases were investigated by a modified technique of gelatin in situ zymography. This technique localizes areas of effective proteolytic activity within tissue sections. In 28/41 (68%) primary melanomas and in 6/6 (100%) metastases, considerable proteolysis was detected at the invading part of the tumour and especially at sites of tumour-stroma interactions, whereas no or only weak proteolytic activity was localized within the centres of solid nests of tumour cells. Zymographic analysis of extracts obtained from different areas of microdissected melanoma specimens identified activated MMP-2 as the enzyme responsible for this activity. Immunohistochemical analysis detected strong staining for MMP-2 and MT1-MMP, even in areas in which no proteolytic activity was found by in situ zymography, emphasizing the importance of more functional techniques for the investigation of balanced proteolytic systems. This technology makes it possible to draw conclusions regarding the balance between activated proteases and inhibitors, which are frequently found to be present together in close proximity in vivo.


CLONAL-DIVERSITY PATTERNS AND BREEDING-SYSTEM VARIATION IN DAPHNIA PULEX, AN ASEXUAL-SEXUAL COMPLEX.
Some individuals of the cladoceran crustacean, Daphnia pulex, reproduce by cyclic parthenogenesis, while others are obligate parthenogens. Cyclic parthenogenesis is the primitive breeding system; the transition to obligate parthenogenesis has been linked to sex-limited meiosis-suppression. Detailed study of patterns of breeding-system distribution and clonal diversity is justified because D. pulex is the first species in which the loss of sex has been related to this mechanism. The present study investigated the genotypic characteristics of 10 D. pulex populations from each of 22 sites in the Great Lakes watershed. This analysis revealed that populations reproducing by cyclic parthenogenesis were uncommon and restricted to southern sites. Most populations reproduced by obligate parthenogenesis, with the electrophoretic survey revealing an average of three clones per pond and 145 unique clones over the watershed. A combinatorial analysis was used to examine the relationships between clone discovery in the asexual populations and both sample size and genetic-sampling intensity. This analysis showed that the few clones found in individual ponds were readily discriminated, while diversity on a regional scale was underestimated. These methods provide a quantitative basis for assessing the level of clonal diversity in asexual populations and in asexually transmitted segments of the genome.


Simultaneous determination of the repertoire of classical neurotransmitters released from embryonal carcinoma stem cells using online microdialysis coupled with hydrophilic interaction chromatography-tandem mass spectrometry.
Dynamic, continuous, and simultaneous multi-analysis of transmitters is important for the delineation of the complex interactions between the neuronal and intercellular communications. But the analysis of the whole repertoire of classical transmitters of diverse structure is challenging due to their different physico-chemical properties and to their high polarity feature which leads to poor retention in traditional reversed-phase columns during LC-MS analysis. Here, an online microdialysis coupled with hydrophilic interaction chromatography-tandem mass spectrometry (online MD-HILIC-MS/MS) detection method was developed for the simultaneous measurement of the repertoire of classical transmitters (acetylcholine, serotonin, dopamine, norepinephrine, glutamate, GABA, and glycine). Stable isotope labeled internal standards and authentic matrix have been applied to guarantee reliable results. The method was successfully employed to reveal the characteristics of transmitter release from embryonal carcinoma stem cells. The method features simple procedure (no sample preparation), high recovery (≥ 73%), high accuracy (89.36%≤RE≤116.89%), good reproducibility (2.18%≤ RSD ≤14.56%), and sensitive limits of detection (2 pg for acetylcholine, serotonin, and glutamate, 10 pg for dopamine, norepinephrine, GABA, and glycine). It can be flexibly applied to determine the contents of the classical transmitters in other biological matrix samples with minor changes.


Early tracheostomal healing in rabbits with use of various tracheal incisions.
Various tracheal incisions (vertical, horizontal, or window) are used by surgeons for creation of a tracheostomy. The inflammatory response and healing varies with each incision and may contribute to complications such as tracheal stenosis. This study evaluates the effect of these tracheotomies on early stomal wound healing in a rabbit model. Male juvenile New Zealand rabbits underwent tracheotomy, with each animal randomized to the type of tracheal incision used (vertical, horizontal, or window). After recovery, they were killed on postoperative days 2, 4, 6, and 8, with tissue removed for histologic examination. Paraffin-embedded stomal sections were analyzed quantitatively for amounts of granulation tissue, fibrosis, and epithelization. Groups were compared statistically using chi-square, ANOVA, Spearman's rho, and Mann-Whitney U tests with p less than 0.05 considered significant. Fibrosis was significantly increased in the vertical and horizontal groups when compared with the window group. This increase was statistically significant between postoperative days 2 and 4 (p < 0.05). The amount of granulation tissue was only significantly increased in the window group, whereas no difference was seen in the rate at which epithelization occurred with the various incisions. Vertical and horizontal tracheal wounds have less granulation tissue formation and more fibrosis compared with window tracheotomies during initial wound healing. This could lead to a "safer" tracheostomy tract in the early postoperative period.


The Evolution of Insulation Performance of Fiber-Reinforced Silica Aerogel after High-Temperature Treatment.
Fiber-reinforced silica aerogel blankets (FRABs) are an important high-temperature thermal insulation material for industry applications that have emerged in recent years. In order to better understand the performance evolution of FRABs at high temperatures, the effect of heat treatment at different temperatures on the performance of FRABs as well as their base material, hydrophobic silica aerogel powder and glass wool, was investigated. The property evolution of the hydrophobic silica aerogel powder showed two stages with an increase in thermal treatment temperatures. The skeleton structure of the aerogel remained unchanged, but the residual organic chemicals, such as hydrophobic groups, were decomposed when the heat treatment temperature was lower than 400 °C. Above 400 °C, the skeleton began to shrink with the increase in temperature, which led to an increase in thermal conductivity. The structure and room-temperature thermal conductivity of the glass wool blanket were less affected by a heat treatment temperature under 600 °C. Therefore, the performance degradation of FRABs at high temperatures is mainly due to the change in the aerogel powder. The insulation performance of the glass wool and FRAB at high temperatures was studied using a heating table which was designed to simulate working conditions. The energy savings of using FRABs instead of glass fiber were calculated and are discussed here.


A three-dimensional Magnetic Resonance Spin Tomography in Time-domain protocol for high-resolution multiparametric quantitative magnetic resonance imaging.
Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) is a multiparametric quantitative MR framework, which allows for simultaneously acquiring quantitative tissue parameters such as T1, T2, and proton density from one single short scan. A typical two-dimensional (2D) MR-STAT acquisition uses a gradient-spoiled, gradient-echo sequence with a slowly varying RF flip-angle train and Cartesian readouts, and the quantitative tissue maps are reconstructed by an iterative, model-based optimization algorithm. In this work, we design a three-dimensional (3D) MR-STAT framework based on previous 2D work, in order to achieve better image signal-to-noise ratio, higher though-plane resolution, and better tissue characterization. Specifically, we design a 7-min, high-resolution 3D MR-STAT sequence, and the corresponding two-step reconstruction algorithm for the large-scale dataset. To reduce the long acquisition time, Cartesian undersampling strategies such as SENSE are adopted in our transient-state quantitative framework. To reduce the computational burden, a data-splitting scheme is designed for decoupling the 3D reconstruction problem into independent 2D reconstructions. The proposed 3D framework is validated by numerical simulations, phantom experiments, and in vivo experiments. High-quality knee quantitative maps with 0.8 × 0.8 × 1.5 mm3 resolution and bilateral lower leg maps with 1.6 mm isotropic resolution can be acquired using the proposed 7-min acquisition sequence and the 3-min-per-slice decoupled reconstruction algorithm. The proposed 3D MR-STAT framework could have wide clinical applications in the future.


Methods for extending working distance using modified photonic crystal for near-field lithography.
Near-field lithography has evident advantages in fabricating super-resolution nano-patterns. However, the working distance (WD) is limited due to the exponential decay characteristic of the evanescent waves. Here, we proposed a novel photolithography method based on a modified photonic crystal (PC), where a defect layer is embedded into the all-dielectric multilayer structure. It is shown that this design can amend the photonic band gap and enhance the desired high-kwaves dramatically, then the WD in air conditions could be extended greatly, which would drastically relax the engineering challenges for introducing the near-field lithography into real-world manufacturing applications. Typically, deep subwavelength patterns with a half-pitch of 32 nm (i.e.,λ/6) could be formed in photoresist layer at an air WD of 100 nm. Moreover, it is revealed that diversified two-dimensional patterns could be produced with a single exposure using linear polarized light. The analyses indicate that this improved dielectric PC is applicable for near-field lithography to produce super-resolution periodic patterns with large WD, strong field intensity, and great uniformity.


Case report. Post-traumatic tibial recurvatum: resolution with growth.
The outcome of proximal tibial fractures in children is often complicated by the development of malalignment. Progressive valgus deformity is frequently seen, but is known to correct spontaneously in a high proportion of cases; however, recurvatum of the tibia usually requires surgical intervention. We present a child with a proximal tibial metaphyseal fracture who developed increasing tibial recurvatum which corrected spontaneously.


J Freezing and Hund's Rules in Spin-Orbit-Coupled Multiorbital Hubbard Models.
We investigate the phase diagram of the spin-orbit-coupled three orbital Hubbard model at arbitrary filling by means of dynamical mean-field theory combined with the continuous-time quantum Monte Carlo method. We find that the spin-freezing crossover occurring in the metallic phase of the nonrelativistic multiorbital Hubbard model can be generalized to a J-freezing crossover, with J=L+S, in the spin-orbit-coupled case. In the J-frozen regime the correlated electrons exhibit a nontrivial flavor selectivity and energy dependence. Furthermore, in the regions near n=2 and n=4 the metallic states are qualitatively different from each other, which reflects the atomic Hund's third rule. Finally, we explore the appearance of magnetic order from exciton condensation at n=4 and discuss the relevance of our results for real materials.


[Alkylphenols in the environment: a risk for human health?].
Endocrine Disrupting Chemicals (ECD) are a class of chemical compounds widely utilized for many industrial and civil applications and, consequently, widely diffused in the environment. Due to their chemical-physical characteristics, ECD may interfere with several endocrine functions in humans. Alkylphenols (APs), mainly produced by biodegradation of alkylphenols polyethoxylates surfactants, are a relevant group of ECD, both for their environmental diffusion and demonstrated estrogenic activity. Aim of this paper is to assess the potential risk of exposure to APs for humans, on the basis of the available data in literature concerning APs: environmental levels, accumulation in sediments and biota, toxicological effects on experimental animals.


Subchronic toxicity studies of the ethanolic root extract of Croton zambesicus.
Subchronic toxicity study of the crude root extract of Croton zambesicus (27-81 mg/kg), which is used traditionally as malarial remedy, was carried out in rodents to evaluate the safety profile. Effect of the extract on body weights, haematological indices as well as liver and kidney functions and histology of various organs were investigated. Subchronic treatment of rats for 21 days caused comparable increase in body weights of rats in extract treated and control groups. The extract caused a dose-dependent increases in RBC, PCV, Hb, WBC, bleeding time and clotting time. The increases were only significant (P<0.05) at the highest dose of the extract (81 mg/kg) for RBC and WBC when compared to control. There was no significant (P>0.05) differences in the means of other haematological parameters in the extract treated groups compared to control. The extract caused significant (P<0.05-0.01) increases in the level of serum total protein, ALT, ALP, total bilirubin and total cholesterol. The was no significant (P>0.05) changes in the levels of albumin and AST. The extract did not produce any significant (P>0.05) changes in the mean concentrations of urea, creatinine, Na+, K+, and Cl- ions of rats in the extract treated groups compared to that of control. Histopathologic analysis of the vital organs revealed no significant lesions in the brain, liver, kidney, heart, spleen, ovary, and testis. The results suggest the extract to be safe when taken orally though with an insignificant effect on the liver.


Is there an association between Vogt-Koyonagi-Harada syndrome and intracranial meningioma?
The authors report a case of Vogt-Koyonagi-Harada syndrome associated with intracranial meningioma. The authors discuss the HLA-DR4 gene as a common and causative factor in both conditions. This case report draws attention to the possibility of a causative association between intracranial meningioma and Vogt-Koyonagi-Harada syndrome, a rare but potentially blinding condition if not detected and treated early.


[Preoperative or palliative embolization of renal tumors].
This study evaluates our experience of renal preoperative or palliative embolization in 72 patients with a localized renal carcinoma or a metastatic disease. Angio-infarction of a renal malignant neoplasm is a helpful procedure to reduce the tumoral vascularization before an operation and to palliate symptoms and paraneoplastic syndromes of a metastatic disease with a very low morbidity.


Reproduction ecology of the recently invasive snake Hemorrhois hippocrepis on the island of Ibiza.
Knowing the causes of biological invasion success can be relevant to combat future invasive processes. The recent invasion of the horseshoe whip snake Hemorrhois hippocrepis on the island of Ibiza provides the opportunity to compare natural history traits between invasive and source populations, and to unravel what makes this snake a successful invader that is threatening the only endemic vertebrate of the island, Podarcis pityusensis. This study compares the basic reproductive traits of mainland native and invasive populations of the snake. Our results revealed that invasive populations were characterized by female maturity at a smaller size, extended reproductive period, and much lower reproduction frequency compared to the native population. In contrast, some major reproductive traits-the abdominal fat body cycle, clutch size, hatchling body size, and hatchling body condition, did not differ between the two populations. Some of these results must reflect the environmental differences in the recently invaded island with respect to the source area, and overall plasticity of reproductive traits. Plasticity is evolutionarily interesting, and may aid the successful growth of this species in their invasiveness of Mediterranean islands like Ibiza. The most significant finding is that this expression of phenotypic plasticity occurred rapidly in this invasive population, within a period of 14 years maximum. Our results on the reproduction ecology of the invasive population were not conclusive regarding the factors determining the invasiveness of the snake and pointed to alternative causes.


Distribution and immunocytochemical colocalization of peptide YY and enteroglucagon in endocrine cells of the rabbit colon.
Peptide YY (PYY) is 36 amino acid peptide hormone present in high concentrations in the colon where it is colocalized with enteroglucagon in L cells. A selective release of PYY and enteroglucagon from the rabbit colon has been described, raising the question of the exact localization of the two hormones in the rabbit colon. We have therefore examined the distribution of PYY and enteroglucagon as well as somatostatin in the rabbit colon using RIA and electron microscopic immunocytochemistry. PYY and enteroglucagon were present in high concentrations in the colorectal mucosa with peak concentrations in the left colon (PYY 544 +/- 87 pmol/g, enteroglucagon 152 +/- 10 pmol/g). Electron microscopic examination of the colonic mucosa demonstrated a large population (65%) of EC cells, a moderate population (30%) of L cells, and a small population (5%) of D cells. By immunogold labeling serotonin was localized to EC cells, PYY and enteroglucagon to L cells, and somatostatin to the D cell. Double immunogold labeling revealed PYY and enteroglucagon in all L cells examined (93 cells). A majority of the secretory granules (83%) were labeled by both PYY and glucagon antibodies, whereas a significant portion of granules (15%) was labeled by the PYY antibodies alone. The results demonstrate that L cells are the sole source of PYY and enteroglucagon in the rabbit colon and that L cells contain different populations of secretory granules. The existence of different secretory granules in L cells may explain the selective release of PYY and enteroglucagon observed in the rabbit colon.


Pattern of mandibular third molar impaction and its association to caries in mandibular second molar: A clinical variant.
Caries in second molar is common and prophylactic removal of the impacted teeth may be considered appropriate. Caries detection and restoration can be difficult and a restored second molar can undergo recurrent caries if the third molar is not removed prophylactically. In this study, the clinical findings related to impaction and its association with angular position and depth of impacted third molar were evaluated. A retrospective descriptive study was carried out among the patients visiting the outpatient, department of Dentistry, RIMS, Ranchi. The clinical examination, periapical radiographs and Pre-op OPG were taken. Teeth positions were analyzed by Pell and Gregory and Winter classification. The angulation and depth of mandibular third molar impaction and caries in the second molar with the eruption status of the mandibular third molar was determined. A total of 200 patients were included in the study between age group 17-45 years. Majority of the Patients reported to the hospital with complaints of decayed tooth (66%) and pain (59%). The most common third molar impaction was mesioangular followed by distoangular. A statistically highly significant difference (P = 0.001) was obtained with the presence of caries in second molar adjacent to mesioangular third molar in class I and level B. According to this study, pattern of mandibular third molar impaction is in association to caries in mandibular second molar. More future studies are needed. In addition, the results of the present study can be used to screen and inform the patients about the possibility of caries in relation to third molar mandibular impaction.


Localization and Possible Function of P2X Receptors in Normal and Diseased Retinae.
Purines, when present in the extracellular space, can mediate fast neurotransmission in the retina and central nervous system. Over the last decade there has been emerging evidence for the expression of P2X and P2Y receptors in a range of retinal neuronal subtypes. These results have highlighted important roles for purines in modulating specific retinal circuits, including the rod pathway and amacrine cell circuits. Traditionally, synaptic release of adenosine triphosphate (ATP) involves the novel anion vesicular nucleotide transporter, VNUT, which has recently been identified in a single wide-field amacrine cell population. In addition, nontraditional, conductive mechanisms of release have also been described in the retina. In the synapse, the enzymes involved in rapid degradation of purines are present in both plexiform layers of the retina. A role for P2X receptors in retinal diseases has also emerged recently. High concentrations of ATP lead to photoreceptor loss, through mechanisms involving P2X7 receptors. In addition, activation of P2X7 receptors is associated with activation of the inflammasome, a protein complex important for the release of proinflammatory cytokines. P2X receptors, especially P2X7, are emerging as targets to combat retinal disease.


N-acetylcysteine administration improves platelet aggregation in hypoxia-reoxygenation injury.
Platelet activation and dysfunction occurs upon hypoxia and reoxygenation and is associated with oxygen free radical generation and matrix metalloproteinase (MMP) -2 and -9 activation. The effect of NAC on platelet function in newborn piglets after asphyxia was studied along with plasma MMP-2 and MMP-9 activities. Piglets (1-4 day, 1.4-2.2 kg) were acutely instrumented for the induction of normocapnic hypoxia (10-15% O2) for 2hr followed by reoxygenation for 1hr with 100% O2 and then 3hr with 21% O2. Animals were randomized to 3 groups (n = 6 each); sham, control and treatment with NAC upon reoxygenation (150 mg/kg i.v. bolus and 100 mg/kg/hr i.v. infusion). Platelet count and collagen (2, 5 and 10 microg/mL)-stimulated whole blood aggregation were studied at baseline and after 4hr reoxygenation. Plasma MMP -2 and -9 activities were analyzed by gelatin zymography. Piglets had severe hypoxia (PaO2 32 +/- 2 vs. 65 +/- 2 mmHg sham; p < 0.05) and metabolic acidosis (pH 6.96 +/- 0.04 vs. 7.33 +/- 0.01 sham; p < 0.05). At 4hr of reoxygenation, platelet counts decreased similarly in all experimental groups, and no animal had a platelet count < 100 x 10(9)/L. Platelet aggregation was significantly reduced with a rightward shift of concentration-response curve. NAC treatment improved platelet aggregatory function at 4hr of reoxygenation (p < 0.05). Plasma MMP-9, but not MMP-2, activities were increased with NAC treatment (147 +/- 19 vs. 51 +/- 20 and 42 +/- 11 AU of control and sham, respectively, p < 0.001). In a newborn piglet model of asphyxia and reoxygenation, NAC treatment effectively improves platelet aggregation when given upon resuscitation.


Infarct growth velocity predicts early neurological outcomes in single subcortical infarction.
In single subcortical infarction (SSI), changes in lesion size are a major determinant of early neurological deterioration. We evaluated the association between END and infarct growth velocity (IGV) in patients with SSI. We included consecutive patients with SSI who underwent MRI within 24 h of symptom onset between 2010 and 2020. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score. IGV was calculated using the following formula: IGV (mL/h) = diffusion-weighted imaging volume (mL)/time to MRI (h). A total of 604 patients with SSI were evaluated. Multivariable logistic regression analysis showed that IGV remained significant after adjusting for confounders (aOR = 1.34, 95% CI 1.12-1.61). In a subgroup analysis based on the type of SSI, only patients with distal SSI showed an association between IGV and END (aOR = 1.64, 95% CI 1.24-2.16). In patients with proximal SSI, IGV did not show any statistical association with END. In conclusion, IGV was positively associated with END in patients with SSI. IGV should be interpreted differently in clinical settings depending on the location of the SSI lesion.


Modeled structure of trypanothione reductase of Leishmania infantum.
Trypanothione reductase is an important target enzyme for structure-based drug design against Leishmania. We used homology modeling to construct a three-dimensional structure of the trypanothione reductase (TR) of Leishmania infantum. The structure shows acceptable Ramachandran statistics and a remarkably different active site from glutathione reductase(GR). Thus, a specific inhibitor against TR can be designed without interfering with host (human) GR activity.


Multiple sclerosis and Hashimoto thyroiditis: two cases.
Multiple sclerosis (MS) occurs with immune-mediated mechanisms, but its pathogenesis is not accurately known. The coexistence of MS with other autoimmune diseases has been reported. The hypothesis that MS coexists with other autoimmune diseases has been supported by the reported association of MS with type I diabetes mellitus and inflammatory disorders. Even though there have been only rare reports of associations between Hashimoto thyroiditis and MS, this association is important for its clinical and therapeutic aspects. Proximal muscle weakness, myalgia, and fatigue are symptoms that are common in both MS and hypothyroidism. When MS patients demonstrate these symptoms, thyroid function tests should be performed. The thyroid hormone levels of MS patients being treated with interferon-beta and Campath-1H also should be monitored. The authors report the clinical data of 2 definite MS patients who also fulfilled criteria for Hashimoto thyroiditis.


Polyethyleneimine-impregnated alkali treated waste bamboo powder for effective dye removal.
In this study, the polyethyleneimine (PEI) modified waste bamboo powder (WBP-Na-PEI) was successfully prepared and applied to adsorbing Congo red (CR) dye from aqueous solution. The obtained materials were characterized by field emission scanning electron microscope, X-ray diffraction, Fourier transform-infrared, and thermogravimetric analysis. The results showed that WBP-Na-PEI(1.8 K-5) was synthesized successfully and PEI uniformly covered the WBP-Na-PEI(1.8 K-5) surface. In the process of adsorption, four kinds of influencing factors were discussed, and the adsorption mechanisms such as kinetics, isotherm, thermodynamics were explored. The maximum adsorption capacity of WBP-Na-PEI(1.8 K-5) was 992.94 mg·g-1 at 298 ± 1 K, and the removal efficiency was over 98%. Pseudo-first-order, pseudo-second-order and intra-particle diffusion models were studied, the results showed that the adsorption process conformed to the pseudo-second-order model, and the rate of this process was controlled by many steps. Furthermore, the removal efficiency of the adsorption kinetics reached 85% within 10 minutes. The results of the isotherm model and thermodynamics showed that the adsorption process was consistent with the Langmuir model and was mainly a spontaneous chemical endothermic process of monolayer. And the removal efficiency of the adsorbent reached 93% at the concentration of 400 mg/L, which can be expected to have a broad prospect in the treatment of CR industrial wastewater.


Effect of Lamisil and azole antifungals in experimental nail infection.
Onychomycosis is primarily caused by dermatophyte fungi but occasionally by yeasts and non-dermatophytic moulds. The aim of this study was to develop an in vitro model of nail invasion by dermatophytes, yeasts and non-dermatophytic moulds, and to provide an alternative system for studying the activity of different classes of antifungal drugs against fungi associated with onychomycosis. In the absence of extraneous nutrients, Trichophyton mentagrophytes was seen in electron microscopy to degrade completely healthy nail plate. Candida albicans germinated on nail fragments, but invasion of the nail plate was not seen. The mould Fusarium formed long channels through the matrix of the nail plate. Aspergillus versicolor appeared to penetrate the outer and intermediate surface of the nail plate only. Acremonium sp. and Scopulariopsis brevicaulis did not invade nail in this model. Exposure of nail fragments to terbinafine (0.25 mg/l for 3 h) inhibited invasion by T. mentagrophytes, C. albicans and the non-dermatophytic moulds. Itraconazole (0.25 mg/l for 3 h) prevented nail plate invasion by T. mentagrophytes, A. versicolor and Fusarium but did not totally inhibit the surface growth of Acremonium or S. brevicaulis. C. albicans grew in the presence of itraconazole. The results indicate that terbinafine is readily absorbed by the nail and that the drug is bio-available in nail keratin. A short exposure of nail to low concentrations of terbinafine acted as a barrier against fungal invasion. Itraconazole appeared to be effective against Trichophyton and some non-dermatophytic moulds.


Efficacy of Moxidectin Versus Ivermectin Against Strongyloides stercoralis Infections: A Randomized, Controlled Noninferiority Trial.
Infections with Strongyloides stercoralis are of considerable public health relevance. Moxidectin, a well-established drug in veterinary medicine under consideration for regulatory submission for the treatment of onchocerciasis, might serve as an alternative to the widely used ivermectin. We conducted an exploratory, randomized, single-blind trial to evaluate the efficacy and safety of moxidectin (8 mg) vs ivermectin (200 μg/kg) against S. stercoralis infections. Cure rate (CR) against S. stercoralis was the primary outcome. Safety and efficacy against coinfections with soil-transmitted helminths and Opisthorchis viverrini were secondary outcomes. Noninferiority required the lower limit of the 95% confidence interval (CI) of the differences in CRs not exceed 7 percentage points. A total of 127 participants were enrolled and randomly assigned to the 2 treatments whereby 1 participant per arm was lost to follow-up. We observed a CR of 93.7% (59/63) for moxidectin compared to 95.2% (59/62) for ivermectin. Differences between CRs were estimated as -1.5% percentage points (95% CI, -9.6 to 6.5), thus the lower limit of the CI exceeds the noninferiority margin of 7 percentage points. No side effects were observed. CRs against hookworm infection were 57% (moxidectin) and 56% (ivermectin). Low efficacy for both drugs against O. viverrini was observed. Moxidectin might be a safe and efficacious alternative to ivermectin for the treatment of S. stercoralis infection, given that only slight differences in CRs were observed. However, noninferiority could not be demonstrated. Larger clinical trials should be conducted once the drug is marketed. Current Controlled Trials: ISRCTN11983645.


Influence of fatty acids on energy metabolism. 2. Kinetics of changes in metabolic rates and changes in subcellular adenine nucleotide contents and pH gradients following addition of octanoate and oleate in perfused rat liver.
The uncoupling-like effect of fatty acids [ Scholz , R., Schwabe , U., and Soboll , S. (1984) Eur. J. Biochem. 141, 223-230] was further substantiated in experiments with perfused rat livers by two ways: firstly the kinetics of changes in metabolic rates (oxygen consumption, ketogenesis, fatty acid oxidation) were analysed; secondly subcellular contents of adenine nucleotides and pH gradients across the mitochondrial membrane were determined following fractionation of freeze-fixed and dried tissues in non-aqueous solvents. The following results were obtained. The relaxation kinetics of the increase in oxygen consumption following fatty acid infusion revealed two components, a rapid one with a half-time around 10 s and a slow one with a half-time of more than 100 s. The rapid component was similar to the kinetics of fatty acid oxidation (ketogenesis and 14CO2 production from labelled fatty acids) whereas the half-time of the slow component was in the range of half-times observed with the increase in oxygen consumption following addition of carbonylcyanide p-trifluoromethoxyphenylhydrazone. In the presence of fatty acids, the cytosolic ATP concentrations and ATP/ADP ratios decreased, whereas the corresponding parameters for the mitochondrial space were either increased (oleate) or decreased (octanoate). The effects of oleate were dependent on the albumin concentrations in the perfusate. The normally large difference between cytosolic and mitochondrial ATP/ADP ratios became smaller. Similar observations were obtained with uncoupling agents. The pH gradient across the mitochondrial membrane as calculated from the subcellular distribution of 5,5 dimethyl[2-14C]oxazolidine-2,4-dione was inversed following the addition of both carbonylcyanide p-trifluoromethoxyphenylhydrazone and fatty acids, i.e. the mitochondrial matrix became more acidic than the cytosol. The pH gradient was not affected when oleate was added in the presence of high albumin concentrations. The data support the hypothesis that the increase in hepatic oxygen consumption due to octanoate or oleate is, in part, caused by a mechanism similar to uncoupling of oxidative phosphorylation. This mechanism seems not to be an artifact of isolated systems; it may be of physiological importance for processes in which reducing equivalents are removed independently of the ATP demand of the hepatocyte.


Pedigree-Based Estimation of Reproductive Value.
How successful an individual or cohort is, in terms of their genetic contribution to the future population, is encapsulated in the concept of reproductive value, and is crucial for understanding selection and evolution. Long-term studies of pedigreed populations offer the opportunity to estimate reproductive values directly. However, the degree to which genetic contributions, as defined by a pedigree, may converge on their long-run values within the time frames of available data sets, such that they may be interpreted as estimates of reproductive value, is unclear. We develop a system for pedigree-based calculation of the expected genetic representation that both individuals and cohorts make to the population in the years following their birth. We apply this system to inference of individual and cohort reproductive values in Soay sheep (Ovis aries) from St Kilda, Outer Hebrides. We observe that these genetic contributions appear to become relatively stable within modest time frames. As such, it may be reasonable to consider pedigree-based calculations of genetic contributions to future generations as estimates of reproductive value. This approach and the knowledge that the estimates can stabilize within decades should offer new opportunities to analyze data from pedigreed wild populations, which will be of value to many fields within evolutionary biology and demography.


CORONARY EFFECT OF FIBRATES ON PROTEINS AND ENZYMES WHICH HYDROLYZE TRIACYLGLYCEROLS.
Clofibric acid derivatives called fibrates, are quite commonly used lipid-lowering drugs, so it is necessary to know beneficial and adverse effects of these compounds on the body. The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has concluded that benefits of four fibrates such as: bezafibrate, ciprofibrate, fenofibrate and gemfibrozil continue outweigh their risk in treatment of people with blood lipid disorders. According to recommendations of the CHMP fibrates should not be used as first-line drugs, except in patients with severe hypertriglyceridemia and patients who cannot use statins. In this paper, we focused on effect of clofibric acid derivatives on lipid metabolism, in particular on apoproteins and regulatory enzymes.


Steroidal or non-steroidal MRAs: should we still enable RAASi use through K binders?
Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients with chronic kidney disease and heart failure, but their use is limited in some patients by the development of hyperkalemia. The risk of hyperkalemia may differ between agents, with one trial showing lower risk of hyperkalemia with the novel non-steroidal MRA finerenone compared with steroidal MRA spironolactone. Novel potassium binders, including patiromer and sodium zirconium cyclosilicate, are available interventions to manage hyperkalemia and enable continuation of RAASi and MRAs in patients who could benefit from these treatments. These agents bind free potassium ions in the lumen of the gastrointestinal tract to prevent the absorption of dietary potassium and increase potassium secretion. Several studies showed that potassium binders are effective compared with placebo for preventing hyperkalemia or steroidal MRA discontinuation, but none has evaluated whether this strategy impacts clinically important endpoints such as cardiovascular events. Due to this and other limitations related to cost, clinical availability, pill burden and patient selection, alternative potential strategies to mitigate hyperkalemia may be more practical. Conservative strategies include increased monitoring and use of loop or thiazide diuretics to increase urinary potassium excretion. Non-steroidal MRAs may have a lower risk of hyperkalemia than steroidal MRAs and have stronger anti-inflammatory and anti-fibrotic effects with resultant reduced risk of kidney disease progression. Sodium-glucose cotransporter-2 inhibitors also decrease hyperkalemia risk in patients on MRAs and decrease cardiovascular events and kidney disease progression. These may be better first-line interventions to obviate the need for potassium binders and offer additional benefits.


Defining Health Across the Cancer Continuum.
Health is not defined by the absence of disease or suffering, but by response to a series of life events that can markedly alter the quality and quantity of life. Patients with cancer experience significant but dynamic physical, psychosocial, and financial challenges. With the increasing number of patients with early stage cancers transitioning to survivorship, there is a critical need to address health promotion and overall well-being. For those with advanced cancer, discussion about prognosis and early integration of palliative care can have a profound impact on the quality of life. Effective communication between healthcare providers and patients is important in aligning treatment recommendations with patient goals and preferences throughout cancer therapy. This review provides a dynamic definition of health and proposes actionable guidelines for health promotion at any point along the cancer continuum: survivorship after early cancer or when goals of care transition to improve quality at the end of life.


Associations between psychiatric home-visit nursing staff's exposure to violence and conditions of visit to community-living individuals with mental illness.
Psychiatric home-visit nursing is key for providing medical services to community-living individuals with mental illness in Japan. However, little is known about factors associated with encountering violent incidents among psychiatric home-visit nursing staff during visits. This cross-sectional study examined associations between staff's exposure to violence and their visit conditions reflecting characteristics of individuals with mental illness. Psychiatric home-visit nursing staff members completed a questionnaire regarding their exposure to violence during the past 12 months and their visits to individuals with 23 characteristics, comprising static (13 items; e.g., psychiatric diagnosis) and dynamic factors (10 items; e.g., hostility/anger). Forty (16.3%) of the 246 participants had experienced violence. Visits to individuals with four static factors (psychiatric diagnoses, i.e., Disorders of Adult Personality and Behavior or Mental Retardation, alcohol/drug abuse with psychiatric diagnoses, and history of violent behavior), and nine dynamic factors were significantly and positively associated with participants' violent experiences. In addition, regarding the static factors of Disorders of Adult Personality and Behavior and history of violent behavior, it was found that overlapping of specific dynamic factors (e.g. hostility/anger) were significantly associated with violent experiences. For visits with limited information on individuals (e.g., initial visits), having information on their static factors could help prevent violence. Additionally, it is important to create educational programs for psychiatric home-visit nursing staff to detect the status of individuals' dynamic factors, and a system to share any related changes in timely fashion.


Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells.
The molecular events involved in the establishment and maintenance of CD4+ central memory and effector memory T cells (TCM and TEM, respectively) are poorly understood. In this study, we demonstrate that ex vivo isolated TCM are more resistant to both spontaneous and Fas-induced apoptosis than TEM and have an increased capacity to proliferate and persist in vitro. Using global gene expression profiling, single cell proteomics, and functional assays, we show that the survival of CD4+ TCM depends, at least in part, on the activation and phosphorylation of signal transducer and activator of transcription 5a (STAT5a) and forkhead box O3a (FOXO3a). TCM showed a significant increase in the levels of phosphorylation of STAT5a compared with TEM in response to both IL-2 (P<0.04) and IL-7 (P<0.002); the latter is well known for its capacity to enhance T cell survival. Moreover, ex vivo TCM express higher levels of the transcriptionally inactive phosphorylated forms of FOXO3a and concomitantly lower levels of the proapoptotic FOXO3a target, Bim. Experiments aimed at blocking FOXO3a phosphorylation confirmed the role of this phosphoprotein in protecting TCM from apoptosis. Our results provide, for the first time in humans, an insight into molecular mechanisms that could be responsible for the longevity and persistence of CD4+ TCM.


Phosphorylation by MAPK regulates simian immunodeficiency virus Vpx protein nuclear import and virus infectivity.
Transport of the viral genome into the nucleus required phosphorylation of components in the preintegration complex by virion-associated host cellular kinases. In this study, we showed that ERK-2/MAPK is associated with simian immunodeficiency virus (SIV) virions and regulated the nuclear transport of Vpx and virus replication in non-proliferating target cells by phosphorylating Vpx. Suppression of the virion-associated ERK-2 activity by MAPK pathway inhibitors impaired both Vpx nuclear import and viral infectivity without affecting virus particle maturation and release. In addition, mutation analysis indicated that the inactivation of Vpx phosphorylation precluded nuclear import and reduced virus replication in macrophage cultures, even when functional integrase and Gag matrix proteins implicated in viral preintegration complex nuclear import are present. In this study, we also showed that co-localization of Vpx with Gag precursor in the cytoplasm is a prerequisite for Vpx incorporation into virus particles. Substitution of hydrophobic Leu-74 and Ile-75 with serines in the helical domain abrogated Vpx nuclear import, and its incorporation into virus particles, despite its localization in the cytoplasm, suggested that the structural integrity of helical domains is critical for Vpx functions. Taken together, these studies demonstrated that the host cell MAPK signal transduction pathway regulated an early step in SIV infection.


Professionalism in physicians in a second-level hospital
It takes many years to acquire abilities and technical skills necessary to do a good work as a doctor and even more years, for being "good professionals". Much of this training is based on old teaching schemes, but medicine has changed. So far no studies in our medium addressing the problem are known. The aim of this paper was to determine the level of professionalism in physicians that work in a second-level hospital. Descriptive cross-sectional study. We apply a survey to physicians, residents and medical interns in a second-level hospital. We developed and implemented a questionnaire on professionalism, which contained 18 items, 3 demographic questions and 15 questions with a Likert scale, which identified four dimensions: specialized knowledge, autonomy in decision-making, self-regulation and social commitment. Descriptive and inferential statistics were used, considering significant a p-value <0.05. We surveyed 228 physicians, 57.5% demonstrated competence in professionalism. 93.3% of the participants were competent in specialized knowledge and 60.5% in social commitment. The physicians and residents got the higher scores, and these differences were significant between autonomy in decision-making and specialized knowledge (p < 0.001). The medical interns obtained lower scores in all dimensions compared with residents and physicians. More than a half of physicians surveyed had a competent level of professionalism but only in some dimensions. We observed higher scores with a higher academic grade.


Body composition and kinematic analysis of the grab start in youth swimmers.
The purposes of this study were to compare the kinematic variables in youth swimmers during the grab start between sexes and to investigate the relationship between body composition and kinematic variables of the participants. Six female (Mage = 13.71 ± 0.49 yrs) and seven male (Mage = 14.00 ± 1.07 yrs) swimmers participated in this study. All participants were required to perform grab start tests in random order (three trials by each participant), while the best attempt was analyzed. Nineteen kinematic parameters consisting of block time, flight time, flight distance, total time, total distance, horizontal and vertical displacement of the center of mass (CM) at take-off, horizontal and vertical displacement of the CM at entry, height of take-off and entry, relative height of take-off, horizontal and vertical velocity of the CM at take-off, horizontal and vertical velocity of the CM at entry, angle of take-off, angle of entry and angle of knee at block were analyzed. Out of the 19 evaluated kinematic parameters, a statistical difference between the female and male group was found only in the total distance. Therefore, both female and male groups are considered as only one group and merged after analyzing the results. Statistical analysis showed positive and negative correlations between horizontal / vertical velocity of CM at take-off and several kinematic variables (e.g. angle of entry (rhorizontal = -.868, p=.000 / rvertical = .591, p=.02), total distance (rhorizontal = .594, p=.02 / rvertical = .54, p=.04), and height of take-off (rvertical = .888, p=.000), respectively). On the other hand, positive and negative correlations were found between somatotype components and several kinematic variables (e.g. horizontal displacement of CM at entry (rendomorphy = -.626, p=.013), angle of entry (rmesomorphy = -.686, p=.005 / rectomorphy = .52, p=.047), total distance (rendomorphy = -.626, p=.012), and height of take-off (rendomorphy = -.633, p=.011 / rectomorphy = .515, p=.05)). In conclusion, results show that in order to be successful at grab start performance, a swimmer should target to get higher horizontal velocity of CM at take-off and optimize the angle of take-off so this movement form supplies more total distance to the swimmer. Coaches should consider improving start performance and adding start training to regular training sessions. Moreover, youth male and female swimmers can participate together in the grab start training.


Occupational therapy for accessory nerve palsy after radical neck dissection.
The subjects in this study were ten patients with accessory nerve palsy after radical neck dissection. All the primary diseases that accounted for radical neck dissection were malignant tumors located at the head or neck. Every patient received occupational therapy and underwent evaluations before and after the therapy. The data we collected included the existence of resting pain and motion pain, and the active and passive range of motion during shoulder flexion and abduction. The occupational therapy programs were not adequately effective for resting and motion pain, however, every patient gained independence for activities of daily living and housekeeping activities. The occupational therapy significantly improved the patient's shoulder elevation in all movements; although, the active abduction was always significantly poor compared with flexion. In the meantime, there were no significant differences between passive shoulder flexion and abduction at all times. We can therefore understand that the accessory nerve palsy especially affects active shoulder abduction induced by the trapezius paralysis. Occupational therapy is an effective treatment for the improvement of shoulder function, however, the occupational therapy has limited effectiveness for coping with the pain.


Foot shape in arboreal birds: two morphological patterns for the same pincer-like tool.
The feet are the only contact between the body and the substrate in limbed animals and as such they provide a crucial interface between the animal and its environment. This is especially true for bipedal and arboreal species living in a complex three-dimensional environment that likely induces strong selection on foot morphology. In birds, foot morphology is highly variable, with different orientations of the toes, making it a good model for the study of the role of functional, developmental, and phylogenetic constraints in the evolution of phenotypic diversity. Our data on the proportions of the phalanges analyzed in a phylogenetic context show that two different morphological patterns exist that depend mainly on habitat and toe orientation. In the anisodactyl foot, the hallux is the only backward-oriented toe and is enlarged in climbing species and reduced in terrestrial ones. Moreover, a proximo-distal gradient in phalanx size is observed depending on the degree of terrestriality. In the two other cases (heterodactyl and zygodactyl) that have two toes that point backward, the hallux is rather small in contrast to the other backward-pointing toe, which is enlarged. The first pattern is convergent and common among tetrapods and follows rules of skeletal development. The second pattern is unique for the clade and under muscle-morphogenetic control. In all cases, the functional result is the same tool, a pincer-like foot.


Interferon therapy in juvenile laryngeal papillomatosis.
Seven cases of severe juvenile laryngeal papillomatosis were treated with exogenous leukocyte interferon (IFN-alpha). Tumor progression occurred in all cases before treatment. During treatment, the tumors decreased in size. When treatment was discontinued (five cases), tumor growth recurred, and after restarting therapy, the tumors once more decreased in size. In one case, the tumor completely vanished. In another case with extensive papillomatosis that extended up to the base of the tongue, a tracheostomy could be closed with only a thin mass of papillomatous tissue that remained on the vocal cords. Exogenous leukocyte interferon therapy can affect the clinical course of juvenile laryngeal papillomatosis. The optimal schedule for therapy has yet to be determined.


How sensitive are physical properties of choline chloride-urea mixtures to composition changes: Molecular dynamics simulations and Kirkwood-Buff theory.
Deep eutectic solvents (DESs) have emerged as a cheaper and greener alternative to conventional organic solvents. Choline chloride (ChCl) mixed with urea at a molar ratio of 1:2 is one of the most common DESs for a wide range of applications such as electrochemistry, material science, and biochemistry. In this study, molecular dynamics simulations are performed to study the effect of urea content on the thermodynamic and transport properties of ChCl and urea mixtures. With increased mole fraction of urea, the number of hydrogen bonds (HBs) between cation-anion and ion-urea decreases, while the number of HBs between urea-urea increases. Radial distribution functions (RDFs) for ChCl-urea and ChCl-ChCl pairs shows a significant decrease as the mole fraction of urea increases. Using the computed RDFs, Kirkwood-Buff Integrals (KBIs) are computed. KBIs show that interactions of urea-urea become stronger, while interactions of urea-ChCl and ChCl-ChCl pairs become slightly weaker with increasing mole fraction of urea. All thermodynamic factors are found larger than one, indicating a non-ideal mixture. Our results also show that self- and collective diffusivities increase, while viscosities decrease with increasing urea content. This is mainly due to the weaker interactions between ions and urea, resulting in enhanced mobilities. Ionic conductivities exhibit a non-monotonic behavior. Up to a mole fraction of 0.5, the ionic conductivities increase with increasing urea content and then reach a plateau.


Palm-sized biodetection system based on localized surface plasmon resonance.
We present a complete palm-sized, battery-operated biodetection system based on highly sensitive localized surface plasmon resonance (LSPR). We have replaced the spectrum analyzer by four pulse-powered light-emitting diodes (LED), each with different emission spectra. The reflected light beams from all LEDs were detected by a single photodiode. Its composite output current was demultiplexed by a four-channel lock-in amplifier. Device performance was demonstrated using an LSPR chip covered with a mixture of ethanol/water and 2-propanol/water at different concentrations. The miniaturized system does not require any external power supply or personal computer and it is therefore suitable for point-of-care and field applications.


Distributed representation of perceptual categories in the auditory cortex.
Categorical perception is a process by which a continuous stimulus space is partitioned to represent discrete sensory events. Early experience has been shown to shape categorical perception and enlarge cortical representations of experienced stimuli in the sensory cortex. The present study examines the hypothesis that enlargement in cortical stimulus representations is a mechanism of categorical perception. Perceptual discrimination and identification behaviors were analyzed in model auditory cortices that incorporated sound exposure-induced plasticity effects. The model auditory cortex with over-representations of specific stimuli exhibited categorical perception behaviors for those specific stimuli. These results indicate that enlarged stimulus representations in the sensory cortex may be a mechanism for categorical perceptual learning.


Cardiac biomarkers predict outcome after hospitalisation for an acute exacerbation of chronic obstructive pulmonary disease.
In chronic obstructive pulmonary disease (COPD), cardiovascular system is involved but less is known about role of specific cardiac biomarkers. We aimed to investigate associations between N-terminal pro B-type natriuretic peptide (NT-proBNP) and troponin T during hospitalisation with 6-month outcome. This was a prospective study conducted in consecutive patients hospitalized for an acute exacerbation of COPD. On admission, and at discharge, NT-proBNP and troponin T were measured, and echocardiography was performed. Hospitalisations and mortality were recorded for 6 months after discharge. We included 127 patients (70 ± 10 years, 70% men, GOLD III/IV 87%). Left ventricular dysfunction was detected in 70 (55%) patients and diastolic dysfunction was the most common type (53 patients-42%). NT-proBNP and troponin T were elevated on admission in 60% and 36%, and at discharge in 28% and 19% of patients. During follow-up, 53 (42%) patients were hospitalized and 17 (13%) patients died. In Kaplan Meier analysis of survival curves, NT-proBNP on admission distinguished between deceased and surviving patients (p=0.011) whilst troponin T at discharge separated hospitalized and non-hospitalized patients (p=0.017). The adjusted Cox proportional hazard model confirmed these findings: discharge troponin T predicted hospitalisations (hazard ratio 2.89, 95% confidence interval 1.13-7.36) and admission NT-proBNP predicted mortality (hazard ratio 4.20, 95% confidence interval 1.07-14.01). Elevated NT-proBNP at discharge and troponin T on admission predict outcome in patients hospitalized for an acute exacerbation of COPD.


Alginate as immobilization material: III. Diffusional properties.
The rate of diffusion of serum albumin (MW 6.9 x 10(4) D) out of beads of calcium alginate gels depends upon the concentration and uronic acid composition of the alginate (ManA/GulA ratio), the conditions under which the beads are produced, the pH, and the temperature. The diffusion coefficient decreases with increasing alginate concentration, and (ManA/GulA) ratio and with decreasing pH. Diffusion out of the beads, in which the alginate is uniformly distributed (homogeneous gel), is faster than out of the beads in which the alginate is concentrated at the surface (inhomogeneous gel). The temperature dependence of the diffusion coefficient follows the Arrhenius law, with an activation energy of approximately 23 kJ x mol(-1).


Effect of folic acid supplementation on proliferation and apoptosis in bovine mammary epithelial (MAC-T) cells.
Folic acid (FA) is known to be an important micronutrient in humans; however, information regarding the effect of FA supplementation on bovine mammary epithelial (BME) cells is insufficient. FA supplementation is reported to increase milk production in dairy cows, but the underlying molecular mechanisms are unknown. This study examined the effects of FA supplementation on the proliferation and apoptosis of a BME cell line (MAC-T). MAC-T cells were treated with various concentrations (deficient in FA (DF) < 0.01 ng/mL; low-level FA (LF) 3.1 ng/mL; normal FA (NF) 15.4 ng/mL; and high-level FA (HF) 30.8 ng/mL) based on serum folate (10-20 ng/mL) in milking cows. HF treatment significantly increased the proliferation of MAC-T cells. Cellular apoptosis was observed mainly in the DF group. The number of apoptotic cells in DF media was significantly higher than that in NF media. The bcl-2/bax mRNA expression ratio was significantly increased in the HF group compared to that in the DF group. FA supplementation significantly increased the ratio of Bcl-2/Bax protein levels in MAC-T cells. FA supplementation increases proliferation and decreases apoptosis in these cells. This study might provide information regarding the molecular mechanism through which FA supplementation is associated with increased milk yield.


Spontaneous coronary artery dissection: Acute findings on coronary computed tomography angiography.
The coronary computed tomography angiography features of acute spontaneous coronary artery dissection, an important cause of acute coronary syndrome in young women, have not been assessed. The "Virtual" Multicenter Mayo Clinic Spontaneous Coronary Artery Dissection Registry was established in 2010 and includes retrospective and prospective patient data. Retrospective assessment of acute coronary computed tomography angiography images was performed for 14 patients (16 vessels) who had images performed within two days of invasive coronary angiography diagnosis of acute spontaneous coronary artery dissection. Four pertinent diagnostic coronary features of acute spontaneous coronary artery dissection were observed in order of prevalence: 1) abrupt luminal stenosis (64%); 2) intramural hematoma (50%); 3) tapered luminal stenosis (36%); and 4) dissection (14%). Additional findings include epicardial fat stranding (42%), coronary tortuosity (29%), and coronary bridge (14%). Fifty percent of patients had myocardial hypoperfusion in the myocardial distribution of the dissected coronary artery. We define key coronary computed tomography angiography features of acute spontaneous coronary artery dissection, the most common of which are abrupt luminal stenosis and intramural hematoma. Importantly, intramural hematoma appears similar to noncalcified atherosclerotic plaque, emphasizing the importance of invasive coronary angiography for acute diagnosis of spontaneous coronary artery dissection until the sensitivity and specificity of coronary computed tomography angiography is better understood.


Immunologic consequences of intraocular implantation of retinal pigment epithelial allografts.
Immune rejection is a major concern for potential therapeutic RPE transplantation. The purpose of this study is to determine the pattern and consequences of immune responses to intraocular retinal pigment epithelial (RPE) allografts. RPE allografts which derive from C57BL/6 newborn mice were implanted into the subretinal space (SR), anterior chamber (AC) and subconjunctival space (SCon) of the eyes of adult BALB/c mice. After implantation, clinical, histological and immunological examinations were conducted. Results revealed that RPE allografts implanted into SR and AC had a prolonged survival which is associated with a suppression of donor-specific delayed hypersensitivity (DH) for at least 12 days. In contrast, similar RPE grafts implanted into the SCon induced conventional DH and grafts were rejected. Moreover, previously healthy intraocular RPE grafts were rejected 2 weeks after a donor-specific challenge and rejection was accomplished with extensive cell infiltration which subsequently damaged intraocular tissue of the host eye. These results suggested that intraocular RPE allografts enjoyed immune privilege and induced a down-regulation of immune responses. However, this privilege is not absolute and static--DH was able to emerge and grafts were rejected in a cell-mediated fashion.


Intrarenal blood flow distribution in hyperdynamic septic shock: Effect of norepinephrine.
To measure changes in medullary and cortical renal blood flow during experimental hyperdynamic sepsis and the effect of subsequent norepinephrine infusion on such flows. DESIGN Experimental animal study. Animal laboratory of university-affiliated physiology institute. SUBJECTS Eighteen anesthetized merino sheep. A transit-time flow probe was placed around the left renal artery. Laser Doppler flow probes were inserted in the left renal medulla and cortex by micromanipulation to measure changes in regional intrarenal blood flow. Systemic pressures, cardiac output, renal, and intrarenal blood flows were measured continuously. A bolus of Escherichia coli (7.5 x 10(9) colony forming units) was given intravenously to induce hyperdynamic sepsis. After the onset of hyperdynamic sepsis, all animals were randomly allocated to either norepinephrine (0.4 microg.kg-1.min-1 for 30 mins) or observation for 30 mins in random order. E. coli injection induced a significant decrease in mean arterial pressure (102.2 +/- 15.2 mm Hg to 74.3 +/- 16.1 mm Hg, p <.05) and an increase in mean cardiac output (4.60 +/- 1.62 L/min to 5.93 +/- 1.18 L/min, p <.05). However, renal blood flow did not change significantly (326.4 +/- 139.4 mL/min to 293.1 +/- 117.5 mL/min, not significant) despite a 30% increase in renal conductance (3.27 +/- 1.52 to 4.13 +/- 2.01 mL.min-1.mm Hg-1, p <.05). Cortical blood flow decreased by 15% (not significant) and medullary flow by 5% (not significant) during sepsis, but individual changes were unpredictable. On the other hand, norepinephrine infusion caused a significant improvement in mean arterial pressure (74.3 +/- 16.1 to 105.7 +/- 17.7 mm Hg, p <.05) and a further increase in cardiac output (5.93 +/- 1.18 to 7.13 +/- 1.52 L/min, p <.05). Mean renal blood flow also increased (293.1 +/- 117.5 to 384.5 +/- 168.1 mL/min, p <.05) despite decreased renal conductance (4.13 +/- 2.01 to 3.73 +/- 1.91 mL.min-1.mm Hg-1, p <.05). Infusion of norepinephrine significantly increased medullary blood flow by 35% compared with baseline (p <.05) and by 54% compared with untreated sepsis (p <.05), whereas the increases in cortical blood flow (16 and 53%, respectively) were not significant. Hyperdynamic sepsis caused renal vasodilation but had limited effects on regional intrarenal blood flow. Norepinephrine infusion (0.4 microg.kg-1.min-1) during sepsis significantly increased global and medullary renal blood flow and restored renal vascular tone toward but not above normal.


Stationary shocks in periodic highly nonlinear granular chains.
We study the existence of stationary shock waves in uniform and periodic heterogeneous highly nonlinear granular chains governed by a power-law contact interaction, comparing discrete and continuum approaches, as well as experiments. We report the presence of quasisteady shock fronts without the need for dissipative effects. When viscous effects are neglected, the structure of the leading front appears to be solely the result of dispersive effects related to the lattice wave dispersion and, for heterogeneous bead chains, to the impedance mismatch between material domains. We report analytically and numerically the shock-width scaling with the variation in the particles periodicity (cell size) and compare the obtained results with experiments. We check the state (-) behind the shock front via quasistatic compression analysis and report a very good agreement between theory and numerical data.