Comparative evaluation of effect of nisin-incorporated ethylenediamine tetraacetic acid and MTAD on endodontic biofilm eradication, smear layer removal, and depth of sealer penetration.
To comparatively evaluate the nisin-incorporated ethylenediamine tetraacetic acid (N-EDTA) and MTAD on cytotoxicity, endodontic biofilm eradication potential, smear layer removal ability, and sealer penetration depth. N-EDTA was prepared and characterized using high-performance liquid chromatography (HPLC). Minimum inhibitory, minimum bactericidal, and minimum biofilm inhibitory concentration (MBC, MIC, and MBIC) were determined on Enterococcus faecalis (E. faecalis) strain. The cytocompatibility of N-EDTA and MTAD was evaluated using 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based colorimetric assay. Dentin specimens (n = 88 for antibacterial analysis, n = 170 for sealer penetration depth) were prepared and subjected to the classical irrigating strategy and obturation, respectively. The scanning electron microscopic evaluation (SEM) was done for the evaluation of biofilm disruption and smear layer removal. Confocal laser scanning microscopy (CLSM) evaluation was done for determining percentage of bacterial viability and sealer penetration depth. Statistical analysis of one-way ANOVA and Tukey's HSD post hoc tests for bacterial viability and Kruskal-Wallis test and Mann-Whitney test for smear layer removal and depth of penetration were done with the significance level set at p < 0.05. MTAD and N-EDTA showed cytocompatibility without any statistical differences from each other. For N-EDTA, the MIC and MBC values were 12.5 μg/ml (1:8), and MBIC values were 36 μg/ml. Biofilm disruption and killed bacterial percentage of N-EDTA was statistically higher than MTAD, whereas both the materials showed similar efficacy in the removal of the smear layer and sealer penetration depth. N-EDTA had negligible cytotoxicity with similar smear layer removal ability, sealer penetration, and better antibiofilm potential than MTAD. N-EDTA can serve as a viable alternative endodontic irrigant.


Role of protein kinase C in the acrosome reaction of mammalian spermatozoa.
Mammalian spermatozoa undergo a Ca(2+)-dependent exocytotic event before fertilization which is known as the acrosome reaction. The process of exocytosis in several cell systems is mediated by a protein kinase C (PKC)-catalysed phosphorylation. Addition of phorbol 12-myristate-13-acetate or the membrane-permeant diacylglycerol analogue 1-oleoyl-2-acetylglycerol, which are potent activators of PKC, to bovine spermatozoa resulted in stimulation of the acrosome reaction. This stimulation was inhibited by low concentrations (50% inhibition at 0.7 nM) of the PKC inhibitor staurosporine. PKC specific activity in bovine spermatozoa is extremely low in comparison with other cells; however, it is comparable with the activity found in human spermatozoa. Immunohistochemical analysis using anti-PKC antibodies revealed staining in the equatorial segment, the post-acrosomal region and the upper region of the head. We propose that PKC is involved in the mammalian sperm acrosome reaction.


Turning over on sticky balls: preparation and catalytic studies of surface-functionalized TiO2 nanoparticles.
We have investigated the reactivity of rhodium(iii) complex-functionalized TiO2 nanoparticles and demonstrate a proof-of-principle study of their catalytic activity in an alcohol oxidation carried out under aqueous conditions water in air. TiO2 nanoparticles (NPs) have been treated with (4-([2,2':6',2''-terpyridin]-4'-yl)phenyl)phosphonic acid, 1, to give the functionalized NPs (1)@TiO2. Reaction between (1)@TiO2 NPs and either RhCl3·3H2O or [Rh2(μ-OAc)4(H2O)2] produced the rhodium(iii) complex-functionalized NPs Rh(1)2@TiO2. The functionalized NPs were characterized using thermogravimetric analysis (TGA), matrix-assisted laser desorption ionization (MALDI) mass spectrometry, 1H NMR and FT-IR spectroscopies; the single crystal structures of [Rh(1)2][NO3]3·1.25[H3O][NO3]·2.75H2O and of a phosphonate ester derivative were determined. 1H NMR spectroscopy was used to follow the reaction kinetics and to assess the recyclability of the NP-supported catalyst. The catalytic activity of the Rh(1)2@TiO2 NPs was compared to that of a homogeneous system containing [Rh(1)2]3+, confirming that no catalytic activity was lost upon surface-binding. Rh(1)2@TiO2 NPs were able to withstand reaction temperatures of up to 100 °C for 24 days without degradation.


CBAP regulates the function of Akt-associated TSC protein complexes to modulate mTORC1 signaling.
The Akt-Rheb-mTORC1 pathway plays a crucial role in regulating cell growth, but the mechanisms underlying the activation of Rheb-mTORC1 by Akt remain unclear. In our previous study, we found that CBAP was highly expressed in human T-ALL cells and primary tumors, and its deficiency led to reduced phosphorylation of TSC2/S6K1 signaling proteins as well as impaired cell proliferation and leukemogenicity. We also demonstrated that CBAP was required for Akt-mediated TSC2 phosphorylation in vitro. In response to insulin, CBAP was also necessary for the phosphorylation of TSC2/S6K1 and the dissociation of TSC2 from the lysosomal membrane. Here we report that CBAP interacts with AKT and TSC2, and knockout of CBAP or serum starvation leads to an increase in TSC1 in the Akt/TSC2 immunoprecipitation complexes. Lysosomal-anchored CBAP was found to override serum starvation and promote S6K1 and 4EBP1 phosphorylation and c-Myc expression in a TSC2-dependent manner. Additionally, recombinant CBAP inhibited the GAP activity of TSC2 complexes in vitro, leading to increased Rheb-GTP loading, likely due to the competition between TSC1 and CBAP for binding to the HBD domain of TSC2. Overexpression of the N26 region of CBAP, which is crucial for binding to TSC2, resulted in a decrease in mTORC1 signaling and an increase in TSC1 association with the TSC2/AKT complex, ultimately leading to increased GAP activity toward Rheb and impaired cell proliferation. Thus, we propose that CBAP can modulate the stability of TSC1-TSC2 as well as promote the translocation of TSC1/TSC2 complexes away from lysosomes to regulate Rheb-mTORC1 signaling.


The meaning of empowerment within Italian nursing care settings.
To examine the current state of empowerment of nurses in Italy. Empowerment is a broad concept that is also relevant to the field of nursing practice. Its comprehension and use are important because empowerment allows nurses to take control of their own practice. A clear understanding of empowerment is necessary for nurses to take advantage of this important tool. Focus groups were conducted. A literature review was performed, and two focus groups were selected between January and February 2014. Sixteen nurses participated in the research. Empowerment is seen as being strongly connected to autonomy and is not associated with power, as the word itself suggests. Italian nurses define empowerment as the creation of conditions that help to establish the possibility for people to develop and express their value and potential. Empowerment is defined as a condition in which the individual nurse takes control of his/her own practice and thereby provides awareness and confidence to a group. Italian nurses need to feel appreciated and supported by their own organisations. If warranted, empowerment would allow them to contribute to enhance care, which is the core of the nursing profession.


A cross-sectional survey of the knowledge, attitudes and practices regarding tuberculosis among general practitioners working in municipalities with and without asylum centres in eastern Norway.
The number of tuberculosis (TB) cases in Norway is increasing due to immigration from countries with high TB prevalence and few studies have been conducted on general practitioners' (GPs) knowledge of TB in low incidence countries. The main purpose of this study was to explore knowledge, attitudes and practices of TB among Norwegian GPs using a modified Knowledge Attitude Practice (KAP) survey template. A cross-sectional survey of 30 questions was distributed by email using SurveyMonkey to GPs working in municipalities either with or without an asylum reception centre in Eastern Norway (GPwAS or GPw/oAS). The questionnaire assessed demographic data and had 14 questions on TB knowledge and 7 questions on attitudes and practices. Descriptive and inferential analysis of the data was carried out using SPSS 18. One hundred ninety five GPs responded and 42% worked in a municipality with an asylum reception centre. There was no significant difference between the two GP groups in relation to demographic variables (all p-values > 0.2). GPwAS were more experienced in diagnosing TB patients compared to GPw/oAS (63.4% vs 44.2%, p = 0.008). There was no significant differences in participation in TB training between the two groups (8.5% vs 7.6%, p = 0.71). The majority of GPs (69%) did not consider TB as a major public health threat and misconceptions of TB epidemiology were identified. Overall, 97 (49.7%) GPs had good TB knowledge level and good TB knowledge level was associated with experience in diagnosing TB patients (p = 0.001) and recent TB training (p = 0.015). Gaps in TB knowledge and awareness among GPs in Norway need to be addressed if GPs are to be more involved in TB management and prevention in the future. TB training had an effect on the GPs knowledge level and GPwAS had more experience with TB patients but our survey revealed no major differences in KAP between GPwAS and GPw/oAS.


Self-promoted DNA interstrand cross-link formation by an abasic site.
The C4'-oxidized abasic site (C4-AP) is produced in DNA as a result of oxidative stress. A recent report suggests that this lesion forms interstrand cross-links. Using duplexes in which C4-AP is produced from a synthetic precursor, we show that the lesion produces interstrand cross-links in which both strands are in tact and cross-links in which the C4-AP containing strand is cleaved. The yields of these products are dependent upon the surrounding nucleotide sequence. When C4-AP is opposed by dA, cross-link formation occurs exclusively with an adjacent dA on the 5'-side. Moreover, formation of the lower molecular weight cross-link is promoted by an opposing adenine. When the opposing dA is replaced by dT, the activity of the adenine can be rescued by adding the free base. This is a rare example in which DNA promotes its own modification, an observation that is all the more important because of the biological significance of the product produced.


Advances in the diagnosis and treatment of leprosy.
Leprosy is a chronic infectious disease caused by Mycobacterium leprae that mainly affects the skin and peripheral nerves. Over recent years, many important advances have been made in developing molecular diagnostics, in identifying highly effective drugs and designing multidrug regimens for treatment, and in unravelling the genomic structure and functions of the leprosy bacillus. Using the new information about specific sequences of M. leprae, several gene probes and gene amplification systems for confirming diagnosis and monitoring treatment have been developed. Among these, polymerase chain reaction (PCR)-based methods have been useful in confirming the diagnosis in paucibacillary leprosy (where few bacilli are present). RNA-targeting systems for monitoring the progress of treatment, in situ hybridisation techniques for analysing specimens with nonspecific histological features, and molecular methods for direct detection of rifampicin/dapsone resistance are other major technological advances with immense applied value. Several effective regimens for the treatment of leprosy have been developed, which include rifampicin, clofazimine and dapsone as core drugs. Although these regimens are generally satisfactory, limitations in terms of persisting activity and late reactions/relapses in paucibacillary leprosy, and persistence of dead and/or live organisms in multibacillary forms of the disease, have been observed.


Measuring Tumor Extent Based on Subtypes Using Magnetic Resonance Imaging: Radiologic-Pathologic Discordance and High Positive Margin Rates in Breast Cancer.
We evaluated the clinical value of breast magnetic resonance imaging (MRI) in patients who underwent breast-conserving surgery (BCS). The degree of correlation between pathology size and MRI or ultrasonography (US) size was compared based on breast cancer subtypes. In addition, we investigated the positive margin rates. Patients with invasive breast cancer who underwent preoperative breast MRI and US between 2011 and 2016 were included in the study. Lin's concordance correlation coefficient was used to measure the correlation between MRI or US andpathologic tumor extent. Tumor extent was defined as pathologic tumor size, including in situ carcinoma. Margin positivity was assessed based on frozen-section examination. A total of 516 patients with a single tumor who underwent BCS were included in the study. The correlation between pathologic size and MRI was significantly higher than that of US (r = 0.6975 vs. 0.6211, p = 0.001). The superiority of MRI over US in measuring the pathologic extent was only observed in triple-negative breast cancer (TNBC; r = 0.8089 vs. 0.6014, p < 0.001). The agreement between MRI or US and tumor extent was low for the human epidermal growth factor receptor 2 (HER2)-positive subtype (MRI: 0.5243, US: 0.4898). Moreover, the positive margin rate was higher in the HER2-positive subtype than in the others (luminal/HER2-negative: 11.6%, HER2-positive: 23.2%, TNBC: 17.8%, p = 0.019). The post hoc analysis showed that the HER2-positive subtype was more likely to show positive margins than the luminal/HER2-negative subtype (p = 0.007). Breast MRI was superior to US in the preoperative assessment of the pathologic extent of tumor size; this was most evident in TNBC. For HER2-positive tumors, imaging-pathologic discordance resulted in higher positive margin rates than that with other subtypes.


The Real-Life Effectiveness and Safety of Omalizumab Updosing in Patients With Chronic Spontaneous Urticaria.
Omalizumab is a third-line treatment for chronic spontaneous urticaria (CSU). Studies investigating the use of higher doses of omalizumab in patients unresponsive to regular doses are limited. This study aims to investigate the effectiveness and safety of omalizumab 450 mg in CSU. A retrospective cohort study was conducted. The response to therapy was evaluated using the Urticaria Activity Score over 7 days (UAS7) and the Urticaria Control Test (UCT). Patients showing complete response (CR) (UAS7: 0-1) to omalizumab 300 mg (Group 1) and patients receiving at least 3 doses of omalizumab 450 mg (Group 2) between 2016 and 2018 were included. A total of 72 patients (Group 1: 59; Group 2: 13) were included. In Group 2, the mean UAS7 score decreased from 18.6 to 5.1 and the mean UCT score increased from 8.6 to 12 after a mean 4.3 courses of 450 mg omalizumab treatment. Of the 13 patients in Group 2, 6 had CR and 3 had good disease control (UAS7: 2-6). The rate of patients with low baseline IgE levels (< 43 IU/mL) was significantly higher in Group 2. Higher doses of omalizumab are effective and safe in patients with CSU that is unresponsive to omalizumab 300 mg. Lower baseline total IgE levels might be used as a predictor of nonresponse to omalizumab and the need for higher doses.


GnRH and GnRH receptors in the pathophysiology of the human female reproductive system.
Human reproduction depends on an intact hypothalamic-pituitary-gonadal (HPG) axis. Hypothalamic gonadotrophin-releasing hormone (GnRH) has been recognized, since its identification in 1971, as the central regulator of the production and release of the pituitary gonadotrophins that, in turn, regulate the gonadal functions and the production of sex steroids. The characteristic peculiar development, distribution and episodic activity of GnRH-producing neurons have solicited an interdisciplinary interest on the etiopathogenesis of several reproductive diseases. The more recent identification of a GnRH/GnRH receptor (GnRHR) system in both the human endometrium and ovary has widened the spectrum of action of the peptide and of its analogues beyond its hypothalamic function. An analysis of research and review articles published in international journals until June 2015 has been carried out to comprehensively summarize both the well established and the most recent knowledge on the physiopathology of the GnRH system in the central and peripheral control of female reproductive functions and diseases. This review focuses on the role of GnRH neurons in the control of the reproductive axis. New knowledge is accumulating on the genetic programme that drives GnRH neuron development to ameliorate the diagnosis and treatment of GnRH deficiency and consequent delayed or absent puberty. Moreover, a better understanding of the mechanisms controlling the episodic release of GnRH during the onset of puberty and the ovulatory cycle has enabled the pharmacological use of GnRH itself or its synthetic analogues (agonists and antagonists) to either stimulate or to block the gonadotrophin secretion and modulate the functions of the reproductive axis in several reproductive diseases and in assisted reproduction technology. Several inputs from other neuronal populations, as well as metabolic, somatic and age-related signals, may greatly affect the functions of the GnRH pulse generator during the female lifespan; their modulation may offer new possible strategies for diagnostic and therapeutic interventions. A GnRH/GnRHR system is also expressed in female reproductive tissues (e.g. endometrium and ovary), both in normal and pathological conditions. The expression of this system in the human endometrium and ovary supports its physiological regulatory role in the processes of trophoblast invasion of the maternal endometrium and embryo implantation as well as of follicular development and corpus luteum functions. The GnRH/GnRHR system that is expressed in diseased tissues of the female reproductive tract (both benign and malignant) is at present considered an effective molecular target for the development of novel therapeutic approaches for these pathologies. GnRH agonists are also considered as a promising therapeutic approach to counteract ovarian failure in young female patients undergoing chemotherapy. Increasing knowledge about the regulation of GnRH pulsatile release, as well as the therapeutic use of its analogues, offers interesting new perspectives in the diagnosis, treatment and outcome of female reproductive disorders, including tumoral and iatrogenic diseases.


Review and Application of Integrin Alpha v Beta 6 in the Diagnosis and Treatment of Cholangiocarcinoma and Pancreatic Ductal Adenocarcinoma.
Integrin Alpha v Beta 6 is expressed primarily in solid epithelial tumors, such as cholangiocarcinoma, pancreatic cancer, and colorectal cancer. It has been considered a potential and promising molecular marker for the early diagnosis and treatment of cancer. Cholangiocarcinoma and pancreatic ductal adenocarcinoma share genetic, histological, and pathophysiological similarities due to the shared embryonic origin of the bile duct and pancreas. These cancers share numerous clinicopathological characteristics, including growth pattern, poor response to conventional radiotherapy and chemotherapy, and poor prognosis. This review focuses on the role of integrin Alpha v Beta 6 in cancer progression. It addition, it reviews how the marker can be used in molecular imaging and therapeutic targets. We propose further research explorations and questions that need to be addressed. We conclude that integrin Alpha v Beta 6 may serve as a potential biomarker for cancer disease progression and prognosis.


Supplementation of Nigella sativa fixed and essential oil mediates potassium bromate induced oxidative stress and multiple organ toxicity.
The plants and their functional ingredients hold potential to cure various maladies and number of plants hold therapeutic potential. The present research was designed study the health promoting potential of black cumin (Nigella sativa) fixed oil (BCFO) and essential oil (BCEO) against oxidative stress with special reference to multiple organ toxicity. For the purpose, thirty rats (Strain: Sprague Dawley) were procured and divided into three groups (10 rats/group). The groups were fed on their respective diets i.e. D1 (control), D2 (BCFO @ 4.0%) and D3 (BCEO @ 0.30%) for a period of 56 days. Mild oxidative stress was induced with the help of potassium bromate injection @ 45 mg/Kg body weight. Furthermore, the levels of cardiac and liver enzymes were assayed. The results indicated that oxidative stress increased the activities of cardiac and liver enzymes. However, supplementation of BCFO and BCEO was effective in reducing the abnormal values of enzymes. Elevated levels of lactate dehydrogenase (LDH), CPK and CPK-MB were reduced from 456 to 231, 176 to 122 and 45 to 36mg/dL, respectively. Similarly, liver enzymes were also reduced. However, the results revealed that BCEO supplementation @ 0.30% is more effectual in ameliorating the multiple organ toxicity in oxidative stressed animal modelling. In the nutshell, it can be assumed that black cumin essential oil is more effective in reducing the extent of potassium bromate induced multiple organ toxicity (cardiac and liver enzymes imbalance) that will ultimately helpful in reducing the extent of myocardial and liver necrosis.


Nuclear trafficking of the POZ-ZF protein Znf131.
Znf131 is a member of the BTB/POZ family of transcription factors with roles in development and carcinogenesis. Like many members of this protein family, Znf131 displays robust nuclear localization in cultured cells, but the mechanism(s) of Znf131 nuclear trafficking is unknown. Here, we report the mechanism of Znf131 nuclear localization. Visual inspection of the Znf131 amino acid sequence revealed three basic regions (BR-1, -2 and -3) with the potential to serve as nuclear localization signals (NLS). Of the three basic regions, only BR-1 functioned independently to efficiently target heterologous beta-gal-GFP fusion proteins to HeLa cell nuclei. However, a Znf131 truncation mutant containing BR-2 and BR-3 efficiently targeted heterologous beta-gal-GFP fusion proteins to HeLa cell nuclei. Mutational analysis of full-length GFP-tagged Znf131 revealed that loss of any one BR alone did not prevent Znf131 nuclear localization. This apparent redundancy in NLS activity was due to the fact that intact BR-1 or BR-2 alone could target full-length Znf131 to nuclei. Consequently, simultaneous mutation of BR-1 and BR-2 abolished full-length Znf131 nuclear localization. Therefore, BR-1 and BR-2 are functional NLSs for Znf131 and as such are designated NLS-1 and NLS-2. Finally, wild type Znf131, and not a Znf131 NLS-defective mutant (NLS-1m/NLS-2m) interacted preferentially with the nuclear import receptor Importin-alpha3 in vitro.


Brown jaw tumors: today's unusual presentation of primary hyperparathyroidism.
Primary hyperparathyroidism (pHPT) has changed its clinical features in the last decade becoming a mild biochemical disease, in which the classical fibrous cystic osteitis is a rare complication. The more frequent bone involvement in primary hyperparathyroidism is observed at the distal 1/3 of the radius, where the cortical bone is primarily represented. However, lumbar and femoral osteopenia or osteoporosis prevalently affect hyperparathyroid post-menopausal women. We report two, otherwise healthy, young male patients, who presented a painful jaw swelling. In both patients standard radiographic imaging revealed a low-density well-defined lesion, which caused jaw bone destruction. High levels of serum calcium (14.1-16.6 mg/dl, n.v. 8.1-10.4) and PTH (1172-1928 pg/ml, n.v. 10-65) indicated the presence of pHPT associated with hypertension, asymptomatic renal involvement and osteoporosis with normal serum 25-hydroxyvitamin D levels in both patients. A single huge parathyroid adenoma was successfully removed and within 2 months jaw lesions were almost completely re-mineralized without any other therapeutic intervention in both patients. In conclusion, although brown jaw tumors are a rare complication of the hyperparathyroidism, they should be considered and identified in young patients with severe pHPT. Moreover, such a complication seems to be independent from vitamin D deficiency, suggesting the involvement of other pathogenetic factors.


Proximal peroneal perforator in dual-skin paddle configuration of fibula free flap for composite oral reconstruction.
Composite defects of the oral cavity are often the result of trauma or advanced-stage tumor extirpation. The resultant deformity frequently requires a three-dimensional reconstruction of bone and soft-tissue. The fibula free flap is the preferred method of reconstruction, with various modifications focused on providing supplemental soft-tissue coverage. The objective of this study was to ascertain both anatomic and clinical data regarding the proximal peroneal perforator and its contribution to the evolution of the fibula free flap. Ten cadaver lower extremities were dissected to isolate the most proximal perforator supplying skin over the proximal lateral lower leg. Data were recorded regarding perforator presence, location, and course. Furthermore, review of clinical cases in which the proximal perforator was used in fibula free flap design was performed for operative data collection. Cadaveric dissections revealed the proximal perforator to be present in 90 percent of specimens. Most commonly, the perforator, originating from the peroneal artery, traveled a short intramuscular course through the soleus muscle prior to supplying the overlying skin. In all clinical cases, the perforator was easily located with Doppler prior to incision, and there were no cases of flap failure or skin paddle loss. Flap inset was found to be optimal in all cases, with no tethering or undue tension. The proximal peroneal perforator was found to be anatomically reliable and clinically useful in composite oral cavity reconstruction following tumor removal. The gained separation between skin paddles allows for greater versatility in flap design and inset. Therapeutic, IV.


Multimodality imaging of intermediate lesions: Data from fractional flow reserve, optical coherence tomography, near-infrared spectroscopy-intravascular ultrasound.
Fractional flow reserve (FFR) assesses a functional impact of the atheroma on the myocardial ischemia, but it does not take into account the morphology of the lesion. Previous optical coherence tomography (OCT), intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) studies presented their potential to detect vulnerable plaques, which is not possible by FFR assessment. With the following study, the intermediate lesions were assessed by FFR, OCT and combined NIRS-IVUS imaging to identify plaque vulnerability. Thirteen intermediate lesions were analyzed simultaneously by FFR, OCT and combined NIRS-IVUS imaging. Two lesions were found to have FFR ≤ 0.80 (0.65 and 0.76). The other 11 lesions had FFR > 0.80 with a mean FFR 0.88 ± 0.049. Two lesions with FFR ≤ 0.80 had plaque burden (PB) > 70% and minimal lumen area (MLA) < 4 mm2, but neither of these 2 lesions were identified as OCT de-fined thin fibrous cap atheroma (TCFA), or NIRS-IVUS possible TCFA. Among the other 11 lesions with FFR > 0.80, 8 were identified as OCT-defined TCFA, 4 had PB > 70%, 6 had MLA < 4 mm2, 2 had both PB > 70% and MLA < 4 mm2, 3 lesions were identified as NIRS-IVUS possible TCFA, and 4 lesions had lipid core burden index > 400. The FFR-negative lesions pose traits of vulnerability as assessed simultaneously by IVUS, OCT and NIRS imaging.


Inhibition of bone morphogenetic proteins signaling suppresses metastasis melanoma: a proteomics approach.
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β superfamily, known to promote the tumor invasion and metastasis. There are continual progresses in understanding the role of BMP signaling pathways in carcinogenesis. However, the biological significance of BMPs in human melanoma has received very little attention. The study aimed to explore the effect of BMP inhibition on melanoma treated with LDN193189 (BMP inhibitor) using a quantitative proteomics approach in a melanoma xenograft model. Melanoma tumor was induced in C57BL6 mice and treated intraperitoneally with LDN193189 for ten consecutive days. Post-treatment, tumors were collected, and comparative proteomics was performed using a high-resolution Orbitrap Fusion Tribrid mass spectrometer. Treatment of melanoma with LDN193189 at 3 mg/kg body weight twice daily showed a significant decrease in the growth rate of the tumor compared to the other doses tested. Quantitative proteomic profiling identified 3231 proteins. Bioinformatics analysis of the 131 differentially expressed proteins selected by their relative abundance revealed that LDN193189 induces alterations in the cellular and metabolic process and the proteins that are involved in protein binding and catalytic activity in melanoma. Down-regulation of metallothionein (MT) 1 and MT2, emerging proteins for their role in tumor formation, progression, and drug resistance and transcription factor EB that plays a crucial role in the regulation of basic cellular processes, such as lysosomal biogenesis and autophagy, were identified upon inhibition of the BMP pathway in melanoma, suggesting their roles in melanoma growth. Understanding the role of these proteins will provide new directions for treating cancer.


Inhibition profile of trifludimoxazin towards PPO2 target site mutations.
Target site resistance to herbicides that inhibit protoporphyrinogen IX oxidase (PPO; EC 184.108.40.206) has been described mainly in broadleaf weeds based on mutations in the gene designated protoporphyrinogen oxidase 2 (PPO2) and in one monocot weed species in protoporphyrinogen oxidase 1 (PPO1). To control PPO target site resistant weeds in future it is important to design new PPO-inhibiting herbicides that can control problematic weeds expressing mutant PPO enzymes. In this study, we assessed the efficacy of a new triazinone-type inhibitor, trifludimoxazin, to inhibit PPO2 enzymes carrying target site mutations in comparison with three widely used PPO-inhibiting herbicides. Mutated Amaranthus spp. PPO2 enzymes were expressed in Escherichia coli, purified and measured biochemically for activity and inhibition kinetics, and used for complementation experiments in an E. coli hemG mutant that lacks the corresponding microbial PPO gene function. In addition, we used ectopic expression in Arabidopsis and structural PPO protein modeling to support the enzyme inhibition study. The generated data strongly suggest that trifludimoxazin is a strong inhibitor both at the enzyme level and in transgenics Arabidopsis ectopically expressing PPO2 target site mutations. Trifludimoxazin is a potent PPO-inhibiting herbicide that inhibits various PPO2 enzymes carrying target site mutations and could be used as a chemical-based control strategy to mitigate the widespread occurrence of PPO target site resistance as well as weeds that have evolved resistance to other herbicide mode of actions. © 2022 BASF SE and The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


A review of the general practitioner obstetric service in Colchester 1970-1979.
I report here on an audit of the work of a general practitioner maternity unit situated in the same building as a consultant obstetric unit. Between 1970 and 1979, 10,588 patients were admitted under the care of general practitioner obstetricians. The perinatal mortality rate averaged 6.9. I show in the report how an audit of such a unit can be carried out, and demonstrate that general practitioner obstetricians still have a valid and useful place in a district obstetric service.


[Nisin adsorption on silica adsorbents].
It has been shown that silica adsorbents can be used for adsorption of nizin from solutions obtained after centrifugation of the fermentation broth. The optimal structure of the adsorbent pores has been determined. Silica with pores 50 to 75 nm in size provided the highest adsorption rates. The value of silica adsorption of nizin depended on the medium pH. The maximum adsorption rates were observed at pH 6.5--7. At pH 3.5 the level of nizin adsorption was low.


[Age-dependent characteristics of signaling lipids in the liver and brain of rats].
The effect of age on signaling lipids contents in rat liver and different brain regions (hippocampus, neocortex) were studied. The contents of free fatty acids in the brain, diacylglycerol in liver and ceramide in all tissues studied have been found to increase with age. Age-dependent accumulation of neutral and sphingolipids evokes the violation of cell sensitivity to extracellular signals.


Self-assessed Dynamic Gait Index correlates with physical therapist assessed Dynamic Gait Index in people with multiple sclerosis.
The Dynamic Gait Index (DGI) is a clinical measure of walking ability comprised of eight walking tasks. In people with multiple sclerosis (PwMS) the DGI has demonstrated validity, reliability, and ability to identify fallers. A self-assessed version of the DGI that demonstrates concurrent validity with the original DGI in people with MS would be valuable for remote assessment of walking ability. We therefore developed a questionnaire-based self-assessed version of the DGI (sDGI) that asks participants to self-rate their predicted ability to perform the eight DGI walking tasks. The purpose of this study was to determine the validity and internal consistency of the sDGI in people with MS who had self-reported gait impairment. We enrolled 53 ambulatory people with MS with self-reported gait impairment. Participants completed the sDGI, the Multiple Sclerosis Walking Scale-12 (MSWS-12), the Telephone Interview for Cognitive Status (TICS), and self-reported their number of falls in the past 3 months. Then, up to 4 weeks later, they completed the DGI by in-person evaluation by a physical therapist (PT). We calculated the internal consistency of the sDGI and concordance between the sDGI and DGI. To determine if cognition impacted concordance, we calculated concordance in the cognitively impaired and non-impaired groups and also tested the difference between groups. We also calculated correlation between the sDGI and the DGI and the MSWS-12. The ability of the sDGI and the DGI to identify fallers was evaluated using receiver operating characteristic curves. 51 participants completed the study. They had a mean age of 60.9 (SD 11.5) years, median PDDS of 4.0 (interquartile range 3, 5), 32 % used walking aids, 25 % were cognitively impaired, and 62 % were female. The sDGI was internally consistent (Cronbach's alpha 0.85, 95 % CI 0.76, 0.90) but was not concordant (CCC = 0.45, 95 % CI: 0.28-0.60) with the DGI. Concordance between the sDGI and DGI was not different for cognitively intact versus cognitively impaired individuals. The sDGI was moderately correlated with the DGI (R = 0.64, p < 0.01) and strongly correlated with the MSWS-12 (R = -0.71, p < 0.01). Neither the sDGI nor the DGI identified fallers in this sample. The moderate to strong correlation among the sDGI, DGI and MSWS-12 supports the validity of the sDGI as a measure of walking ability in people with MS. However, because there is poor concordance between the sDGI and the DGI performed in clinic by a PT in both cognitively intact and cognitively impaired participants, the sDGI should not be used as a substitute for the DGI. The sDGI could be used as a screening tool because most participants underestimated their walking performance compared to assessment by a PT so the sDGI would be unlikely to miss poor walking ability. As neither the sDGI nor the DGI identified fallers in this sample, our results do not support using these tools to identify fallers in people with MS and self-reported gait impairment.


DOTA-tetrazine probes with modified linkers for tumor pretargeting.
Pretargeted radioimmunoimaging and -therapy approaches building on the bioorthogonal inverse-electron-demand Diels-Alder (IEDDA) reaction between strained trans-cyclooctenes (TCO) and electron-deficient tetrazines (Tz) have yielded impressive results in recent years and have proven a vital alternative to biological pretargeting systems. After improvement of the TCO-antibody conjugates, we here report on our evaluation of a new series of radiolabeled Tz-probes. Four new Tz-probes were synthesized, radiolabeled with lutetium-177, and characterized in vitro in terms of lipophilicity, reactivity, and stability in PBS and mouse serum. The in vivo biodistribution profile and tumor-targeting potential of the probes were evaluated in LS174T tumor-bearing mice pretargeted with TCO-antibody conjugates using non-pretargeted mice as control. Radiolabeling of all probes proceeded in high yields providing the 177Lu-labeled tetrazines in >95% radiochemical purity without any further purification. In mouse serum, half-lives of the probes varied between 8 and 13 h, with the exception of the most lipophilic probe, [177Lu]1b, with a serum half-life of less than 1 h. This probe also showed the fastest blood clearance (t1/2 = 5.4 min), more than 2-fold faster than PEG-linked probes [177Lu]3 and [177Lu]4, and even 3-fold faster than the other small probes without the PEG-linker, [177Lu]1a and [177Lu]2. In the pretargeting experiments, tumor uptake of the lead probe [177Lu]4 (~6 %ID/g) was most closely approached by [177Lu]2, followed by [177Lu]3 and [177Lu]1a. While all the smaller and more lipophilic probes suffered from increased liver uptake, the PEG-linked probe [177Lu]3 with its additional negative charge surprisingly showed the highest kidney uptake among all of the probes. The in vitro performance of some of the new tetrazine probes turned out to be comparable to the established lead probe [177Lu]Lu-DOTA-PEG11-Tz ([177Lu]4). However, tumor pretargeting studies in vivo showed lower tumor uptake and increased uptake in non-target organs.


Fetal calf serum contains activities that induce fetal hemoglobin in adult erythroid cell cultures.
Cultures of peripheral blood or bone marrow erythroid progenitors display stimulated production of fetal hemoglobin. We investigated whether this stimulation is due to factors contained in the sera of the culture medium. Comparisons of gamma/gamma + beta biosynthetic ratios in erythroid colonies grown in fetal calf serum (FCS) or in charcoal treated FCS (C-FCS) showed that FCS-grown cells had significantly higher gamma/gamma + beta ratios. This increase in globin chain biosynthesis was reflected by an increase in relative amounts of steady-state gamma-globin mRNA. In contrast to its effect on adult cells, FCS failed to influence gamma-chain synthesis in fetal burst forming units-erythroid (BFU-E) colonies. There was a high correlation of gamma-globin expression in paired cultures done with C-FCS or fetal sheep serum. Dose-response experiments showed that the induction of gamma-globin expression is dependent on the concentration of FCS. These results indicate that FCS contains an activity that induces gamma-globin expression in adult erythroid progenitor cell cultures.


PM10 exposure interacts with abdominal obesity to increase blood triglycerides: a cross-sectional linkage study.
Blood lipids and glucose levels dysregulation represent potential mechanisms intermediating the adverse cardiovascular effects of ambient particulate matter (PM) exposure. This study aims to estimate the effect of long-term PM10 exposure on blood lipids and glucose levels and to assess the potential mediation and/or modification action of abdominal obesity (AO) (waist-to-height ratio). Our study was based on 2,390 participants of the first Portuguese Health Examination Survey (INSEF, 2015) with available data on blood lipids and glucose parameters and living within a 30-km radius of an air quality monitoring station with available PM10 measurements. PM10 concentrations were acquired from the air quality monitoring network of the Portuguese Environment Agency. Generalized linear models were used to assess the effect of 1-year PM10 exposure on blood lipids and glucose levels. An interaction term was introduced in the models to test the modification action of AO. We found an association between PM10 and non-fasting blood triglycerides (TG) after adjustment for age, sex, education, occupation, lifestyles-related variables and temperature but only in participants with AO. Per each 1 µg/m3 PM10 increment, there was a 1.84% (95% confidence interval: 0.02-3.69) increase in TG. For the remaining blood lipid and glucose parameters, no associations were found. Our study demonstrates that even at low levels of exposure, long-term PM10 exposure interacts with AO to increase blood TG. Our findings suggest that reducing both AO prevalence and PM10 below current standards would result in additional health benefits for the population.


[Mollusc diversity in an Arca zebra (Mollusca: Bivalvia) community, Chacopata, Sucre, Venezuela].
The diversity of a subtidal epifaunal mollusk community was studied from September, 1990 to September, 1991 in Chacopata, Sucre State, Venezuela. There were 40 species (24 bivalves and 16 gastropods). The diversity indexes (H' = 2.087, J' = 0.392, 1/D = 0.528) were low when compared with other tropical zones. Monthly diversity reached its maximum in September, 1990 (1.63 bits/ind.) and July, 1991 (1.60 bits/ind.); minimum diversity occurred in June, 1991 (0.52 bits/ind.). A Log series model applied to species abundance data showed a straight line with a diversity index alpha of 5.56. Of 40 species identified, the turkeywing Arca zebra was dominant (69% in number of individuals and 72% of biomass) followed by Pinctada imbricata, Modiolus squamosus, Chama macerophyla and Anadara notabilis. The predatory snails Phyllonotus pomum, Chicoreus brevifrons and Murex recurvirostris seemed to have trophic relationships with A. zebra. The total mean biomass in wet weight (469.20 +/- 263 g m-2, shell included) was high which indicates that A. zebra, a species with a rapid growth rate, occupies a central role in the assemblage as an efficient filter feeder that converts planktonic food into available biomass, supporting one of the most important fisheries in Venezuela.


Expression and function of fibroblast growth factor 18 in the ovarian follicle in cattle.
Fibroblast growth factors (FGF) are involved in paracrine signaling between cell types in the ovarian follicle. FGF8, for example, is secreted by oocytes and controls cumulus cell metabolism. The closely related FGF18 is also expressed in oocytes in mice. The objective of this study was to assess the potential role of FGF18 in follicle growth in a monovulatory species, the cow. Messenger RNA encoding FGF18 was detected primarily in theca cells, and in contrast to the mouse, FGF18 was not detected in bovine oocytes. Addition of FGF18 protein to granulosa cell cultures inhibited estradiol and progesterone secretion as well as the abundance of mRNA encoding steroidogenic enzymes and the follicle-stimulating hormone receptor. In vivo, onset of atresia of the subordinate follicle was associated with increased thecal FGF18 mRNA levels and FGF18 protein in follicular fluid. In vitro, FGF18 altered cell cycle progression as measured by flow cytometry, resulting in increased numbers of dead cells (sub-G1 peak) and decreased cells in S phase. This was accompanied by decreased levels of mRNA encoding the cell cycle checkpoint regulator GADD45B. Collectively, these data point to a unique role for this FGF in signaling from theca cells to granulosa cells and suggest that FGF18 influences the process of atresia in ovarian follicles.


Strain engineering of the electronic and transport properties of monolayer tellurenyne.
Two-dimensional (2D) materials exhibiting quality electronic properties such as suitable band gap, giant Rashba effect and high carrier mobility are essential for promising applications in electronics and spintronics. Strain engineering has been recognized as an effective strategy to engineer the atomic and electronic properties of 2D materials. Herein, based on density functional theory, we demonstrate that the electronic properties of tellurenyne can be tuned well by using uniaxial strain. We find that tellurenyne retains the unique noncovalent bond structure and exhibits good stability under the uniaxial strain. Meanwhile, the band gap of tellurenyne can be tuned to a large scale (0.33-1.18 eV and 0.73-1.27 eV under the uniaxial strain along and perpendicular to the chain direction, respectively). Under 10% tension strain along the chain direction, the Rashba constant reaches 2.96 eV Å, belonging to giant Rashba systems. More importantly, the hole mobility of tellurenyne along the chain direction reaches 1.1 × 105 cm2 V-1 s-1 under 10% tension strain along the chain direction, which is one order of magnitude larger than that of phosphorene. Therefore, these remarkable electronic properties of tellurenyne engineered by using strain indicate its potential applications in electronics and spintronics.


The influences of face inversion and facial expression on sensitivity to eye contact in high-functioning adults with autism spectrum disorders.
We examined the influences of face inversion and facial expression on sensitivity to eye contact in high-functioning adults with and without an autism spectrum disorder (ASD). Participants judged the direction of gaze of angry, fearful, and neutral faces. In the typical group only, the range of directions of gaze leading to the perception of eye contact (the cone of gaze) was narrower for upright than inverted faces. In both groups, the cone of gaze was wider for angry faces than for fearful or neutral faces. These results suggest that in high-functioning adults with ASD, the perception of eye contact is not tuned to be finer for upright than inverted faces, but that information is nevertheless integrated across expression and gaze direction.


Molecular Biomarkers of Prognosis in Advanced Renal Cell Carcinoma Patients Treated With Pazopanib Plus Interferon Alpha (INF-2A) in a Phase I/II Study by the Spanish Oncology Genitourinary Group.
The therapeutic repertoire available for advanced renal cell carcinoma (RCC), including tyrosine kinase inhibitors (TKIs) and immunotherapy, required for molecular biomarkers for response. This was a phase I to II trial on the combination of pazopanib with interferon-alpha (INF-2A) as first-line treatment for advanced RCC. The primary endpoint was recommended phase II dose (RP2D) and efficacy in terms of objective response rate (ORR, RECIST 1.1 criteria). Secondary endpoints included safety and a translational study of molecular biomarkers in serum and exosomes from peripheral blood samples at three-time points: baseline, 8 weeks of treatment, and progression of the disease. Between July 2011 and July 2017, 53 eligible patients were treated and followed up (I, n = 20; II, n = 33). Pazopanib 800 mg + INF-2A 3 MIUs showed a manageable safety profile; therefore, it was selected for dose expansion. Overall, grade 3/4 toxicities were reported in 24 (72.7%) patients. The ORR was 27.2%. The 12-month OS rate was 83.6% (median not reached), and after 30.9 months of follow-up, 24 (72.7%) patients were still alive. CCL2, IL8, TNF-α, and PD-L1 were significantly overexpressed after treatment initiation, while TGF-β1 and CCL5 were significantly decreased. TNF-α, endoglin, and PD-L1 expression are correlated with the response after treatment initiation. The trial did not reach its pre-specified target ORR. However, OS was longer than expected with pazopanib monotherapy. Changes in the molecular profile suggest a crucial role of vascular remodeling and inflammatory-mediated immune cell infiltration in optimal response to pazopanib plus INF-2A.


Erythroid progenitor cells from pig bone marrow and peripheral blood.
With the intention of using the pig as a large animal model in haematopoietic research, a clonal assay in methylcellulose was developed and the optimal conditions for raising erythroid progenitors from adult pig bone marrow (BM) and peripheral blood (PB) have been established. Progenitor cells were stimulated to proliferate and differentiate in vitro by growth factors containing leucocyte condition medium (LCM), and with recombinant human erythropoietin (rhEpo). The number of PB BFU-E (burst forming units - erythroid) directly depended on the concentration of LCM, but BM BFU-E were not dependent on LCM. Both CFU-E (colony forming units - erythroid) and BFU-E were rhEpo dependent. Despite relatively high but expected individual variations, the mean number of colonies, as well as the functional characteristics of progenitor cells investigated, were similar to those of miniature pigs and some other mammals.


Studies on anthrax in food animals and persons occupationally exposed to the zoonoses in Eastern Nigeria.
A total of 221 blood and 174 carcase swab samples obtained from food animals (cattle, sheep, goats, pigs and horses) slaughtered at urban and rural slaughter houses in Nsukka area were studied. 51 blood samples and 180 samples of vesicle fluid were also collected from persons occupationally exposed (butchers/skinners, meat retailers, meat inspectors, veterinarians and tanners) to these animals and their products. All the samples were studied culturally and microscopically. Confirmation of infection was by subcutaneous inoculation of guinea pigs and mice with samples of human and animal blood, carcase swabs and vesicle fluid got from suspected cutaneous lesions on the hands of persons studied in this survey. Of the blood samples obtained from food animals, 5 per cent (3/60) of cattle and 3.3 per cent (1/30) of sheep were positive. The rest of the blood samples from other animals were negative. For the carcase swab samples, 5.7 per cent (5/88) from cattle and 3.1 per cent (1/33) from sheep were positive. The rest of the carcase swabs from goats, pigs and horses were negative. Only the blood samples from butchers/skinners, 20 per cent (2/10), meat retailers, 9.1 per cent (1/11) and tanners, 11.1 per cent (1/9) were positive. Malignant pustule was confirmed in 13.3 per cent (6/45) of butchers/skinners, 10 per cent (3/30) of tanners and 6 per cent (3/50) of meat retailers. The results show that food animals and their products constitute a potential danger to those persons whose occupation necessitates handling animal products or contact with animals.(ABSTRACT TRUNCATED AT 250 WORDS)


T Cell Deficits and Overexpression of Hepatocyte Growth Factor in Anti-inflammatory Circulating Monocytes of Middle-Aged Patients with Bipolar Disorder Characterized by a High Prevalence of the Metabolic Syndrome.
We previously reported T cell deficits and pro-inflammatory gene activation in circulating monocytes of two cohorts of bipolar disorder (BD) patients, a cohort of postpartum psychosis patients and in bipolar offspring. Pro-inflammatory gene activation occurred in two clusters of mutually correlating genes, cluster 1 for inflammation-related cytokines/factors, cluster 2 for motility, chemotaxis, and metabolic factors. To verify these cellular immune abnormalities in yet another cohort [the bipolar stress study (BiSS) cohort] of relative old (52 years, median) BD patients and to relate immune abnormalities to hair cortisol levels, measured in this cohort and representing long-term systemic cortisol levels, and to the presence of the metabolic syndrome (MetS), which was prevalent in 29% of the BiSS patients. Monocyte immune gene activation (quantitative polymerase chain reaction) and T cell deficits (fluorescence-activated cell sorting analysis) were determined in 97 well-controlled, largely euthymic BiSS BD patients. Monocyte genes included the cluster 1 and 2 genes, the genes for the glucocorticoid receptor (GR) α and GRβ, and the gene for hepatocyte growth factor [HGF, a marker of monocyte-derived circulating angiogenic cells (CACs)]. CACs serve vessel repair. Abnormal numbers are found in patients with MetS and vascular damage. As compared to healthy controls: (1) the pro-inflammatory cluster 1 genes were downregulated, and the GRα and the HGF gene were upregulated in the monocytes of the BiSS patients and (2) T cell deficits were shown (reduced numbers of lymphocytes in particular of T cells). Within the reduced T cell population, a shift had taken place in the T-helper populations: T-helper 17 and T-helper 2 increased and T regulatory cells decreased. Correlations between hair cortisol, the MetS, monocyte gene activation, and T cell deficits were not found. T cell deficits most likely are a trait phenomenon of BD, since they have also been found in the other cohorts of BD patients and in bipolar offspring. Monocytes of this cohort showed an anti-inflammatory set point, suggesting that pro- and anti-inflammation are state characteristics of BD. The monocyte gene profile indicated an increased CAC activity; the question arises whether this is due to putative vessel damage in these relatively old patients with a high prevalence of the MetS.


Pharmacokinetics of stavudine (2',3'-didehydro-3'-deoxythymidine) in the neonatal macaque (Macaca nemestrina).
Our objective was to determine whether age effects the pharmacokinetics of stavudine (2',3'-didehydro-3'-deoxythymidine) in the neonatal pig-tailed macaque (Macaca nemestrina). The drug (5 mg/kg of body weight) was administered serially as a single intravenous bolus to the same four macaques at the ages of < 1 week, 1 month, and 4 months. Plasma clearance at < 1 week of age was significantly lower (P < 0.05) than the corresponding values at 1 month and 4 months. Our data indicate that the pharmacokinetics of stavudine change significantly with age in M. nemestrina.


Retinopathy of dermatomyositis.
A recent case of childhood dermatomyositis with striking retinopathy is reported. The patient's vision was initially at the 20/80 to 20/100 level with associated macular edema and extensive cotton-wool infarction of the retina. Visual recovery to the level of 20/20 in both eyes was achieved following treatment with high-dose corticosteroids.


Establishment of iPSC lines from a high-grade Klinefelter Syndrome patient (49-XXXXY) and two genetically matched healthy relatives (KAUSTi003-A, KAUSTi004-A, KAUSTi004-B, KAUSTi005-A, KAUSTi005-B, KAUSTi005-C).
Klinefelter Syndrome (KS) is the most frequent X chromosome aneuploidy in males. KS patients with 47-XXY, 48-XXXY and 49-XXXXY karyotypes endure inter-individual phenotypic variabilities including infertility, cardiac diseases, metabolic and psychiatric disorders. We derived iPSC lines from a high-grade 49-XXXXY KS and two healthy donors' fibroblasts. Importantly, the healthy controls XY and XX are direct relatives to KS patients, thus enabling functional comparisons of healthy and disease iPSCs with partially matched genetic backgrounds. These iPSC lines provide an unprecedented cellular tool to study KS pathophysiology at the pluripotent stage as well as during differentiation into disease relevant cell types.


Isoinertial Eccentric-Overload Training in Young Soccer Players: Effects on Strength, Sprint, Change of Direction, Agility and Soccer Shooting Precision.
The isoinertial training method owes its efficacy to an accommodated resistance and optimal individualized eccentric overload. The aim of this study was to assess the effects of a 6-week isoinertial eccentric-overload training program - using a flywheel inertial device during the execution of specific soccer exercises - on explosive and reactive strength, sprint ability, change of direction (COD) performance and soccer shooting precision. Thirty-four junior soccer players were randomly assigned to a plyometric training group (PT) (n = 16, aged 13.36 ± 0.80), which underwent a six-week traditional soccer training program, and a flywheel eccentric overload group (FEO) (n = 18, aged 13.21 ± 1.21), which received additional training consisting of two inertial eccentric-overload training sessions per week. Pre and post intervention tests were carried out to assess explosive and reactive strength, sprint ability, COD ability, agility using the Y-agility test (YT) and soccer shooting precision. The FEO showed significantly higher values than the PT in squat jump height (SJh) (p = 0.01), drop jump height (DJh) (p = 0.003), 7 repeated hop test heights (p = 0.001), the Illinois test (ILL) (p = 0.001), and the Loughborough Soccer Shooting Test (SHOT) (p = 0.02). Finally, the FEO showed significant between-group differences in DJh (p = 0.007), ILL (p = 0.0002), YT (p = 0.002), a linear sprint test (SPRINT) (p = 0.001), and SHOT (p = 0.003). These results confirmed the positive effect of isoinertial training. The use of an isoinertial device to overload multidirectional movements in specific sport conditions leads to greater performance improvements than conventional soccer training. The absence of knowledge of the eccentric overload applied by the isoinertial device, which is different in any exercise repetition, may stimulate the athlete's neural adaptations, improving their soccer skills and in particular their soccer shooting precision.


Controlling growth and chemical composition of saplings by iteratively matching nutrient supply to demand: a bootstrap fertilization technique.
We developed a fertilization technique that results in the control, and maintenance at defined rates and levels, of growth and tissue composition of plants of different sizes and developmental stages growing at exponential and nonexponential rates in solid media under naturally fluctuating light and temperature regimes. Clonal cottonwood (Populus deltoides Bartr.) saplings were grown in sand. Low concentrations of nutrient solution were added daily at different constant exponentially increasing rates for 20-30 days to produce plants with different growth rates and tissue nutrient composition. Matching nutrient supply to measured growth demand by bootstrapping, where bootstrapping is the use of an iterative equation that calculates demand from either actual or desired growth rates, maintained these differences for 20-40 days. Nutrient additions controlled growth of saplings with growth rates between 2.0 and 4.0% day(-1), heights between 13.9 and 37.5 cm, dry weights between 0.70 and 3.90 g, leaf nitrogen contents between 1.2 and 3.9%, and leaf carbon/nitrogen ratios between 42.1 and 12.5. The technique was reproducible in a greenhouse without temperature, humidity, or light control, and is easily modified to suit different plant species, plants of various sizes, and various growing conditions.


[Vessels of the brachial plexus].
The blood supply of brachial plexus is described by means of lightened injected specimens of older human fetus. The following arteries have direct branches to brachial plexus: the aortic arch/brachiocephalica trunk, subclavia a., thyrocervical trunk, ascending cervical a., transverse cervical a., suprascapular a., and the acromial network. Secondary branches leave them that partly anastomose and also return from distal to proximal. The blood supply is luxurious.


Characteristics and uses of biologic dressings and skin substitutes.
Biologic dressings used for temporary coverage of open wounds exert both mechanical and physiologic effects by protecting the wound, maintaining microbial control, and hastening wound maturation. Synthetic wound dressings modeled after the biologic dressings have been evaluated by several investigators. Those studies have shown unilaminate synthetic membranes to be ineffective when applied to full-thickness wounds and have identified a bilaminate construction as being necessary for membranes to serve as effective skin substitutes. The desirable properties of skin substitutes have been identified and incorporated in the design of recently developed membranes. Recent studies in this and other laboratories have resulted in the development of collagen-synthetic bilaminates, a totally synthetic biologically inert bilaminate, and tissue culture-derived membranes. The characteristics and limitations of each skin substitute determine the optimum usage of these composite membranes and define the modifications needed to improve the effectiveness of such dressings.


From anatomy to function: the role of the somatosensory cortex in emotional regulation.
Since the pioneering work of Penfield and his colleagues in the 1930s, the somatosensory cortex, which is located on the postcentral gyrus, has been known for its central role in processing sensory information from various parts of the body. More recently, a converging body of literature has shown that the somatosensory cortex also plays an important role in each stage of emotional processing, including identification of emotional significance in a stimulus, generation of emotional states, and regulation of emotion. Importantly, studies conducted in individuals suffering from mental disorders associated with abnormal emotional regulation, such as major depression, bipolar disorder, schizophrenia, post-traumatic stress disorder, anxiety and panic disorders, specific phobia, obesity, and obsessive-compulsive disorder, have found structural and functional changes in the somatosensory cortex. Common observations in the somatosensory cortices of individuals with mood disorders include alterations in gray matter volume, cortical thickness, abnormal functional connectivity with other brain regions, and changes in metabolic rates. These findings support the hypothesis that the somatosensory cortex may be a treatment target for certain mental disorders. In this review, we discuss the anatomy, connectivity, and functions of the somatosensory cortex, with a focus on its role in emotional regulation.


A subjective outcome analysis of tendo-Achilles rupture.
This clinical outcomes study examined factors affecting patient satisfaction after treatment of Achilles tendon rupture. There were 35 patients; 14 treated nonsurgically and 21 treated by open surgical repair. A retrospective chart review was performed to determine the mechanism and type of injury, the time to treatment, any comorbidities, and the length of follow-up. Patients completed a questionnaire that evaluated their pre- and postinjury activity levels, occupation, and overall satisfaction with their function by using a visual analogue scale. The mean follow-up was 2 years. Seventy percent were very satisfied with the outcome of treatment, with a mean visual analogue score of 8.4 of 10. Age, sex, and occupation did not have any significant influence on the satisfaction level. The dissatisfied group showed a significantly reduced postinjury leisure activity level (P =. 003). A delay in initiation of treatment had a significant negative impact on satisfaction (P = .015). Regression analysis showed that physiotherapy after treatment increased the postinjury activity level and the level of satisfaction (P = .034). There was no significant difference in the overall outcome between the surgical and nonsurgical groups.


Live-cell imaging with Aspergillus fumigatus-specific fluorescent siderophore conjugates.
Live-cell imaging allows the in vivo analysis of subcellular localisation dynamics of physiological processes with high spatial-temporal resolution. However, only few fluorescent dyes have been custom-designed to facilitate species-specific live-cell imaging approaches in filamentous fungi to date. Therefore, we developed fluorescent dye conjugates based on the sophisticated iron acquisition system of Aspergillus fumigatus by chemical modification of the siderophore triacetylfusarinine C (TAFC). Various fluorophores (FITC, NBD, Ocean Blue, BODIPY 630/650, SiR, TAMRA and Cy5) were conjugated to diacetylfusarinine C (DAFC). Gallium-68 labelling enabled in vitro and in vivo characterisations. LogD, uptake assays and growth assays were performed and complemented by live-cell imaging in different Aspergillus species. Siderophore conjugates were specifically recognised by the TAFC transporter MirB and utilized as an iron source in growth assays. Fluorescence microscopy revealed uptake dynamics and differential subcellular accumulation patterns of all compounds inside fungal hyphae.[Fe]DAFC-NBD and -Ocean Blue accumulated in vacuoles, whereas [Fe]DAFC-BODIPY, -SiR and -Cy5 localised to mitochondria. [Fe]DAFC -FITC showed a uniform cytoplasmic distribution, whereas [Fe]DAFC-TAMRA was not internalised at all. Co-staining experiments with commercially available fluorescent dyes confirmed these findings. Overall, we developed a new class of fluorescent dyes that vary in intracellular fungal targeting , thereby providing novel tools for live-cell imaging applications for Aspergillus fumigatus.


Structure of an interleukin-1 beta mutant with reduced bioactivity shows multiple subtle changes in conformation that affect protein-protein recognition.
Site-specific mutagenesis was used to obtain the human interleukin-1 beta mutant protein with glycine substituted for threonine at position 9 (IL-1 beta Thr9Gly). The mutant maintains receptor binding but exhibits significantly reduced biological activity. The crystal structure of IL-1 beta Thr9Gly has been determined at 2.4-A resolution by molecular replacement techniques and refined to a crystallographic R-factor of 19.0%. IL-1 beta Thr9Gly crystallizes in a different space group (P6(5)22) than does native IL-1 beta (P4(3)); thus the molecules pack differently. Their overall structure is similar, nevertheless, with both composed of 153 amino acids which form 12 antiparallel beta-strands. However, significant conformational differences both close to and far from the site of the mutation may explain the mutant's altered properties.


Understanding dietary decision-making in patients attending a secondary prevention clinic following myocardial infarction.
This study aimed to explore the issues that influence the dietary choices made by patients attending a secondary prevention clinic following a myocardial infarction. Secondary prevention clinics play an important role in promoting dietary advice, yet evidence suggests that many individuals are neither implementing nor maintaining the lifestyle changes recommended. Research largely focuses on compliance to lifestyle changes in general, and only a small number of quantitative studies address the issues surrounding adherence to dietary advice. Phenomenology was selected as the most appropriate approach for this qualitative study, enabling patients' lived experiences of dietary decision-making to be explored. A purposive sample of nine participants was selected from a cardiac secondary prevention clinic. Semi-structured interviews were taped, transcribed and analysed using an interpretative approach. Data analysis produced six central themes contributing to patients' decision-making. Fear, determination and self-control were enabling factors and poor recall of information, a need for additional support and a lack of will power were disabling factors. Findings suggest that patient motivation and ability to make sustainable dietary change can decline as disabling factors reduce determination and self-control, and initial fear of their heart condition subsides. In this study, patients' motivation regarding dietary decision-making changed over time and was strongly influenced by a fear of future heart problems. Health care professionals need to understand the temporal nature of decision-making postmyocardial infarction and adopt a wide repertoire of responsive strategies that support patients to follow a healthy diet in the longer term.


Variation in meal-skipping rates of Korean adolescents according to socio-economic status: results of the Korea Youth Risk Behavior Web-based Survey.
To identify and evaluate the trend of meal-skipping rates among Korean adolescents with their contributing causes and the influence of household income level on meal skipping. Using 2008, 2010, and 2012 data from the Korea Youth Risk Behavior Web-based Survey of 222 662 students, a cross-sectional study with subgroup analysis was performed. We calculated odds ratios for skipping each meal 5 or more times in a week by household socio-economic status using a multiple logistic regression model. The secular change in the meal-skipping rates by the students' family affluence scale was analyzed by comparing the meal-skipping students within each subgroup and odds ratios for the same event over time. Through 2008 to 2012, most of the meal-skipping rates generally showed a continuous increase or were almost unchanged in both sexes, except for breakfast skipping in several subgroups. Students in low-income households not living with both parents had the highest meal-skipping rates and odds ratios for frequent meal skipping. In a time-series subgroup analysis, the overall odds ratios for the same event increased during 2008 to 2012, with a slight reduction in the gap between low and higher income levels with regard to meal skipping during 2010 to 2012. Household socio-economic status and several other factors had a significant influence on Korean adolescent meal-skipping rates. Although the gap in eating behavior associated with household socio-economic differences is currently decreasing, further study and appropriate interventions are needed.


Cloning and mapping of BamHi endonuclease fragments of DNA from the transforming B95-8 strain of Epstein-Barr virus.
DNA from the B95-8 strain of Epstein-Barr virus was cleaved into 29 different fragments by BamHI endonuclease (EC 126.96.36.199). All of the fragments except the terminal fragments have been inserted into the pBR322 cloning vector and replicated in Escherichia coli. The location of each cloned DNA fragment in the viral genome has been determined, providing a more detailed physical map of the genome than has been available previously.


Endoplasmic Reticulum and Mitochondria Contacts Correlate with the Presence and Severity of NASH in Humans.
The interaction between the mitochondria and the endoplasmic reticulum (ER) is essential for hepatocyte function. An increase in ER-mitochondria contacts (ERMCs) is associated with various metabolic diseases. Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes, and its progressive form non-alcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma. However, the role of ERMCs in the progression of NAFL to NASH is still unclear. We assessed whether ERMCs could correlate with NAFLD severity. We used a proximity ligation assay to measure the abundance of ERMCs in liver biopsies from patients with biopsy-proven NAFLD (n = 48) and correlated the results with histological and metabolic syndrome (MetS) features. NAFLD patients were included according to inclusion and exclusion criteria, and then assigned to NAFL (n = 9) and NASH (n = 39) groups. ERMCs density could discriminate NASH from NAFL (sensitivity 61.5%, specificity 100%). ERMCs abundance correlated with hepatocellular ballooning. Moreover, the density of ERMCs increased with an increase in the number of MetS features. In conclusion, ERMCs increased from NAFL to NASH, in parallel with the number of MetS features, supporting a role for this interaction in the pathophysiology of NASH.


The formation of lithocholic acid, chenodeoxycholic acid and alpha- and beta-muricholic acids from cholesterol incubated with rat-liver mitochondria.
1. When rat-liver mitochondria were incubated with [4-(14)C]cholesterol in the presence of a soluble supernatant fraction, various steroids more polar than cholesterol were formed. These included 3beta-hydroxycholest-5-en-26-oic acid, 3beta-hydroxychol-5-enoic acid, lithocholic acid, chenodeoxycholic acid and alpha- and beta-muricholic acids. 2. All the radioactive C(24) bile acids recovered were in conjugated form, probably as taurine conjugates. 3. The formation of 3beta-hydroxychol-5-enoic acid from cholesterol shows that liver mitochondria are capable of carrying out the oxidative removal of the isopropyl unit of the side chain before any modification has occurred in the ring system.


Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms.
Rupture of an intracranial aneurysm (IA) causes a systemic response that involves an immune/inflammatory reaction. Our previous study revealed a downregulation of genes related to T lymphocytes and an upregulation of genes related to monocytes and neutrophils after IA rupture. It remains unknown whether that resulted from alterations in transcription or cell count. We sought to characterize the systemic response to IA rupture through analysis of transcript expression profiles in peripheral blood cells. We also investigated effects of IA rupture on the composition of mononuclear cells in peripheral blood. We included 19 patients in the acute phase of IA rupture (RAA, first 72 h), 20 patients in the chronic phase (RAC, 3-15 months), and 20 controls. Using deep transcriptome sequencing, we analyzed the expression of protein-coding and noncoding RNAs. Expression levels, transcript biotypes, alternative splicing and other features of the regulated transcripts were studied. A functional analysis was performed to determine overrepresented ontological groups among gene expression profiles. Flow cytometry was used to analyze alterations in the level of mononuclear leukocyte subpopulations. Comparing RAA and controls, we identified 491 differentially expressed transcripts (303 were downregulated, and 188 were upregulated in RAA). The results indicate that the molecular changes in response to IA rupture occur at the level of individual transcripts. Functional analysis revealed that the most impacted biological processes are related to regulation of lymphocyte activation and toll-like receptor signaling pathway. Differences between RAC and controls were less prominent. Analysis of leukocyte subsets revealed a significantly decreased number of CD4+ lymphocytes and increase of classical and intermediate monocytes in RAA patients compared to controls. IA rupture in the acute phase strongly influences the transcription profiles of peripheral blood cells as well as the composition of mononuclear cells. A specific pattern of gene expression alteration was found, suggesting a depression of lymphocyte response and enhancement of monocyte activity.


Cellular internalization of lactoferrin in intestinal epithelial cells.
We studied the cellular internalization of lactoferrin (Lf) in an intestinal epithelial cell line, Caco-2, to investigate the mechanism of biological actions of ingested Lf. RT-PCR and Western blotting analyses revealed that differentiated Caco-2 cells express LfR mRNA and its protein with a 34 kD molecular weight under reducing conditions. Biotin-labeled Lf showed specific binding to the cellular membrane of differentiated Caco-2 cells with a dissociation constant (Kd) of 0.16 microM. The cellular internalization of Lf was studied in differentiated Caco-2 cells grown as monolayers on Transwell inserts, and compared to that of human transferrin (Tf). After labeling with fluorescent dye, either Lf or Tf was added to Caco-2 cells from the apical side or the basolateral one. Laser scanning confocal microscopy showed that labeled Lf was internalized only from the apical side and localized to the nuclei. On the other hand, labeled Tf was internalized from the basolateral side, not from the apical side, and localized in the cytoplasm. The internalization of labeled Lf was inhibited by excess of unlabeled Lf, but not of Tf. The internalization of labeled Lf, but not of labeled Tf, was also suppressed by heparin. This indicates that a heparin-binding site in the N-terminal region of Lf could be important for the internalization of Lf. These findings suggest that ingested Lf might be internalized by the intestinal epithelium in a manner different from Tf and might function in the nucleus.


Affinity labelling of E. coli leucyl-tRNA synthetase with 3'-oxidized tRNA(Leu).
The E. coli leucyl-tRNA synthetase (E.C. 18.104.22.168) was specifically labelled with 3'-oxidized tRNA(Leu) (tRNA(oxLeu)). The procedure involves a Schiff's base formation and its subsequent reduction by sodium cyanoborohydride. Stoichiometric inactivation of aminoacylation was achieved with the incorporation of 1 mol of tRNA(oxLeu) per mol LeuRS. On the other hand, the amino acid activation activity of LeuRS-tRNA(ox) complex was partially inhibited. After extensive digestion of the complex by pancreatic ribonuclease, the amino acid activation activity was fully recovered, while the aminoacylation activity was not restored at all.


Cetirizine inhibits bradykinin-induced cutaneous wheal and flare in atopic and healthy subjects.
Kinins are vasoactive mediators involved in allergic reactions. When applied on the skin or in the nose, bradykinin (BK) elicits inflammation that is poorly affected by previous H1-blockade. The aim of this study was to compare the possible effect of cetirizine (an H1-antagonist) on wheal and flare responses to BK, histamine, and compound 48/80 in atopic and healthy subjects. In a randomized, double-blind, crossover study, eight atopic and eight healthy subjects received cetirizine (10 mg/day) or placebo for 3 days before cutaneous tests. Intradermal tests (IDT) and prick tests (PT) were performed with BK (20 nmol/ml for IDT and 20 micromol/ml for PT), histamine (100 microg/ml IDT and 100 mg/ml PT), and compound 48/80 (100 microg/ml IDT and 100 mg/ml PT) as positive controls and saline as negative control. The skin responses were monitored by measurement of wheal and flare areas. BK, histamine, and 48/80 induced wheal and flare reactions in all placebo-treated subjects. Histamine elicited larger wheal and flare reactions than BK and 48/80. IDT with BK induced four- to sixfold larger wheal and flare reaction than PT. No differences in BK-induced wheal and flare were observed between atopic and healthy subjects. In atopic subjects, cetirizine induced a significant reduction of flare reactions after the BK test (80% for IDT, and 94% for PT [P < 0.01]). Moreover, cetirizine reduced significantly BK-induced wheals by 70% for IDT (P < 0.01) and 65% for PT (P < 0.01). A similar inhibiting effect of cetirizine was also observed in healthy subjects. These findings showed that the wheal and flare reactions induced by BK challenge were markedly inhibited by previous intake of cetirizine. The mechanism by which this effect is mediated cannot be established at present.


Taekwondo training improves the neuromotor excitability and reaction of large and small muscles.
This study measured the neuromotor excitability and reaction time in professional and amateur Taekwondo (TKD) practitioners and compared them with non-athletes. A cross-sectional cohort study design. Exercise laboratory setting. 40 TKD practitioners (20 professionals, 20 amateurs) and 20 non-athletes. Neuromotor excitability (rheobase), premotor reaction time (PRT), total reaction time (TRT) and electromechanical delay (EMD) of rectus femoris (RF) and flexor pollicis brevis (FPB) in response to audio and visual stimuli were measured. The professional TKD practitioners have shorter TRT than non-athletes with sport-specific visual stimuli but they have longer PRT and TRT in response to audio stimuli than the amateur practitioners and non-athletes. The professional practitioners have longer EMD than the amateurs in responding to audio (p = 0.032) and sports-specific visual stimuli (p = 0.03) in FPB. Professional practitioners have higher excitability in RF (p < 0.001) than the amateurs and non-athletes. We conclude that professional TKD practitioners have better neuromotor ability in both large and small muscles with faster reactions to sport-specific stimuli, suggesting a generalized training effect across muscles. They react slower to non-sport specific stimuli, which suggested a decreased sensitivity to irrelevant sensory inputs after intensive TKD training.


[The characteristics of the relationships of arthropods of the refuge complex with the causative agents of transmissible viral infections in bird rookeries].
The isolation of viruses of tick-borne encephalitis, West Nile fever, and Omsk hemorrhagic fever from arthropods of nests of colonial birds (rook, sand martin, tree sparrow, Laridae) in different zones of West Siberia (from tundra to steppe) has been analyzed. The role of gamasid mites, hematophages and saprophages, characteristic inhabitants of nests of colonial birds, and of the tick Ixodes lividus in connection with their biology, coadaptation with hosts, microclimatic nest conditions, etc. has been evaluated. It has been concluded that the whole nest community of arthropods in a nest rather than one infected individual has to be regarded as an infective unit in colonies.


Lymphangiomatous macroglossia. Medical and surgical treatment.
The case of an 8-year-old male diagnosed both clinically and histologically as having lymphangiomatous macroglossia is presented. It is a case that did not require surgical intervention as there were no functional or respiratory deficits. Cases in which there are deficits will require intervention as described.


Swellable, water- and acid-tolerant polymer sponges for chemoselective carbon dioxide capture.
To impact carbon emissions, new materials for carbon capture must be inexpensive, robust, and able to adsorb CO2 specifically from a mixture of other gases. In particular, materials must be tolerant to the water vapor and to the acidic impurities that are present in gas streams produced by using fossil fuels to generate electricity. We show that a porous organic polymer has excellent CO2 capacity and high CO2 selectivity under conditions relevant to precombustion CO2 capture. Unlike polar adsorbents, such as zeolite 13x and the metal-organic framework, HKUST-1, the CO2 adsorption capacity for the hydrophobic polymer is hardly affected by the adsorption of water vapor. The polymer is even stable to boiling in concentrated acid for extended periods, a property that is matched by few microporous adsorbents. The polymer adsorbs CO2 in a different way from rigid materials by physical swelling, much as a sponge adsorbs water. This gives rise to a higher CO2 capacities and much better CO2 selectivity than for other water-tolerant, nonswellable frameworks, such as activated carbon and ZIF-8. The polymer has superior function as a selective gas adsorbent, even though its constituent monomers are very simple organic feedstocks, as would be required for materials preparation on the large industrial scales required for carbon capture.


Pregnancy in women with cystic fibrosis and diabetes: An audit of outcomes at two tertiary obstetric hospitals in Australia in the pre-cystic fibrosis transmembrane conductance regulator modulator era.
Pregnancy in women with cystic fibrosis (CF) is becoming more common. Long-term metabolic issues such as diabetes are also becoming more common and have potentially important impacts on pregnancy outcomes. This study aimed to assess the impact of diabetes on pregnancy outcomes for women with CF. We undertook a retrospective chart audit of pregnancies to women with CF at the two tertiary obstetric hospitals in Southeast Queensland associated with CF and transplant management clinics between 2006 and 2016. A total of 38 pregnancies among 26 women were identified. Four women (five pregnancies) had cystic fibrosis-related diabetes (CFRD) diagnosed prior to pregnancy, and 12 women (15 pregnancies) developed gestational diabetes (GDM) complicating pregnancy. CFRD and GDM were associated with higher rates of delivery complications, prematurity, and the need for neonatal intensive care unit admission. Diabetes is common during pregnancy in women with CF and impacts pregnancy outcomes.


A perspective of adaptation in healthcare.
Emerging new technologies in healthcare has proven great promises for managing patient care. In recent years, the evolution of Information and Communication Technologies pushes many research studies to think about treatment plan adaptation in this area. The main goal is to accelerate the decision making by dynamically generating new treatment due to unexpected situations. This paper portrays the treatment adaptation from a new perspective inspired from the human nervous system named autonomic computing. Thus, the selected potential studies are classified according to the maturity levels of this paradigm. To guarantee optimal and accurate treatment adaptation, challenges related to medical knowledge and data are identified and future directions to be explored in healthcare systems are discussed.


Data-Driven Sampling Matrix Boolean Optimization for Energy-Efficient Biomedical Signal Acquisition by Compressive Sensing.
Compressive sensing is widely used in biomedical applications, and the sampling matrix plays a critical role on both quality and power consumption of signal acquisition. It projects a high-dimensional vector of data into a low-dimensional subspace by matrix-vector multiplication. An optimal sampling matrix can ensure accurate data reconstruction and/or high compression ratio. Most existing optimization methods can only produce real-valued embedding matrices that result in large energy consumption during data acquisition. In this paper, we propose an efficient method that finds an optimal Boolean sampling matrix in order to reduce the energy consumption. Compared to random Boolean embedding, our data-driven Boolean sampling matrix can improve the image recovery quality by 9 dB. Moreover, in terms of sampling hardware complexity, it reduces the energy consumption by 4.6× and the silicon area by 1.9× over the data-driven real-valued embedding.


Amphiphilic tribasic galactosamines potentiate rifampicin in Gram-negative bacteria at low Mg++/Ca++concentrations.
Many antibiotics specific to Gram-positive bacteria like rifampicin (RIF) are inactive in Gram-negative bacteria because of outer membrane (OM) impermeability. Enhancing the OM permeability of these antibiotics with the help of OM perturbants is a promising strategy to develop new agents against Gram-negative bacteria. Here we report the synthesis and biological properties of amphiphilic tribasic galactosamines as potential RIF potentiators. Our results demonstrate that tribasic galactose-based amphiphiles potentiate RIF in multidrug-resistant Acinetobacter baumannii and Escherichia coli but not Pseudomonas aeruginosa in low salt-containing media. Under these conditions, lead compounds 20, 22 and 35 lowered the minimum inhibitory concentration of RIF by 64- to 256-fold against Gram-negative bacteria. However, the RIF-potentiating effect was reduced when bivalent Mg++ or Ca++ ions were added in the media at physiological concentrations. Overall, our results indicate that amphiphilic tribasic galactosamine-based compounds show reduced RIF-potentiating effects when compared to amphiphilic tobramycin antibiotics at physiological salt concentrations.


Who practices yoga? A systematic review of demographic, health-related, and psychosocial factors associated with yoga practice.
Yoga has become increasingly popular in the US and around the world, yet because most yoga research is conducted as clinical trials or experiments, little is known about the characteristics and correlates of people who independently choose to practice yoga. We conducted a systematic review of this issue, identifying 55 studies and categorizing correlates of yoga practice into sociodemographics, psychosocial characteristics, and mental and physical well-being. Yoga use is greatest among women and those with higher socioeconomic status and appears favorably related to psychosocial factors such as coping and mindfulness. Yoga practice often relates to better subjective health and health behaviors but also with more distress and physical impairment. However, evidence is sparse and methodological limitations preclude drawing causal inferences. Nationally representative studies have minimally assessed yoga while studies with strong assessment of yoga practice (e.g., type, dose) are generally conducted with convenience samples. Almost all studies reviewed are cross-sectional and few control for potential confounding variables. We provide recommendations for future research to better understand the correlates of yoga practice.


IcmS-dependent translocation of SdeA into macrophages by the Legionella pneumophila type IV secretion system.
Legionella pneumophila replicates inside alveolar macrophages and causes an acute, potentially fatal pneumonia called Legionnaires' disease. The ability of this bacterium to grow inside of macrophages is dependent on the presence of a functional dot/icm type IV secretion system (T4SS). Proteins secreted by the Dot/Icm T4SS are presumed to alter the host endocytic pathway, allowing L. pneumophila to establish a replicative niche within the host cell. Here we show that a member of the SidE family of proteins interacts with IcmS and is required for full virulence in the protozoan host Acanthamoeba castellanii. Using immunofluorescence microscopy and adenylate cyclase fusions, we show that SdeA is secreted into host cells by L. pneumophila in an IcmS-dependent manner. The SidE-like proteins are secreted very early during macrophage infection, suggesting that they are important in the initial formation of the replicative phagosome. Secreted SidE family members show a similar localization to other Dot/Icm substrates, specifically, to the poles of the replicative phagosome. This common localization of secreted substrates of the Dot/Icm system may indicate the formation of a multiprotein complex on the cytoplasmic face of the replicative phagosome.


Tobacco and other risk factors for oesophageal cancer in alcohol non-drinkers.
Information on the aetiology of oesophageal cancer in alcohol non-drinkers will help us to understand and quantitate risk factors for the disease in the absence of alcohol. Out of a total of 316 cases with histologically confirmed incident cancers of the oesophagus, 40 (22 men and 18 women) who described themselves as alcohol non-drinkers were considered. These patients were compared with 151 alcohol non-drinkers (79 men and 72 women) admitted to hospital for acute, non-neoplastic, non-alcohol-, non-smoking-related conditions. The major risk factor for cancer of the oesophagus in non-drinkers was current elevated cigarette smoking: compared with never smokers, the odds ratio (OR) for all current smokers was 3.4 [95% confidence interval (CI), 1.5-8.1]. The OR was 0.8 (95% CI 0.2-3.4) for ex-smokers, 1.3 (95% CI 0.4-4.2) for current smokers of fewer than 20 cigarettes per day and 7.5 (95% CI 2.7-20.4) for current smokers of more than 20 cigarettes per day. Risk also increased with duration of smoking (OR 4.9 for more than 30 years smoking), and in smokers starting the habit when aged 25 or younger (OR 3.9). Few years of education and gastrectomy were also associated with elevated risk, while a high fruit intake was associated with reduced risk (OR 0.6 and 0.4, respectively, for 7-13 and > 13 portions per week compared with < 7). When the combined effect of smoking and fruit intake on the risk of oesophageal cancer was considered, compared with non-smokers eating more than 7 fruit portions per week, the OR for current smokers eating 7 or less fruit portions per week was 7.3. Thus, even in the absence of alcohol drinking, cigarette smoking and a diet poor in fruit are important avoidable risk factors for oesophageal cancer.


Refractive status at birth: its relation to newborn physical parameters at birth and gestational age.
Refractive status at birth is related to gestational age. Preterm babies have myopia which decreases as gestational age increases and term babies are known to be hypermetropic. This study looked at the correlation of refractive status with birth weight in term and preterm babies, and with physical indicators of intra-uterine growth such as the head circumference and length of the baby at birth. All babies delivered at St. Stephens Hospital and admitted in the nursery were eligible for the study. Refraction was performed within the first week of life. 0.8% tropicamide with 0.5% phenylephrine was used to achieve cycloplegia and paralysis of accommodation. 599 newborn babies participated in the study. Data pertaining to the right eye is utilized for all the analyses except that for anisometropia where the two eyes were compared. Growth parameters were measured soon after birth. Simple linear regression analysis was performed to see the association of refractive status, (mean spherical equivalent (MSE), astigmatism and anisometropia) with each of the study variables, namely gestation, length, weight and head circumference. Subsequently, multiple linear regression was carried out to identify the independent predictors for each of the outcome parameters. Simple linear regression showed a significant relation between all 4 study variables and refractive error but in multiple regression only gestational age and weight were related to refractive error. The partial correlation of weight with MSE adjusted for gestation was 0.28 and that of gestation with MSE adjusted for weight was 0.10. Birth weight had a higher correlation to MSE than gestational age. This is the first study to look at refractive error against all these growth parameters, in preterm and term babies at birth. It would appear from this study that birth weight rather than gestation should be used as criteria for screening for refractive error, especially in developing countries where the incidence of intrauterine malnutrition is higher.


Histopathological parameters reported in microinvasive oral squamous cell carcinoma: a systematic review.
Microinvasive oral squamous cell carcinoma (OSCCmi) is an incipient stage of oral cancer. Through this systematic review, we aim to assess patterns of histopathological outcomes reported in OSCCmi cases. An online search in major databases was performed without period restriction, and 2,024 publications in English, Spanish and Portuguese were obtained. After screening and eligibility, 4 studies were selected. The risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Checklist. A descriptive synthesis was conducted. All 4 publications included were retrospective, reporting a total of 116 OSCCmi patients, with a male predominance (1.6:1) and a mean age of 55.9 years. The main parameters considered for microinvasion were tumor thickness (TT) (range 4-10mm) and depth of invasion (DOI) (range 0,02-5mm). Definition, cut-off values, and assessment of microscopic features were not standardized. Other relevant measures such as perineural or lymphovascular invasion and pattern of invasive front were barely described, and cytological/architectural characteristics were not discussed. TT and DOI are currently the primary histopathological criteria used to define OSCCmi. Nonetheless, the outcomes of this systematic review showed the absence of standardized quantitative parameters to render the diagnosis of microinvasive OSCC. Therefore, additional studies aiming to standardize histopathological features to diagnose OSCCmi are paramount.


RETRACTED: Hierarchical organization of guidance receptors: silencing of netrin attraction by slit through a Robo/DCC receptor complex.
Axonal growth cones that cross the nervous system midline change their responsiveness to midline guidance cues: They become repelled by the repellent Slit and simultaneously lose responsiveness to the attractant netrin. These mutually reinforcing changes help to expel growth cones from the midline by making a once-attractive environment appear repulsive. Here, we provide evidence that these two changes are causally linked: In the growth cones of embryonic Xenopus spinal axons, activation of the Slit receptor Roundabout (Robo) silences the attractive effect of netrin-1, but not its growth-stimulatory effect, through direct binding of the cytoplasmic domain of Robo to that of the netrin receptor DCC. Biologically, this hierarchical silencing mechanism helps to prevent a tug-of-war between attractive and repulsive signals in the growth cone that might cause confusion. Molecularly, silencing is enabled by a modular and interlocking design of the cytoplasmic domains of these potentially antagonistic receptors that predetermines the outcome of their simultaneous activation.


Whispering gallery modes of a curved antiresonant reflecting optical waveguide.
The whispering gallery modes of a curved antiresonant reflecting optical waveguide are described and analyzed. We present a ray analysis method that can be used to derive an eigenmode equation and to analyze the loss characteristics of a waveguide in rectangular coordinates by using conformal transformation. With an optimized design of an antiresonant reflecting optical waveguide structure, the propagation loss of such a waveguide can be significantly reduced.


A case with improvement of blepharospasm by zolpidem.
Zolpidem is usually used for the treatment of insomnia as a hypnotic drug. It was also suggested to be effective in the treatment of dystonia in some studies. A 74-year-old woman had been suffering from frequent and intense bilateral spasms of the eyelids for 20 years. She has been treated with botulinum toxin injection and taken some medications. But, she experienced a little effect and was not satisfied with those treatments. Her symptom was improved after taking Zolpidem which had been prescribed for insomnia by her primary physician. She did not show any improvement after placebo injection and neostigmine test. This is the first report which shows improvement of isolated blepharospasm by Zolpidem in Korea. Zolpidem can be one of useful alternative pharmacological treatments for blepharospasm. Further randomized, blinded, placebo-controlled studies are needed to validate this finding.