Varying genetic imprints of road networks and human density in North American mammal populations.
Road networks and human density are major factors contributing to habitat fragmentation and loss, isolation of wildlife populations, and reduced genetic diversity. Terrestrial mammals are particularly sensitive to road networks and encroachment by human populations. However, there are limited assessments of the impacts of road networks and human density on population-specific nuclear genetic diversity, and it remains unclear how these impacts are modulated by life-history traits. Using generalized linear mixed models and microsatellite data from 1444 North American terrestrial mammal populations, we show that taxa with large home range sizes, dense populations, and large body sizes had reduced nuclear genetic diversity with increasing road impacts and human density, but the overall influence of life-history traits was generally weak. Instead, we observed a high degree of genus-specific variation in genetic responses to road impacts and human density. Human density negatively affected allelic diversity or heterozygosity more than road networks (13 vs. 5-7 of 25 assessed genera, respectively); increased road networks and human density also positively affected allelic diversity and heterozygosity in 15 and 6-9 genera, respectively. Large-bodied, human-averse species were generally more negatively impacted than small, urban-adapted species. Genus-specific responses to habitat fragmentation by ongoing road development and human encroachment likely depend on the specific capability to (i) navigate roads as either barriers or movement corridors, and (ii) exploit resource-rich urban environments. The nonuniform genetic response to roads and human density highlights the need to implement efforts to mitigate the risk of vehicular collisions, while also facilitating gene flow between populations of particularly vulnerable taxa.


Stacking-controlled phototransformations of the 5-fluorouracil residues in dinucleotide model compounds.
5-Fluorouracil residues can form cyclobutane-type photodimers in a direct excitation stacking-controlled process. The stacking also has an important effect on the photohydration of uracil and 5-fluorouracil in our model compounds 5RUra(CH2)35FUra, where R = H, CH3, C2H5, C3H7, F or Cl.


Unusual finding of the human-adapted hypervirulent serotype III/ST17 clone in a historical bovine Group B Streptococcus isolate from Brazil.
Group B Streptococcus (GBS) is a leading cause of human neonatal infections and bovine mastitis. We report here the unusual finding of the human-adapted hypervirulent serotype III/ST17 clone in a bovine GBS isolated in 1987 in Brazil. This isolate shared several phenotypic and genotypic characteristics with serotype III/ST17 strains obtained from human sources, including PFGE pattern, pilus genes, lactose fermentation, DNase activity, and antimicrobial susceptibility profile, highlighting the importance of continued tracking of GBS in the One Health scope. The study brings new evidence for the potential interspecies transmission and sheds new light into evolution aspects of the pathogen Group B Streptococcus (GBS) by reporting the occurrence of an ancient bovine GBS isolate belonging to a variant currently known to be exclusively found in human hosts.


Fish tissues for biomonitoring toxic and essential trace elements in the Lower Amazon.
Brazilian soils can have high concentrations of toxic elements, mainly mercury (Hg) and arsenic (As), metals also associated with anthropogenic activities (e.g. intensive agriculture, mining, deforestation and hydroelectric plants). This can lead to large amounts of these elements reaching and/or being mobilized in the aquatic ecosystem, which constitutes a serious threat to the environment and to the health of local populations. Thus, we evaluate the feasibility of analyzing the tissues of freshwater fish species for monitoring toxic and trace element accumulation within the aquatic ecosystem in the Lower Amazon, Brazil. Two fish species were considered: Cichla temensis (Tucunaré), a carnivorous species, and Pterygoplichthys pardalis (Acari), a detritivorous species. Samples of liver and muscle from both species were evaluated in relation to their potential use for biomonitoring purposes. The study findings clearly demonstrate the value these fish species and tissues, particularly liver, for biomonitoring toxic and trace element concentrations in the aquatic environment across the study region. While Tucunaré liver proved the best option for biomonitoring elements that accumulate through the food chain (e.g. Hg), Acari liver better reflected elements that typically accumulate in the sediments (e.g. As). Moreover, the trace element profiles, determined using chemometric (multivariate) techniques, differed greatly in specimens from waters in the Andean mountain range (sampling sites located in the main course of the Amazon River) with high sediment concentrations, and in specimens from the Guyana and Brazilian shields (Porto Trombetas on the Trombetas River and Itaituba on the Tapajós River). The findings also indicate that deposition of elements in freshwater fish in this area is mainly associated with the geological origin of the soils and that large amounts of toxic elements can reach the aquatic ecosystem due to anthropogenic activities, thereby posing a serious danger to the environment and the health of the riverside communities.


Protection and controlled release of vitamin C by different micro/nanocarriers.
Ascorbic acid, known as vitamin C, is an important antioxidant and food ingredient, and highly sensitive to environmental conditions, which makes its incorporation into food, cosmetic and pharmaceutical products more difficult. The evaluation of its nano/microencapsulation enables the improvement of its stability and controlled release. There are various investigations regarding ascorbic acid encapsulation; however, a deep study related to the scale-up of encapsulation process, its application into food products and digestibility study are still needed. This review highlights the main physicochemical and health properties of vitamin C, recent advances of its encapsulation into micro/nanocarriers, and application in food products. Also, the controlled release and bioavailability of encapsulated forms within different carriers is underlined. The results of published studies clearly show that vitamin C can be successfully protected within micro/nanoencapsulation systems and it can be applied as an efficient ingredient in the formulation of various food products such as bakery goods.


Hospital-Based Credentialing and Privileging: Overview and Implications for the Clinical Nurse Specialist.
The purpose of this article is to provide an overview of hospital-based credentialing and privileging processes for clinical nurse specialists (CNSs), describe barriers to success, and share lessons learned from CNSs who have successfully navigated the credentialing and privileging process. This article shares knowledge, experiences, and lessons learned from an initiative to achieve hospital credentialing and privileging for CNSs at 1 academic medical center. Policies and procedures for credentialing and privileging CNSs are now consistent with other advanced practice providers.


Management of hypertension in the digital era: Perspectives and future directions.
Information and communication technology (ICT) have advanced remarkably in recent years. In the field of medicine, the problem of hypertension management seems especially well-suited to the application of novel methods. In patients with hypertension, it is important to assess blood pressure (BP) levels throughout the day and night, along with circadian BP variation, using out-of-office BP monitoring. ICT is an attractive tool to facilitate such monitoring and promises to change the current management of hypertension. The combination of self-telemonitoring of BP with lifestyle modification appears to be effective for strict BP control. ICT could be a solution to the challenging problem of nonadherence to antihypertensive medications and could reduce so-called clinical inertia in the treatment of hypertension. ICT approaches would be especially useful in geographically isolated areas or during natural disasters or complex health emergencies such as the ongoing coronavirus pandemic. However, it will be necessary to develop innovative ICT devices for easy and accurate BP measurement in a range of individuals, including the elderly, and to confirm their effectiveness in large scale clinical trials. ICT-based management of hypertension is expected to be pivotal for reducing the public-health burden of cardiovascular diseases and to be widely adopted in daily clinical practice in the future.


The pre-hospital delay in seeking treatment in patients with acute myocardial infarction referring to a central hospital in Kashan, Iran.
A cardiovascular disease, especially the acute myocardial infarction (AMI), is the most important health problem worldwide. Pre-hospital delay in seeking medical treatment is an effective factor on patients' outcomes. The aim of this study was to identify the patients' reactions to the signs and symptoms of AMI and identifying the factors contributing to the pre-hospital delay in a central hospital in Kashan, Iran. In this cross-sectional study, a random sample of 248 patients suffering from AMI was recruited. A questionnaire used, which contained demographic data, the time, and place of experiencing the symptoms, and the manner of responding to the initial symptoms. The SPSS software (version, 19 was used for data analysis. 248 patients participated in the study, 183 (73.8%) were males and 65 (26.2%) were females. The mean delay time was 127 ± 174 min. Moreover, 162 patients had arrived at the hospital during the first 60 min after the onset of the symptoms. The variables of being female (P = 0.024), low level of education (P = 0.014), living in urban area (P = 0.01) and referring to the hospital by one's own car instead of using ambulance were accompanied by more pre-hospital delay. 63 patients (25.4%) referred to the hospital by ambulance. Despite having only 25% of the patients referring to this center by ambulance, most patients arrived on time to the hospital.


Development and validation of the Male Body Talk Scale: a psychometric investigation.
This paper details the development of the Male Body Talk (MBT) scale and five studies supporting the psychometric soundness of scores on this new measure. Participants were 18-65-year-old men recruited via Amazon's Mechanical Turk, introductory psychology courses, and snowball sampling. The MBT scale assesses the frequency with which men engage in negatively valenced body-related conversations with others. Two subscales were identified through a combination of exploratory and confirmatory factor analysis. The Muscle Talk subscale assesses men's tendency to express concerns regarding degree of muscularity and being too small. The Fat Talk subscale assesses men's tendency to express concerns regarding level of body fat and being overweight. Scores on the MBT scale demonstrated strong internal consistency and moderate test-retest reliability. Evidence of convergent, discriminant, and incremental validity of scores on the MBT scale is presented. This new measure is a useful tool for examining how often men engage in negative body talk.


An Asymmetric Investigation of Remittance and Trade Openness Impact on Inequality: Evidence From Selected South Asian Countries.
This study's motivation is to explore the relationship pattern between remittance, trade openness, and inequality of selected south Asian countries for the 1976-2018 period. The study performed non-linear tests, including unit root tests, non-linearity applying ordinary least squares (OLS) and BDS tests, non-linear autoregressive distributed lagged (NARDL) tests, and asymmetry causality tests to assess their association. Study findings with non-linear unit root tests suggest that the research variables follow the non-linear process of becoming stationary from non-stationary. The non-linear OLS and BDS test results confirm the existence of non-linearity among research variables, implying rejection of the null hypothesis of "no non-linearity." Furthermore, the results of the Wald test in NARDL confirm the availability of asymmetric links among variables. Besides this, the results of NARDL confirm the long-run asymmetric relationship between remittances, trade openness, and inequality in all sample nations. Findings suggest that both positive and negative shocks in remittances and trade openness is critical to either instituting or vexing the present state of inequality in the economy in the long term. In the directional relationship with asymmetry causality, the study shows that the feedback hypothesis holds to explain the asymmetric causal effects that are positive shocks in remittances and trade openness toward inequality.


Comparison of (-)-eseroline with (+)-eseroline and dihydroseco analogues in antinociceptive assays: confirmation of rubreserine structure by X-ray analysis.
The enantiomers of eseroline bind to opiate receptors of rat brain membranes with equal affinities and show opiate agonist properties as inhibitors of adenylate cyclase in vitro. However, only (-)-eseroline shows potent narcotic agonist activity in vivo, similar to that of morphine. Neither (-)-noreseroline, (+)-eseroline, nor the open dihydroseco analogue (-)-8 shows analgetic effects in vivo. The structure of rubreserine being a resonance hybrid of an o-quinone with its zwitterionic mesomer is confirmed by solid-state X-ray diffraction analysis.


Cancer stem cell biology: from leukemia to solid tumors.
The biology of stem cells and their intrinsic properties are now recognized as integral to tumor pathogenesis in several types of cancer. This observation has broad ramifications in the cancer research field and is likely to impact our understanding of the basic mechanisms of tumor formation and the strategies we use to treat cancers. A role for stem cells has been demonstrated for cancers of the hematopoietic system, breast and brain. Going forward it is likely that stem cells will also be implicated in other malignancies. Hence, a detailed understanding of stem cells and how they mediate tumor pathogenesis will be critical in developing more effective cancer therapies.


FLT3 targeting in the modern era: from clonal selection to combination therapies.
Fms-like tyrosine kinase 3 (FLT3) is the most frequently mutated gene in acute myeloid leukemia (AML). Modern targeting of FLT3 with inhibitors has improved clinical outcomes and FLT3 inhibitors have been incorporated into the treatment of AML in all phases of the disease, including the upfront, relapsed/refractory and maintenance settings. This review will discuss the current understanding of FLT3 biology, the clinical use of FLT3 inhibitors, resistance mechanisms and emerging combination treatment strategies.


Enhancing effects of angiotensin I on the vasopressin-stimulated water flow of toad bladder through increased cyclic AMP in mucosal cells.
The effects of angiotensins I and II on 10 mU/ml vasopressin-stimulated water flow across toad bladder were examined. Angiotensin I at concentrations of 10(-6) and 10(-7) M enhanced the water flow, but angiotensin II failed to do so at these concentrations. Angiotensin I had no effect on 5 mM cyclic AMP-stimulated water flow. After being preincubated for 30 min with angiotensin II, angiotensin I failed to have any stimulatory effect on vasopressin-stimulated water flow. At 10(-6) M angiotensin I significantly enhanced vasopressin-stimulated cyclic AMP content in bladder mucosal cells. These results indicate that angiotensin I enhances vasopressin-stimulated water flow by increasing cyclic AMP production in bladder cells and that angiotensin II may possibly interfere with angiotensin I in a competitive manner.


CD56+ putative natural killer cell lymphomas: production of cytolytic effectors and related proteins mediating tumor cell apoptosis?
Apoptosis is a regulated form of cell death that may be triggered by natural killer (NK) or cytotoxic T cells, which effect target cell lysis by cytolytic effector and related proteins through complex intracellular signals. This study was aimed to investigate whether there is selective expression of these cytolytic markers in the putative NK-cell lymphomas and whether there is correlation with zonal tumor cell death in these tumors. Expression of the cytolytic effectors perforin, granzyme B9, and the granule membrane protein TIA1 were examined in 24 putative NK-cell lymphomas, 18 postthymic T-cell lymphomas (one case CD8+ CD56+ and three anaplastic large cell lymphomas (ALCL), three T-lymphoblastic lymphomas, and 20 B-cell lymphomas. Nineteen (79%) putative NK-cell lymphomas expressed perforin, and all 24 cases expressed granzyme B9 and TIA1. The only CD8+ CD56+ postthymic T-cell lymphoma also expressed all three cytolytic markers, two CD8- ALCL expressed TIA1; other postthymic T-cell, T-lymphoblastic, and B-cell lymphomas were consistently negative. There was strong correlation between percentage perforin-positive cells and zonal tumor cell death. Angioinvasion, in contrast, was present only in a proportion (37%) of these lymphomas despite the frequent presence of zonal tumor cell death (71%). We propose that cytolytic effector and related proteins produced by putative NK and some CD8+ CD56+ postthymic T-cell lymphomas, probably in conjunction with other mechanisms, may effect massive tumor cell apoptosis. The frequent expression of cytolytic effector markers in the CD2+ surface CD3- CD56+ putative NK-cell lymphomas lends further support to their probable NK cell origin.


Biodistribution of aqueous suspensions of carbon nanotubes in mice and their biocompatibility.
In this study, we prepared two-types of water-dispersible carbon nanotubes (CNTs) and investigated their biodistribution in mice as well as bio-/cyto-compatibility. After administration, their organs were excised at various post-injection times, then observed using both optical and transmission electron microscopy (TEM). The color of the liver and lung markedly darkened, suggesting that administered CNTs reached these organs. By TEM observation, the CNTs were found in the liver and lung. They were observed even in the kidney and spleen, though their distributions in those organs were very low compared with that in liver and lung. Therefore, most of the administered CNTs would be accumulated in the liver or lung. However, the time profile of the body weight of CNT-administered mice was close to that of control mice. In addition, we estimated the cytocompatibility of the water-dispersible CNTs for hepatocytes. According to a TNF-alpha assay of the cells cultured with CNTs, the expression level was almost the same as that of the control. These results suggested that the water-dispersible CNTs have good bio-/cyto-compatibility under this condition.


Efficacy of intravenous acetaminophen in multimodal management for pain relief following total knee arthroplasty: a meta-analysis.
The efficacy of intravenous acetaminophen in multimodal pain management in patients undergoing total knee arthroplasty (TKA) is controversial. The purpose of this meta-analysis was to compare the efficacy of intravenous acetaminophen versus placebo in TKA. Randomized controlled trials (RCTs) or retrospective cohort studies (RCSs) concerning related topics were retrieved from PubMed (1996-June 2018), Embase (1980-June 2018), and the Cochrane Library (CENTRAL June 2018). Any studies comparing intravenous acetaminophen with a placebo were included in this meta-analysis. Meta-analysis results were collected and analyzed by Stata 12.0. Subgroup analysis was performed according to the general characteristics of the patients. In total, the patients from six studies met the inclusion criteria. Our meta-analysis results indicated that compared with a control group, intravenous acetaminophen was associated with reductions in total morphine consumption and visual analogue scale (VAS) score at postoperative day (POD) 3. However, there was no significant difference in morphine consumption at POD 1 or in VAS at POD 1 or POD 2. Moreover, there was no significant difference in the length of hospital stay. Based on our results, intravenous acetaminophen in multimodal management has shown better efficacy in pain relief at POD 3 and has morphine-sparing effects. High-quality studies with more patients are needed in the future.


In Vivo Therapeutic Effect of Some Medicinal Plants' Methanolic Extracts on the Growth and Development of Secondary Hydatid Cyst Infection.
The current study aimed to explore the in vivo therapeutic effects of the methanolic extracts of Citrullus colocynthis, Ruta graveolens, and Peganum harmala against hydatid cyst secondary infection. Aerial parts of P. harmala and R. graveolens, including leaves and stems, and seeds of C. colocynthis were collected and extracted using absolute methanol. Rats that are infected with secondary infection of hydatid cysts were treated orally and intraperitoneally according to the determined lethal doses for 30 days. Histological, hematological, and biochemical investigations were done 8 months after the infection. Compared to Albendazole drug, C. colocynthis, and P. harmala, the methanol extract of R. graveolens showed higher and significant (P < 0.05) therapeutic effects on the secondary hydatid cysts growth. Those effects were represented by the reduction in the cysts' number, size, and weight; as well as the significant changes (P < 0.05) in values of hematological and biochemical parameters, the elevation of IFN-γ levels, and the decline of IL-10 and IL-4 cytokines, compared to the negative control group in both routes of treatment (oral and IP). Moreover, the histological sections showed that R. graveolens has a clear damaging effect on the hydatid cysts GL in the infected rats represented by the detachment of GL from LL and AL. This study can open an avenue to find new therapeutics for secondary hydatid cyst infections using the studied plant extracts, especially the extract of R. graveolens.


Results of a 10-year hearing screening using automated auditory brainstem response in newborns: The two-step AABR method.
Approximately 1-6 in every 1000 children are born with hearing loss. An automated auditory brainstem response (AABR) test is essential for screening newborns for abnormal hearing. At the tertiary hospital, we have been using a two-step AABR protocol for newborn hearing assessment since 2005. This study aimed to report the 10-year hearing screening results of newborns at the institution, and prove the efficacy of the two-step AABR protocol. From August 2005 to January 2015, 3059 newborns were screened through AABR testing using the MASTER ABaer system. The first screening test was performed after the first 24 h of life. If a newborn was referred, the test was performed within 1 month after discharge from the hospital. The results were regarded as pass when the point optimized variance ratio was >3.5, using a stimulus level of 35 dB HL. When newborns were referred for the second AABR, they received follow-up tests including tympanometry, ABR, auditory steady-state response, and otoacoustic emission within 3 months. A total of 3059 newborns underwent newborn hearing screening tests over a period of 10 years. One hundred and twenty (3.9%) newborns were referred with the initial AABR, and 104 (3.4%) were referred with a subsequent AABR. Of the newborns, 42 (1.37%) were confirmed to have a bilateral hearing impairment. It is known that the referral rate for the AABR test is 3-4%, as recommended by the Joint Committee on Infant Hearing. Our data showed a referral rate of 3.4%. The two-step AABR test has been useful for screening hearing loss in newborns at tertiary hospital.


Nitric oxide stimulates PC12 cell proliferation via cGMP and inhibits at higher concentrations mainly via energy depletion.
We investigated the mechanisms by which nitric oxide (NO) from an NO donor (DETA/NO) regulates proliferation of pheochromocytoma PC12 cells. The NO donor stimulated proliferation at low concentrations, but reversibly and completely inhibited proliferation at higher concentrations. The stimulation (but not the inhibition) of proliferation was apparently due to NO stimulation of soluble guanylate cyclase to produce cGMP, as it was prevented by a specific cyclase inhibitor (ODQ), and replicated by a cell-permeable form of cGMP. The NO-induced cytostasis was not reversed by inhibitors of MEK kinase or poly(ADP-ribose)polymerase, or by treatments that bypass inhibition of ribonucleotide reductase or ornithine decarboxylase. Cytostatic concentrations of DETA/NO strongly inhibited respiration of PC12 cells, and specific respiratory inhibitors (rotenone, myxothiazol, or azide) caused complete cytostasis. Uridine and pyruvate reversed the cytostasis induced by the specific respiratory inhibitors, but not that induced by DETA/NO. However, the combination of uridine, pyruvate, and N-acetyl-cysteine did reverse DETA/NO-induced cytostasis. DETA/NO strongly and progressively inhibited glycolysis measured by glucose consumption, lactate production, and ATP level, and a specific glycolytic inhibitor (5 mM 2-deoxy-d-glucose) caused complete cytostasis. Our results indicate that NO at low concentrations increases cell proliferation via cGMP, while high concentrations of NO block proliferation via inhibition of both glycolysis and respiration, causing energy depletion.


Laboratory parameter-based machine learning model for excluding non-alcoholic fatty liver disease (NAFLD) in the general population.
Non-alcoholic fatty liver disease (NAFLD) affects 20%-40% of the general population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Electronic medical records facilitate large-scale epidemiological studies, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases. To develop and validate a laboratory parameter-based machine learning model to detect NAFLD for the general population. We randomly divided 922 subjects from a population screening study into training and validation groups; NAFLD was diagnosed by proton-magnetic resonance spectroscopy. On the basis of machine learning from 23 routine clinical and laboratory parameters after elastic net regulation, we evaluated the logistic regression, ridge regression, AdaBoost and decision tree models. The areas under receiver-operating characteristic curve (AUROC) of models in validation group were compared. Six predictors including alanine aminotransferase, high-density lipoprotein cholesterol, triglyceride, haemoglobin A1c , white blood cell count and the presence of hypertension were selected. The NAFLD ridge score achieved AUROC of 0.87 (95% CI 0.83-0.90) and 0.88 (0.84-0.91) in the training and validation groups respectively. Using dual cut-offs of 0.24 and 0.44, NAFLD ridge score achieved 92% (86%-96%) sensitivity and 90% (86%-93%) specificity with corresponding negative and positive predictive values of 96% (91%-98%) and 69% (59%-78%), and 87% of overall accuracy among 70% of classifiable subjects in the validation group; 30% of subjects remained indeterminate. NAFLD ridge score is a simple and robust reference comparable to existing NAFLD scores to exclude NAFLD patients in epidemiological studies.


Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one derivatives structurally related with piracetam.
Three 2,3-dihydro-1H-isoindol-1-ones structurally related with piracetam (=2-oxopyrrolidine-1-acetamide) have been synthesized and tested for their nootropic effects in the passive avoidance test in mice. Compounds (RS)-2, (R,R)-3, and (R,S)-3 were obtained in good yields in only two steps starting from methyl DL-phthaloylalanine. Compound (RS)-2 exhibited nootropic activity at lower doses than piracetam, used as reference drug, but it showed lower efficacy. Whereas diastereoisomers (R,R)-3 and (R,S)-3 were as potent as piracetam to revert amnesia induced by scopolamine, (R,S)-3 showed lower efficacy than (R,R)-3. Only (R,R)-3 showed myorelaxant effect at doses of 10 and 30 mg/kg; other compounds did not exhibit any anticonvulsant, sedative, myorelaxant, or impaired motor-coordination effect in mice. These synthesized 2,3-dihydro-1H-isoindol-1-one derivatives constitute a new kind of nootropic compounds.


Role of magnetic substances in adsorption removal of ciprofloxacin by gamma ferric oxide and ferrites co-modified carbon nanotubes.
Antibiotics have been considered an evolving environmental challenge in the last few decades due to their mutagenic and persistent effects. Herein, we synthesized γ-Fe2O3 and ferrites nanocomposites co-modified carbon nanotubes (γ-Fe2O3/MFe2O4/CNTs, M: Co, Cu, and Mn) with high crystallinity, thermostability, and magnetization for the adsorption removal of ciprofloxacin. The experimental equilibrium adsorption capacities of ciprofloxacin on γ-Fe2O3/MFe2O4/CNTs were 44.54 (Co), 41.13 (Cu), and 41.53 (Mn) mg/g, respectively. The adsorption behaviors followed the Langmuir isotherm and pseudo-first-order models. Density functional theory calculations revealed that the active sites preferentially appeared on the oxygen of the carboxyl group in ciprofloxacin, and the calculated adsorption energies of ciprofloxacin on CNTs, γ-Fe2O3, CoFe2O4, CuFe2O4, and MnFe2O4 were -4.82, -1.08, -2.49, -0.60, and 5.69 eV, respectively. The addition of γ-Fe2O3 changed the adsorption mechanism of ciprofloxacin on MFe2O4/CNTs and γ-Fe2O3/MFe2O4/CNTs. CNTs and CoFe2O4 controlled the cobalt system of γ-Fe2O3/CoFe2O4/CNTs, while CNTs and γ-Fe2O3 ruled the adsorption interaction and capacity of copper and manganese systems. This work reveals the role of magnetic substances, which is beneficial to the preparation and environmental application of similar adsorbents.


Synthesized trade-off analysis of flood control solutions under future deep uncertainty: An application to the central business district of Shanghai.
Coastal mega-cities will face increasing flood risk under the current protection standard because of future climate change. Previous studies seldom evaluate the comparative effectiveness of alternative options in reducing flood risk under the uncertainty of future extreme rainfall. Long-term planning to manage flood risk is further challenged by uncertainty in socioeconomic factors and contested stakeholder priorities. In this study, we conducted a knowledge co-creation process together with infrastructure experts, policy makers, and other stakeholders to develop an integrated framework for flexible testing of multiple flood-risk mitigation strategies under the condition of deep uncertainties. We implemented this framework to the reoccurrence scenarios in the 2050s of a record-breaking extreme rainfall event in central Shanghai. Three uncertain factors, including precipitation, urban rain island effect and the decrease of urban drainage capacity caused by land subsidence and sea level rise, are selected to build future extreme inundation scenarios in the case study. The risk-reduction performance and cost-effectiveness of all possible solutions are examined across different scenarios. The results show that drainage capacity decrease caused by sea-level rise and land subsidence will contribute the most to the rise of future inundation risk in central Shanghai. The combination of increased green area, improved drainage system, and the deep tunnel with a runoff absorbing capacity of 30% comes out to be the most favorable and robust solution which can reduce the future inundation risk by 85% (±8%). This research indicates that to conduct a successful synthesized trade-off analysis of alternative flood control solutions under future deep uncertainty is bound to be a knowledge co-creation process of scientists, decision makers, field experts, and other stakeholders.


Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics.
Multiple sclerosis (MS) is a complex inflammatory and neurodegenerative chronic disease that involves the immune and central nervous systems (CNS). The pathogenesis involves the loss of blood-brain barrier integrity, resulting in the invasion of lymphocytes into the CNS with consequent tissue damage. The MS etiology is probably a combination of immunological, genetic, and environmental factors. It has been proposed that T lymphocytes have a main role in the onset and propagation of MS, leading to the inflammation of white matter and myelin sheath destruction. Cyclic AMP (cAMP), mitochondrial dysfunction, and oxidative stress exert a role in the alteration of T lymphocytes homeostasis and are involved in the apoptosis resistance of immune cells with the consequent development of autoimmune diseases. The defective apoptosis of autoreactive lymphocytes in patients with MS, allows these cells to perpetuate, within the CNS, a continuous cycle of inflammation. In this review, we discuss the involvement in MS of cAMP pathway, mitochondria, reactive oxygen species (ROS), apoptosis, and their interaction in the alteration of T lymphocytes homeostasis. In addition, we discuss a series of nutraceutical compounds that could influence these aspects.


Identification of suitable endogenous control genes for quantitative RT-PCR analysis of miRNA in bovine solid tissues.
Quantitative reverse transcription polymerase chain reaction (qRT-PCR) has become the preferred technique for studying low-abundance RNA expression. Proper normalization is a critical but often underappreciated aspect of quantitative gene expression analysis; popular endogenous control genes are usually selected with little knowledge of their real suitability. To date, there are very few reports regarding the general validation of endogenous control genes for microRNA (miRNA) expression analysis in bovine tissue. In the present study, eight candidate reference genes (U6, 18S rRNA, GAPDH, ACTB, miR-191, miR-15a, miR-18a, let-7f) were tested for use as normalizers of bovine miRNA in RT-qPCR assays. Their selection was based on publicly available data concerning normalization, hierarchical clustering and sequencing. Three of the genes (miR-191, U6-1 and let-7f) were found to be highly consistent in their expression across eight different bovine solid tissues. It is commonly accepted that gene expression studies should be normalized using more than one endogenous control gene. Based on our results, we propose using the combined results for miR-191, U6-1 and let-7f as the endogenous control for normalization of miRNA levels in qRT-PCR analysis of diverse bovine tissues. This result could act a guideline for future work on bovine miRNA expression.


Is body image a predictor of women's depression and anxiety in postmenopausal women?
Women in perimenopausal and postmenopausal period are at increased risk of depression and anxiety. Physiologic changes in menopause can change body's appearance and function that may disturb body and then lead to anxiety and depression. This study aims to assess the relationship between body image with anxiety and depression among postmenopausal women. This descriptive study was performed on 307 women attending to the health centers in Tehran- Iran. Sampling was performed by a multi-staged randomized method. Data were collected by using Beck Depression questionnaire, Spielberger Anxiety Questionnaire, Fisher Body Image Questionnaire and Socio-demographic questionnaires. Data were analyzed by SPSS 21 and using t-test, Pearson and Spearman correlation tests and multiple linear regression methods. The average age of the participants was 55.19 ± 4.034 years. Mean scores for body image, anxiety and depression were 163.26 ± 20.38, 12.00 ± 7.71 and 42.70 ± 8.40 respectively. Fifty five percent of women had mild to severe depression and 83.7% of them had mild to severe anxiety. Total score and all domains of body image had a negative correlation with depression and anxiety scores (P < 0.001). Multiple linear correlation showed that body image is a predictor for depression and anxiety (P < 0.001). Body image of women can be effective on occurrence of depression and anxiety in menopause. Therefore, women's health policies should consider body image to control cognitive problems including depression and anxiety in menopause.


Antimelanoma Effects of Concomitant Inhibition of SIRT1 and SIRT3 in BrafV600E/PtenNULL Mice.
Novel therapeutic strategies are required for the effective and lasting treatment of metastatic melanoma, one of the deadliest skin malignancies. In this study, we determined the antimelanoma efficacy of 4'-bromo-resveratrol (4'-BR), which is a small-molecule dual inhibitor of SIRT1 and SIRT3, in a BrafV600E/PtenNULL mouse model that recapitulates human disease, including metastases. Tumors were induced by topical application of 4-hydroxy-tamoxifen on shaved backs of mice aged 10 weeks, and the effects of 4'-BR (5‒30 mg/kg of body weight, intraperitoneally, 3 days per week for 5 weeks) were assessed on melanoma development and progression. We found that 4'-BR at a dose of 30 mg/kg significantly reduced the size and volume of primary melanoma tumors as well as lung metastasis with no adverse effects. Furthermore, mechanistic studies on tumors showed significant modulation in the markers of proliferation, survival, and melanoma progression. Because SIRT1 and SIRT3 are linked to immunomodulation, we performed differential gene expression analysis using a PanCancer Immune Profiling Panel (770 genes). Our data showed that 4'-BR significantly downregulated the genes related to metastasis promotion, chemokine/cytokine regulation, and innate/adaptive immune functions. Overall, inhibition of SIRT1 and SIRT3 by 4'-BR is a promising antimelanoma therapy with antimetastatic and immunomodulatory activities warranting further detailed studies, including clinical investigations.


Photo induced mechanistic activity of GO/Zn(Cu)O nanocomposite against infectious pathogens: Potential application in wound healing.
Treating infection causing microorganisms is one of the major challenges in wound healing. These may gain resistance due to the overuse of conventional antibiotics. A promising technique is antimicrobial photodynamic therapy (aPDT) used to selectively cause damage to infectious pathogenic cells via generation of reactive oxygen species (ROS). We report on biocompatable nanomaterials that can serve as potential photosensitizers for aPDT. GO/Zn(Cu)O nanocomposite was synthesized by co-precipitation method. Graphene Oxide (GO) is known for its high surface to volume ratio, excellent surface functionality and enhanced antimicrobial property. ZnO nanoparticle induces the generation of reactive oxygen species (ROS) under light irradiation and it leads to recombination of electron-hole pair. Nanocomposites of GO and Cu doped ZnO increases visible light absorption and enhances the photocatalytic property. It generates more ROS and increases the bacterial inhibition. GO/Zn(Cu)O nanocomposite was tested against Staphylococcus aureus (S. aureus), Enterococcus faecium (E. faecium), Escherichia coli (E. coli), Salmonella typhi (S. typhi), Shigella flexneri (S. flexneri) and Pseudomonas aeruginosa (P. aeruginosa) by well diffusion method, growth curve, colony count, biofilm formation under both dark and visible light condition. Reactive Oxygen Species assay (ROS), Lactate dehydrogenase leakage (LDH) assay, Protein estimation assay and membrane integrity study proves the mechanism of inhibition of bacteria. Inhibition kinetics shows the sensitivity between bacteria and GO/Zn(Cu)O nanocomposite.


The transmission of vesicoureteral reflux from parent to child.
Vesicoureteral reflux is now recognized to be hereditary and familial. The incidence of reflux in siblings has proved to be significant but less is known about the incidence of reflux in the offspring of known reflux patients. In an ongoing prospective series of reflux screening we identified 23 patients of childbearing age with a known history of reflux and screened their 36 offspring with an awake voiding cystourethrogram. Of these 36 offspring 24 (66%) exhibited vesicoureteral reflux. The literature was also reviewed to determine the incidence of parent/child reflux from reported cases. This review revealed a 65% rate of reflux in the offspring of known patients. Our preliminary results coupled with those in the literature signify a need to screen the offspring of known reflux patients and suggest a rethinking of the genetic transmission for this trait. While vesicoureteral reflux could still be a multifactorial genetic trait with a major gene, consideration must also be given to an autosomal dominant inheritance pattern.


Development of leading first-generation vaccines against SARS-CoV-2.
SARS-CoV-2 has infected more than 167 million individuals globally. Highly effective and safe vaccines are required to accelerate the development of herd immunity to end the pandemic. This review focuses on vaccines that are being developed at unprecedented speed globally and are completing late phase clinical trials to meet this urgent need.


Association between Heated Tobacco Product Use during Pregnancy and Fetal Growth in Japan: A Nationwide Web-Based Survey.
Combustible cigarette smoking impacts fetal growth during pregnancy. However, the risk associated with heated tobacco products (HTPs) remains unclear. This nationwide cross-sectional study investigated whether HTP use during pregnancy is associated with small for gestational age (SGA) outcomes among 5647 post-delivery women with singleton pregnancies, which were divided into four groups: lifetime never-smokers, former smokers before pregnancy, and current smokers for each of the tobacco products during pregnancy (sole HTP and sole combustion smokers). Information on the prevalence of SGA, defined as birth weight and height below the 10th percentile, was retrieved from the Maternal and Child Health Handbooks of post-delivery women. Using logistic regression, the association between sole HTP smokers during pregnancy and SGA, adjusted for covariates, with lifetime never-smokers as reference, was investigated. The prevalence was: current sole HTP smokers during pregnancy, 1.8% (102/5647); and SGA, 2.9% (164/5647). Sole HTP smokers during pregnancy had a higher prevalence of SGA (5.9% [6/102] vs. 2.7% [111/4144]) with an adjusted odds ratio (OR) of 2.50 (95% confidence interval [CI], 1.03-6.05) than lifetime never-smokers. Among sole combustion smokers, the adjusted OR for SGA was 1.95 (95% CI, 0.81-4.67). In Japan, HTP smoking during pregnancy may be associated with an increased risk for SGA.


T Stage and Pretreatment Standardized Uptake Values Predict Tumor Recurrence With 5-Fraction SABR in Early-Stage Non-Small Cell Lung Cancer.
Five-fraction stereotactic ablative radiotherapy (SABR) regimens are frequently used to treat centrally located early-stage non-small cell lung cancer or disease in the proximity of the chest wall as a means of optimizing tumor control and reducing treatment toxicity. However, increasing these SABR regimens to 5 fractions may reduce tumor control outcomes. We sought to identify the clinical parameters predictive of treatment failures with these 5-fraction courses. Ninety patients with T1-2 non-small cell lung cancer were treated with 50 or 60 Gy in 5 fractions. Failure over time was modeled using cumulative incidences of local, regional, or distant failure, with death as a competing risk. Cox proportional hazards analysis for incidences of failure was performed to control for patient variables. Of 90 patients, 24 of 53 patients with T1 tumors and 19 of 37 patients with T2 tumors received 50 Gy SABR, and the other 47 patients received 60 Gy. Two-year overall survival and progression-free survival for the whole cohort were 75.8% and 59.3%, respectively. Total SABR dose (50 vs 60 Gy) did not influence survival nor failure rates at 2 and 5 years. Within 2 years of treatment, 7.8% of all patients developed local failure. For all patient and tumor characteristics evaluated, only T stage and pretreatment positron emission tomography standardized uptake values served as predictors of local, regional, and distant failure at 2 and 5 years posttreatment on univariate and multivariable analysis. Five-fraction SABR provides excellent in-field control. T2 and high fluorodeoxyglucose uptake tumors have increased failure rates, suggesting the potential need for adjuvant therapies, which are being assessed in randomized phase 3 trials.


Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells.
The year 2020 begins with the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that cause the disease COVID-19, and continue till today. As of March 23, 2021, the outbreak has infected 124,313,054 worldwide with a total death of 2,735,707. The use of traditional medicines as an adjuvant therapy with western drugs can lower the fatality rate due to the COVID-19. Therefore, in silico molecular docking study was performed to search potential phytochemicals and drugs that can block the entry of SARS-CoV-2 into host cells by inhibiting the proteolytic cleavage activity of furin and TMPRSS2. The protein-protein docking of the host proteases furin and TMPRSS2 was carried out with the virus spike (S) protein to examine the conformational details and residues involved in the complex formation. Subsequently, a library of 163 ligands containing phytochemicals and drugs was virtually screened to propose potential hits that can inhibit the proteolytic cleavage activity of furin and TMPRSS2. The phytochemicals like limonin, gedunin, eribulin, pedunculagin, limonin glycoside and betunilic acid bind at the active site of both furin and TMPRSS2. Limonin and gedunin found mainly in the citrus fruits and neem showed the highest binding energy at the active site of furin and TMPRSS2, respectively. The polyphenols found in green tea can also be useful in suppressing the furin activity. Among the drugs, the drug nafamostat may be more beneficial than the camostat in suppressing the activity of TMPRSS2.


Fatal non-traumatic spontaneous hemoperitoneum in second trimester of pregnancy--autopsy findings.
Spontaneous hemoperitoneum in second trimester of pregnancy is a very rare but lethal condition which demands prompt diagnosis and management for the survival of both mother and fetus. A 21-year old primigravida woman was presented at 29 weeks of pregnancy with acute abdominal pain and hypovolumic shock. In a District Hospital patient was managed conservatively and referred but was brought dead at tertiary level hospital. On autopsy gross hemoperitoneum was found without any injury and uterine artery found ruptured against the suspicion of brutal beating by the relatives of husband.


A neuromuscular transmission block produced by a cancer tissue extract derived from a patient with the myasthenic syndrome.
The myasthenic syndrome occasionally is associated with bronchogenic carcinoma. The neuromuscular transmission defect in this syndrome is characterized by a reduction of acetylcholine release from motor nerve endings. This paper reports that an acetone extract of cancer tissue from a patient with the syndrome reduces the acetylcholine release from motor nerve endings and produces a neuromuscular transmission defect in the frog nerve-muscle preparation. This suggests that the pathogenic substance(s) contained in the extract may be produced by certain types of bronchogenic carcinoma and may cause the myasthenic syndrome.


Intermittent meromixis controls the trophic state of warming deep lakes.
Vertical mixing modulates nutrient dynamics in lakes. However, surface warming reduces the range of vertical mixing and the probability of full circulation events. Important consequences of reduced vertical mixing include the sequestration of phosphorus (P) within a stagnant zone and the promotion of oligotrophication. Nevertheless, warming-induced shifts from full to partial mixing (meromixis) are not permanent and are partially reversible during exceptionally cold or windy winters. In this study, we investigated how intermittent meromixis affects lake P budgets. We examined the P cycle of a perialpine lake with variable mixing depths by pairing sedimentation and release flux measurements with sedimentary archives. We found that the amount of dissolved P surpassed that of the potentially mobile P in the sediments by a 13:1 ratio. At least 55% of the settled P was rapidly released to bottom waters isolated from flushing, illustrating the general biogeochemical mechanism that promotes deep-water P storage when lakes undergo warming. This storage process is abruptly inverted when meromixis suddenly retreats, deeper mixing introduces P pulses to the surface waters, thereby promoting phytoplankton proliferation. Our estimates showed that lakes containing up to 40% of the global freshwater volume could shift towards intermittent meromixis if the atmospheric warming trend continues. Thus, these lakes might accumulate 0-83% of their P load in irregularly circulating waters and are prone to large P pulses.


Factors associated with community commitment among older adults: a stratified analysis of community group leaders and members.
Community commitment through group activities in the community is associated with improved health outcomes in older adults and has a ripple effect on community development. However, factors associated with community commitment through group activities in the community have not been examined. The purpose of this study was to examine individual factors and group-related factors in association with community commitment among older adult leaders and members of community groups in Japan. We mailed self-administered questionnaires to all older adults participating in a community group (N = 1,898) in a ward of Yokohama city, the largest designated city in Japan. Variables included demographic characteristics, community commitment (Community Commitment Scale), individual factors, and group-related factors. We used logistic regression analysis to assess the association among study variables. A total of 1,154 people completed the questionnaire. The valid response rate was 48.8%. Respondents' mean age was 78.3 years (standard deviation [SD] = 6.1, range 65-100 years), 79.6% were women, 55.9% were married, and 10.0% were employed. Factors associated with community commitment among group leaders were scores for self-efficacy in the health promotion scale (SF-15; mean ± SD: 48.5 ± 7.1), 5-item World Health Organization Well-Being Index (mean ± SD: 17.9 ± 4.3), and Lubben Social Network Scale, Japanese version (mean ± SD: 19.5 ± 6.9), as well as a perception of deriving pleasure from group participation (mean ± SD: 91.2 ± 9.4). Factors associated with community commitment among group members were economic status (Sufficient; n [%]: 749 [85.9]), frequency of going out (mean ± SD: 5.1 ± 1.8), years of group participation (mean ± SD: 6.2 ± 5.0), and perceptions of their role in the group (Yes; n [%]: 254 [30.4]) as well as the above factors for leaders. A supplementary qualitative analysis of participants' free-text responses extracted seven categories: community support, resource mobilization, partnership action, asset management, participatory decision-making, linkages and networking, and community dissemination, related to perception of a role in the group. Our results emphasize the importance of considering the different associations of community commitment through group activities in the community between group leaders and members, including the role of older adults in community groups, and suggest different approaches for group leaders and members.


Fractures of implant fixtures: a retroscccpective clinical study.
The aim of this study was to evaluate the factors that may affect implant fixture fractures. Patients who experienced implant fixture removal at Seoul National University Bundang Hospital from 2007 to 2015 due to implant fixture fracture were included. Implant/crown ratio, time of implant fracture, clinical symptoms before implant fracture, treatment of fractured implants, and the success and survival rate of the replaced implants were evaluated retrospectively. Thirteen implants were fractured in 12 patients. Patient mean age at the time of fracture was 59.3 years. Of the 13 implants, 7 implants were placed at our hospital, and 6 were placed at a local clinic. The mean crown/implant ratio was 0.83:1. The clinical symptoms before fracture were screw loosening in five implants, marginal bone loss in five implants, and the presence of peri-implant diseases in five implants. All the fractured implants were removed, and 12 out of the 13 sites were re-implanted. Parafunctions were observed in two patients: one with bruxism and one with attrition due to a strong chewing habit. Several clinical symptoms before the fracture of an implant can predict implant fixture failure. Therefore, if these clinical symptoms are observed, appropriate treatments can be taken before more serious complications result.


Reaching trans women in San Francisco for efforts to eliminate hepatitis C.
Hepatitis C infections continue to rise among marginalized communities, including among transgender people. Efforts to eliminate hepatitis C from San Francisco require successful identification of active HCV infections among transgender women and subsequent treatment of infection. This secondary analysis of the National HIV Behavioral Surveillance Transgender Women (NHBS-Trans) Study aims to identify areas of improvement in the hepatitis C care cascade and associated barriers that preclude successful treatment. One hundred and eighty (89.6%) trans women reported being previously screened for HCV, 47 (26.1%) reported being diagnosed with HCV, twenty-eight of the 47 (59.6%) who reported HCV diagnosis also reported that they received HCV treatment, with and 24 of the 28 (85.7%) reported completing their treatment. Overall, we detected HCV antibodies among 23.9% of participants and detected HCV RNA among 6.0%. This suggests that despite improvements in screening for HCV, active cases may not be successfully treated. Efforts to reduce barriers to HCV care should be prioritized, with heightened consideration for trans-specific needs.


Heterotrophic bacteria in water distribution systems. II. Sampling design for monitoring.
In this paper, which is a continuation of the work presented in Part I in this issue, previous information on the spatial and temporal variability of bacteriological data from a water distribution system is used to develop a sampling design for use in future water quality monitoring. The water distribution system is considered to be composed of several zones where the variation of bacterial counts in each zone is modelled by the negative binomial distribution. Under the assumption that the objective of monitoring is to determine whether or not the mean bacterial density of the water exceeds a specific standard, a criterion is given which determines the optimal number of sampling stations allocated to each zone. These stations are determined by assuming that either the risk of sampling (i.e. making the wrong decision) is prespecified or that the total number of stations to be sampled is predetermined. Sequential sampling to evaluate the compliance of the water with the standard is also discussed.


Development of a Time-Resolved Fluorescence Immunoassay for the Diagnosis of Hepatocellular Carcinoma Based on the Detection of Glypican-3.
Glypican-3(GPC3), an oncofetal protein, is a potential novel marker for hepatocellular carcinoma (HCC). In this study, we attempted to establish a new method to detect serum GPC3 using the antibodies identified in our previous research, and then evaluated its clinical application for the diagnosis of HCC. Herein, a sandwich time-resolved fluorescence immunoassay (TRFIA) for detecting serum GPC3 was developed. The detection limit, analytical recovery, specificity and precision of the proposed TRFIA assay were satisfactory. A total of 415 patients were collected and divided into seven groups: hepatocellular carcinoma (101), colorectal cancer (67), gastric cancer (44), esophageal cancer (15), cirrhosis (55), hepatitis (61), normal liver (72). Using this proposed method, the concentration of serum GPC3 in these clinical samples was detected. The results demonstrated that the levels of GPC3 in serum from HCC patients were significantly higher than that in others. Compared with the results of chemiluminescence immunoassay (CLIA), a high consistency (Kappa =0.84) was observed. Thus, an effective, sensitive and reliable TRFIA-GPC3 kit for diagnosing HCC was successfully developed. It offers a suitable alternative to existed methods of determining GPC3 and is expected to be used in clinic in the future.


Risk of malignancy in solid breast nodules according to their sonographic features.
The purpose of this study was to assess the risk of malignancy for each type of sonographic feature in solid breast nodules. The study included 304 patients from the Department of Gynecology and Obstetrics of the Federal University of Goiás who had solid breast nodules. A medical trainee, working under the supervision of a preceptor, obtained the sonographic images of the breast, and the features were recorded in a questionnaire. Each sonographic feature was analyzed and compared with the anatomic and pathologic findings after the lesion was excised. Of the 304 patients included in the study, 292 (96%) had a conclusive diagnosis. Among these women, 216 (74%) had benign tumors and 76 (26%) had malignant tumors. The odds ratio of malignancy in breast nodules, as calculated by multivariate analysis, was as follows: lesions without circumscribed margins, 17.02 (95% confidence interval, 5.28-54.90); lesions with heterogeneous echo texture, 7.70 (2.99-19.84); lesions with thickened Cooper ligaments, 15.61 (1.08-225.10); nodules whose anteroposterior dimension was larger than their width, 3.29 (1.09-9.96); those with an anterior echogenic rim, 2.59 (0.80-8.40); and those with posterior shadowing, 1.57 (0.62-4.01). Among the 133 cases that had all the sonographic features of a benign lesion, 3 nodules (2.3%) had a histologic diagnosis of malignant. Sonography is a diagnostic method that can help establish the differentiation between benign and malignant solid tumors. A lack of circumscribed margins, heterogeneous echo patterns, thickened Cooper ligaments, and an increased anteroposterior dimension can indicate a higher probability of malignancy in solid breast nodules.


Coeliac disease in chronic hepatitis C: a French multicentre prospective study.
A prevalence of 1.2% of coeliac disease (CD) in patients with chronic hepatitis C was recently reported, suggesting a possible epidemiological link between these two diseases. However, other studies have not found this relationship. To conduct a French multicentre prospective study to assess the prevalence of CD in hepatitis C virus (HCV)-infected patients. Between June 2003 and November 2005, 624 consecutive HCV-positive out-patients were tested for antiendomysial IgA antibodies (AEA), antigliadin IgA and IgG antibodies (AGA). Patients with positive AEA or IgA AGA and positive IgG AGA in a context of a high suspicion of CD were asked to undergo gastroscopy with duodenal biopsies. Isolated IgA AEA, IgA AGA and IgG AGA were 0.16%, 5.7% and 4.4%, respectively. Gastroscopy was required for 39 patients, 31 were performed (eight refusals), but only 25 duodenal biopsies were performed as six patients had cirrhosis. CD was never detected. The prevalence of CD in HCV-positive patients was 0% (95% confidence interval: 0-0.59%), but there is a low prevalence of CD in the whole French population.


Immune localization of prolactin receptor in the mitochondria-rich cells of the euryhaline teleost (Oreochromis mossambicus) gill.
The present work demonstrates, by Western blotting and immunofluorescent staining, the presence and localization of prolactin (PRL) receptor in tilapia (ti) Oreochromis mossambicus gills. Gill epithelial cells that reacted with PRL receptor antibody were found to be labelled concomitantly with Con A, a marker of the apical crypts in mitochondria-rich (MR) cells. No positive staining was observed in pavement cells or mucus cells with PRL receptor antibody. This indicates that PRL receptors are located specifically in the gill MR cells. Further, the tiPRL receptors were found only in the MR cells of seawater-adapted tilapia gills. The effects of salinity and ions on the expression of tiPRL receptors are discussed.


Electrochemical Intermolecular Monofluoroalkylation of α,β-Unsaturated Carboxylic Acids and Heteroaromatics with 2-Fluoromalonate Esters.
An electrochemical approach for the preparation of monofluorides from α,β-unsaturated carboxylic acids and heteroaromatics with readily available 2-fluoromalonate esters as monofluoroalkyl radical precursors has been developed. The electrosynthesis employs ferrocene (Cp2Fe) as a catalyst in a simple undivided cell with a broad substrate scope, which obviates the need for sacrificial oxidizing reagents.


Molecular characterization and transcriptional regulation of two types of H+-pyrophosphatases in the scuticociliate parasite Philasterides dicentrarchi.
Proton-translocating inorganic pyrophosphatases (H+-PPases) are an ancient family of membrane bound enzymes that couple pyrophosphate (PPi) hydrolysis to H+ translocation across membranes. In this study, we conducted a molecular characterization of two isoenzymes (PdVP1 and PdVP2) located in respectively the alveolar sacs and in the membranes of the intracellular vacuoles of a scuticociliate parasite (Philasterides dicentrarchi) of farmed turbot. We analyzed the genetic expression of the isoenzymes after administration of antiparasitic drugs and after infection in the host. PdVP1 and PdVP2 are encoded by two genes of 2485 and 3069 bp, which respectively contain 3 and 11 exons and express proteins of 746 and 810 aa of molecular mass 78.9 and 87.6 kDa. Topological predictions from isoenzyme sequences indicate the formation of thirteen transmembrane regions (TMRs) for PdVP1 and seventeen TMRs for PdVP2. Protein structure modelling indicated that both isoenzymes are homodimeric, with three Mg2+ binding sites and an additional K+ binding site in PdVP2. The levels of identity and similarity between the isoenzyme sequences are respectively 33.5 and 51.2%. The molecular weights of the native proteins are 158 kDa (PdVP1) and 178 kDa (PdVP2). The isoenzyme sequences are derived from paralogous genes that form a monophyletic grouping with other ciliate species. Genetic expression of the isoenzymes is closely related to the acidification of alveolar sacs (PdVP1) and intracellular vacuoles (PdVP2): antiparasitic drugs inhibit transcription, while infection increases transcription of both isoenzymes. The study findings show that P. dicentrarchi possesses two isoenzymes with H+-PPase activity which are located in acidophilic cell compartment membranes and which are activated during infection in the host and are sensitive to antiparasitic drugs. The findings open the way to using molecular modelling to design drugs for the treatment of scuticociliatosis.


Combinatorial effect of fermentation and drying on the relationship between the structure and expansion properties of tapioca starch and potato starch.
Naturally fermented and sundried tapioca starch is reportedly the traditional material for polvilho azedo and the primary ingredients of gluten-free food items in Brazil. This study aimed to investigate starch structure and expansion rate, high rate is acclaimed in baking application, changes of tapioca starch and potato starch during combinatorial fermentation and drying. The rate of expansion changed from 3.37 mL/g in native tapioca starch to 3.71 mL/g in fermented oven-dried tapioca starch and 6.97 mL/g in fermented sun-dried tapioca starch, while potato starch sample displayed lesser expansion on all treatments. Rapid viscosity analysis, size-exclusion chromatography, X-ray diffraction (XRD), and attenuated total reflectance Fourier transform infrared (ATR-FTIR) and electron paramagnetic resonance spectrometry (EPR) were performed to determine the structure and investigate its relationship with the expansion rate. Fermentation attacked amorphous area and cleaved glycosidic bonds. Sunlight exposure facilitated complex interactions, and crosslinking increased the molecular weight distribution (MWD) in fermented sun-dried potato starch and led to depolymerization in tapioca starch. EPR revealed an initial free radical distribution in both starches, and our results show that intensity changes in tapioca starch are essential for a high expansion capacity.


Current therapy and drug resistance in metastatic castration-resistant prostate cancer.
Castration-resistant prostate cancer (CRPC), especially metastatic castration-resistant prostate cancer (mCRPC) is one of the most prevalent malignancies and main cause of cancer-related death among men in the world. In addition, it is very difficult for clinical treatment because of the natural or acquired drug resistance of CRPC. Mechanisms of drug resistance are extremely complicated and how to overcome it remains an urgent clinical problem to be solved. Thus, a comprehensive and thorough understanding for mechanisms of drug resistance in mCRPC is indispensable to develop novel and better therapeutic strategies. In this review, we aim to review new insight of the treatment of mCRPC and elucidate mechanisms governing resistance to new drugs: taxanes, androgen receptor signaling inhibitors (ARSIs) and poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Most importantly, in order to improve efficacy of these drugs, strategies of overcoming drug resistance are also discussed based on their mechanisms respectively.


Mid-infrared-perturbed molecular vibrational signatures in plasmonic nanocavities.
Recent developments in surface-enhanced Raman scattering (SERS) enable observation of single-bond vibrations in real time at room temperature. By contrast, mid-infrared (MIR) vibrational spectroscopy is limited to inefficient slow detection. Here we develop a new method for MIR sensing using SERS. This method utilizes nanoparticle-on-foil (NPoF) nanocavities supporting both visible and MIR plasmonic hotspots in the same nanogap formed by a monolayer of molecules. Molecular SERS signals from individual NPoF nanocavities are modulated in the presence of MIR photons. The strength of this modulation depends on the MIR wavelength, and is maximized at the 6-12 μm absorption bands of SiO2 or polystyrene placed under the foil. Using a single-photon lock-in detection scheme we time-resolve the rise and decay of the signal in a few 100 ns. Our observations reveal that the phonon resonances of SiO2 can trap intense MIR surface plasmons within the Reststrahlen band, tuning the visible-wavelength localized plasmons by reversibly perturbing the localized few-nm-thick water shell trapped in the nanostructure crevices. This suggests new ways to couple nanoscale bond vibrations for optomechanics, with potential to push detection limits down to single-photon and single-molecule regimes.


Molecular mechanisms of trigeminal neuralgia: A systematic review.
To conduct a systematic review of the available literature for primary research articles identifying potential gene mutations, polymorphisms and other molecular regulatory mechanisms related to trigeminal neuralgia in order to identify the genetic and molecular models of primary trigeminal neuralgia currently being investigated. PubMed and Web of Science were systematically searched to identify primary research articles discussing genetic predictors of trigeminal neuralgia and neuropathic pain that were published prior to July 2020. This review was conducted according to PRISMA guidelines. Out of the 333 articles originally identified, a total of 14 papers were selected for study inclusion. These articles included 5 human studies, 6 mouse studies and 3 rat studies. Four articles investigated sodium channels, 1 investigated a sodium channel and nerve growth factor receptor, 2 investigated potassium channels, 1 investigated calcium channels, 1 investigated the downstream regulatory element antagonist modulator protein, 1 investigated the dynorphin-kappa opioid receptor system, 1 investigated TRPA1, 1 investigated the Nrg1/ErbB3/ErbB2 signaling complex, 1 investigated a serotonin transporter and 1 investigated potassium channels, sodium channels, calcium channels, chloride channels, TRP channels and gap junctions. Researchers have identified multiple genetic and molecular targets involved with potential pathophysiologies that have a relationship to the creation of trigeminal neuralgia. At this time, there does not seem to be clear causal frontrunner, demonstrating the possibility that genetic predisposition to trigeminal neuralgia may involve multiple genes and/or downstream products, such as ion channels.


Cigarette-specific disgust aroused by smoking warning images strengthens smokers' inhibitory control under smoking-related background in Go/NoGo task.
Reduced inhibitory control is more pronounced during substance-related cue exposure among addicts. However, it is inconclusive whether smokers' inhibitory control would be impaired by smoking-related background. Furthermore, few studies explored whether the cigarette-specific disgust aroused by smoking warning images would alleviate the negative effect of smoking-related cues on smokers' inhibitory control. Experiment 1 investigated the effect of smoking-related background on inhibitory control in cigarette smokers with a modified Go/NoGo task and experiment 2 explored whether cigarette-specific disgust aroused by smoking warning images would alleviate the negative effect of smoking-related background on smokers' inhibitory control. Sixty-two male participants (32 smokers and 30 non-smokers) were recruited in experiment 1 and 51 male smokers were recruited in experiment 2. Experiment 1 found that compared to neutral background, smokers made more commission errors (i.e., executing a response to a no-go target) under smoking-related background, indicating that smoking-related background has a negative effect on smokers' inhibitory control. Experiment 2 found that after experiencing cigarette-specific disgust, smokers made fewer commission errors at post-mood induction than pre-mood induction, indicating that cigarette-specific disgust aroused by smoking warning images alleviates the negative effect of smoking-related background on smokers' inhibitory control. These results suggest that the negative effect of smoking-related cues on smokers' inhibitory control would be alleviated by cigarette-specific disgust aroused by smoking warning images, which emphasizes the important role of cigarette-specific disgust in strengthening smokers' inhibitory control towards smoking-related cues.


Bipolar family history of the hypomanic symptoms and dimensions of mixed depression.
There are no data on the bipolar family history (BPFH) of the hypomanic symptoms and dimensions of mixed depression (defined as a depression plus concurrent hypomanic symptoms). These data may be important for the genetics of mixed depression. The study aim was to investigate the BPFH of the hypomanic symptoms of mixed depression. Consecutive 243 bipolar II disorder (BP II) and 189 major depressive disorder (MDD) outpatients, presenting for treatment of a major depressive episode (MDE), were interviewed using the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen. Mixed depression was defined as an MDE plus 3 or more intra-MDE hypomanic symptoms (following a definition validated by Akiskal and Benazzi [J Affect Disord 2003;73:113-22]). Major depressive episode with BPFH vs MDE without BPFH had significantly more BP II, lower age of onset, more MDE recurrences, more atypical depressions, more mixed depressions, and more intra-MDE hypomanic symptoms (irritability, racing/crowded thoughts, psychomotor agitation, more talkativeness, distractibility). Factor analysis of intra-MDE hypomanic symptoms found 2 factors (dimensions): one factor including psychomotor agitation and more talkativeness, and one factor including racing/crowded thoughts, irritability, and distractibility. Logistic regression showed that mixed depression was more strongly associated with BPFH than hypomanic symptoms and dimensions. There was a dose-response relationship between number of intra-MDE hypomanic symptoms and BPFH loading (marked increase at n = 3) in the entire BP II and MDD sample. Findings showed that hypomanic symptoms were more common in the MDE with BPFH of BP II and of MDD, suggesting that a bipolar vulnerability may be required for mixed depression. Mixed depression was more strongly associated with BPFH than hypomanic symptoms and dimensions, suggesting that it could be the focus of future FH studies.


Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function.
Activation of lymphocytes is a complex, yet finely regulated cascade of events that results in the expression of cytokine receptors, production and secretion of cytokines and expression of several cell surface molecules that eventually lead to divergent immune responses. Assessing the qualitative and quantitative nature of lymphocyte function following immunotherapy provides valuable information about the immune responses mediated by a therapeutic agent. To facilitate evaluation of the immunomodulatory activity of therapeutic agents, we have established a platform of in vitro immunoassays with normal human peripheral blood mononuclear cells (PBMCs) treated with several polyclonal activators that are known to exhibit different modes of action. We evaluated the kinetics of cell surface marker expression and cytokine release from PBMCs stimulated in parallel with various activating agents over a time course. These stimulating agents induced early (CD69 and CD71) and late (CD25 and HLA-DR) activation markers to varying antigen densities, indicated different cytokine profiles, and showed differential inhibition with dexamethasone (DEX), an inhibitor of early signaling events. Based on the association or correlation of the kinetics of activation marker expression and secreted cytokines, the results of our study indicate the appropriate time points for the simultaneous measurement of both these activation products. This study defines the kinetics for both measures of T cell activation and provides a comprehensive review with various polyclonal activators that can serve as a reference for monitoring lymphocyte function in clinical study samples.


Mode of action and determination of antioxidant activity in the dietary sources: An overview.
Determination of antioxidant/capacity in the dietary, food, drugs, and biological samples is an interesting approach for testing the safety of these compounds and for drug development. Investigating the google searching engines for the words (measurement + antioxidant + capacity) yielded more than 20 million results, which makes it very difficult to follow. Therefore, collecting the common methods to measure the antioxidant activity/capacity in the food products and biological samples will reduce the burden for both the students and researchers. Nowadays, it is widely accepted that a plant-based diet with a high intake of dietary sources such as vegetables, fruits, and other nutrient-rich plant foods may decrease the effect of oxidative stress-related diseases. In this review article, we have provided the most recent advances in the most common in vitro methods used for evaluating the antioxidant potential of numerous food products, plant extracts, and biological fluids. We have also provided detailed procedures on how to perform them and analyze the results. This review article shall be a comprehensive reference for all techniques used in this area.


Assessment of physical maturation and somatomedin levels during puberty.
The chronologic age, skeletal age, and somatomedin level of thirty-nine Caucasian girls of various developmental stages were compared. The results showed that there was a significant difference between the somatomedin levels in the plasma of circumpubertal and postpubertal females. No significant difference was noted between the prepubertal and the circumpubertal subjects tested. In addition, the skeletal age appears to be a better indicator of physical maturation than does the chronologic age of an individual. In order to substantiate the concept of somatomedin as a true marker for the pubertal growth spurt, this study should be continued on a longitudinal basis utilizing rate-of-growth data.


Amiodarone keratopathy and rigid contact lens wear.
Two cases are presented of patients wearing rigid gas permeable contact lenses who exhibited the typical fan-shaped patterns of corneal pigment deposition related to long-term medication containing amiodarone. The vortex corneal epitheliopathy and contact lens tolerance were monitored over several years. In both cases, the lens material was replaced with one incorporating an ultra-violet light inhibitor in view of the possibility of medically induced photosensitivity.


Effects of slight flexion-extension and radial-ulnar deviation postures on carpal tunnel volume.
Non-neutral wrist postures are a commonly reported risk factor for carpal tunnel syndrome. It is unclear how slight flexion-extension and radial-ulnar deviation postures affect the carpal tunnel. The objective was to determine the effects of slight non-neutral postures by quantifying carpal tunnel volume. Computed tomography images were collected on ten cadaveric specimens in target postures of -20°, -10°, -5°, 0°, 5°, 10°, and 20° of flexion and - 10°, -5°, 0°, 5°, and 10° of radial-ulnar deviation. Surface meshes of the carpal tunnel, carpal bones, radius, and third metacarpal were generated with manual segmentation. Carpal tunnel volume was calculated as the volume between proximal and distal boundaries defined with anatomical landmarks and the orientation of the tunnel. The precise wrist posture of each scan was determined with inertial-based coordinate systems of the radius and third metacarpal. Through multiple linear regression it was determined that, over the observed range of postures, flexion-extension angle does not have a significant effect (p = 0.99) while radial-ulnar deviation angle has a significant effect of -5.9 mm3/degree (p = 0.003). The findings were consistent with previous studies of postural effects on carpal tunnel pressure. For the treatment and prevention of carpal tunnel syndrome, results suggest that attention should be given to slight radial-ulnar deviation postures (<10°), while slight flexion-extension postures (<20°) are of lesser consequence to carpal tunnel volume.


Iron Administration, Infection, and Anemia Management in CKD: Untangling the Effects of Intravenous Iron Therapy on Immunity and Infection Risk.
Patients with chronic kidney disease (CKD) are at increased risk for infection, attributable to immune dysfunction, increased exposure to infectious agents, loss of cutaneous barriers, comorbid conditions, and treatment-related factors (eg, hemodialysis and immunosuppressant therapy). Because iron plays a vital role in pathogen reproduction and host immunity, it is biologically plausible that intravenous iron therapy and/or iron deficiency influence infection risk in CKD. Available data from preclinical experiments, observational studies, and randomized controlled trials are summarized to explore the interplay between intravenous iron and infection risk among patients with CKD, particularly those receiving maintenance hemodialysis. The current evidence base, including data from a recent randomized controlled trial, suggests that proactive judicious use of intravenous iron (in a manner that minimizes the accumulation of non-transferrin-bound iron) beneficially replaces iron stores while avoiding a clinically relevant effect on infection risk. In the absence of an urgent clinical need, intravenous iron therapy should be avoided in patients with active infection. Although serum ferritin concentration and transferrin saturation can help guide clinical decision making about intravenous iron therapy, definition of an optimal iron status and its precise determination in individual patients remain clinically challenging in CKD and warrant additional study.


Manipulating mouse embryonic stem cells.
Murine embryonic stem (ES) cells are derived from the inner cell mass of 3.5-day-old embryo and have the ability to colonize the germline and form normal gametes following in vitro genetic manipulations. This remarkable characteristic of ES cells has provided the basis for studying normal gene function in the mouse by targeted mutagenesis. Nevertheless, ES cells are very sensitive and need to be manipulated with care for them to retain totipotency after extensive in vitro manipulations. Here we provide straightforward protocols for proper care of these cells. Special emphasis is placed on aspects that are particularly critical for proper culture of this cell type.


Aluminum and Alzheimer's disease.
There are many medical conditions that increase brain Al concentrations without producing the dementia or neuronal degeneration (with "paired-helical filaments" [PHFs]) typical of Alzheimer's disease (AD). Aluminum accumulations have been found in the nuclei of PHF-containing neurons in the brains of AD patients and elderly normal controls. We have, however, found no elevations of Al concentrations in the serum, cerebrospinal fluid, or hair in AD patients. These findings suggest that Al alone is not a "cause" of AD. Aluminum may be just a "marker" of PHF-bearing neurons, or AD patients may be "vulnerable" to Al neurotoxicity on the basis of some other neuronal dysfunction allowing Al to enter neuronal nuclei. It is too soon to tell whether any of the variety of experimental anti-Al approaches currently being evaluated have any effect on the rate of progression of AD symptoms.


Risk Assessment and Determination of Heavy Metals in Home Meal Replacement Products by Using Inductively Coupled Plasma Mass Spectrometry and Direct Mercury Analyzer.
This study quantified six heavy metals (Pb, Cd, As, Sn, Hg, and Me-Hg) in home meal replacement products. Satisfactory linearity (R2 > 0.99), recovery (80.65-118.02%), limits of detection (0.02-2.81 μg/kg), limits of quantification (0.05-8.51 μg/kg), accuracy (80.49-119.87%), precision (0.26-14.93%), standard uncertainty (0.082-0.321%) and relative standard uncertainty (0.084-0.320%) of the six heavy metals were obtained. The average concentration of the six heavy metals was 8.87 μg/kg. Heavy metal concentrations were converted to food intake data of 0.009 μg/kg to recalculate the 95th percentile food intake data (g/day) of individual heavy metals. These were then divided by age group to evaluate the average exposure to heavy metals and determine the 95th percentile of exposure from daily intake and for the whole population, of home meal replacement products. The chronic daily intake amount of six heavy metals was 1.60 × 10-2 μg/kg/day. Based on total chronic daily intake values, the risk and margin of exposure of each of the heavy metals was 9.13 × 107, demonstrating that intake associated with home meal replacement products is negligible.


Antioxidant and antimicrobial collagen films incorporating Pickering emulsions of cinnamon essential oil for pork preservation.
Cinnamon essential oil (CEO)-based Pickering emulsions were prepared using chitosan (CS) and soy protein isolate (SPI) colloid particles as stabilizers and genipin as cross-linker. Pickering emulsions have smaller particle sizes, higher stability, and encapsulation efficiency at a CS:SPI ratio of 1:4. The Pickering emulsion-modified collagen films showed enhanced thermal stability, UV-blocking properties, and water resistance. In addition, the antioxidant (DPPH scavenging activity, 18.35%-50.59%) and antimicrobial activities (inhibition zone, Escherichia coli, 0-1.85 cm; Staphylococcus aureus, 0-1.57 cm; Pseudomonas fluorescens, 0-1.34 cm) of the films were improved due to the sustained release of CEO, with the release kinetics following the Fickian diffusion of the Ritger-Peppas model. When the functionalized film was used for pork preservation, a four-day extension of shelf life was observed. Collectively, our findings suggest that Pickering emulsions provide great potential for the application of collagen film in pork preservation.


Successful implantation of intravenously administered stem cells correlates with severity of inflammation in murine myocarditis.
The present study was designed to determine whether cardiac inflammation is important for the successful homing of stem cells to the heart after intravenous injection in a murine myocarditis model. Male Bagg albino/c mice were infected with encephalomyocarditis virus (EMCV) to produce myocarditis. Subgroups of mice received single injections by tail vein of embryonic stem cells (ESCs) transfected with green fluorescent protein (GFP) as a marker at days 3, 14, or 60 after infection; other subgroups without stem cell injections were killed at each of these time points to assess the degree of inflammation present. The surviving mice were killed at day 90 after virus infection and hemodynamics, gross pathology, histology, and inflammatory cytokine production in the hearts were measured. Our results indicate that myocardial inflammation was most severe and cytokine production highest at day 14 after EMCV inoculation, and in particular, was strongly positive for interleukin 6. Mice receiving intravenous ESC injections on day 14 after EMCV inoculation showed the largest number of GFP-positive cells at the time of death and the greatest functional improvement compared to uninfected controls without inflammation. We conclude that factors released from myocardium during inflammation are important for enhancing the homing, migration, and implantation of systemically infused stem cells.


Efgartigimod Alfa in Generalised Myasthenia Gravis: A Profile of Its Use.
Intravenous efgartigimod alfa (also known as efgartigimod alfa-fcab in the USA; Vyvgart®) is the first neonatal Fc receptor antagonist approved in several countries worldwide, including the USA and EU for the treatment of generalised myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive, and in Japan for the treatment of gMG regardless of antibody status. In the double-blind, placebo-controlled phase 3 ADAPT trial in patients with gMG, efgartigimod alfa significantly and rapidly reduced disease burden and improved muscle strength and quality of life compared with placebo. The clinical benefits of efgartigimod alfa were durable and reproducible. Furthermore, in an interim analysis of the ongoing open-label phase 3 ADAPT+ extension trial, efgartigimod alfa provided consistent clinically meaningful improvements in patients with gMG. Efgartigimod alfa was generally well tolerated, with most adverse events being mild to moderate in severity.


Combining Lindblad Master Equation and Surface Hopping to Evolve Distributions of Quantum Particles.
Motivated by the need to study nonequilibrium evolutions of many-electron systems at the atomistic ab initio level, as they occur in modern devices and applications, we developed a quantum dynamics approach bridging master equations and surface hopping (SH). The Lindblad master equation (LME) allows us to propagate efficiently ensembles of particles, while SH provides nonperturbative evaluation of transition rates that evolve in time and depend explicitly on nuclear geometry. We implemented the LME-SH technique within real-time time-dependent density functional theory using global flux SH, and we demonstrated its efficiency and utility by modeling metallic films, in which charge-phonon dynamics was studied experimentally and showed an unexpectedly strong dependence on adhesion layers. The LME-SH approach provides a general framework for modeling efficiently quantum dynamics in a broad range of complex many-electron condensed-matter and nanoscale systems.


Comparing radial extracorporeal shockwave therapy and corticosteroid injection in the treatment of piriformis syndrome: A randomized clinical trial.
This study was designed to compare the effects of shockwave therapy and corticosteroid injection in the treatment of piriformis syndrome. In this randomized clinical trial, thirty-five patients with piriformis syndrome were randomly divided into two groups of 18 in the shockwave group and 17 in the corticosteroid group. The Shockwave group underwent three sessions of shockwave therapy per week (2000 pulses per session with 5Hz frequency and pressure equal to 4 Bar) and the corticosteroid group underwent an injection of 40 mg methylprednisolone with 1 mL of 1% lidocaine under ultrasound guidance. All patients were assessed by SF-36 questionnaire and visual analogue scale (VAS). The SF-36 questionnaire was used to evaluate the quality of life before and 4 weeks after the intervention. VAS scale was used to evaluate pain before the intervention, and 1, 4, 8, and 12 weeks after the intervention. The baseline characteristics of the two groups were not significantly different. At the end of the study, both groups had a significant improvement in pain and quality of life compared to before the intervention. However, according to the VAS, in the shockwave group improvement was seen in the first follow-up while not seen in the corticosteroid group (P-value <0.001 and P-value 1.00, respectively). According to the SF-36 questionnaire, the overall score in both groups had a significant improvement (P-value <0.05). It seems that shockwave therapy and corticosteroid injection are both effective in the treatment of piriformis syndrome. There was no significant difference between the two groups in the quarterly follow-up. Because shockwave therapy is a relatively non-invasive treatment with fewer side effects, it can be useful to improve pain and the quality of life of patients with piriformis syndrome.


Assessment of the dental and skeletal effects of fan-type rapid maxillary expansion screw and Hyrax screw on craniofacial structures.
The purpose of the study was to assess the skeletal and dental effects of fan-type rapid maxillary expansion (RME) appliance and Hyrax RME appliance on the craniofacial structures. The sample of the study included 12 patients with constricted maxillary arches. Acrylic bonded type of attachment was used for both groups. Changes in sagittal, vertical, and transverse relationship were assessed with lateral and frontal cephalograms, respectively. Intercanine and intermolar widths were measured with stone models. Pre- and immediate post-treatment records were statistically analyzed with Wilcoxon signed-rank test. The differences between the groups were evaluated using Mann-Whitney U-test. Since the data pertaining to intercanine width and intermolar width were normally distributed, parametric test of significance (unpaired t-test) was used to compare them. Results showed that Hyrax presented with significantly greater increments for both nasal cavity width and maxillary width when compared to fan-type RME. Both groups had retroclination of incisors. The increase in the intercanine width was almost similar in both groups. Fan-type RME caused only minimal expansion of the intermolar width when compared to the Hyrax. The ratio between the intercanine and intermolar width expansion was nearly 4:1 in the fan-type RME and 0.75:1 in Hyrax.


Breakpoints Identification of a Balanced Complex Chromosome Rearrangement Case: 46,XX, t(6;15;10;9)(q13;q15;p11.2;q34.3) ins(9;8)(q22.33;q21.1q21.3).
Balanced complex chromosome rearrangement (CCR) carriers are phenotypically normal but at high risk of reproductive failure, recurrent miscarriages, and affected offspring, so that cytogenetic characterizations of CCR carriers are crucial. We report a case of CCR: 46,XX, t(6;15;10;9)(q13;q15;p11.2;q34.3) ins(9;8)(q22.33;q21.1q21.3). The peripheral blood was collected for karyotyping, single nucleotide polymorphism array (SNP-array) analysis, and whole genome mate-pair sequencing. The patient's karyotype is detected and identified as 46,XX, t(6;15;10;9)(q13;q15;p11.2;q34.3) ins(9;8) (q22.33;q21.1q21.3), with no significant duplication and deletion found by SNP-array analysis. There are 16 break-points among chromosomes 6, 8, 9, 10, and 15 identified by whole genome sequencing. With a variety of detection techniques, we can deeply study the genetic characteristics of CCRs, thus providing a basis for genetic counseling and choice of fertility.


Modulation of carcinogen metabolizing enzymes by chromanone A; a new chromone derivative from algicolous marine fungus Penicillium sp.
A marine fungal isolate, Penicillium sp. fungus isolated from seaweed, Ulva sp., led to the isolation of a new chromone derivatives, 2-(hydroxymethyl)-8-methoxy-3-methyl-4H-chromen-4-one (chromanone A). The structure was determined by interpretation of their spectroscopic data (1D and 2D NMR, MS, UV and IR). At the nitiation stage of carcinogenesis, carcinogens is activated by cytochrome P-450 1A (CYP1A) and detoxified by glutathione S-transferases (GST), quinine reductase (QR), and epoxide hydrolase (mEH). We tested the modulatory effect of chromanone A on these carcinogen metabolizing enzymes. The results indicated that chromanone A (4μg/ml) is a promising inhibitor of CYP1A activity up to 60% of the stimulated-CYP1A in murine hepatoma cells (Hepa1c1c7), and it significantly induced GST but not total thiols at low concentrations. Chromanone A had no influence on QR activity, while it resulted in a significant dose-dependant enhancement mEH activity in Hepa1c1c7 cells (P<0.05-0.01). Additionally, chromanone A possessed a potent specific radical scavenging activity against hydroxyl radicals more than peroxyl radicals that may be responsible for the inhibitory effect of chromanone A on the induced-DNA damage in cells. In conclusion, this study proved that chromanone A may act as an active tumor anti-initiating via modulation of carcinogen metabolizing enzymes and protection from DNA damage.


Bacterial Vipp1 and PspA are members of the ancient ESCRT-III membrane-remodeling superfamily.
Membrane remodeling and repair are essential for all cells. Proteins that perform these functions include Vipp1/IM30 in photosynthetic plastids, PspA in bacteria, and ESCRT-III in eukaryotes. Here, using a combination of evolutionary and structural analyses, we show that these protein families are homologous and share a common ancient evolutionary origin that likely predates the last universal common ancestor. This homology is evident in cryo-electron microscopy structures of Vipp1 rings from the cyanobacterium Nostoc punctiforme presented over a range of symmetries. Each ring is assembled from rungs that stack and progressively tilt to form dome-shaped curvature. Assembly is facilitated by hinges in the Vipp1 monomer, similar to those in ESCRT-III proteins, which allow the formation of flexible polymers. Rings have an inner lumen that is able to bind and deform membranes. Collectively, these data suggest conserved mechanistic principles that underlie Vipp1, PspA, and ESCRT-III-dependent membrane remodeling across all domains of life.


Chronic ethanol consumption upregulates the cytosolic and plasma membrane sialidase genes, but down regulates lysosomal membrane sialidase gene in rat liver.
We have previously shown that chronic ethanol feeding stimulates liver cytosolic sialidase (CS) and plasma membrane sialidase (PMS), whereas it decreases lysosomal membrane sialidase (LMS) activities with concomitant alterations in their relative synthetic rate in rat. To understand the molecular mechanism(s) for these changes, we have evaluated the effect of ethanol administration in male Wistar rats as a function of increasing dietary ethanol concentration after 8 weeks of pair-feeding on (i) the expression of CS, PMS, and LMS genes by real-time quantitative polymerase chain reaction method; (ii) their relative transcription rates by nuclear run-on assay; and (iii) the actual amount of these sialidase proteins in the liver fractions of the respective groups by Western blot method. We have demonstrated that the animals fed with 10.6%, 20.8%, and 36% of total calories as ethanol showed a 20% (P<.05), 34% (P<.01), and 69% (P<.01) increase in CS mRNA level, and 22% (P<.05), 26% (P<.01), and 47% (P<.01) increase in PMS mRNA level, but a decrease in LMS mRNA level by 35% (P<.05), 50% (P<.01), and 80% (P<.01), respectively, as compared to controls. Western blot analyses of CS, PMS, and LMS in the liver subfractions showed that changes in protein levels of CS, LMS, and PMS were consistent with the corresponding changes in the respective mRNA levels. Thus, the upregulation of CS and PMS, but not LMS which is down regulated by chronic ethanol, may account for the appearance of asialoconjugates in alcoholics.


Cosmetic Bone-Contouring Surgery for Asians.
The major needs for cosmetic facial bone surgery come from anatomic differences in facial shape and in personal preference. Especially when consulting patients with different national or ethnic backgrounds, careful attention should be paid during consultation for the ideal or desirable facial shape that they have in mind. Patients generally seek a slim and smooth-contoured face. Surgery of the cosmetic facial bone has developed from surgical experiences in facial bone trauma and congenital anomalies. A limited approach is recommended for satisfactory aesthetic outcome. Surgeons should understand the basic procedures of L-shaped osteotomy of the zygoma and intraoral mandible reduction.