Advanced Management of Patients With Ulcerative Interstitial Cystitis/Bladder Pain Syndrome.
To describe a stepwise management of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) with Hunner's lesions and present single institution long-term outcomes. This is a retrospective review of a single tertiary center experience with management of patients with Hunner's lesions from January 2005 to January of 2015. Patients who met the diagnostic criteria for IC/BPS were included. Systematic approach to treatment of patients with Hunner's lesions is proposed based on our results. Fifty-five patients with IC/BPS and Hunner's lesions were included. Mean age was 65.0 ±12.7 years, 76.4% (42/55) were female, and median symptom duration was 2 years (interquartile range [IQR] 1.7). All patients had a biopsy to rule out malignancy with therapeutic fulguration which resulted in subjective symptom improvement in 81.8% (45/55) and median time to repeat procedures was 12 months (IQR 621). Triamcinolone injection into the lesion was done in 35 patients and 91.4% (32/35) reported subjective improvement. Repeat injections were done for 74% (26/35) and median time between injections was 8 months (IQR 4, 13). AUA symptom scores and quality of life improved significantly with both treatment modalities. Adjunctive treatment with cyclosporine was used in 47.2% (26/55), and 7.2% (4/55) went on to have a cystectomy. Patients with Hunner's lesions benefit from early progression from conservative treatments to endoscopic management. Excellent symptom control can be achieved with biopsy/fulguration and triamcinolone injections but recurrence is common and repeat treatments are needed for most patients.


Impairment in people with anterior cruciate ligament reconstruction in adjusting ground reaction force in running.
In healthy individuals, maximum vertical ground reaction force (MVGRF) remains close to constant during constant velocity running, despite variation in stiffness of the surface underfoot. Because the anterior cruciate ligament (ACL) possesses mechanoreceptors that influence recruitment of knee muscles, it may play a role in regulation of lower limb force output. This study was designed to examine the effect of recent ACL reconstruction on MVGRF in running. Seven patients who were 5-13 weeks post-ACL reconstruction and 7 healthy participants ran for 60 seconds in shoes modified with hard and with soft 1-cm outsoles. The MVGRF during running was measured for the ACL reconstructed and nonsurgical limbs of patients and limbs of healthy participants. The difference in MVGRF between running in hard and soft shoes was significantly greater in ACL reconstructed limbs than nonsurgical limbs (p = 0.003) and compared to limbs of healthy participants (p = 0.001). In contrast, a difference in MVGRF between shoes was not found between patients' nonsurgical limbs and those of healthy participants. A lack of mechanoreceptive feedback from the ACL graft may be among the factors explaining the difference between the ACL reconstructed limbs and the other two limb conditions.


Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem.
To respond to pathogen attack, selection and associated evolution has led to the creation of plant immune system that are a highly effective and inducible defense system. Central to this system are the plant defense hormones jasmonic acid (JA) and salicylic acid (SA) and crosstalk between the two, which may play an important role in defense responses to specific pathogens or even genotypes. Here, we used the Arabidopsis thaliana-Botrytis cinerea pathosystem to test how the host's defense system functions against genetic variation in a pathogen. We measured defense-related phenotypes and transcriptomic responses in Arabidopsis wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1, individually challenged with 96 diverse B. cinerea isolates. Those data showed genetic variation in the pathogen influences on all components within the plant defense system at the transcriptional level. We identified four gene coexpression networks and two vectors of defense variation triggered by genetic variation in B. cinerea This showed that the JA and SA signaling pathways functioned to constrain/canalize the range of virulence in the pathogen population, but the underlying transcriptomic response was highly plastic. These data showed that plants utilize major defense hormone pathways to buffer disease resistance, but not the metabolic or transcriptional responses to genetic variation within a pathogen.


Highly optimized tolerance: robustness and design in complex systems
Highly optimized tolerance (HOT) is a mechanism that relates evolving structure to power laws in interconnected systems. HOT systems arise where design and evolution create complex systems sharing common features, including (1) high efficiency, performance, and robustness to designed-for uncertainties, (2) hypersensitivity to design flaws and unanticipated perturbations, (3) nongeneric, specialized, structured configurations, and (4) power laws. We study the impact of incorporating increasing levels of design and find that even small amounts of design lead to HOT states in percolation.


Meldonium use by athletes at the Baku 2015 European Games.
The aim of this report was to estimate the prevalence of meldonium use in athletes competing in the Baku 2015 European Games to contribute to the surveillance of substances on the 2015 World Anti-Doping Agency (WADA) Monitoring Program. Meldonium is reported to be used by athletes to potentially enhance personal performance and shorten the recovery period after physical activity. Three sources of data were reviewed to determine the prevalence of meldonium use during the Games including: (1) athlete self-reported declarations of drug and supplement use; (2) declarations from National Olympic Committee medical teams of the list of medicines that they imported into Azerbaijan as part of their stock of drugs for administration; (3) results from the antidoping laboratories reporting the detection of meldonium. Meldonium was declared as imported into Azerbaijan by 2 of 50 National Olympic Committee medical teams at the Games, but athletes from 6 countries declared the use of meldonium. Only 23 of the 662 (3.5%) athletes tested from 8 to 28 June 2015 declared the personal use of meldonium, which included 13 competition winners. However, 66 of the total 762 (8.7%) athlete urine samples analysed during the Games and during precompetition tested positive for meldonium. Meldonium use was detected in athletes competing in 15 of the 21 sports during the Games. This study highlights the widespread and inappropriate use and prescribing of this prescription drug in a generally healthy athlete population. Subsequent to these findings, WADA has included meldonium as a prohibited substance on the 2016 List of Prohibited Substances.


Fluoride mouthrinses for preventing dental caries in children and adolescents.
The Mission of the Cochrane Nursing Care Field (CNCF) is to improve health outcomes through increasing the use of the Cochrane Library and supporting Cochrane's role by providing an evidence base for nurses and related health care professionals involved in delivering, leading, or researching nursing care. The CNCF produces "Cochrane Corner" columns (summaries of recent nursing-care-relevant Cochrane Reviews) that are regularly published in collaborating nursing-care-related journals. Information on the processes this Field has developed can be accessed at: http://cncf.cochrane.org/evidence-transfer-program-review-summaries.


Quantification analysis for saccadic eye movements.
Traditional parameters, such as latency and peak velocity, have been used for quantitative analysis of saccade dynamics. However, saccades of equal magnitude which differ substantially in dynamics may still have the same peak velocity. This lack of selectivity might degrade the efficacy of the peak velocity measurement in discriminating patients from normal subjects. In this study, an alternative parameter, the damping ratio of a second-order response, is proposed to concisely and accurately describe saccadic dynamics. A measurement of damping ratio is made by considering the response curve of saccade as the step response of a second-order transfer function. Using the least-mean-square algorithm, the second-order function has been optimized to fit the response of the saccade dynamics with the latency removed. Nineteen normal subjects (ten young and nine older) and 16 patients of Parkinson's disease (eight mildly affected and eight advanced affected) were tested for eye movements in response to pseudorandom saccadic stimuli. While the traditional peak velocity had difficulties in differentiating between the saccadic dynamics of normal and Parkinson subjects, the damping ratio is sensitive enough not only to highlight the difference between a group of patients mildly affected with Parkinson's disease and an age-matched normal group (p<0.01; abnormal versus normal), but also to distinguish between groups at different ages (p<0.01; younger versus older). It is proposed that the damping ratio could be a useful parameter in analyzing saccadic dynamics.


Growth, respiration and nutrient acquisition by the arbuscular mycorrhizal fungus Glomus mosseae and its host plant Plantago lanceolata in cooled soil.
Although plant phosphate uptake is reduced by low soil temperature, arbuscular mycorrhizal (AM) fungi are responsible for P uptake in many plants. We investigated growth and carbon allocation of the AM fungus Glomus mosseae and a host plant (Plantago lanceolata) under reduced soil temperature. Plants were grown in compartmented microcosm units to determine the impact on both fungus and roots of a constant 2.7 °C reduction in soil temperature for 16 d. C allocation was measured using two (13)CO(2) pulse labels. Although root growth was reduced by cooling, AM colonization, growth and respiration of the extraradical mycelium (ERM) and allocation of assimilated (13)C to the ERM were all unaffected; the frequency of arbuscules increased. In contrast, root respiration and (13)C content and plant P and Zn content were all reduced by cooling. Cooling had less effect on N and K, and none on Ca and Mg content. The AM fungus G. mosseae was more able to sustain activity in cooled soil than were the roots of P. lanceolata, and so enhanced plant P content under a realistic degree of soil cooling that reduced plant growth. AM fungi may therefore be an effective means to promote plant nutrition under low soil temperatures.


Gendered relationship between HIV stigma and HIV testing among men and women in Mozambique: a cross-sectional study to inform a stigma reduction and male-targeted HIV testing intervention.
Increasing and sustaining engagement in HIV care for people living with HIV are critical to both individual therapeutic benefit and epidemic control. Men are less likely to test for HIV compared with women in sub-Saharan African countries, and ultimately have delayed entry to HIV care. Stigma is known to impede such engagement, placing an importance on understanding and addressing stigma to improve HIV testing and care outcomes. This study aimed to assess the gendered differences in the relationship between stigma and HIV testing. A cross-sectional, household probability survey was implemented between November and December 2016 in the Sofala province of Mozambique. Data were restricted to men and women participants who reported no prior diagnosis of HIV infection (N=2731). Measures of sociodemographic characteristics, stigma and past exposure to HIV interventions were included in gender-stratified logistic regression models to estimate the relationship between stigma and recent testing for HIV, as well as to identify other relevant correlates. Significantly fewer men (38.3%) than women (47.6%; p<0.001) had recently tested for HIV. Men who reported previous engagement in community group discussions about HIV had an increased odds of testing in the past 12 months compared to those who had not participated (adjusted OR (aOR)=1.92; 95% CI 1.51 to 2.44). Concerns about stigma were not a commonly reported barrier to HIV testing; however, men who expressed anticipated individual HIV stigma had a 35% lower odds of recent HIV testing (aOR=0.65; 95% CI 0.44 to 0.96). This association was not observed among women. Men have lower uptake of HIV testing in Mozambique when compared to women. Even amidst the beneficial effects of HIV messaging, individual stigma is negatively associated with recent HIV testing among men. Intervention efforts that target the unique challenges and needs of men are essential in promoting men's engagement into the HIV care continuum in sub-Saharan Africa.


X-ray induction of persistent hypersensitivity to mutation.
The progeny of x-irradiated V79 cells are hypersensitive to PUVA-(8-methoxypsoralen plus longwave ultraviolet light) induced mutation at the locus for hypoxanthine-guanine phosphoribosyl transferase. This hypersensitivity is most evident at low doses of pUVA that do not induce mutation in non-x-irradiated cells. The hypersensitivity is evoked by x-irradiation delivered as a single dose or as multiple fractions over a long period and persists for at least 108 days of exponential growth. This radiation-induced hypersensitivity to subsequent mutation is a new phenomenon that may be relevant to multistage carcinogenesis.


Measuring costs in cost-utility analyses. Variations in the literature.
Although cost-utility analysis (CUA) has been recommended by some experts as the preferred technique for economic evaluation, there is controversy regarding what costs should be included and how they should be measured. The purpose of this study was to: a) identify the cost components that have been included in published CUAs; b) catalogue the sources of valuation used; c) examine the methods employed for estimating costs; and d) explore whether methods have changed over time. We conducted a comprehensive search of the published literature and systematically collected data on the cost estimation of CUAs. We audited the cost estimates in 228 CUAs. In most studies (99%), analysts included some direct healthcare costs. However, the inclusion of direct non-healthcare and time costs (17%) was generally lacking, as was productivity costs (8%). Only 6% of studies considered future costs in added life-years. In general, we found little evidence of change in methods over time. The most frequently used source for valuation of healthcare services was published estimates (73%). Few studies obtained utilization data from RCTs (10%) or relied on other primary data (23%). About two-thirds of studies conducted sensitivity analyses on cost estimates. We found wide variations in the estimation of costs in published CUAs. The study underscores the need for more uniformity and transparency in the field, and continued vigilance over cost estimates in CUAs on the part of analysts, reviewers, and journal editors.


Antimetastatic Effect of Fucoidan-Sargassum against Liver Cancer Cell Invadopodia Formation via Targeting Integrin αVβ3 and Mediating αVβ3/Src/E2F1 Signaling.
Background: Fucoidan is a fucose-enriched, sulfated polysaccharide found in brown algae; in recent years, this polysaccharide has been found to exert several biological effects, including antitumor effects, such as antiproliferation, activating apoptosis, and anti-angiogenesis of cancer cells. However, the antimetastatic effect of fucoidan and the related targeting receptors remain unknown. In the present study, we examined the inhibition of invadopodia formation and underlying mechanism of fucoidan on human liver cancer cells. Methods: We used 98% purified fucoidan from Sargassum species to treat the hepatocellular carcinoma (HCC) cells SMMC-7721, Huh7 and HCCLM3 in vitro and the HCCLM3 cell line in vivo. The HCC cells were cultured with various concentrations of Fucoidan-Sargassum (0-30 mg/mL). Migration, invasion and wound healing assays were performed to determine the antimetastatic effect of fucoidan on the HCC cells. Western blot analysis and immunofluorescence staining were conducted to determine the expression levels of invadopodia formation-regulating proteins and the targeting membrane receptor proteins. Results: Fucoidan-Sargassum inhibited the migration and invasion of HCC SMMC-7721, Huh7 and HCCLM3 cells in a dose-dependent manner. In the HCCLM3 cells, Fucoidan-Sargassum also decreased the expression levels of invadopodia-related proteins including Src, Cortactin, N-WASP, ARP3, CDC42, MMP2, MT1-MMP, and the targeting receptors integrin αV and β3 in a dose-dependent manner. Fucoidan-Sargassum also increased the levels of endoplasmic reticulum-related proteins, including GRP78, IRE1, SPARC, and the type IV collagen receptor proteins integrin α1 and β1. In vivo, Fucoidan-Sargassum reduced the size of liver tumors and decreased the number of lung metastatic foci in nude mice with hepatocellular carcinoma xenografts. Conclusion: These findings indicate that Fucoidan-Sargassum has an antimetastatic effect on SMMC-7721, Huh7 and HCCLM3 liver cancer cells, and the underlying mechanism involves targeting ITGαVβ3 and mediating the ITGαVβ3/SRC/E2F1 signaling pathway. These results suggest that Fucoidan-Sargassum may be a promising therapeutic antimetastatic compound in the development of a metastasis-preventive drug for treating liver cancer.


The central role of the Thalamus in psychosis, lessons from neurodegenerative diseases and psychedelics.
The PD-DLB psychosis complex found in Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) includes hallucinations, Somatic Symptom/Functional Disorders, and delusions. These disorders exhibit similar presentation patterns and progression. Mechanisms at the root of these symptoms also share similarities with processes promoting altered states of consciousness found in Rapid Eye Movement sleep, psychiatric disorders, or the intake of psychedelic compounds. We propose that these mechanisms find a crucial driver and trigger in the dysregulated activity of high-order thalamic nuclei set in motion by ThalamoCortical Dysrhythmia (TCD). TCD generates the loss of finely tuned cortico-cortical modulations promoted by the thalamus and unleashes the aberrant activity of the Default Mode Network (DMN). TCD moves in parallel with altered thalamic filtering of external and internal information. The process produces an input overload to the cortex, thereby exacerbating DMN decoupling from task-positive networks. These phenomena alter the brain metastability, creating dreamlike, dissociative, or altered states of consciousness. In support of this hypothesis, mind-altering psychedelic drugs also modulate thalamic-cortical pathways. Understanding the pathophysiological background of these conditions provides a conceptual bridge between neurology and psychiatry, thereby helping to generate a promising and converging area of investigation and therapeutic efforts.


Cold exposure and left ventricular diastolic performance in coronary artery disease.
It is known that cold exposure is accompanied by coronary artery vasoconstriction and ischemia in patients with coronary artery disease (CAD). The aim of the present study was to evaluate the response of left ventricular (LV) diastolic and systolic functions, estimated by means of Doppler echocardiography, to cold pressor test (CPT) in patients with CAD. Twenty-five male patients (mean age 50.8 +/- 8.1 years) with documented CAD underwent CPT with Doppler echocardiographic assessment of LV diastolic and systolic functions. According to the development of ischemic response to CPT, all patients were divided into 2 groups: group 1, 10 patients with ischemia and group 2, 15 patients without ischemia during CPT. Cold exposure caused significant increase in blood pressure with no changes in heart rate in all CAD patients. Patients with signs of ischemia during cold exposure had lower transmitral flow velocity during early filling (p < 0.001), prolonged isovolumic relaxation time (p < 0.04), shortened deceleration time of early transmitral flow velocity (p < 0.001), and higher values of Doppler-derived index of myocardial performance (p < 0.0001) than those without ischemic response to CPT. Cold exposure in CAD patients through stimulating of vasoconstriction and ischemia was associated with derangements in LV myocardial performance, manifested by delayed relaxation, impaired stiffness, and reduced contractility.


Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer's disease.
The objective of the study described here was to evaluate the efficacy, tolerability, and cognitive effects of levetiracetam (LEV) in patients with seizures and Alzheimer's disease (AD). This was a prospective, randomized, three-arm parallel-group, case-control study of 95 patients taking LEV (n=38), phenobarbital (PB) (n=28), and lamotrigine (LTG) (n=29). A 4-week dose adjustment was followed by a 12-month evaluation period. The three groups were compared to a control group (n=68) to evaluate cognitive effects of the antiepileptic drugs. We examined drug effects cross-sectionally at baseline, 6 months, and 12 months. There were no significant differences in efficacy among the three AEDs. LEV caused fewer adverse events than the other AEDs. PB produced persistent negative cognitive side effects. LEV was associated with improved cognitive performance, specifically attention level and oral fluency items. LTG had a better effect on mood. LEV had a benign neuropsychological side effect profile, making it a cognitively safe drug to use for controlling established seizures in elderly patients with Alzheimer's disease.


Novel PEGylated cholephytosomes for targeting fisetin to breast cancer: in vitro appraisal and in vivo antitumoral studies.
Fisetin (FIS) is a multifunctional bioactive flavanol that has been recently exploited as anticancer drug against various cancers including breast cancer. However, its poor aqueous solubility has constrained its clinical application. In the current work, fisetin is complexed for the first time with soy phosphatidylcholine in the presence of cholesterol to form a novel biocompatible phytosomal system entitled "cholephytosomes." To improve fisetin antitumor activity against breast cancer, stearylamine bearing cationic cholephytosomes (mPHY) were prepared and furtherly modified with hyaluronic acid (HPHY) to allow their orientation to cancer cells through their surface exposed phosphatidylserine and CD-44 receptors, respectively. In vitro characterization studies revealed promising physicochemical properties of both modified vesicles (mPHY and HPHY) including excellent FIS complexation efficiency (˷100%), improved octanol/water solubility along with a sustained drug release over 24 h. In vitro cell line studies against MDA-MB-231 cell line showed about 10- and 3.5-fold inhibition in IC50 of modified vesicles compared with free drug and conventional drug-phospholipid complex, respectively. Preclinical studies revealed that both modified cholephytosomes (mPHY and HPHY) had comparable cytotoxicity that is significantly surpassing free drug cytotoxicity. TGF-β1and its non-canonical related signaling pathway; ERK1/2, NF-κB, and MMP-9 were involved in halting tumorigenesis. Thus, tailoring novel phytosomal nanosystems for FIS could open opportunity for its clinical utility against cancer.


Multiparametric magnetic resonance imaging enhances detection of significant tumor in patients on active surveillance for prostate cancer.
To determine whether multiparametric magnetic resonance imaging (MRI) of the prostate (mpMRI) combined with MRI fusion technology during transrectal ultrasound-guided biopsy can enhance the detection of significant disease in patients with apparent low-risk prostate cancer on active surveillance (AS). We reviewed the charts of 603 patients on AS for localized prostate cancer between January 2006 and September 2013. mpMRI before repeat transrectal ultrasound-guided biopsy was obtained in 111 patients, of whom 69 underwent subsequent fusion biopsy (39 true and 30 cognitive) in addition to standard template biopsy. The results of fusion biopsy were compared with the standard biopsy. The primary endpoint was termination of AS. mpMRI detected 118 suspicious lesions in 70 patients (63%). Of these, 42 patients (60%) had lesions with Prostate imaging, reporting, and data system (PIRADS) score 3, and 28 patients (40%) had PIRADS score 4 or 5 lesions. AS was terminated in 27 (24.3%) of the 111 patients who underwent mpMRI. Seventeen patients stopped AS based on mpMRI findings including 16 for pathologic progression in target biopsies and 1 for lesion size increase, whereas the other 10 stopped AS because of pathologic progression in the standard cores (n = 6) or other reasons (n = 4). Use of mpMRI increased the rate of AS termination (27 vs. 10; P = .002). On multivariate analysis, PIRADS score 4-5 (vs. 3) was the only significant predictor of AS termination (P = .015). These preliminary retrospective findings suggest that mpMRI with subsequent fusion biopsy enhances the identification of AS patients requiring definitive treatment.


Prognostic factors in cancer patients with palliative needs identified by the NECPAL CCOMS-ICO© tool.
The early identification of patients with palliative needs has shown benefits in terms of quality of life and treatment goals. No prospective methods have been applied in Argentina to identify palliative needs in cancer patients. The NECPAL tool combines the physician's own insight with objective indicators of disease progression and indicators of chronic advanced conditions. The aim of this study was to identify prognostic factors of mortality in hospitalized and ambulatory patients with cancer and palliative needs according to the NECPAL tool in a University Hospital in Buenos Aires city. Study variables were obtained by interviews with 10 physicians in charge of 317 patients with cancer over a 2-year follow-up period. A total of 183 patients with palliative needs were labelled as NECPAL+. Of these, 137 died after a median 4-month follow-up period. The death rate was 11% patients/month. The mortality was higher in inpatients during the first month (p < 0.003). In the multivariate model, the best predictors of mortality combining relevant indicators were: inpatients (HR 1.87; 95% CI 1.24-2.84; p = 0.003), initial diagnosis other than breast cancer (HR 2.04; 95% CI 1.23-3.40; p = 0.006), metastatic disease (HR 1.67; 95% CI 1.15-2.42; p = 0.007), functional deterioration (HR 1.95; 95% CI 1.28-2.97; p = 0.002), and malnutrition (HR 1.53; 95% CI 1.04-2.23; p = 0.02 9). The major breakthrough was the systematic prospective identification of palliative needs in cancer patients for the first time in Argentina. The NECPAL tool can improve the prediction of mortality in hospital settings.


Whither allergy or wither allergy.
The specialty of allergy appears to be at a scientific and economic crossroad. With a significant number of scientific papers questioning the value of immunotherapy, the movement of the country towards prepaid care and the necessity for demonstrating cost/benefit ratio for all therapeutic procedures, the specialty of allergy can present an enigma.


Long-term Intracellular Recording of Optogenetically-induced Electrical Activities using Vertical Nanowire Multi Electrode Array.
Continuous recording of intracellular activities in single cells is required for deciphering rare, dynamic and heterogeneous cell responses, which are missed by population or brief single-cell recording. Even if the field of intracellular recording is constantly proceeding, several technical challenges are still remained to conquer this important approach. Here, we demonstrate long-term intracellular recording by combining a vertical nanowire multi electrode array (VNMEA) with optogenetic stimulation to minimally disrupt cell survival and functions during intracellular access and measurement. We synthesized small-diameter and high-aspect-ratio silicon nanowires to spontaneously penetrate into single cells, and used light to modulate the cell's responsiveness. The light-induced intra- and extracellular activities of individual optogenetically-modified cells were measured simultaneously, and each cell showed distinctly different measurement characteristics according to the cell-electrode configuration. Intracellular recordings were achieved continuously and reliably without signal interference and attenuation over 24 hours. The integration of two controllable techniques, vertically grown nanowire electrodes and optogenetics, expands the strategies for discovering the mechanisms for crucial physiological and dynamic processes in various types of cells.


An insight to osmotic drug delivery.
In a typical therapeutic regimen the drug dose and the dosing interval are optimized to maintain drug concentration within the therapeutic window, thus ensuring efficacy while minimizing toxic effects. For many decades treatment of acute disease or a chronic illness has been mostly accomplished by delivery of drugs to patients using various pharmaceutical dosage forms. The immediate release conventional dosage form does not provide the proper plasma concentration of drug for prolonged period. This results in the development of various controlled drug delivery system. Among which the osmotic drug delivery systems (ODDS) are gaining importance as these systems deliver the drug at specific time as per the path physiological need of the disease, resulting in improved patient therapeutic efficacy and compliance. They work on the principle of osmotic pressure for controlling the delivery of the drug. Osmotic drug delivery systems with their versatility and their highly predictable drug release rates offer various biomedical advantages when given parenterally like reduced dose, targeting of site, avoiding gastrointestinal stability, hepatic bypass of drug molecule and follows zero order kinetics. Osmosis is an aristocratic phenomenon that seizes the attention for its exploitation in zero-order drug delivery systems. The release of the drug is independent of pH and physiological factors of the GIT to a large extent. Optimizing semi-permeable membrane characteristics and osmotic agent can modulate delivery of drug from the system. This review highlights the theoretical concept of drug delivery, history, types of oral osmotic drug delivery systems, factors affecting the drug delivery system, advantages and disadvantages of this delivery system, theoretical aspects, applications, and the marketed status.


Cigarette smoke exposure impairs dendritic cell maturation and T cell proliferation in thoracic lymph nodes of mice.
Respiratory tract dendritic cells (DCs) are juxtaposed to directly sample inhaled environmental particles. Processing and presentation of these airborne Ags could result in either the development of immunity or tolerance. The purpose of this study was to determine the consequences of cigarette smoke exposure on DC function in mice. We demonstrate that while cigarette smoke exposure decreased the number of DCs in the lungs, Ag-induced DC migration to the regional thoracic lymph nodes was unaffected. However, cigarette smoking suppressed DC maturation within the lymph nodes as demonstrated by reduced cell surface expression of MHC class II and the costimulatory molecules CD80 and CD86. Consequently, DCs from cigarette smoke-exposed animals had a diminished capacity to induce IL-2 production by T cells that was associated with diminished Ag-specific T cell proliferation in vivo. Smoke-induced defects in DC function leading to impaired CD4(+) T cell function could inhibit tumor surveillance and predispose patients with chronic obstructive pulmonary disease to infections and exacerbations.


Manganese complexes with chelating and bridging di-triazolylidene ligands: synthesis and reactivity.
New manganese complexes bearing di-triazolylidene (di-trz) ligands are described. Depending on the wingtip substituents of the triazolylidene ligand and the synthetic procedure, two different ligand coordination modes were observed, i.e, bridging and chelating. A series of Mn(i) complexes of the general type fac-[Mn(di-trzR)(CO)3Br] (R = Me, Et, Mes) with a chelating di-trz ligand were prepared via Ag-transmetalation. In contrast, the in situ deprotonation of the triazolium salts with KOBut yielded the bimetallic Mn(0) complexes [Mn2(CO)8(μ-di-trzR)] with a bridging di-trz ligand when short alkyl chains (Me, Et, i-Pr) are present as the N1 substituents of the triazolylidene ligand. The molecular structures of monometallic and bimetallic complexes were determined by X-ray diffraction studies. In addition, the cationic fac-[Mn(di-trzEt)(CO)2(PPh3)2]Br complex, a rare example of a dicarbonyl Mn(i) N-heterocyclic carbene, was obtained when fac-[Mn(di-trzEt)(CO)3Br] was irradiated with visible light in the presence of PPh3. The crystal structure revealed a slightly distorted octahedral geometry around the Mn(i) centre, with the chelating di-triazolylidene ligand situated in trans position to the two CO ligands in the equatorial plane, and the two phosphine ligands occupying the axial positions. Cyclic voltammetry studies show reversible redox processes for the monometallic Mn(i) complexes, and a quasi-reversible EC mechanism for the oxidation of the bimetallic complexes. Infrared spectroelectrochemical studies along with DFT calculations for fac-[Mn(di-trzEt)(CO)3Br] suggest that the observed two consecutive reductions both occur at the metal centre.


Thermoelectric Properties of Highly-Crystallized Ge-Te-Se Glasses Doped with Cu/Bi.
Chalcogenide semiconducting systems are of growing interest for mid-temperature range (~500 K) thermoelectric applications. In this work, Ge20Te77Se₃ glasses were intentionally crystallized by doping with Cu and Bi. These effectively-crystallized materials of composition (Ge20Te77Se₃)100-xMx (M = Cu or Bi; x = 5, 10, 15), obtained by vacuum-melting and quenching techniques, were found to have multiple crystalline phases and exhibit increased electrical conductivity due to excess hole concentration. These materials also have ultra-low thermal conductivity, especially the heavily-doped (Ge20Te77Se₃)100-xBix (x = 10, 15) samples, which possess lattice thermal conductivity of ~0.7 Wm-1 K-1 at 525 K due to the assumable formation of nano-precipitates rich in Bi, which are effective phonon scatterers. Owing to their high metallic behavior, Cu-doped samples did not manifest as low thermal conductivity as Bi-doped samples. The exceptionally low thermal conductivity of the Bi-doped materials did not, alone, significantly enhance the thermoelectric figure of merit, zT. The attempt to improve the thermoelectric properties by crystallizing the chalcogenide glass compositions by excess doping did not yield power factors comparable with the state of the art thermoelectric materials, as these highly electrically conductive crystallized materials could not retain the characteristic high Seebeck coefficient values of semiconducting telluride glasses.


Diet qualities: healthy and unhealthy aspects of diet quality in preschool children.
Diet quality indexes combine the healthy and unhealthy aspects of diet within a single construct, but few studies have evaluated their association. Emerging evidence suggests that predictors differ for the more and less healthy components of children's diets. Our objectives were to determine whether preschool-aged children's frequency of eating healthy foods was inversely related to their intake of unhealthy foods and to determine whether this differed by household income, maternal education, or child race-ethnicity. We analyzed data from a representative sample of 8900 US children (mean age: 52.5 mo) who were born in 2001 and participated in the Early Childhood Longitudinal Study-Birth Cohort. Primary caregivers reported the frequency with which children consumed fruit, vegetables, milk, juice, sugar-sweetened beverages (SSBs), fast food, sweets, and salty snacks in the past week. Response options ranged from none to ≥4 times/d. We created healthy (fruit, vegetables, milk) and unhealthy (SSBs, fast food, sweets, salty snacks) diet scores. Healthy diet behaviors were defined as ≥2 daily servings of fruit, vegetables, and milk. The prevalence of consuming fruit, vegetables, and milk ≥2 times/d (i.e., having 3 healthy diet behaviors) was 18.5%, and a similar proportion (17.6%) of children had none of these healthy behaviors. Contrary to our hypotheses, children with more healthy diet behaviors did not have lower unhealthy diet scores. The intake of healthy foods was not inversely associated with unhealthy foods overall or within any subgroup. Overall, the Spearman rank correlation between healthy and unhealthy diet scores was positive (r = 0.09). From the lowest to the highest strata of household income, these correlations were 0.12, 0.14, 0.14, 0.05, and 0.00, respectively. No evidence was found in US preschool-aged children of an inverse association between eating healthy and unhealthy foods. The implications of combining healthy and unhealthy aspects of diet quality within an overall index should be considered by researchers.


Vitamin A Deficiency Due to Selective Eating as a Cause of Blindness in a High-Income Setting.
Vitamin A is a fat-soluble micronutrient involved in the regulation of several physiologic functions, such as visual acuity, epithelial tissue integrity, immune response, and gene expression, thus playing a crucial role in childhood growth and development. Although vitamin A deficiency (VAD) in resource-limited settings is still an actual issue and represents the leading cause of preventable childhood blindness, its occurrence in high-income countries is rare, although possibly underdiagnosed because of its nonspecific early manifestations. A good awareness of VAD symptoms and risk factors could aid its early diagnosis, which is fundamental to undertake a prompt treatment and to prevent ocular complications. Nevertheless, the role of restrictive dietary habits, increasingly common in developed countries, is often overlooked in infants and children. We present a case of VAD with permanent ocular sequelae in a 5-year-old girl from a high-income country. In the case described, VAD ensued from a highly restricted diet, mainly limited to oat milk, which had been followed for more than 2 years. This child presented with ocular symptoms, opportunistic infection, anemia, poor growth, and a diffuse squamous metaplasia of the bladder; after commencing retinol supplementation, a gradual healing of clinical VAD manifestations occurred, with the exception of the ocular sequelae, which resulted in irreversible visual loss.


Coronary revascularization with the left internal thoracic artery and radial artery: comparison of short-term clinical evolution between elective and emergency surgery.
Left internal thoracic artery-to left anterior descending artery grafting has become a fundamental part of coronary artery bypass grafting. This grafting has led to increased use of other arterial conduits, of which the radial artery is most popular. Whether radial grafting can be used in the emergency patient is not known. This study compares the short-term clinical evolution between elective vs emergency coronary artery bypass grafting surgery with left internal thoracic artery and radial artery. A retrospective study of 47 patients who underwent elective or emergency coronary artery bypass grafting from 1996 to 2003. All patients had coronary stenosis>70% in all target vessels. Only the left internal thoracic artery and radial artery were used as grafts. Patients were divided into elective group (23 patients) and emergency group (24 patients). Emergency criteria were unstable angina and/or critical coronary stenosis with high risk for acute myocardial infarction. Groups were similar for age and number of diseased vessels. The mean number of left internal thoracic artery grafts per patient in the elective and emergency groups were respectively 1.17 and 1.38 (P=.17). The mean number of radial artery grafts per patient in the elective and emergency groups was respectively 2.26 and 2.08 (P=.48). The 30-day mortality was 0. There was no postoperative cardiogenic shock. The elective group had 1 acute myocardial infarction (4.4%) postoperatively, and emergency group had 5 (20.8%). A nonsignificant trend towards acute myocardial infarction was noted in the emergency group (P=.18). Intensive care unit and postoperative stay were similar in both groups. Coronary artery bypass grafting using left internal thoracic artery and radial artery accomplishing complete revascularization can be performed in emergency patients with results similar to those for elective patients.


Dual role of Ovol2 on the germ cell lineage segregation during gastrulation in mouse embryogenesis.
In mammals, primordial germ cells (PGCs), the origin of the germ line, are specified from the epiblast at the posterior region where gastrulation simultaneously occurs, yet the functional relationship between PGC specification and gastrulation remains unclear. Here, we show that OVOL2, a transcription factor conserved across the animal kingdom, balances these major developmental processes by repressing the epithelial-to-mesenchymal transition (EMT) that drives gastrulation and the upregulation of genes associated with PGC specification. Ovol2a, a splice variant encoding a repressor domain, directly regulates EMT-related genes and, consequently, induces re-acquisition of potential pluripotency during PGC specification, whereas Ovol2b, another splice variant missing the repressor domain, directly upregulates genes associated with PGC specification. Taken together, these results elucidate the molecular mechanism underlying allocation of the germ line among epiblast cells differentiating into somatic cells through gastrulation. This article has an associated 'The people behind the papers' interview.


Testing the heterogeneity of F values: a suggestion and a correction.
The use of a pair of populations removes the problems posed by a structured phylogeny (pointed out by A. ROBERTSON) and permits the application of the original test of LEWONTIN and KRAKAUER. In the case of 2n populations studied a suggestion is made to use only n pairs in such a way that no population appears in more than one pair. Data on Dacus analyzed this way show that at least two out of six genes studied are or have been selected.


Effects of disulfiram on apoptosis in PANC-1 human pancreatic cancer cell line.
Pancreatic carcinoma is currently considered as a rapidly progressive and fatal disease, and is typically diagnosed late in its natural course. It is characterized by a poor diagnosis and lack of response to conventional therapy. Recent studies have suggested that disulfiram (DSF), a member of the dithiocarbamate family, may have antitumor activity. This study aimed to evaluate the in vitro effect of DSF on apoptosis in human pancreatic cancerous cell line (PANC-1). PANC-1 cells were cultured and treated with DSF at doses of 5, 10, 13 μM for 24 h and apoptosis was measured. Methylation specific PCR (MS-PCR) and real-time quantitative PCR were carried out to detect the methylation pattern and to estimate the mRNA expression levels of RASSF1A, p21 and Bax. MS-PCR analysis demonstrated that no unmethylated band was apeared in PANC-1 cell line after DSF treatments. The real-time quantitative PCR results showed no significant mRNA expression for RASSF1A (p>0.05); whereas p21 and Bax expression were significantly (p<0.01) enhanced after treatment with DSF. The results of the current study indicated that DSF can induce appoptosis in PANC-1 through p21 and Bax pathway but not through RASSF1A.


"We do not know how to screen and provide treatment": a qualitative study of barriers and enablers of implementing perinatal depression health services in Ethiopia.
Qualitative studies evaluating maternal mental health services are lacking in Ethiopia, and the available evidence targets severe mental illnesses in the general population. We conducted a qualitative study to explore barriers to, enablers of, or opportunities for perinatal depression health services implementations in Ethiopia. We conducted a total of 13 face to face interviews with mental and maternal health service administrators from different levels of the Ethiopian healthcare system. We interviewed in Amharic (a local language), transcribed and translated into English, and imported into NVivo. We analysed the translated interviews inductively using thematic framework analysis. The study identified: (i) health administrators' low literacy about perinatal depression as individual level barriers; (ii) community low awareness, health-seeking behaviours and cultural norms about perinatal depression as socio-cultural level barriers; (iii) lack of government capacity, readiness, and priority of screening and managing perinatal depression as organisational level barriers; and (iv) lack of mental health policy, strategies, and healthcare systems as structural level barriers of perinatal mental health implementation in Ethiopia. The introduction of the new Mental Health Gap Action Programme (mhGap), health professionals' commitment, and simplicity of screening programs were identified enablers of, or opportunities for, perinatal mental health service implementation. This qualitative inquiry identified important barriers and potential opportunities that could be used to address perinatal depression in Ethiopia. Building the capacity of policy makers and planners, strengthening the mental healthcare system and governance should be a priority issue for an effective integration of maternal mental health care with the routine maternal health services in Ethiopia.


Multiple hereditary exostoses (MHE): elucidating the pathogenesis of a rare skeletal disorder through interdisciplinary research.
Abstract An interdisciplinary and international group of clinicians and scientists gathered in Philadelphia, PA, to attend the fourth International Research Conference on Multiple Hereditary Exostoses (MHE), a rare and severe skeletal disorder. MHE is largely caused by autosomal dominant mutations in EXT1 or EXT2, genes encoding Golgi-associated glycosyltransferases responsible for heparan sulfate (HS) synthesis. HS chains are key constituents of cell surface- and extracellular matrix-associated proteoglycans, which are known regulators of skeletal development. MHE affected individuals are HS-deficient, can display skeletal growth retardation and deformities, and consistently develop benign, cartilage-capped bony outgrowths (termed exostoses or osteochondromas) near the growth plates of many skeletal elements. Nearly 2% of patients will have their exostoses progress to malignancy, becoming peripheral chondrosarcomas. Current treatments are limited to the surgical removal of symptomatic exostoses. No definitive treatments have been established to inhibit further formation and growth of exostoses, prevent transition to malignancy, or address other medical problems experienced by MHE patients, including chronic pain. Thus, the goals of the Conference were to assess our current understanding of MHE pathogenesis, identify key gaps in information, envision future therapeutic strategies and discuss ways to test and implement them. This report provides an assessment of the exciting and promising findings in MHE and related fields presented at the Conference and a discussion of the future MHE research directions. The Conference underlined the critical usefulness of gathering experts in several research fields to forge new alliances and identify cross-fertilization areas to benefit both basic and translational biomedical research on the skeleton.


Tetanus in a camel (Camelus dromedarius)--a case report.
Twenty days after an open castration, a 5-year-old dromedary was presented to the Dubai Camel Hospital with severe central nervous symptoms. The dromedary showed the following signs: off feed, stiff gait with extended neck, external swelling of the preputial sheath and groin region, and foamy saliva drooling from the mouth. The dromedary was unable to swallow. Three days after admission, the camel developed lockjaw, and on the fifth day it was unable to stand owing to paralysis of the hindquarters. Because of the severity of the disease and because it did not respond to treatment, the camel was euthanized 26 days after the operation and submitted to the Central Veterinary Research Laboratory for further investigation. Both castration wounds were closed and spermiducts were filled with necrotic masses from which Clostridium tetani was isolated. Two mice, which were injected with the filtrate of the thioglycolate broth, developed typical signs of tetanic spasm of the hind leg. Faecal samples from camel and horse paddocks that were only 50 metres apart were negative for C. tetani. However, C. tetani was isolated from two soil samples of the horse paddock. It is recommended that camels should be vaccinated against tetanus prior to castration.


[Various criteria for the choice of the empirical antibiotic treatment of pneumonia in intensive care].
In this paper we present a synopsis of the recommendations of three Consensus Conferences (from the American Thoracic Society and the American Society of Infectious Diseases) for the empirical antibiotic treatment of severe community and hospital acquired pneumonia. Several groups are defined according to the existence of specific risk factors, severity of the disease and timing of the onset of pneumonia (in the case of nosocomial pneumonia). Each group has more likely pathogens and several antimicrobial agents are proposed. However the option must always rely on the local microbiological sensitivity pattern.


Subnuclear localization, rates and effectiveness of UVC-induced unscheduled DNA synthesis visualized by fluorescence widefield, confocal and super-resolution microscopy.
Unscheduled DNA synthesis (UDS) is the final stage of the process of repair of DNA lesions induced by UVC. We detected UDS using a DNA precursor, 5-ethynyl-2'-deoxyuridine (EdU). Using wide-field, confocal and super-resolution fluorescence microscopy and normal human fibroblasts, derived from healthy subjects, we demonstrate that the sub-nuclear pattern of UDS detected via incorporation of EdU is different from that when BrdU is used as DNA precursor. EdU incorporation occurs evenly throughout chromatin, as opposed to just a few small and large repair foci detected by BrdU. We attribute this difference to the fact that BrdU antibody is of much larger size than EdU, and its accessibility to the incorporated precursor requires the presence of denatured sections of DNA. It appears that under the standard conditions of immunocytochemical detection of BrdU only fragments of DNA of various length are being denatured. We argue that, compared with BrdU, the UDS pattern visualized by EdU constitutes a more faithful representation of sub-nuclear distribution of the final stage of nucleotide excision repair induced by UVC. Using the optimized integrated EdU detection procedure we also measured the relative amount of the DNA precursor incorporated by cells during UDS following exposure to various doses of UVC. Also described is the high degree of heterogeneity in terms of the UVC-induced EdU incorporation per cell, presumably reflecting various DNA repair efficiencies or differences in the level of endogenous dT competing with EdU within a population of normal human fibroblasts.


Mechanical circulatory support versus vasopressors alone in patients with acute myocardial infarction and cardiogenic shock undergoing percutaneous coronary intervention.
Previous studies have compared Impella use to intra-aortic balloon pump (IABP) use in patients with acute myocardial infarction and cardiogenic shock (AMI-CS) undergoing percutaneous coronary intervention (PCI). Our objective was to compare clinical outcomes in patients with AMI-CS undergoing PCI who received Impella (percutaneous left ventricular assist device) without vasopressors, IABP without vasopressors, and vasopressors without mechanical circulatory support (MCS). We queried the National Inpatient Sample (NIS) using ICD-10 codes (2015-2018) to identify patients with AMI-CS undergoing PCI. We created three propensity-matched cohorts to examine clinical outcomes in patients receiving Impella versus IABP, Impella versus vasopressors without MCS, and IABP versus vasopressors without MCS. Among 17,762 patients, Impella use was associated with significantly higher in-hospital major bleeding (31.4% vs. 13.6%; p < 0.001) and hospital charges (p < 0.001) compared to IABP use, with no benefit in mortality (34.1% vs. 26.9%; p = 0.06). Impella use was associated with significantly higher mortality (42.3% vs. 35.7%; p = 0.02), major bleeding (33.9% vs. 22.7%; p = 0.001), and hospital charges (p < 0.001), when compared to the use of vasopressors without MCS. There were no significant differences in clinical outcomes between IABP use and the use of vasopressor without MCS. In this analysis of retrospective data of patients with AMI-CS undergoing PCI, Impella use was associated with higher mortality, major bleeding, and in-hospital charges when compared to vasopressor therapy without MCS. When compared to IABP use, Impella was associated with no mortality benefit, along with higher major bleeding events and in-hospital charges. A vasopressor-only strategy suggested no difference in clinical outcomes when compared to IABP. This study uses the NIS for the first time to highlight outcomes in AMI-CS patients undergoing PCI when treated with vasopressor support without MCS, compared to Impella and IABP use.


Preparation and Characterization of Electrostatically Crosslinked Polymer⁻Liposomes in Anticancer Therapy.
pH-sensitive polymer⁻liposomes can rapidly release their payloads. However, it is difficult to simultaneously achieve stability and pH-responsiveness in the polymer⁻liposomes. In this study, stable and pH-sensitive crosslinked polymer⁻liposomes were fabricated through electrostatic interactions. The pH-sensitive copolymer methoxy poly(ethylene glycol)-block-poly(methacrylic acid)-cholesterol (mPEG-b-P(MAAc)-chol) and crosslinking reagent poly(ethylene glycol) with end-capped with lysine (PEG-Lys2) were synthesized and characterized. At physiological conditions, the pH-sensitive copolymers were anionic and interacted electrostatically with the cationic crosslinker PEG-Lys2, forming the electrostatically-crosslinked polymer⁻liposomes and stabilizing the liposomal structure. At pH 5.0, the carboxylic groups in mPEG-b-P(MAAc)-chol were neutralized, and the liposomal structure was destroyed. The particle size of the crosslinked polymer⁻liposomes was approximately 140 nm and the polymer⁻liposomes were loaded with the anticancer drug doxorubicin. At pH 7.4, the crosslinked polymer⁻liposomes exhibited good stability with steady particle size and low drug leakage, even in the presence of fetal bovine serum. At pH 5.0, the architecture of the crosslinked polymer⁻liposomes was damaged following rapid drug release, as observed by using transmission electron microscopy and their apparent size variation. The crosslinked polymer⁻liposomes were pH-sensitive within the endosome and in the human breast cancer cells MDA-MB-231, as determined by using confocal laser scanning microscopy. The intracellular drug release profiles indicated cytotoxicity in cancer cells. These results indicated that the highly-stable and pH-sensitive electrostatically-crosslinked polymer⁻liposomes offered a potent drug-delivery system for use in anticancer therapies.


Attraction of the parasitoid Cotesia marginiventris to host (Spodoptera frugiperda) frass is affected by transgenic maize.
We assessed in the laboratory the attraction of the parasitoid Cotesia marginiventris (Cresson) toward odors emitted by conventional maize (Zea mays L. ssp. mays) and Bt (Bacillus thuringiensis) maize seedlings following actual or simulated injury by Spodoptera frugiperda (Smith), the parasitoid's host, and emitted by the host's frass, produced following consumption of conventional or Bt maize seedlings. Females of C. marginiventris exhibited similarly strong responses to conventional and Bt maize seedlings injured by the host or with simulated injury, and these were stronger than responses to clean air. In contrast, the responses of C. marginiventris females were consistently weaker toward host frass derived from Bt maize tissue compared to frass derived from conventional maize tissue. We hypothesized that the weakened response was due to a detrimental effect of Bt endotoxins, present in the Bt maize tissue, on the bacterial community present in the host's gut and frass, including bacteria that produce odors attractive to C. marginiventris. As an initial test of our hypothesis, we compared between the responses of C. marginiventris females to host frass produced following consumption of Bt maize and frass produced from conventional maize which had been treated with an antibiotic (tetracycline) to eliminate host gut bacteria. Our results showed that C. marginiventris females responded similarly weakly to host frass derived from conventional maize tissue treated with antibiotic and to frass derived from Bt maize tissue, treated or untreated with antibiotic, while they responded strongly to frass derived from conventional maize untreated with antibiotic, so provided initial, partial support for our hypothesis. We discussed the weakened response of C. marginiventris females to host frass derived from Bt maize in the context of plausible impacts of transgenic crop cultivars on parasitoid foraging and populations, and the implications for biological control of non-target, polyphagous pests, such as S. frugiperda.


Identification and characterization of a seven transmembrane hormone receptor using differential display.
Targeted mutagenesis analysis has shown that the Cmyb proto-oncogene, which encodes a sequence-specific DNA binding protein, is required for normal murine fetal liver erythropoiesis and myelopoiesis. To identify novel genes involved in hematopoiesis, differential display analysis was conducted using total liver RNA isolated from 14.5-day postcoitus Cmyb wildtype, heterozygous, and homozygous mutant littermates. Using 4 oligo(dT) 3' primers and 5 arbitrary decamers as 5' primers, 22 differentially expressed genes have been identified. Eight putatively novel genes were identified from 12 cDNAs that were sequenced. One gene, initially designated DD7A5-7, is primarily expressed in cells of the myeloid lineage. The full-length DD7A5-7 cDNA is 3239 nucleotides, encoding a putative protein of 931 amino acids. The protein is a member of a family of hormone receptors containing 7 transmembrane segments. The receptor also contains 7 epidermal growth factor-like (Egf-like) motifs at the amino terminal of the predicted protein. The gene is alternatively spliced, resulting in the deletion of one or more copies of the Egf-like motif. DD7A5-7 maps to mouse Chromosome 17 and is the putative homologue of EMR1, a recently described Egf-like module containing mucin-like hormone receptor with 7 transmembrane segments in humans. Our results indicate that the Cmyb mutant fetuses represent a unique resource for identifying genes involved in hematopoiesis.


[The autologous transplantation of hematopoietic precursors on an outpatient basis: an analysis of its feasibility at the Hospital Clínic de Barcelona].
Autologous stem cell transplantation (ASCT) is increasingly performed on an outpatient basis. Preliminary results show a significant financial saving without modifying the therapeutic results. The aim of this study has been to evaluate the feasibility of this procedure in our the Hospital Clínic of Barcelona, Spain. All patients in whom an ASCT due to a hematological malignancy, having a good performance status, a caregiver 24 h per day, a lodging near to the hospital and an appropriate cultural and social environment, were offered an outpatient management starting the day after stem cell administration (day +1). During the study period (April, 1997-June, 1998) 64 ASCT were performed. Fifteen patients (23%) were managed on an outpatient basis. The remaining patients were not included in the study due to patient preference (26%), medical reasons (22%), distant home (18%) and social problems (9%). Seven patients (47%) had to be readmitted in the hospital due to fever (n = 4), nausea (n = 2) or respiratory distress (n = 1). Patients receiving total body radiation (TBI) in the conditioning regimen did not have a higher readmission rate than those conditioned without TBI. The median hospital stay (since day +1) was 6 (range: 0-22) and 17 (13-117) days for outpatient and inpatients respectively (p = 0.0016). This reduction would imply a saving of 65% in hospitalization charges and of 12% in total charges. All patients having elected the outpatient management were very satisfied by having made that choice. With an appropriate patient selection, outpatient ASCT is a feasible method that may improve the quality of life of the patients and can reduce the costs of the procedure.


[Membrane potential of muscle fibers exposed to corticotropin and hydrocortisone].
The effect of a single intraperitoneal administration of corticotropin (1 unit) and hydrocortisone (5 mg) per 100 g of a body weight on the membrane potential (MP) as well as on the response rate of miniature end plate potentials (RRMEPP) of musculus soleus fibres of various polarization levels has been investigated in rats. It is shown that administration of corticotropin does not change the MP value, while that of hydrocortisone elicits its increase at the low initial polarization level of the muscle fibre membrane and its decrease at the high level. Hydrocortisone administration does not change the MP value at normal levels of fibre polarization. Corticotropin having been administered, RRMEPP of fibres both with high MP levels and with low ones has increased. Fibres with normal polarization also show a tendency to increase. Administration of hydrocortisone has induced a substantial increase of RRMEPP in fibres with high polarization levels within 45 min, while PRMEPP of fibres with normal polarization levels increased within first 5 min., and that of fibres with low levels of polarization remained unchanged.


RG-I galactan side-chains are involved in the regulation of the water-binding capacity of potato cell walls.
Potato cell walls (PCW) are a low value by-product from the potato starch industry. Valorisation of PCW is hindered by its high water-binding capacity (WBC). The composition of polysaccharides and interactions between these entities, play important roles in regulating the WBC in the cell wall matrix. Here, we show that in vivo exo-truncation of RG-I β-(1→4)-D-galactan side-chains decreased the WBC by 6-9%. In contrast, exo-truncation of these side-chains increased the WBC by 13% in vitro. We propose that degradation of RG-I galactan side-chains altered the WBC of PCW, due to cell wall remodelling and loosening that affected the porosity. Our findings reinforce the view that RG-I galactan side-chains play a role in modulating WBC, presumably by affecting polysaccharide architecture (spacing) and interactions in the matrix. Better understanding of structure-function relationships of pectin macromolecules is needed before cell wall by-products may be tailored to render added-value in food and biobased products.


Effects of the COVID-19 Pandemic on Physical Function of Community-Dwelling People with Disabilities in Japan.
In 2020, COVID-19 spread throughout the world, and international measures such as travel bans, quarantines, and increased social distancing were implemented. In Japan, the number of infected people increased, and a state of emergency was declared from 16 April to 25 May 2020. Such a change in physical activity could lead to a decline in physical function in people with disabilities. A retrospective study was conducted to determine the impact of the pandemic on the physical function of disabled persons living in the community. Data were collected at four points in time: two points before the declaration of the state of emergency was issued and two points after the declaration period had ended. Time series data of physical function at four points in time were compared for 241 people with disabilities. The mean age was 72.39 years; 157 had stroke, 59 musculoskeletal disease, and 26 other diseases. Overall, there was a long-term decrease in walking speed (p < 0.001) and a worsening of the Timed Up-and-Go (TUG) score (p < 0.001) after the period of the state of emergency. The TUG score worsened only in the group with a walking speed of 1.0 m/s or less before the state of emergency (p = 0.064), suggesting that this group was more susceptible.


Infant feeding practices of low-income, African-American, adolescent mothers: an ecological, multigenerational perspective.
The early introduction of non-milk foods among African-American infants has been well documented. Several studies report the addition of semi-solids as early as 1-2 weeks of age. This study investigated, through ethnographic, repeat indepth interviews with teen mothers and grandmothers of infants, the determinants of such feeding practices and the inter-generational factors involved in infant feeding decision-making. Nineteen adolescent mothers were recruited from Baltimore City WIC programs. The teen mothers were interviewed in their homes during four separate visits and the grandmothers at least twice. Ethnographic field guides focused on questions about what, why and how infants were fed and on the 'ethnotheories' of parenting and infant care in this population. All interviews were taped and transcripts were analyzed using text retrieval software. Results confirmed that it is the cultural norm to feed cereal in the bottle and to feed other semi-solid foods within the first month of life. Most grandmothers played the dominant role in deciding what the infant should eat and the timing of the introduction of solids. This pattern occurred both because grandmothers had extensive physical access to their grandchildren and because teen mothers were dependent upon grandmothers. The use of qualitative research methods, with an ecological, multi-generational focus, provides a rich description of the context within which infant feeding decisions are made.


Genetic Diagnosis of Hereditary Hemorrhagic Telangiectasia: Four Novel Pathogenic Variations in Turkish Patients
Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by telangiectasia, epistaxis, and vascular malformations. Pathogenic mutations were found in ENG, AVCRL1, SMAD4, and GDF genes. In this study, we present our database of patients with hereditary hemorrhagic telangiectasia regarding the phenotype-genotype relations and discuss two novel ENG gene pathogenic variations in two unrelated families. Next Generation Sequencing analysis was performed on the peripheral blood of nine patients with hereditary hemorrhagic telangiectasia in four unrelated families. All patients were diagnosed with hereditary hemorrhagic telangiectasia according to the Curaçao criteria. Data on treatment and screenings of visceral involvement were recorded from files. We have found a pathogenic variation in either the ENG or ACVRL1 gene in each family. Two novel pathogenic variations in the ENG gene, including NM_000118.3 (ENG): c.416delC (p.P139fs*24) and NM_000118.3(ENG): c.1139dupT (p.Leu380PhefsTer16), were found in the same family. The NM_000020.2(ACVRL1): c.1298C>T (p.Pro433Leu) pathogenic variation in the ACVRL1 gene in our first family and a novel heterozygous likely pathogenic NM_000020.2(ACVRL1): c.95T>C (p.Val32Ala) variation was found in our second family. Seven of the nine patients were treated with thalidomide for controlling bleeding episodes. All patients responded to thalidomide. In one patient, the response to thalidomide was lost and switched to bevacizumab. In HHT certain type of mutations correlates with disease phenotypes and with next generation sequencing method, new pathogenic variations can be revealed which might help managing HHT patients.


Biomechanical evaluation of tendon regeneration with adipose-derived stem cell.
The use of Adipose-Derived Stem Cells (ADSC) has been presented as a new alternative for tendon reconstruction. Have been admitted that ADSCs are related to better outcomes when used in tendon healing. This research was designed to apply the potential of ADSCs in tendon healing. Flexor digitorum superficialis tendon lesion was performed on both legs of eleven New Zealand rabbits and them, at the same time, treated as follows: Suture alone (Group III - Suture, n:10), suture associated with ADSC (Group IV - Suture + ADSC, n:10) or without suture (Group II - SHAN, n:2). At four weeks after the tendon surgery, the animal was euthanized, and the tendon evaluated (biomechanically and macroscopically). We used 5 additional New Zealand rabbits in the control group "Group I - Control, n:10". In the macroscopic evaluation, the group with ADSC presented a more homogeneous gross morphology compared with the group III. Biomechanical testing showed a lower ultimate tensile load, stiffness and a higher cross-sectional area in the group III and IV compared with the control group. The group with ADSC showed a greater ultimate tensile load, a larger cross-sectional area and bigger deformation at the ultimate tensile load when compared to the group without ADSC. In general terms, the use of ADSCs in tendon healing have biomechanical advantages compared to the non-use of ADSCs at 4 weeks after surgery. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1281-1286, 2019.


Incidence of Abnormal Findings During Pelvic Examinations in Women Aged 21-35 Years.
To describe the incidence of abnormal gynecologic examination findings in asymptomatic compared with symptomatic patients during preventive visits, we conducted a retrospective study of 1,121 visits for patients between the ages of 21 and 35 years from January 2017 to March 2017. Only 1.2% (95% CI, 0.5%,1.9%) of asymptomatic patients had abnormal findings on pelvic examination, compared with 32.4% (95% CI, 27.0%, 37.8%) of those with symptoms ( P ≤.001). In symptomatic patients, the most common symptoms were vaginal discharge (25.1%), pelvic pain (16.4%), and vaginal bleeding (15.7%). In asymptomatic patients, the most common findings were bacterial vaginosis and Candida infection. Asymptomatic patients presenting for a routine preventive visit have low rates of abnormalities detected on examination, and routine pelvic examinations should be re-considered.


Individual differences in adult attachment are systematically related to dream narratives.
Self-reported individual differences in attachment insecurities (anxiety and avoidance) are sometimes assumed to tap only conscious mental processes, although many studies have found correlations between such measures and responses to the Thematic Apperception Test, the Rorschach Inkblot Test, and diverse laboratory measures of unconscious mental processes. Dreams offer another route into the unconscious, as Freud famously claimed: a route found useful in psychotherapy. In this study, approximately 1000 dreams reported by 68 young adults who kept dream diaries for a month were analyzed using the Core Conflictual Relationships Theme method, and the themes were examined in relation to (a) scores on the Experiences in Close Relationships measure of attachment anxiety and avoidance and (b) stress experienced the day before each dream. In line with attachment theory and previous research, attachment-related avoidance predicted avoidant wishes and negative representations of other people in dreams. Attachment anxiety predicted wishes for interpersonal closeness, especially in dreams following stressful days, and negative representations of self and both positive and negative representations of others, with negative representations being more common in dreams following stressful days.


Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients.
Delirium occurs in most ventilated patients and is independently associated with more deaths, longer stay, and higher cost. Guidelines recommend monitoring of delirium in all intensive care unit (ICU) patients, though few data exist in non-ventilated patients. The study objective was to determine the relationship between delirium and outcomes among non-ventilated ICU patients. A prospective cohort investigation of 261 consecutively admitted medical ICU patients not requiring invasive mechanical ventilation during hospitalization at a tertiary-care, university-based hospital between February 2002 and January 2003. ICU nursing staff assessed delirium and level of consciousness at least twice per day using the Confusion Assessment Method for the ICU (CAM-ICU) and Richmond Agitation-Sedation Scale (RASS). Cox regression with time-varying covariates was used to determine the independent relationship between delirium and clinical outcomes. Of 261 patients, 125 (48%) experienced at least one episode of delirium. Patients who experienced delirium were older (mean +/- SD: 56 +/- 18 versus 49 +/- 17 years; p = 0.002) and more severely ill as measured by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (median 15, interquartile range (IQR) 10-21 versus 11, IQR 6-16; p < 0.001) compared to their non-delirious counterparts. Patients who experienced delirium had a 29% greater risk of remaining in the ICU on any given day (compared to patients who never developed delirium) even after adjusting for age, gender, race, Charlson co-morbidity score, APACHE II score, and coma (hazard ratio (HR) 1.29; 95% confidence interval (CI) 0.98-1.69, p = 0.07). Similarly, patients who experienced delirium had a 41% greater risk of remaining in the hospital after adjusting for the same covariates (HR 1.41; 95% CI 1.05-1.89, p = 0.023). Hospital mortality was higher among patients who developed delirium (24/125, 19%) versus patients who never developed delirium (8/135, 6%), p = 0.002; however, time to in-hospital death was not significant the adjusted (HR 1.27; 95% CI 0.55-2.98, p = 0.58). Delirium occurred in nearly half of the non-ventilated ICU patients in this cohort. Even after adjustment for relevant covariates, delirium was found to be an independent predictor of longer hospital stay.


Synergistic inhibition of growth and induction of apoptosis by 8-chloro-cAMP and paclitaxel or cisplatin in human cancer cells.
8-Chloro-cAMP (8-Cl-cAMP) is a novel agent that is able to inhibit the growth of a wide variety of cancer cell types in vitro and in vivo and, at doses devoid of toxicity, to achieve plasma concentrations in cancer patients in a range effective for cancer cell growth inhibition. In this study, we have demonstrated that 8-Cl-cAMP, at a dose causing mild or no growth inhibition, synergistically increased the growth-inhibitory effect of paclitaxel or cisplatin in a wide series of cell lines including human breast, lung, ovary, colon, and head carcinomas and melanoma. A similar effect was also observed with another taxane, docetaxel, and with the platinum-derivative carboplatin. 8-Cl-cAMP also markedly enhanced apoptotic cell death induced by each cytotoxic drug. A cooperative antitumor effect was also observed in vivo, because treatment with paclitaxel followed by 8-Cl-cAMP markedly inhibited the growth of GEO human colon cancer xenografts as compared to paclitaxel alone without signs of toxicity. These data demonstrate that 8-Cl-cAMP synergistically increases the antiproliferative activity of taxanes and platinum-derived compounds and provide a rationale to use 8-Cl-cAMP in combination with taxanes and platinum-derived compounds.


Association between carotid intima-media thickness and pericardial fat in the Multi-Ethnic Study of Atherosclerosis (MESA).
Carotid intima-media thickness (IMT) is a subclinical marker of atherosclerosis and a strong predictor of stroke. Pericardial fat (PF), the fat depot around the heart, has been associated with several atherosclerosis risk factors. We sought to examine the association between carotid IMT and PF, and to examine whether such an association is independent from common atherosclerosis risk factors including measures of overall adiposity. Unadjusted and multivariable-adjusted linear regression analysis was used to examine associations between common carotid artery (CCA) IMT and internal carotid artery (ICA) IMT with PF in a random sample of 996 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent carotid ultrasound and chest computed tomography at baseline examination. A significant positive correlation was observed between PF and CCA-IMT (r=0.27, P < .0001) and ICA-IMT (r=0.17, P < .0001). In an unadjusted sex-specific linear regression analysis, there was a significant association between PF (1-SD difference) and CCA-IMT (mm) in both women (beta coefficient [95% confidence interval]: 0.06 [0.04, 0.08], P < .0001) and men (0.03 [0.01, 0.05], P < .0002), an association that persisted after further adjusting for age and ethnicity (0.02 [+0.00, 0.04], P=.0120 for women, and 0.02 [+0.00, 0.03], P=.0208 for men). However, after additional adjustment for atherosclerosis risk factors and either body mass index or waist circumference, these relations were no longer significant in either sex. In similar analyses, PF was significantly associated with ICA-IMT in both men (0.11 [0.06, 0.15], P < .0001) and women (0.08 [0.02, 0.13], P=.0041). These relations were no longer significant in women in multivariable-adjusted models, but persisted in men in all models except after adjusting for age, ethnicity, and waist circumference. In the general population PF is associated with carotid IMT, an association that possibly is not independent from markers of overall adiposity or common atherosclerosis risk factors.


Repeat Gamma Knife Radiosurgery for Recurrent Glossopharyngeal Neuralgia: A Systematic Review and Our Initial Experience.
Glossopharyngeal neuralgia (GPN) is a rare facial pain syndrome with debilitating symptoms. For medication-resistant GPN, stereotactic radiosurgery (SRS) is an emerging treatment option with a promising role; however, recurrence rates after SRS are fairly high. We present a patient who underwent repeat SRS for recurrent GPN and subsequently maintained over 3 years of complete pain relief. For the first time, we present a systematic review of repeat SRS for recurrent GPN. Twelve cases of repeat SRS for GPN have previously been reported in the literature (13 studies including ours). Among patients with follow-up, initial pain relief was achieved in 83% (n = 10) of cases a median of 5 weeks after repeat SRS; 2 patients failed to obtain any pain relief. A favorable pain response (BNI I-IIIb) was achieved in 67 and 58% of cases at 6 and 12 months, respectively. All 13 were targeted to the glossopharyngeal meatus. Three patients (23%) experienced adverse radiation effects. Five patients (50%) experienced recurrence a median of 14 months after repeat SRS. Two patients (17%) required additional surgical intervention. At the final follow-up, 75% (n = 9) of the patients had a favorable pain outcome. Key Messages: Repeat SRS may be a viable alternative to open surgery for the treatment of recurrent GPN, albeit with an increased risk of adverse radiation effects. Though limited by a small cohort of patients, the best predictors of an effective second treatment may be a response to initial SRS for >5 months, a maximum dose >75 Gy, and a target at the glossopharyngeal meatus. Larger prospective studies are needed to better define its role.


Mediterranean Founder Mutation Database (MFMD): Taking Advantage from Founder Mutations in Genetics Diagnosis, Genetic Diversity and Migration History of the Mediterranean Population.
The Mediterranean basin has been the theater of migration crossroads followed by settlement of several societies and cultures in prehistoric and historical times, with important consequences on genetic and genomic determinisms. Here, we present the Mediterranean Founder Mutation Database (MFMD), established to offer web-based access to founder mutation information in the Mediterranean population. Mutation data were collected from the literature and other online resources and systematically reviewed and assembled into this database. The information provided for each founder mutation includes DNA change, amino-acid change, mutation type and mutation effect, as well as mutation frequency and coalescence time when available. Currently, the database contains 383 founder mutations found in 210 genes related to 219 diseases. We believe that MFMD will help scientists and physicians to design more rapid and less expensive genetic diagnostic tests. Moreover, the coalescence time of founder mutations gives an overview about the migration history of the Mediterranean population. MFMD can be publicly accessed from http://mfmd.pasteur.ma.


Diversity of Chlamydia trachomatis major outer membrane protein genes.
Genomic DNA libraries were constructed for Chlamydia trachomatis serovars B and C by using BamHI fragments, and recombinants that contained the major outer membrane protein (omp1) gene for each serovar were identified and sequenced. Comparisons between these gene sequences and the gene from serovar L2 demonstrated fewer base pair differences between serovars L2 and B than between L2 and C; this finding is consistent with the serologic and antigenic relationships among these serovars. The translated amino acid sequence for the major outer membrane proteins (MOMPs) contained the same number of amino acids for serovars L2 and B, whereas the serovar C MOMP contained three additional amino acids. The antigenic diversity of the chlamydial MOMP was reflected in four sequence-variable domains, and two of these domains were candidates for the putative type-specific antigenic determinant. The molecular basis of omp1 gene diversity among C. trachomatis serovars was observed to be clustered nucleotide substitutions for closely related serovars and insertions or deletions for distantly related serovars.


Prognostic significance of mediastinal standardized uptake value on positron emission tomography/computed tomography in patients with left upper lobe non-small cell lung cancer: Is invasive staging of aortopulmonary window lymph nodes necessary?
This study aims to investigate whether the invasive staging of aortopulmonary window lymph nodes could be omitted in the presence of a suspected isolated metastasis in the aortopulmonary window lymph node on positron emission tomography/computed tomography. Between January 2010 and January 2016, a total of 67 patients (54 males, 13 females; mean age: 59.9±8.7 years; range, 44 to 76 years) with metastatic left upper lobe tumors to aortopulmonary window lymph nodes were retrospectively analyzed. According to positron emission tomography/computed tomography findings in clinical staging, the patients were classified as positive (+) (n=33) and negative (-) (n=34) groups. There was a statistically significant difference between the two groups in terms of sex distribution, lymph node diameter on computed tomography, maximum standardized uptake value of aortopulmonary window lymph nodes, and tumor diameter (p<0.001 for all). A trend toward significance was found to be in pT status, LN #6 metastases, and pathological stage between the two groups (p=0.067). The five-year overall survival rate for all patients was 42.4% and there was no significant difference between the groups (p=0.896). The maximum standardized uptake value of the aortopulmonary window lymph nodes was a poor prognostic factor for survival (area under the curve=0.533, 95% confidence interval: 0.407-0.675, p=0.648). Invasive staging of aortopulmonary window lymph nodes can be omitted in patients with isolated suspected metastasis to aortopulmonary window lymph nodes in non-small cell lung cancer of the left upper lobe.


Metagenomic discovery of lipases with predicted structural similarity to Candida antarctica lipase B.
Here we employed sequence-based and structure-based screening for prospecting lipases that have structural homolog to Candida antarctica lipase B (CalB). CalB, a widely used biocatalyst, was used as structural template reference because of its enzymatic properties. Structural homolog could aid in the discovery of novel wild-type enzymes with desirable features and serve as a scaffold for further biocatalyst design. The available metagenomic data isolated from various environments was leveraged as a source for bioprospecting. We identified two bacteria lipases that showed high structural similarity to CalB with <40% sequence identity. Partial purification was conducted. In comparison to CalB, the enzymatic characteristics of two potential lipases were examined. A candidate exhibited optimal pH of 8 and temperature of 50°C similar to CalB. The second lipase candidate demonstrated an optimal pH of 8 and a higher optimal temperature of 55°C. Notably, this candidate sustained considerable activity at extreme conditions, maintaining high activity at 70°C or pH 9, contrasting with the diminished activity of CalB under similar conditions. Further comprehensive experimentation is warranted to uncover and exploit these novel enzymatic properties for practical biotechnological purposes.


Self-Powered Organometal Halide Perovskite Photodetector with Embedded Silver Nanowires.
Metal-semiconductor-metal (MSM) configuration of perovskite photodetectors (PPDs) suggests easy and low-cost manufacturing. However, the basic structures of MSM PPDs include vertical and lateral configurations, which require the use of expensive materials such as transparent conductive oxides or/and sophisticated fabrication techniques such as lithography. Integrating metallic nanowire-based electrodes into the perovskite photo-absorber layer to form one-half of the MSM PPD structure could potentially resolve the key issues of both configurations. Here, a manufacturing of solution-processed and self-powered MSM PPDs with embedded silver nanowire electrodes is demonstrated. The embedding of silver nanowire electrode into the perovskite layer is achieved by treating the silver nanowire/perovskite double layer with a methylamine gas vapor. The evaporated gold layer is used as the second electrode to form MSM PPDs. The prepared MSM PPDs show a photoresponsivity of 4 × 10-5 AW-1 in the UV region and 2 × 10-5 AW-1 in the visible region. On average, the devices exhibit a photocurrent of 1.1 × 10-6 A under white light (75 mW cm-2) illumination with an ON/OFF ratio of 83.4. The results presented in this work open up a new method for development and fabrication of simple, solution-processable MSM self-powered PPDs.


Wax-bonding 3D microfluidic chips.
We report a simple, low-cost and detachable microfluidic chip incorporating easily accessible paper, glass slides or other polymer films as the chip materials along with adhesive wax as the recycling bonding material. We use a laser to cut through the paper or film to form patterns and then sandwich the paper and film between glass sheets or polymer membranes. The hot-melt adhesive wax can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate (PMMA) film, glass sheets, or metal plate. The bonding process is reversible and the wax is reusable through a melting and cooling process. With this process, a three-dimensional (3D) microfluidic chip is achievable by vacuating and venting the chip in a hot-water bath. To study the biocompatibility and applicability of the wax-based microfluidic chip, we tested the PCR compatibility with the chip materials first. Then we applied the wax-paper based microfluidic chip to HeLa cell electroporation (EP). Subsequently, a prototype of a 5-layer 3D chip was fabricated by multilayer wax bonding. To check the sealing ability and the durability of the chip, green fluorescence protein (GFP) recombinant Escherichia coli (E. coli) bacteria were cultured, with which the chemotaxis of E. coli was studied in order to determine the influence of antibiotic ciprofloxacin concentration on the E. coli migration.


Recent Advances in Functional Materials through Cellulose Nanofiber Templating.
Advanced templating techniques have enabled delicate control of both nano- and microscale structures and have helped thrust functional materials into the forefront of society. Cellulose nanomaterials are derived from natural polymers and show promise as a templating source for advanced materials. Use of cellulose nanomaterials in templating combines nanoscale property control with sustainability, an attribute often lacking in other templating techniques. Use of cellulose nanofibers for templating has shown great promise in recent years, but previous reviews on cellulose nanomaterial templating techniques have not provided extensive analysis of cellulose nanofiber templating. Cellulose nanofibers display several unique properties, including mechanical strength, porosity, high water retention, high surface functionality, and an entangled fibrous network, all of which can dictate distinctive aspects in the final templated materials. Many applications exploit the unique aspects of templating with cellulose nanofibers that help control the final properties of the material, including, but not limited to, applications in catalysis, batteries, supercapacitors, electrodes, building materials, biomaterials, and membranes. A detailed analysis on the use of cellulose nanofibers templating is provided, addressing specifically how careful selection of templating mechanisms and methodologies, combined toward goal applications, can be used to directly benefit chosen applications in advanced functional materials.


Capillary electrophoresis separation of protein composition of γ-irradiated food pathogens Listeria monocytogenes and Staphylococcus aureus.
A capillary electrophoresis method using UV detection was developed to analyse protein composition of the lysates of two foodborne pathogens, Listeria monocytogenes and Staphylococcus aureus which were previously treated at different irradiation doses. Bacterial samples were γ-irradiated at different doses to produce damage cells, to kill cells and to provoke viable but non culturable cells (VBNC) in order to evaluate the respective expression of stress proteins. In Listeria monocytogenes, two proteins (MW of 70.2 and 85.4 kDa) were significantly changed (P ≤ 0.05) at different doses of irradiation. In Staphyloccocus aureus, one protein (50 S ribosomal protein) with the MW of 16.3 kDa was significantly decreased at a low dose of irradiation treatment and the other protein (transcriptional regulator CtsR) with the MW of 17.7 kDa was increased significantly (P ≤ 0.05) at all doses of irradiation treatment compared to control. Expression of two proteins from the acyltransferase family in Listeria monocytogenes was statistically changed during irradiation treatment (P ≤ 0.05). In Staphylococcus aureus, expression of the 50 S ribosomal protein decreased and the transcriptional regulator CtsR espression increased significantly (P ≤ 0.05) following irradiation treatment. These expressed proteins do not belong to the well-known heat shock proteins family of Listeria monocytogenes and Staphylococcus aureus. The research further confirmed that capillary electrophoresis is a useful method to separate and analyse proteins expression which may be related to the resistance or sensitivity of food pathogens to γ-irradiation.


Resolving 20 years of inconsistent interactions between lexical familiarity and orthography, concreteness, and polysemy.
Numerous word recognition studies conducted over the past 2 decades are examined. These studies manipulated lexical familiarity by presenting words of high versus low printed frequency and most reported an interaction between printed frequency and one of several second variables, namely, orthographic regularity, semantic concreteness, or polysemy. However, the direction of these interactions was inconsistent from study to study. Six new experiments clarify these discordant results. The first two demonstrate that words of the same low printed frequency are not always equally familiar to subjects. Instead, subjects' ratings of "experimental familiarity" suggest that many of the low-printed-frequency words used in prior studies varied along this dimension. Four lexical decision experiments reexamine the prior findings by orthogonally manipulating lexical familiarity, as assessed by experiential familiarity ratings, with bigram frequency, semantic concreteness, and number of meanings. The results suggest that of these variables, only experiential familiarity reliably affects word recognition latencies. This in turn suggests that previous inconsistent findings are due to confounding experiential familiarity with a second variable.


Ruthenium-catalysed multicomponent synthesis of the 1,3-dienyl-6-oxy polyketide motif.
Polyketide natural products are an important class of biologically active compounds. Although substantial progress has been made on the synthesis of repetitive polyketide motifs through the iterative application of a single reaction type, synthetic access to more diverse motifs that require more than one type of carbon-carbon bond connection remains a challenge. Here we describe a catalytic, multicomponent method for the synthesis of the privileged polyketide 1,3-dienyl-6-oxy motif. The method allows for the formation of two new carbon-carbon bonds and two stereodefined olefins. It generates products that contain up to three contiguous sp3 stereocentres with a high stereoselectivity in a single operation and can be used to generate chiral products. The successful development of this methodology relies on the remarkable efficiency of the ruthenium-catalysed alkene-alkyne coupling reaction between readily available vinyl boronic acids and alkynes to provide unsymmetrical 3-boryl-1,4-diene reagents. In the presence of carbonyl compounds, these reagents undergo highly diastereoselective allylations to afford the desired 1,3-dienyl-6-oxy motif and enable complex polyketide synthesis in a rapid and asymmetric fashion.


In vivo analysis of Nef's role in HIV-1 replication, systemic T cell activation and CD4(+) T cell loss.
Nef is a multifunctional HIV-1 protein critical for progression to AIDS. Humans infected with nef(-) HIV-1 have greatly delayed or no disease consequences. We have contrasted nef(-) and nef(+) infection of BLT humanized mice to better characterize Nef's pathogenic effects. Mice were inoculated with CCR5-tropic HIV-1JRCSF (JRCSF) or JRCSF with an irreversibly inactivated nef (JRCSFNefdd). In peripheral blood (PB), JRCSF exhibited high levels of viral RNA (peak viral loads of 4.71 × 10(6) ± 1.23 × 10(6) copies/ml) and a progressive, 75% loss of CD4(+) T cells over 17 weeks. Similar losses were observed in CD4(+) T cells from bone marrow, spleen, lymph node, lung and liver but thymocytes were not significantly decreased. JRCSFNefdd also had high peak viral loads (2.31 × 10(6) ± 1.67 × 10(6)) but induced no loss of PB CD4(+) T cells. In organs, JRCSFNefdd produced small, but significant, reductions in CD4(+) T cell levels and did not affect the level of thymocytes. Uninfected mice have low levels of HLA-DR(+)CD38(+)CD8(+) T cells in blood (1-2%). Six weeks post inoculation, JRCSF infection resulted in significantly elevated levels of activated CD8(+) T cells (6.37 ± 1.07%). T cell activation coincided with PB CD4(+) T cell loss which suggests a common Nef-dependent mechanism. At 12 weeks, in JRCSF infected animals PB T cell activation sharply increased to 19.7 ± 2.9% then subsided to 5.4 ± 1.4% at 14 weeks. HLA-DR(+)CD38(+)CD8(+) T cell levels in JRCSFNefdd infected mice did not rise above 1-2% despite sustained high levels of viremia. Interestingly, we also noted that in mice engrafted with human tissue expressing a putative protective HLA-B allele (B42:01), JRCSFNefdd exhibited a substantial (200-fold) reduced viral load compared to JRCSF. Nef expression was necessary for both systemic T cell activation and substantial CD4(+) T cell loss from blood and tissues. JRCSFNefdd infection did not activate CD8(+) T cells or reduce the level of CD4(+) T cells in blood but did result in a small Nef-independent decrease in CD4(+) T cells in organs. These observations strongly support the conclusion that viral pathogenicity is mostly driven by Nef. We also observed for the first time substantial host-specific suppression of HIV-1 replication in a small animal infection model.


Exploratory study on the clinical and mycological effectiveness of a herbal medicinal product from Solanum chrysotrichum in patients with Candida yeast-associated vaginal infection.
Mexican traditional medicine uses Solanum chrysotrichum to treat fungi-associated dermal and mucosal illness; its methanolic extract is active against dermatophytes and yeasts. Different spirostanic saponins (SC-2-SC-6) were identified as the active molecules; SC-2 was the most active in demonstrating a fungicidal effect against Candida albicans and non-albicans strains. The aim of the present study was to compare the clinical (elimination of signs and symptoms) and mycological effectiveness (negative mycological studies) of an S. chrysotrichum herbal medicinal product (Sc-hmp), standardized in 1.89 mg of SC-2, against ketoconazole (400 mg) in the topical treatment of cervical and/or vaginal infection by Candida. Both treatments (vaginal suppositories) were administered daily during 7 continuous nights. The study included 101 women (49 in the experimental group) with a confirmed clinical condition and positive mycological studies (direct examination and/or culture) of Candida infection. Basal conditions did not show differences between the groups; a moderate clinical picture was present in 62% of the cases, direct examination was positive in 69%, and the culture was positive with C. albicans predominating (65%). At the end of the administration period, both treatments demonstrated 100% tolerability, and clinical cure in 57.14% of S. chrysotrichum-treated cases and in 72.5% of ketoconazole-treated cases (p = 0.16), as well as 62.8% and 97.5% of mycological effectiveness, respectively (p = 0.0 001). We conclude that, at the doses used, Sc-hmp exhibits the same clinical effectiveness as ketoconazole, but with lower percentages of mycological eradication. Additional clinical studies with Sc-hmp are necessary, with increasing doses of SC-2, for improving the clinical and mycological effectiveness.