Dynamic model for biospeckle.
This paper reports the development of a simple dynamic microscopic model to describe the main features of the phenomenon known as dynamic speckle, or biospeckle. Biospeckle is an interference pattern formed when a biological surface is illuminated with coherent light. The dynamic characteristics of biospeckle have been investigated as possible tools for assessing the quality of biological products. Our model, despite its simplicity, was able to reproduce qualitatively the main features of biospeckle. We were able to correlate variations in a microscopic parameter associated with movement of the particles comprising the organic surface with changes in a macroscopic parameter that measures the change rate of a dynamic interference pattern. We showed that this correlation occurs only within a limited range of parameter microscope values. We also showed how our model was able to describe nonuniform surfaces composed of more than one type of particles.


Creatine and guanidinoacetate: diagnostic markers for inborn errors in creatine biosynthesis and transport.
In this study, measurements of guanidinoacetate (GAA) and creatine (Cr) in urine, plasma, and cerebrospinal fluid (CSF) were performed using stable isotope dilution gas chromatography-mass spectrometry. Both compounds were analyzed in a single analysis. Reference values were established for GAA and Cr. These values were age dependent. No differences with gender were observed. Eight guanidinoacetate methyltransferase (GAMT) deficient patients and eight creatine transporter SLC6A8 deficient patients were investigated. In urine, plasma, and CSF of GAMT deficient patients increased levels of GAA are present. The SLC6A8 deficient patients all show increased creatine/creatinine (Cr/Crn) ratio in urine demonstrating the importance of the Cr/Crn ratio as a pathognomonic marker of the SLC6A8 deficiency.


The activity of selective sigma-1 receptor ligands in seizure models in vivo.
Sigma-1 receptor (Sig1R) is a ligand-regulated protein which, since its discovery, has been widely studied as a novel target to treat neurological disorders, including seizures. However, the roles and mechanisms of Sig1R in the regulation of seizures are not fully understood. The aim of the present study was to test and compare effects of often used selective Sig1R ligands in models of experimentally induced seizures. The anti-seizure activities and interactions of selective Sig1R agonist PRE-084, selective Sig1R antagonist NE-100 and novel positive allosteric Sig1R modulator E1R were evaluated in pentylenetetrazol (PTZ) and (+)-bicuculline (BIC)-induced seizure models in mice. Sig1R antagonist NE-100 at a dose of 25mg/kg demonstrated pro-convulsive activity on PTZ-induced seizures. Agonist PRE-084 did not change the thresholds of chemoconvulsant-induced seizures. Positive allosteric modulator E1R at a dose of 50mg/kg showed anti-convulsive effects on PTZ- and BIC-induced clonic and tonic seizures. The anti-seizure activity of E1R was blocked by NE-100. Surprisingly, NE-100 at a dose of 50mg/kg induced convulsions, but E1R significantly alleviated the convulsive behaviour induced by NE-100. In conclusion, the selective Sig1R antagonist NE-100 induced seizures that could be partially attenuated by positive allosteric Sig1R modulator. Our results confirm that Sig1R could be a novel molecular target for new anti-convulsive drugs.


Failure of BCG immunostimulation to affect the clinical course of Burkitt's lymphoma.
A controlled randomised trial was carried out to evaluate the efficacy of BCG immunotherapy in preventing relapse in patients with Burkitt's lymphoma in whom remission had been induced with cyclophosphamide. Twenty-one patients were treated with BCG, and 19 were controls. Eleven patients in each group relapsed during a follow-up period long enough to make it unlikely that further relapses would occur. There were no significant differences in the length of remission or the site of relapse that could be attributed to treatment. Eleven patients died: of these none of the six patients in the BCG group but all of the five in the control group had stage D lymphomas. BCG treatment increased the rate of recovery from tumour-induced immunosuppression, but within the BCG group immunocompetence improved most rapidly in the patients who relapsed-a finding that appears to contradict the tenet retionalising the use of immunological adjuvants as treatment.


Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by [6]-gingerol.
Many spices, including plants of the ginger family, possess anticarcinogenic activity. However, the molecular mechanisms by which they exert their antitumorigenic effects are unknown. Activator protein 1 (AP-1) has a critical role in tumor promotion, and blocking of tumor promoter-induced activation of AP-1 inhibits neoplastic transformation. Epidermal growth factor induces cell transformation and AP-1 activity. The purpose of this study was to investigate the effect of two structurally related compounds of the ginger family, [6]-gingerol and [6]-paradol, on EGF-induced cell transformation and AP-1 activation. Our results provide the first evidence that both block EGF-induced cell transformation but act by different mechanisms.


Correlation between psychosocial stresses, stress coping ability, pain intensity and degree of disability in patients with non-specific neck pain.
This study was conducted to find out which factor among stress inducing factors and stress coping factors that can affect patients with non-specific neck pain has more correlation with the intensity of neck pain and the degree of disability. This study is a cross-sectional correlational study. 100 patients diagnosed with non-specific neck pain participated in this study. The characteristics of the participants in this study are as follows. There were 56 men and 44 women, with an average age of 34.11 years, height of 169.91, and weight of 66.97kg. The participant`s pain intensity was 5.18 and disability index was 21.44. In order to evaluate the pain intensity and disability level of patients with non-specific neck pain, Numeric Pain Rating SCALE (NPRS), and Neck Disability Index (NDI) were investigated, respectively. Depression, Anxiety, Stress Scale-21 (DASS-21), and Tampa Scale of Kinesiophobia (TSK) were used to evaluate stress inducing factors. Brief Resolution Scale (BRS), Latack Coping Scale (LCS), and Pain Self-Efficacy Questionnaire (PSEQ) were used to evaluate stress coping factors. Spearman correlation coefficients were used to determine the correlation between NPRS, NDI, and DASS-21, TSK, BRS, LCS, and PSEQ in patients with non-specific neck pain. As a results of this study, the NPRS was correlated with NDI and TSK. The NPRS and NDI were found to have a moderate correlation, but they were correlated with TSK, but showed a weak correlation. The NDI was found to be correlated with TSK, DASS, BRS, and PSEQ. In addition, NDI showed a weak correlation with TSK, BRS, and PSEQ, but the DASS showed a moderate correlation, showing the strongest correlation among the factors. These outcomes suggest that psychosocial factors, particularly stress-related factors such as depression, anxiety, and fear of movement, exert a more pronounced influence on pain intensity and disability in individuals with non-specific neck pain.


Expression of Xfz3, a Xenopus frizzled family member, is restricted to the early nervous system.
Recent advances in analyzing wnt signaling have provided evidence that frizzled proteins can function as wnt receptors. We have identified Xfz3, a Xenopus frizzled family member. The amino acid sequence is 89% identical to the product of the murine gene Mfz3, and is predicted to be a serpentine receptor with seven transmembrane domains. Xfz3 is a maternal mRNA with low levels of expression until the end of gastrulation. The expression level increases significantly from neurulation onward. Whole-mount in situ hybridization analysis shows that expression of Xfz3 is highly restricted to the central nervous system. High levels of expression are detected in the anterior neural folds. Low levels of expression are also detected in the optic and otic vesicles, as well as in the pronephros anlage. In addition, Xfz3 mRNA is concentrated in a large band in the midbrain. Overexpression of Xfz3 blocks neural tube closure, resulting in embryos with either bent and strongly reduced anteroposterior axis in a dose-dependent manner. However, it does not affect gastrulation, the expression and localization of organizer-specific genes such as goosecoid, chordin and noggin. Therefore, Xfz3 is not involved in early mesodermal patterning. Injection of RNA encoding GFP-tagged Xfz3 shows that overexpressed proteins can be detected on the cell surface until at least late neurula stage, suggesting that they can exert an effect after gastrulation. Our expression data and functional analyses suggest that the Xfz3 gene product has an antagonizing activity in the morphogenesis during Xenopus development.


Predictive Nomogram for Recurrence following Surgery for Nonmetastatic Renal Cell Cancer with Tumor Thrombus.
Following surgery for nonmetastatic renal cell carcinoma with tumor thrombus the risk of recurrence is significant but variable among patients. The purpose of this study was to develop and validate a predictive nomogram for individual estimation of recurrence risk following surgery for renal cell carcinoma with venous tumor thrombus. Comprehensive data were collected on patients with nonmetastatic renal cell carcinoma and thrombus treated at a total of 5 institutions from 2000 to 2013. Independent predictors of recurrent renal cell carcinoma from a competing risks analysis were developed into a nomogram. Predictive accuracy was compared between the development and validation cohorts, and between the nomogram and the UISS (UCLA Integrated Staging System, SSIGN (Stage, Size, Grade and Necrosis) and Sorbellini models. A total of 636 patients were analyzed, including the development cohort of 465 and the validation cohort of 171. Independent predictors, including tumor diameter, body mass index, preoperative hemoglobin less than the lower limit of normal, thrombus level, perinephric fat invasion and nonclear cell histology, were developed into a nomogram. Estimated 5-year recurrence-free survival was 49% overall. Five-year recurrence-free survival in patients with 0, 1, 2 and more than 2 risk factors was 77%, 53%, 47% and 20%, respectively. Predictive accuracy was similar in the development and validation cohorts (AUC 0.726 and 0.724, respectively). Predictive accuracy of the thrombus nomogram was higher than that of the UISS (AUC 0.726 vs 0.595, p = 0.001), SSIGN (AUC 0.713 vs 0.612, p = 0.04) and Sorbellini models (AUC 0.709 vs 0.638, p = 0.02). We present a predictive nomogram for postoperative recurrence in patients with nonmetastatic renal cell carcinoma with venous thrombus. Improving individual postoperative risk assessment may allow for better design and analysis of future adjuvant clinical trials.


Procedure-related morbidity in bariatric surgery: a retrospective short- and mid-term follow-up of a single institution of the American College of Surgeons Bariatric Surgery Centers of Excellence.
Our objective was to ascertain procedure-related morbidity among laparoscopic Roux-en-Y gastric bypass (LRYGB), laparoscopic sleeve gastrectomy (LSG), and laparoscopic adjustable gastric banding (LAGB) patients. These are the 3 most common bariatric procedures performed worldwide. We reviewed our experience since the introduction of LSG and compared the procedure-related morbidity among all 3 procedures. We conducted a retrospective review of a prospectively collected database of all morbidly obese patients who underwent bariatric surgery between the years 2005 and 2011. We identified and compared complications, mortality, readmissions, and reoperations in patients who underwent LRYGB, LAGB, and LSG. A total of 2,199 bariatric procedures were performed during this period of time. Of those procedures, 1,327 were LRYGB, 619 were LSG, and 253 were LAGB. Perioperative mortality was not applicable for all 3 procedures. The leak rate was 0.5% for LRYGB and 0.3% for LSG, and was not applicable for LAGB. The average number of readmissions postoperatively was less than 2 times for all 3 procedures: LRYGB 1.96 times, LSG 1.49 times, and LAGB 1.54 times. The percentages of procedures requiring reoperations due to complications or failures were 14.6% in the LAGB group, 6.6% in the LRYGB group, and 1.8% in the LSG group. In short- and mid-term follow-up, LSG appears to have the lowest procedure-related morbidity when compared with LRYGB and LAGB.


Coronary artery-positive remodeling in current smokers.
This study aims to evaluate the association of the coronary artery-positive remodeling (CAPR) observed on cardiac computed tomography angiography (CCTA) with cigarette smoking. This retrospective case-control study enrolled 178 consecutive patients with CAPR plaque (case group) and 180 consecutive patients with coronary artery plaque, but no positive remodeling (control group). CAPR was evaluated in CCTA images and defined as at least 10% larger vessel diameter at the plaque site compared with a normal reference segment. The average age of this population was 61.8±11.5 years (30.4% women). In the case group, the prevalences of current smokers, former smokers, and nonsmokers were 15.7, 26.4, and 57.9%, respectively. In the control group, the prevalences were 6.1, 20.6, and 73.3%, respectively, which were significantly different from the control group (P=0.002 for all). In a subanalysis of the CAPR location in the CAPR group, CAPR was more prevalent in the proximal than the distal segments of the major coronary arteries. Most of the patients in the case group had only one segment involvement with CAPR (71.35%). Logistic regression analyses showed that a history of current smoking has a significant correlation with CAPR in both unadjusted and adjusted models after controlling for risk factors. Current smokers have a 3.5-fold higher risk of having CAPR compared with nonsmokers (P<0.01). There is a significant independent association between a history of cigarette smoking and CAPR evaluated by CCTA. Current cigarette smokers have a 3.5 times higher risk of having CAPR.


NEPTUNE'S DYNAMIC ATMOSPHERE FROM KEPLER K2 OBSERVATIONS: IMPLICATIONS FOR BROWN DWARF LIGHT CURVE ANALYSES.
Observations of Neptune with the Kepler Space Telescope yield a 49 day light curve with 98% coverage at a 1 minute cadence. A significant signature in the light curve comes from discrete cloud features. We compare results extracted from the light curve data with contemporaneous disk-resolved imaging of Neptune from the Keck 10-m telescope at 1.65 microns and Hubble Space Telescope visible imaging acquired nine months later. This direct comparison validates the feature latitudes assigned to the K2 light curve periods based on Neptune's zonal wind profile, and confirms observed cloud feature variability. Although Neptune's clouds vary in location and intensity on short and long timescales, a single large discrete storm seen in Keck imaging dominates the K2 and Hubble light curves; smaller or fainter clouds likely contribute to short-term brightness variability. The K2 Neptune light curve, in conjunction with our imaging data, provides context for the interpretation of current and future brown dwarf and extrasolar planet variability measurements. In particular we suggest that the balance between large, relatively stable, atmospheric features and smaller, more transient, clouds controls the character of substellar atmospheric variability. Atmospheres dominated by a few large spots may show inherently greater light curve stability than those which exhibit a greater number of smaller features.


[Specific characteristics of skin basal cell carcinoma invasion].
Histological, electron-microscopic and immunomorphologic studies were made in 30 cases of basal cell carcinoma (BCC) of the skin. In the immunomorphological study the antibodies to pankeratin, to keratins of N8, 17 (K N8, K N17) and to laminin were used. Two microscopical types of BCC growth distinguished by their clinical manifestations were revealed: compact-nodulous and diffuse-infiltrative. In BCC with diffuse-infiltrative type of growth the basement membrane was markedly fragmentated or completely absent in some regions. This indicates aggressive character of these tumors. This type of BCC growth was characterized by pronounced expression of K N8. The expression of K N17 was revealed in all BCCs.


Semi-parametric estimation of age-time specific infection incidence from serial prevalence data.
Many infections cause lasting detectable immune responses, whose prevalence can be estimated from cross-sectional surveys. However, such surveys do not provide direct information on the incidence of infection. We address the issue of estimating age and time specific incidence from a series of prevalence surveys under the assumption that incidence changes exponentially with time, but make no assumption about the age specific incidence. We show that these assumptions lead to a proportional hazards model and estimate its parameters using semi-parametric maximum likelihood methods. The method is applied to tuberculin surveys in The Netherlands to explore age dependence of the risk of tuberculous infection in the presence of a strong secular decline in this risk.


Imaging drug delivery to skin with stimulated Raman scattering microscopy.
Efficient drug delivery to the skin is essential for the treatment of major dermatologic diseases, such as eczema, psoriasis and acne. However, many compounds penetrate the skin barrier poorly and require optimized formulations to ensure their bioavailability. Here, stimulated Raman scattering (SRS) microscopy, a recently developed, label-free chemical imaging tool, is used to acquire high resolution images of multiple chemical components of a topical formulation as it penetrates into mammalian skin. This technique uniquely provides label-free, nondestructive, three-dimensional images with high spatiotemporal resolution. It reveals novel features of (trans)dermal drug delivery in the tissue environment: different rates of drug penetration via hair follicles as compared to the intercellular pathway across the stratum corneum are directly observed, and the precipitation of drug crystals on the skin surface is visualized after the percutaneous penetration of the cosolvent excipient in the formulation. The high speed three-dimensional imaging capability of SRS thus reveals features that cannot be seen with other techniques, providing both kinetic information and mechanistic insight into the (trans)dermal drug delivery process.


A survey of the phosphorus and calcium contents of pastures and the serum inorganic phosphorus and calcium contents of cows on four Manawatu dairy farms.
Serum inorganic phosphorus (Pi) and calcium (Ca) concentrations were assessed in 20 cows on each of four Manawatu factory supply dairy farms. Blood was taken from each cow before calving and at six-week intervals during lactation. Bleeding coincided with herd testing. Herds of Friesian or Friesian X cows and Jersey or Jersey X cows were compared on adjacent farms on a Central Yellow-brown Sand and on adjacent farms on a Peat Loam overlying a Central Yellow-brown Earth soil. Pasture mass and composition were estimated to grazing height in the next two paddocks to be grazed in the rotation. Mean serum Pi concentration was higher in cows on sandy soils (1.55 mmol Pi/l than in cows on the peat loam (1.34 mmol Pi/l (P<0.001). Concentrations were highest before calving (1.69 mmol Pi/l) but fell to low levels at peak lactation (1.17mmol Pi/l when 70% of cows were below the minima of the 'normal range', and during the drought (1.29 mmol Pi/l. Pasture phosphorus (P) concentrations were adequate to support cow nutrition for lactation (>0.33% DM, ad lib. feeding) until the summer drought when low herbage mass would have restricted milk production. Serum Ca was adequate for lactating cows and changed little between months or between cows (mean 2.12 mmol Ca/l). No metabolic disorders relating to mineral deficiencies were observed. It appears that serum Pi in a high proportion of cows falls below the normal range during peak lactation without cows displaying clinical deficiency symptoms or a depression in butterfat production.


Frequency of medication errors with intravenous acetylcysteine for acetaminophen overdose.
Acetadote, an intravenous preparation of acetylcysteine, became commercially available in the US in June 2004 for the treatment of acetaminophen poisoning. The dosing regimen is complex, consisting of a loading dose followed by 2 maintenance doses, each with different infusion rates. To analyze the frequency of medication errors related to the complex dosing regimen for intravenous acetylcysteine. A retrospective chart review of a regional poison center's records was performed for all patients treated with intravenous acetylcysteine from August 1, 2006, to August 31, 2007. Data collected included acetylcysteine dose, infusion rate, interruptions in therapy, unnecessary administration, and medical outcome. Records that revealed medication errors were further examined for the time and location of the errors. There were 221 acetaminophen overdose cases treated with intravenous acetylcysteine that met inclusion criteria. Of these, 84 medication errors occurred in 74 (33%) patients. The frequency and types of errors were 1.4% incorrect dose, 5% incorrect infusion rate, 18.6% more than 1 hour of interruption in therapy, and 13.1% unnecessary administration. The frequency and types of medication errors in pediatric patients were similar to those in the total patient population. Errors occurred most frequently in the emergency department compared with intensive care units or general medical floors. In addition, errors occurred most frequently on third shift, compared with first or second shift. Evaluation of medical outcomes in cases involving acetaminophen only found that medication errors did not have an impact on coded outcomes. Medication administration errors occur frequently with intravenous acetylcysteine. Awareness of this problem, coupled with increased vigilance in identifying factors associated with errors, should decrease medication errors with intravenous acetylcysteine therapy for acetaminophen poisoning.


Schottky nanocontact of one-dimensional semiconductor nanostructures probed by using conductive atomic force microscopy.
To develop the advanced electronic devices, the surface/interface of each component must be carefully considered. Here, we investigate the electrical properties of metal-semiconductor nanoscale junction using conductive atomic force microscopy (C-AFM). Single-crystalline CdS, CdSe, and ZnO one-dimensional nanostructures are synthesized via chemical vapor transport, and individual nanobelts (or nanowires) are used to fabricate nanojunction electrodes. The current-voltage (I -V) curves are obtained by placing a C-AFM metal (PtIr) tip as a movable contact on the nanobelt (or nanowire), and often exhibit a resistive switching behavior that is rationalized by the Schottky (high resistance state) and ohmic (low resistance state) contacts between the metal and semiconductor. We obtain the Schottky barrier height and the ideality factor through fitting analysis of the I-V curves. The present nanojunction devices exhibit a lower Schottky barrier height and a higher ideality factor than those of the bulk materials, which is consistent with the findings of previous works on nanostructures. It is shown that C-AFM is a powerful tool for characterization of the Schottky contact of conducting channels between semiconductor nanostructures and metal electrodes.


Assessment of uncertainty in functional-structural plant models.
Constructing functional-structural plant models (FSPMs) is a valuable method for examining how physiology and morphology interact in determining plant processes. However, such models always have uncertainty concerned with whether model components have been selected and represented effectively, with the number of model outputs simulated and with the quality of data used in assessment. We provide a procedure for defining uncertainty of an FSPM and how this uncertainty can be reduced. An important characteristic of FSPMs is that typically they calculate many variables. These can be variables that the model is designed to predict and also variables that give indications of how the model functions. Together these variables are used as criteria in a method of multi-criteria assessment. Expected ranges are defined and an evolutionary computation algorithm searches for model parameters that achieve criteria within these ranges. Typically, different combinations of model parameter values provide solutions achieving different combinations of variables within their specified ranges. We show how these solutions define a Pareto Frontier that can inform about the functioning of the model. The method of multi-criteria assessment is applied to development of BRANCHPRO, an FSPM for foliage reiteration on old-growth branches of Pseudotsuga menziesii. A geometric model utilizing probabilities for bud growth is developed into a causal explanation for the pattern of reiteration found on these branches and how this pattern may contribute to the longevity of this species. FSPMs should be assessed by their ability to simulate multiple criteria simultaneously. When different combinations of parameter values achieve different groups of assessment criteria effectively a Pareto Frontier can be calculated and used to define the sources of model uncertainty.


On the discovery, biological effects, and use of Cisplatin and metallocenes in anticancer chemotherapy.
The purpose of this paper is to summarize mode of action of cisplatin on the tumor cells, a brief outlook on the metallocene compounds as antitumor drugs as well as the future tendencies for the use of the latter in anticancer chemotherapy. Molecular mechanisms of cisplatin interaction with DNA, DNA repair mechanisms, and cellular proteins are discussed. Molecular background of the sensitivity and resistance to cisplatin, as well as its influence on the efficacy of the antitumor immune response was evaluated. Furthermore, herein are summarized some metallocenes (titanocene, vanadocene, molybdocene, ferrocene, and zirconocene) with high antitumor activity.


Ophidian accident-related multi-organ failure: a case report.
Ophidian accidents are not rare in Brazil. Its frequency is of about 30,000 cases/year in Brazil, although ranging between different regions. The gender Bothrops, which includes snakes popularly known as 'jararaca', is by far the most frequently involved, followed by the gender Crotalus, mainly represented by the rattlesnake. Other genders as Micrurus and Lachesis have lower epidemiological relevance. Critical cases are uncommon, and the most severe complications include renal failure and blood coagulation disorders. Adult respiratory distress syndrome and multi-organ systems failure are described, although rare. This report is aims to describe a case involving a Bothrops ophidian accident progressing to adult respiratory distress syndrome and multi-organ and systems failure, and to discuss the therapy used.


Development, reliability and validity of the Diabetes Illness Representations Questionnaire: four studies with adolescents.
This article reports on the development and validity of a Diabetes-specific Illness Representations Questionnaire (DIRQ) to assess all five dimensions of an individual's perception of diabetes, for adolescents with Type 1 diabetes mellitus. There were two development studies. Study 1: participants (n = 115) completed a questionnaire assessing perceptions of the consequences of diabetes and the effectiveness of treatment, along with a questionnaire assessing self-care. Study 2: participants (n = 79) completed a questionnaire assessing their identity, timeline and causal beliefs, along with a diabetes self-efficacy and barriers to adherence questionnaire. Subsequently there were two validation studies. Study 3: participants (n = 44 adolescents and 28 parents) completed the DIRQ and questionnaires assessing their self-care and psychological well-being. Glycaemic control was assessed through retrieval of routine assay results. Study 4: participants (n = 70) completed the DIRQ and questionnaires to assess their psychological well-being, with glycaemic control assessed through retrieval of routine assay results. The development studies suggest that the perceived consequences of diabetes consist of two subscales, perceived threat and perceived impact, and provide further support for the distinction between treatment effectiveness to control diabetes and treatment effectiveness to prevent complications. Along with the validation studies, the results indicate that the questionnaire scales showed good internal consistency and construct validity through their associations with measures of self-care and psychological well-being. The data reported here suggest that the DIRQ has the potential to be a useful tool for clinical assessment and evaluating the impact of psycho-educational and medical interventions.


Supramolecular Aggregation of Carbon Nanodots.
Supramolecular aggregation has provided the archetype concept to understand the variants in an emerging systems property. Herein, we have achieved the supramolecular assembly of carbon nanodots (CDs) for the first time and employ supramolecular aggregation to understand their alteration in photophysical properties. In detail, we have employed the CDs as a block to construct the supramolecular assembly of aggregates in the CDs' antisolvent of ethanol. The CD-based aggregates exhibit complex and organized morphologies with another long-wavelength excitation-dependent emission band. The experimental results and density functional theoretical calculations reveal that the supramolecular assembly of CDs can decrease the energy gap between the ground and excited states, contributing to the new long-wavelength excitation-dependent emission. The supramolecular aggregation can be employed as one universal strategy to manipulate and understand the luminescence of CDs. These findings cast new light to build the emerging systems and understand the light emission of CDs through supramolecular chemistry.


Characteristics and current direct costs of hospital admissions due to occupational accidents in the southwest of Bahia from 2005 to 2007.
This study aimed to identify the profile and cost of admissions for occupational accidents, under the Unified Health System (UHS) in municipalities of the southwest of Bahia, in the period of 2005 to 2007. It was conducted a descriptive study using the records of the Hospital Information System (HIS), from which were extracted data about the sociodemographic, occupational and hospitalization profiles. To express the results, indicators were used as absolute frequencies and proportions, the average stay, Total Cost of Hospitalization (TCH), Hospital Mortality (HM), Average Spenditure (AS) and Cost per Day (CD). 962 admissions were recorded, of which 94.1% were related to path accidents. Among the admitted subjects 65.7% were male, and the most affected age groups were 5 to 14 and 15 to 24 years. There were forearm fractures on 26 cases of typical accidents. 248 cases of intracranial injuries happened during commuting to work, which accounted for 78.2% of traffic accidents and 28.8% of falls. The average stay was of 2.6 days and the deaths occurred in 0.5% of patients discharges. The total cost of the admissions was of R$ 243,125.06, being the AS of R$ 252.73 and CD of R$ 97.44, lower than the external causes. The frequencies of the variables related to the occupation were not verified due to missing values. The data from the HIS Systems were limited for identify the profile of the admitted workers. However, they are important and can be used on occupational health surveillance.


E3 ubiquitin-protein ligase TRIM21-mediated lysine capture by UBE2E1 reveals substrate-targeting mode of a ubiquitin-conjugating E2.
The E3 ubiquitin-protein ligase TRIM21, of the RING-containing tripartite motif (TRIM) protein family, is a major autoantigen in autoimmune diseases and a modulator of innate immune signaling. Together with ubiquitin-conjugating enzyme E2 E1 (UBE2E1), TRIM21 acts both as an E3 ligase and as a substrate in autoubiquitination. We here report a 2.82-Å crystal structure of the human TRIM21 RING domain in complex with the human E2-conjugating UBE2E1 enzyme, in which a ubiquitin-targeted TRIM21 substrate lysine was captured in the UBE2E1 active site. The structure revealed that the direction of lysine entry is similar to that described for human proliferating cell nuclear antigen (PCNA), a small ubiquitin-like modifier (SUMO)-targeted substrate, and thus differs from the canonical SUMO-targeted substrate entry. In agreement, we found that critical UBE2E1 residues involved in the capture of the TRIM21 substrate lysine are conserved in ubiquitin-conjugating E2s, whereas residues critical for SUMOylation are not conserved. We noted that coordination of the acceptor lysine leads to remodeling of amino acid side-chain interactions between the UBE2E1 active site and the E2-E3 direct interface, including the so-called "linchpin" residue conserved in RING E3s and required for ubiquitination. The findings of our work support the notion that substrate lysine activation of an E2-E3-connecting allosteric path may trigger catalytic activity and contribute to the understanding of specific lysine targeting by ubiquitin-conjugating E2s.


Unawareness of olfactory dysfunction and its association with cognitive functioning in middle aged and old adults.
The objective of this study was (a) to investigate the accordance of self-reported and objectively assessed olfactory functioning and (b) to compare performance on cognitive tests of individuals unaware of their olfactory dysfunction with individuals aware of their olfactory status. Two hundred forty participants, constituting two age groups, were evaluated with the Scandinavian Odor Identification Test, a question of self-evaluated olfactory function, tests of cognitive function, and a memory questionnaire. The proportion of individuals being unaware of an olfactory dysfunction was high in both middle aged (86%) and old (78%) participants. Performance on neuropsychological tests showed that persons unaware of their olfactory dysfunction performed poorer on tests of verbal learning and memory and attention/processing speed compared to individuals aware of a normal olfactory status as well as individuals aware of their olfactory dysfunction. The clinical relevance of unawareness of olfactory dysfunction, as suggested earlier, needs further investigation and stresses the need of an extensive multi-modal and longitudinal assessment of unawareness of sensory and cognitive function to learn more about the facets of the concept of unawareness.


The Prevalence and Clinical Characteristics of Primary Stabbing Headache.
Objective: This study aimed to determine the prevalence and characteristics of primary stabbing headache in children and adolescents that presented because of headache. Materials and Methods: The medical files of 772 children and adolescents who presented with headache to the Pediatric Neurology Outpatient Clinic at Başkent University between 2012 and 2020 were retrospectively reviewed. In total, 77 patients (9.97%) with primary stabbing headache and those thought to have primary stabbing headache were included in the study. Patient data, including demographic features, headache characteristics, family history of primary headache, electroencephalographic (EEG) findings, and cranial magnetic resonane imaging (MRI) findings, were noted. Results: Age at presentation was <6 years in 16.9% of the patients and onset time of headache was below 3 months in 55.8%. Daily headache attacks occurred in 46.8% of the patients. Headache localization was frontal in 54.5% of patients and bilateral in 68.8%, whereas the quality of headache was undefined in 40.3%. Headache attack duration was seconds long in 37.7% of the patients, attacks occurred at any time of the day in 83.1%, and 80.5% did not have accompanying symptoms. In all, 54.5% of the patients had a negative family history of primary headache. In 95.8% of the patients, EEG findings were normal and cranial MRI findings were normal in 100% of the patients. Conclusion: The prevalence of primary stabbing headache is not rare in children and adolescents. Clinician awareness of the diagnosis and underlying causes of primary stabbing headache should be increased.


Public funding of US syringe exchange programs.
Although there has been no federal government funding of syringe exchange, there is substantial state and local government funding. We report here on program characteristics associated with receiving state and local government funding. Annual telephone surveys were made of program directors of syringe exchange programs known to the North American Syringe Exchange Network. The number of syringe exchange programs known to this network has increased from 63 in 1994-1995 to 127 in 2000. Approximately 80% of programs participated in each of the surveys. Approximately 50% of programs receive state and local government funding, and this has remained constant from 1994 to 2000. Receiving state and local government funding was associated with larger numbers of syringes exchanged per year and providing more on-site services. Among programs that received state or local government funding, this funding accounted for a mean of 87% of the budget for syringe exchange services. In the absence of federal funding, state and local government support is associated with better syringe exchange performance.


Emergency medicine residents' beliefs about contributing to a Google Docs presentation: a survey protocol.
Web 2.0 collaborative writing technologies have shown positive effects on medical education. One such technology, Google Docs(™), offers collaborative writing applications that improve healthcare students' sharing of information. Since 2008, all graduating residents in emergency medicine in Canada have had access to an online Google Docs(™) slideshow designed to help them share summaries of landmark articles in preparation for their Royal College of Physicians and Surgeons of Canada certification exam. A recent evaluation showed that contributions to the presentation were low. This study will identify the factors that influence residents' decision to contribute or not to contribute to this online collaborative project. Using the Theory of Planned Behaviour, semistructured interviews will be conducted with 25 graduating emergency medicine residents in Canada. Content from the interviews will be analysed to determine the most important beliefs in relation to the defined behaviour. To our knowledge, this study will be the first to use a theory based framework to identify healthcare trainees' salient beliefs concerning their decision whether to contribute to an online collaborative writing project using Google Docs(™).


The truth and bias model of judgment.
We present a new model for the general study of how the truth and biases affect human judgment. In the truth and bias model, judgments about the world are pulled by 2 primary forces, the truth force and the bias force, and these 2 forces are interrelated. The truth and bias model differentiates force and value, where the force is the strength of the attraction and the value is the location toward which the judgment is attracted. The model also makes a formal theoretical distinction between bias and moderator variables. Two major classes of biases are discussed: biases that are measured with variables (e.g., assumed similarity) and directional bias, which refers to the extent to which judgments are pulled toward 1 end of the judgment continuum. Moderator variables are conceptualized as variables that affect the accuracy and bias forces but that do not affect judgments directly. We illustrate the model with 4 examples. We discuss the theoretical, empirical, methodological, measurement, and design implications of the model.


[Effect of hydrogen ion concentration in the medium on the state of chromatin in lymphoid cells].
Effect of medium acidity (pH 7.2 divided by 6.6) on the state of lymphoid tissue cells was studied by microspectrofluorimetry, electrophoresis and IR-spectroscopy. Two stages of the cell structural-functional changes were found at H2CO3 acidification of the medium. The first one is a reversible transition of chromatin from the state of dense sphere to the margination state when chromatin is located along the membrane. The second one is an irreversible destruction of chromatin and the cell death. The margination stage is related to the formation of non-specific DNA-membrane contacts, while the chromatin destruction stage to the "proton breakdown" of the macromolecules and their supramolecular complexes. A relationship between the degree of margination reversibility and the value of the medium acidification and the time of cell incubation in it is shown. Different functional significance of chromatin marginated state is discussed.


Diaphragm Activation in Ventilated Patients Using a Novel Transvenous Phrenic Nerve Pacing Catheter.
Over 30% of critically ill patients on positive-pressure mechanical ventilation have difficulty weaning from the ventilator, many of whom acquire ventilator-induced diaphragm dysfunction. Temporary transvenous phrenic nerve pacing using a novel electrode-bearing catheter may provide a means to prevent diaphragm atrophy, to strengthen an atrophied diaphragm, and mitigate the harms of mechanical ventilation. We tested the initial safety, feasibility, and impact on ventilation of this novel approach. First-in-Humans case series. Angiogram suite. Twenty-four sedated, mechanically ventilated patients immediately prior to an elective atrial septal defect repair procedure. A 9.5-Fr central venous catheter with 19 embedded electrodes was placed via Seldinger technique into the left subclavian vein and superior vena cava and evaluated for up to 90 minutes. The electrode combinations determined to provide best transvenous stimulation of the right and left phrenic nerves were activated in synchrony with mechanically ventilated breaths. One patient could not be tested for reasons unrelated to the device. In the 23 patients who underwent the full protocol, transvenous stimulation activated the diaphragm in 22 of 23 (96%) left phrenic capture attempts and 20 of 23 (87%) right phrenic capture attempts. In one subject, a congenital left-sided superior vena cava precluded right-sided capture. Significant reductions in ventilator pressure-time-product were achieved during stimulation assisted breaths in all 22 paced subjects (range, 9.9-48.6%; p < 0.001). There were no adverse events either immediately or at 2-week follow-up. In this First-in-Human series, diaphragm pacing with a temporary catheter was safe and effectively contributed to ventilation in conjunction with a mechanical ventilator.


Almost ready: how leaders move up.
Most designated CEO successors are talented, hardworking, and smart enough to go all the way--yet fail to land the top job. What they don't realize is, the qualities that helped them in their climb to the number two position aren't enough to boost them to number one. In addition to running their businesses well, the author explains, would-be CEOs must master the art of forming coalitions and winning support. They must also sharpen their self-awareness and their sensitivity to the needs of bosses and influential peers because they typically receive little performance feedback once they're on track to become CEO. Indeed, the ability to pick up on subtle cues is often an important part of the test. When succession doesn't go well--or fails altogether--many people pay the price: employees depending on a smooth handoff at the top, investors expecting continuous leadership, and families uprooted when jobs don't pan out. Among those at fault are boards that do not keep a close watch on the succession process, human resource organizations that should have the capacity to help but are not up to the task, and CEOs who do a poor job coaching potential successors. But the aspiring CEO also bears some responsibility. He can dramatically increase his chances of success by understanding his boss's point of view, knowing his own limitations, and managing what psychologist Gerry Egan has called the "shadow organization"--the political side of a company, characterized by unspoken relationships and alliances--without being labeled "political." Most of all, he must learn to conduct himself with a level of maturity and wisdom that signals he is ready--not almost ready--to be chief executive.


Prevalence of cervical cancer and feasibility of screening in rural China: a pilot study for the Shanxi Province Cervical Cancer Screening Study.
For cervical cancer screening to be feasible in developing countries, it must be accurate, inexpensive, and easy to administer. We conducted a pilot study in rural Shanxi Province, People's Republic of China, to determine disease prevalence and study feasibility in preparation for a large-scale comparative trial of 6 screening tests. One-hundred and thirty-six nonpregnant women with no history of hysterectomy, pelvic radiation, or Papanicolaou tests were screened in a rural clinic. Ten percent of the women enrolled reported abnormal vaginal bleeding and 45% reported abnormal vaginal discharge. The tests were the Papanicolaou test (both conventional and ThinPrep), a self-administered swab test by Hybrid Capture II for high-risk human papillomavirus (HPV), a test for high-risk HPV from residual PreservCyt medium, fluorescence spectroscopy, and visual inspection of the cervix by a clinician. All women also underwent colposcopy and biopsies as the reference standard. Biopsies showed 12 of 136 women had >/= high-grade squamous intraepithelial lesions (HGSIL). Screening was completed in 5 half-day sessions, the procedures went smoothly, and local cooperation was enthusiastic. Disease prevalence in Xiangyuan and Yangcheng Counties, Shanxi Province, can be estimated at 8.8% (95% CI, 4.5% to 15.0%). Screening 1000-2000 patients would be sufficient to detect a 10% difference in accuracy between diagnostic tests. The proposed large-scale trial is feasible.


Fuzzy SLIQ decision tree algorithm.
Traditional decision tree algorithms face the problem of having sharp decision boundaries which are hardly found in any real-life classification problems. A fuzzy supervised learning in Quest (SLIQ) decision tree (FS-DT) algorithm is proposed in this paper. It is aimed at constructing a fuzzy decision boundary instead of a crisp decision boundary. Size of the decision tree constructed is another very important parameter in decision tree algorithms. Large and deeper decision tree results in incomprehensible induction rules. The proposed FS-DT algorithm modifies the SLIQ decision tree algorithm to construct a fuzzy binary decision tree of significantly reduced size. The performance of the FS-DT algorithm is compared with SLIQ using several real-life datasets taken from the UCI Machine Learning Repository. The FS-DT algorithm outperforms its crisp counterpart in terms of classification accuracy. FS-DT also results in more than 70% reduction in size of the decision tree compared to SLIQ.


Sugammadex induced bradycardia and hypotension: A case report and literature review.
There is evidence that sugammadex can facilitate extubation post-surgery and attenuate postoperative pulmonary complications resulting from postoperative residual neuromuscular blockade. However, it may induce adverse effects, including bronchospasm, laryngospasm, bradycardia, hypotension, and cardiac arrest. Here, we present a case of sugammadex-induced bradycardia and hypotension. An 82-year-old female received video-assisted thoracic surgery decortication and wedge resection of the lung for empyema. Post-surgery, she developed bradycardia, hypotension, hypoxia, and weakness. The patient was suspected to have sugammadex-induced bradycardia, hypotension, hypoxia and weakness. The patient received immediate treatment with atropine (0.5 mg) for bradycardia. Glycopyrrolate (0.1 mg) and neostigmine (1 mg) were administered to improve the train-of-four (TOF) ratio. Following initial management, we observed improvement in the hemodynamics of the patient. She was discharged without any sequelae. Sugammadex-induced bradycardia or cardiac arrest are rare; however, anesthesiologists must consider the possibility of the occurrence of such events and initiate appropriate management measures. Immediate treatment with atropine and inotropic or vasopressors is warranted if the patient presents with bradycardia.


Percolative switching in transition metal dichalcogenide field-effect transistors at room temperature.
We have addressed the microscopic transport mechanism at the switching or 'on-off' transition in transition metal dichalcogenide (TMDC) field-effect transistors (FETs), which has been a controversial topic in TMDC electronics, especially at room temperature. With simultaneous measurement of channel conductivity and its slow time-dependent fluctuation (or noise) in ultrathin WSe2 and MoS2 FETs on insulating SiO2 substrates where noise arises from McWhorter-type carrier number fluctuations, we establish that the switching in conventional backgated TMDC FETs is a classical percolation transition in a medium of inhomogeneous carrier density distribution. From the experimentally observed exponents in the scaling of noise magnitude with conductivity, we observe unambiguous signatures of percolation in a random resistor network, particularly, in WSe2 FETs close to switching, which crosses over to continuum percolation at a higher doping level. We demonstrate a powerful experimental probe to the microscopic nature of near-threshold electrical transport in TMDC FETs, irrespective of the material detail, device geometry, or carrier mobility, which can be extended to other classes of 2D material-based devices as well.


Multicenter study of diffuse pleural mesothelioma. Histopathological and immunohistochemical features.
The pathological diagnosis of diffuse pleural mesothelioma (DPM) contributes to treatment selection and clinical trials interpretation. To know its characteristics and evaluate the viability of comprehensive pathological diagnosis of DPM in Argentina we did a retrospective descriptive study of DPM cases reported from 2009 to 2018. We analyzed 398 cases corresponding to 238 (60%) men and 160 (40%) women, median age 66 years, from surgical biopsies (78%), small biopsies (16.5%) and surgical resections (5.5%). The 77% were epithelioid (E-DPM), 12% biphasic, 10% sarcomatoid, and 4 cases transitional variant. In E-DPM the main pattern was tubular in 36% and solid in 33%. There was a second pattern in 179 cases. Considering the main pattern and the second together, 48% presented tubular subtype and 48% solid subtype. Stroma, necrosis, and nuclear score showed significant differences between E-DPM and non-epithelioid mesotheliomas. Overall tumor grade was predominantly low in E-DPM, except for 42% of the solid main pattern. We recognized the transitional variant extensively in 4 cases and focally in 8. The immunohistochemical antibody panel used included pan-cytokeratin, calretinin, WT-1, cytokeratin 5, CEA and TTF-1. The expression of cytokeratin 5, calretinin and WT-1 was lower in the sarcomatoid type (43%, 87 and 37%) than in the epithelioid type (92%, 98% and 93%). This study highlights the tumor heterogeneity of DPM that shows the diagnostic difficulty, and the feasibility of evaluating histological aggressiveness in E-DPM, B-DPM and S-DPM in our country.


Methods for primary concentration of viruses from water samples: a review and meta-analysis of recent studies.
Since the beginning of environmental virology in the mid-twentieth century, a key challenge to scientists in the environmental field has been how to collect, isolate and detect pathogenic viruses from water that is used for drinking and/or recreational purposes. Early studies investigated different types of membrane filters, with more sophisticated technologies being developed more recently. The purpose of this study was to look at the current state of the science of methods for the concentration of viruses from water. Several technologies were reviewed, and associated data were included in a meta-analysis which showed that electronegative filters, electropositive filters and ultrafilters are comparable in performance and that significant differences in recovery are due to virus type rather than filter type, water matrix or sample volume. This information is useful, as it will help to determine which method(s) should be used, particularly if there is a specific viral type being targeted for a particular study. In addition, it will be helpful when sampling different environmental water matrices and/or when budget allowance must be taken into consideration. Taken together, this will be useful in performing viral occurrence studies, which ultimately can help ensure safer water for both humans and the environment.


The evasive plausibility.
A frequent practical problem is to assess the probability of a potential single event (X). The event probability P(X) is usually conditional to some assumption (A) and is then written P(X / A). Whether the assumption is valid or not is an unknown fact, but its validity may be assigned a weight psi(A) indicating the observer's belief in its validity. The weighted quantity would be the unconditional probability of X if the weighting factor were a true probability. However, it is not a stochastic quantity even though in Bayesian statistics it would be treated as a probability. It follows that the weighted quantity, i.e. psi (A) x P(X / A), is not an unconditional probability in the usual sense. It is suggested that it be given a special name, for example 'plausibility'.


Randomized CRISPR-Cas Transcriptional Perturbation Screening Reveals Protective Genes against Alpha-Synuclein Toxicity.
The genome-wide perturbation of transcriptional networks with CRISPR-Cas technology has primarily involved systematic and targeted gene modulation. Here, we developed PRISM (Perturbing Regulatory Interactions by Synthetic Modulators), a screening platform that uses randomized CRISPR-Cas transcription factors (crisprTFs) to globally perturb transcriptional networks. By applying PRISM to a yeast model of Parkinson's disease (PD), we identified guide RNAs (gRNAs) that modulate transcriptional networks and protect cells from alpha-synuclein (αSyn) toxicity. One gRNA identified in this screen outperformed the most protective suppressors of αSyn toxicity reported previously, highlighting PRISM's ability to identify modulators of important phenotypes. Gene expression profiling revealed genes differentially modulated by this strong protective gRNA that rescued yeast from αSyn toxicity when overexpressed. Human homologs of top-ranked hits protected against αSyn-induced cell death in a human neuronal PD model. Thus, high-throughput and unbiased perturbation of transcriptional networks via randomized crisprTFs can reveal complex biological phenotypes and effective disease modulators.


Correlation of insulin resistance by various methods with fasting insulin in obese.
Several studies indicate that obesity is closely related to insulin resistance (IR). However, this relationship has not been adequately explored. This study aims to evaluate the prevalence of IR among obese using some indirect methods for assessment of IR. We analyzed the correlation of fasting insulin (FI) with body mass index. We examined 100 obese and overweight. Anthropometric measurements were done for all individuals. Blood lipids parameters, glucose, and insulin were assayed after a 10 h fast. The indices McAuley (McA), homeostasis model assessments (HOMA), quantitative insulin sensitivity check index (QUICKI) were used to assess IR. In this study, the correlations of FI with McA, HOMA and QUICKI were significant (P < 0.05). FI test had significant sensitivity and specificity when compared with McA, HOMA and QUICKI indices. FI gives parallel results to the assessment of IR by other methods. Validity of FI was further analyzed by Cohen's kappa test and had a satisfactory agreement (χ =0.940). Altogether, this study suggested that FI was sensitive and also specific as McA in assessment of IR in obese. Thus, FI can be used as an easy test to detect IR also in obese.


[Aging mechanisms of proteins].
All the living molecules appear to suffer from the deleterious effects of aging, but the primary mechanisms of this inexorable evolution are still unknown. In the case of proteins, two major types of chemical reactions participate in the aging phenomena: 1) structural transformations induced by the addition of radicals by enzymic or non-enzymic reactions, 2) proteolytic cleavages. Among the reactions of the first group, the nonenzymatic glycation is the more generalized, not only in diabetic patients but also in non diabetic subjects. This glycation depends on the probabilities of encounters between circulating glucose molecules and free amino groups existing either at the N-terminal end of the polypeptide chains or on the lysyl side chains. These reactions are more frequent in the extracellular spaces and connective tissues because glucose circulates freely in these spaces, because the level of glucose is better controlled inside the cells (and even lower in diabetes mellitus), and finally because the proteins of these regions, such as the collagens, fibronectin and elastin, are relatively long lived, even if their life-span is really shorter than it was precedently believed. The binding of sugar residues to protein amino groups determines frequent modifications of structure that often make the molecule inactive. For instance, when a glucose unit binds to a lysyl radical located in the active center of an enzyme, it suppresses the activity of this enzyme. More generally, in the case of the connective tissue proteins that participate in complex supramolecular assemblies, the presence of additional radicals on some ponctual locations may interfere with the correct association of molecules. This is particularly true for basement membranes whose structure is impaired in diabetes. Glycation might also introduce abnormal cross-links between polypeptides or modify the antigenic power of some proteins and explain the formation of autoantibodies. Another property of glycated proteins is their reaction with oxygen leading to the formation of superoxide. The binding of a reducing sugar on an amino function is followed by an Amadori rearrangement that forms a ketol group. Ketols groups have the property to transmit electrons to molecular oxygen, and to forming superoxide radicals. Superoxide is capable of degrading only one protein: collagen, but it is also able to transform itself into hydrogen peroxide and hydroxyl radicals, which are far more toxic than O2-. The result of the formation of these oxygen free radicals from glycated proteins is the initiation of the degradation of several types of proteins, like the collagens.(ABSTRACT TRUNCATED AT 400 WORDS)


Feasibility of laser-induced breakdown spectroscopy (LIBS) for classification of sea salts.
We have investigated the feasibility of laser-induced breakdown spectroscopy (LIBS) as a fast, reliable classification tool for sea salts. For 11 kinds of sea salts, potassium (K), magnesium (Mg), calcium (Ca), and aluminum (Al), concentrations were measured by inductively coupled plasma-atomic emission spectroscopy (ICP-AES), and the LIBS spectra were recorded in the narrow wavelength region between 760 and 800 nm where K (I), Mg (I), Ca (II), Al (I), and cyanide (CN) band emissions are observed. The ICP-AES measurements revealed that the K, Mg, Ca, and Al concentrations varied significantly with the provenance of each salt. The relative intensities of the K (I), Mg (I), Ca (II), and Al (I) peaks observed in the LIBS spectra are consistent with the results using ICP-AES. The principal component analysis of the LIBS spectra provided the score plot with quite a high degree of clustering. This indicates that classification of sea salts by chemometric analysis of LIBS spectra is very promising. Classification models were developed by partial least squares discriminant analysis (PLS-DA) and evaluated. In addition, the Al (I) peaks enabled us to discriminate between different production methods of the salts.


In vitro and in vivo evaluation of phenylbutenoid dimers as inhibitors of P-glycoprotein.
The expression of P-glycoprotein (P-gp), an ATP-dependent efflux transporter, is closely associated with the failure of chemotherapy and drug absorption. Two synthesized optically active phenylbutenoid dimers, 3S-(3,4-dimethoxyphenyl)-4R-{(E)-3,4-dimethoxystyryl}cyclohex-1-ene (1) and 3R-(3,4-dimethoxyphenyl)-4S-{(E)-3,4-dimethoxystyryl}cyclohex-1-ene (2), were tested for their P-gp inhibitory effects by measuring cellular accumulation and efflux of daunomycin in P-gp-overexpressed human breast cancer cells (MCF-7/ADR). Compound 2 significantly increased the accumulation of daunomycin (539%) and decreased the efflux of this compound (55.4%), and similar results were observed for 1. ATPase assays and Western blot analysis were performed to identify the mechanisms by which compounds 1 and 2 inhibit P-gp. In addition, changes in the pharmacokinetic profile of paclitaxel coadministered with 2 in rats were evaluated. Paclitaxel (25 mg/kg) when orally administered with 2 (5 mg/kg) improved its relative bioavailability by 185%. Compound 2 effectively improved cellular accumulation by reducing the efflux of daunomycin and significantly enhanced oral exposure to paclitaxel. Therefore, compound 2 may be useful for improving oral exposure and cellular availability of drugs that are also substrates of P-gp.


Probiotic characteristics of Lactobacillus fermentum strains isolated from tulum cheese.
The aim of this study was to characterize the probiotic characteristics of Lactobacillus fermentum strains isolated from Tulum cheese. Seven L. fermentum strains were selected among the isolated and identified lactobacillus strains due to their abundance. When the gastric condition was considered, L. fermentum LP3 and LP4 were able to tolerate pH 2.5 and 1% bile salt. All L. fermentum strains had similar enzymatic activity and antibiotic resistance pattern but the highest antagonistic effect was detected within LP3, LP4 and LP6. Cholesterol assimilation amount of L. fermentum strains ranged between 12.1 and 45.3% in MRS and 20.7-71.1% in MRS with bile. The highest cholesterol assimilation in MRS and MRS with bile was occurred by LP3 and LP4, respectively. L. fermentum LP2 adhered to caco-2 cells more than Lactobacillus rhamnosus LGG where LP3, LP4 and LP5 adhered at similar level. In conclusion, L. fermentum LP3 and LP4 fulfilled sufficient criteria to be probiotics for use as a starter culture in the production of tulum cheese or other dairy products. Also this study indicated that some food-associated Lactobacillus strains non-predominant for gut biota have significant probiotic potential.


Low-level calibration study for a new ion chromatographic column to determine borate in deionized water.
In the semiconductor industry, there is interest in determining borate at sub-ppb levels in ultrapure water, since borate is an early breakthrough ion from ion-exchange resin beds. Although dissolved silica is the most common species currently used to monitor the breakdown of the deionization systems, it is thought that borate probably breaks through earlier than silicate. To be of use as an early-warning indicator, borate must be determined at ppt levels. This paper discusses benchtop results with several new column products designed to deliver low-ppt detection limits for boron as borate. The system uses a prototype borate-specific concentrator column that is coupled to an ion-exclusion separator and suppressed-conductivity detection. The acidic eluent, containing mannitol, quantitatively elutes the borate from the concentrator. The analytical separation is performed using a specially designed ion-exclusion column. Data presented are from two multilevel calibration studies. Included is a discussion of detection-limit calculations and recommended formats for reporting results.


Nosocomial outbreak of VIM-1-producing Klebsiella pneumoniae isolates of multilocus sequence type 15: molecular basis, clinical risk factors, and outcome.
We study the epidemiology, molecular basis, clinical risk factors, and outcome involved in the clonal dissemination of VIM-1-producing Klebsiella pneumoniae isolates in the hospital setting. All patients infected/colonized by carbapenem-nonsusceptible K. pneumoniae (CNSKP) in 2009 were included. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Antibiotic resistance genes were analyzed by PCR and sequencing. Plasmids were studied by PFGE with S1 nuclease digestion and for incompatibility group by a PCR-based replicon typing scheme. Risk factors associated with CNSKP colonization/infection were assessed by an observational case-control study. All 55 patients studied were infected (n = 28) or colonized (n = 27) by VIM-1-producing K. pneumoniae. All but one acquired isolates of a single clone (PFGE cluster 1 [C1], sequence type 15 [ST15]), while another clone (PFGE C2, ST340) was detected in four patients. C1 isolates also produced the new extended-spectrum β-lactamase SHV-134. bla(VIM-1) was carried in a class 1 integron and an untypeable plasmid of ∼50 bp. The number of days that the patient received mechanical ventilation, the use of parenteral nutrition, previous treatment with linezolid, and treatment with extended-spectrum cephalosporins for more than 7 days were detected to be independent risk factors for CNSKP acquisition. The VIM-1-producing K. pneumoniae ST15 clone has a high capacity to spread among intensive care unit patients with severe underlying conditions. A high rate of associated mortality and great difficulty in controlling the spread of this clone, without permanent behavioral changes in the personnel, were observed.


Phase unwrapping of MR phase images using Poisson equation.
The authors have developed a technique based on a solution of the Poisson equation to unwrap the phase in magnetic resonance (MR) phase images. The method is based on the assumption that the magnitude of the inter-pixel phase change is less than pi per pixel. Therefore, the authors obtain an estimate of the phase gradient by "wrapping" the gradient of the original phase image. The problem is then to obtain the absolute phase given the estimate of the phase gradient. The least-squares (LS) solution to this problem is shown to be a solution of the Poisson equation allowing the use of fast Poisson solvers. The absolute phase is then obtained by mapping the LS phase to the nearest multiple of 2 K from the measured phase. The proposed technique is evaluated using MR phase images and is proven to be robust in the presence of noise. An application of the proposed method to the 3-point Dixon technique for water and fat separation is demonstrated.


Barriers and facilitators to a healthy lifestyle in postpartum women: A systematic review of qualitative and quantitative studies in postpartum women and healthcare providers.
A healthy postpartum lifestyle is vital for the promotion of optimal maternal health, return to pre-pregnancy weight and prevention of postpartum weight retention, but barriers exist. We performed a systematic review that aimed to describe the barriers and facilitators to a healthy lifestyle in the first 2 years postpartum from the perspectives of women and healthcare providers. Databases were searched for eligible studies published up to 26 August 2019. Following thematic analysis, identified themes were mapped to the Theoretical Domains Framework and the Capability, Opportunity, Motivation and Behaviour model. We included 28 qualitative and quantitative studies after screening 15,643 citations and 246 full texts. We identified barriers and facilitators relating to capability (e.g., lack of knowledge regarding benefits of lifestyle behaviours; limitations in healthcare providers' skills in providing lifestyle support), opportunity (e.g., social support from partners, family, friends and healthcare providers; childcare needs) and motivation (e.g., identifying benefits of exercise and perception of personal health; enjoyment of the activity or food). We suggest intervention components to include in lifestyle interventions for postpartum women based on the identified themes. Our findings provide evidence to inform the development of interventions to support postpartum women in adopting and maintaining a healthy lifestyle.


Strategies for hydrogen storage in metal--organic frameworks.
Increased attention is being focused on metal-organic frameworks as candidates for hydrogen storage materials. This is a result of their many favorable attributes, such as high porosity, reproducible and facile syntheses, amenability to scale-up, and chemical modification for targeting desired properties. A discussion of several strategies aimed at improving hydrogen uptake in these materials is presented. These strategies include the optimization of pore size and adsorption energy by linker modification, impregnation, catenation, and the inclusion of open metal sites and lighter metals.


Short-Term Subcutaneous Allergy Immunotherapy and Dupilumab are Well Tolerated in Allergic Rhinitis: A Randomized Trial.
Subcutaneous immunotherapy (SCIT) has been proven as an effective therapy against some allergens for seasonal allergic rhinitis (SAR) patients unresponsive to intranasal corticosteroids and/or antihistamines but carries risk of systemic allergic reactions. Dupilumab blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation in multiple diseases. To evaluate the efficacy and safety of SCIT+dupilumab vs SCIT alone. This phase 2a, multicenter, double-blind, placebo-controlled parallel-group study conducted in 103 adults with grass pollen-induced SAR (NCT03558997) randomized patients 1:1:1:1 to SCIT, dupilumab (300 mg every 2 weeks), SCIT+dupilumab, or placebo. SCIT was administered using an 8-week cluster protocol followed by 8 weeks of maintenance injections. Primary endpoint was change from pre-treatment baseline in area under the curve (AUC) in total nasal symptom score (TNSS) 0-1 h following nasal allergen challenge (NAC) with timothy grass extract at Week 17. Although 16 weeks of treatment with SCIT+dupilumab did not significantly improve TNSS AUC (0-1 h) following NAC at Week 17 vs SCIT (least squares mean -56.76% vs -52.03%), a higher proportion of SCIT+dupilumab-treated patients (61.5%) achieved SCIT maintenance dose vs SCIT (46.2%). A lower proportion of SCIT+dupilumab-treated patients (7.7%) required epinephrine rescue treatment vs SCIT (19.2%). There were significantly fewer withdrawals in the SCIT+dupilumab group than in the SCIT group (n = 2 [7.7%] vs n = 8 [30.8%]; P = 0.0216); the majority of SCIT group withdrawals were due to SCIT-related intolerability, compared with no discontinuations from the SCIT+dupilumab group. In SAR patients, 16 weeks of SCIT+dupilumab may improve SCIT tolerability but did not incrementally reduce post-allergen challenge nasal symptoms compared with SCIT alone. NCT03558997.


The effect of dietary curcumin and capsaicin on hepatic fetuin-A expression and fat accumulation in rats fed on a high-fat diet.
Effects of curcumin (turmeric) and capsaicin (red pepper) on hepatic fat accumulation and fetuin-A expression in rats fed high-fat diet (HFD) is aimed to be investigated. Male Sprague-Dawley rats received HFD (60% of total calories from fat) and 0.15 g capsaicin/kg HFD and/or 1.5 g curcumin/kg HFD for 16 weeks. Hepatic AMPK, p-AMPK and fetuin-A expressions were determined by western blotting, liver lipid levels were measured with colorimetric methods and serum fetuin-A, insulin, leptin and adiponectin levels were detected using commercial ELISA kits. HFD increased hepatic lipid levels, fetuin-A expression and serum leptin, insülin and fetuin-A levels. Curcumin and capsaicin treatments significantly reduced hepatic fat accumulation and leptin levels; liver fetuin-A expression was decreased significantly by the curcumin treatment. Curcumin and capsaicin treatments attenuated hepatic fat accumulation and increased leptin levels related to inflammation. The suppression of hepatic fetuin-A expression is observed to be especially sensitive to curcumin.


Self-care and Subjectivity among Mexican Diabetes Patients in the United States.
Type 2 diabetes is considered a public health crisis, particularly among people of Mexican descent in the United States. Clinical approaches to diabetes management increasingly emphasize self-care, which places responsibility for illness on individuals and mandates self-regulation. Using narrative and free-list data from a two-phase study of low-income first- and second-generation Mexican immigrants living with diabetes, we present evidence that self-care among our participants involves emotion regulation as well as maintenance of and care for family. These findings suggest, in turn, that the ideology of selfhood on which these practices are based does not correspond with the ideology of selfhood cultivated in the U.S. clinical sphere. Divergence between these ideologies may lead to self-conflict for patients and the experience of moral blame. We argue that our participants use their explanations of diabetes causality and control as a form of self-making, which both resists such blame and asserts an alternative form of selfhood that may align more closely with the values held by our Mexican-American participants.


Monoclonal anti-human aldolase C antibodies that react to the isozyme group-specific sequences and generally conserved sequences of human aldolase C1.
Nine monoclonal mouse anti-human aldolase C antibodies, mAbs A4, A8, B4, B7, B8, C1, D9, E10, and H1, were isolated and characterized. These mAbs fall substantially into four groups according to their reactivity with antigens. (i) Human aldolase C-specific mAbs (B8, D9, and H1). (ii) Type C aldolase-specific mAbs (B4 and E10). (iii) Ubiquitous mAbs, which react with vertebrate aldolases irrespective of type of isozyme and species (A4 and B7). (iv) Sub-ubiquitous mAbs, which are closely similar to the ubiquitous mAbs but differ slightly in terms of antigenic specificity (A8 and C1). Aldolase C-specific mAbs B8, H1, B4, and E10, but not D9, have their epitopes on a region within amino acid positions 79-193 of antigens, where the type-C isozyme group-specific sequence-3 (IGS-3) is situated. In contrast, ubiquitous mAbs A4 and B7 and sub-ubiquitous mAb A8 may have their epitopes on the commonly conserved regions of the three isozyme groups. The epitope of sub-ubiquitous mAb C1 appears to be on the IGS-2/3 but this is yet to be resolved. These nine mAbs can be classified into two groups based on the mode of epitope recognition, which was determined by ELISA, immunoblotting, and immunoprecipitation assays: (i) primary sequence-epitope mAbs such as B4, E10, and B7; and (ii) conformation-epitope mAbs (B8, D9, H1, A4, A8, and C1). Among these mAbs, aldolase C-specific mAbs H1 and E10 appear to be useful as probes for detection of conformational change around the type-C IGS-3 motif of human aldolase C because, when assessed by immunoprecipitation assay, mAb H1 reacts only with human aldolase C but not with CA250 and CA306, while mAb E10 reacts with CA250 and CA306 but not with aldolase C, even though these antigens have a common type-C IGS-3 motif. Similarly, the ubiquitous mAb B7 should serve as a probe for general use to detect vertebrate aldolases irrespective of isozyme groups and species.


Electrografted aryl diazonium initiators for surface-confined photopolymerization: a new approach to designing functional polymer coatings.
This article reports on the preparation of polystyrene (PS), poly(methyl methacrylate) (PMMA), and poly(2-hydroxyethyl methacrylate) (PHEMA) ultrathin grafts on gold substrates modified by 4-benzoylphenyl (BP) moieties derived from the electroreduction of the parent diazonium salt BF(4)(-), (+)N(2)-C(6)H(4)-CO-C(6)H(5) (DS). The grafted organic species -C(6)H(4)-CO-C(6)H(5) was found to be very effective in the surface-initiating photopolymerization (SIPP) of vinylic monomers in the presence of an aromatic tertiary amine co-initiator acting as a hydrogen donor. This novel tandem diazonium salt electroreduction/SIPP was found to be effective in grafting PS, PMMA, and PHEMA from the surface of gold-coated silicon wafers. The polymer films were characterized in terms of chemical structure and wettability by infrared reflection absorption spectroscopy and X-ray photoelectron spectroscopy, and contact angle measurements, respectively. The polymer grafts were further evaluated as adsorbents for bovine serum albumin (BSA) used as a model protein. It was found gold/PHEMA resisted BSA adsorption because of its hydrophilic character, whereas PS and PMMA grafts adsorbed BSA via interfacial hydrophobic interaction. The XPS-determined extent of adsorbed BSA was found to increase linearly with the hydrophobic character of the polymer grafts as measured by water contact angles. This work shows that this novel tandem diazonium salt electroreduction/SIPP is a facile, ultrafast, efficient protocol for grafting polymer chains to surfaces. It broadens the enormous possibilities offered by aryl diazonium salts to generate functional organic coatings.


Double trouble. Trait food craving and impulsivity interactively predict food-cue affected behavioral inhibition.
Impulsivity and food craving have both been implicated in overeating. Recent results suggest that both processes may interactively predict increased food intake. In the present study, female participants performed a Go/No-go task with pictures of high- and low-calorie foods. They were instructed to press a button in response to the respective target category, but withhold responses to the other category. Target category was switched after every other block, thereby creating blocks in which stimulus-response mapping was the same as in the previous block (nonshift blocks) and blocks in which it was reversed (shift blocks). The Food Cravings Questionnaires and the Barratt Impulsiveness Scale were used to assess trait and state food craving and attentional, motor, and nonplanning impulsivity. Participants had slower reaction times and more omission errors (OE) in high-calorie than in low-calorie blocks. Number of commission errors (CE) and OE was higher in shift blocks than in nonshift blocks. Trait impulsivity was positively correlated with CE in shift blocks while trait food craving was positively correlated with CE in high-calorie blocks. Importantly, CE in high-calorie-shift blocks were predicted by an interaction of food craving × impulsivity such that the relationship between food craving and CE was particularly strong at high levels of impulsivity, but vanished at low levels of impulsivity. Thus, impulsive reactions to high-calorie food-cues are particularly pronounced when both trait impulsivity and food craving is high, but low levels of impulsivity can compensate for high levels of trait food craving. Results support models of self-regulation which assume that interactive effects of low top-down control and strong reward sensitive, bottom-up mechanisms may determine eating-related disinhibition, ultimately leading to increased food intake.


Enhancing autism spectrum disorder classification in children through the integration of traditional statistics and classical machine learning techniques in EEG analysis.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder hallmarked by challenges in social communication, limited interests, and repetitive, stereotyped movements and behaviors. Numerous research efforts have indicated that individuals with ASD exhibit distinct brain connectivity patterns compared to control groups. However, these investigations, often constrained by small sample sizes, have led to inconsistent results, suggesting both heightened and diminished long-range connectivity within ASD populations. To bolster our analysis and enhance their reliability, we conducted a retrospective study using two different connectivity metrics and employed both traditional statistical methods and machine learning techniques. The concurrent use of statistical analysis and classical machine learning techniques advanced our understanding of model predictions derived from the spectral or connectivity attributes of a subject's EEG signal, while also verifying these predictions. Significantly, the utilization of machine learning methodologies empowered us to identify a unique subgroup of correctly classified children with ASD, defined by the analyzed EEG features. This improved approach is expected to contribute significantly to the existing body of knowledge on ASD and potentially guide personalized treatment strategies.


Plasticity Induced Recovery of Breathing Occurs at Chronic Stages after Cervical Contusion.
Severe midcervical contusion injury causes profound deficits throughout the respiratory motor system that last from acute to chronic time points post-injury. We use chondroitinase ABC (ChABC) to digest chondroitin sulphate proteoglycans within the extracellular matrix (ECM) surrounding the respiratory system at both acute and chronic time points post-injury to explore whether augmentation of plasticity can recover normal motor function. We demonstrate that, regardless of time post-injury or treatment application, the lesion cavity remains consistent, showing little regeneration or neuroprotection within our model. Through electromyography (EMG) recordings of multiple inspiratory muscles, however, we show that application of the enzyme at chronic time points post-injury initiates the recovery of normal breathing in previously paralyzed respiratory muscles. This reduced the need for compensatory activity throughout the motor system. Application of ChABC at acute time points recovered only modest amounts of respiratory function. To further understand this effect, we assessed the anatomical mechanism of this recovery. Increased EMG activity in previously paralyzed muscles was brought about by activation of spared bulbospinal pathways through the site of injury and/or sprouting of spared serotonergic fibers from the contralateral side of the cord. Accordingly, we demonstrate that alterations to the ECM and augmentation of plasticity at chronic time points post-cervical contusion can cause functional recovery of the respiratory motor system and reveal mechanistic evidence of the pathways that govern this effect.


Local ancestry analysis reveals genomic convergence in extremophile fishes.
The molecular basis of convergent phenotypes is often unknown. However, convergence at a genomic level is predicted when there are large population sizes, gene flow among diverging lineages or strong genetic constraints. We used whole-genome resequencing to investigate genomic convergence in fishes ( Poecilia spp.) that have repeatedly colonized hydrogen sulfide (H2S)-rich environments in Mexico. We identified genomic similarities in both single nucleotide polymorphisms (SNPs) and structural variants (SVs) among independently derived sulfide spring populations, with approximately 1.2% of the genome being shared among sulfidic ecotypes. We compared these convergent genomic regions to candidate genes for H2S adaptation identified from transcriptomic analyses and found that a significant proportion of these candidate genes (8%) were also in regions where sulfidic individuals had similar SNPs, while only 1.7% were in regions where sulfidic individuals had similar SVs. Those candidate genes included genes involved in sulfide detoxification, the electron transport chain (the main toxicity target of H2S) and other processes putatively important for adaptation to sulfidic environments. Regional genomic similarity across independent populations exposed to the same source of selection is consistent with selection on standing variation or introgression of adaptive alleles across divergent lineages. However, combined with previous analyses, our data also support that adaptive changes in mitochondrially encoded subunits arose independently via selection on de novo mutations. Pressing questions remain on what conditions ultimately facilitate the independent rise of adaptive alleles at the same loci in separate populations, and thus, the degree to which evolution is repeatable or predictable. This article is part of the theme issue 'Convergent evolution in the genomics era: new insights and directions'.


Community-based interventions to reduce overweight and obesity in China: a systematic review of the Chinese and English literature.
Overweight and obesity pose a challenge to public health in China. According to Chinese definition, 303 million Chinese are overweight (body mass index, BMI >or= 24 kg m(-2)). Among them, 73 million are clinically obese (BMI >or= 28 kg m(-2)). In line with the global trend, the rate of obesity in China continues to increase, with associated morbidity and mortality. This study was to identify interventions, which are effective in Mainland Chinese society. All non-drug-controlled interventions (>or=3 months) in Mainland China, which used anthropometric outcome measures, were selected from three Chinese and nine international electronic databases (before May 2006) and included in this systematic review. A total of 20 studies met the selection criteria and were included in the review. Among them only one was published in an international journal. Most studies combined at least physical activity, dietary intervention and health education. Seventeen studies (85%) reported significant effects in anthropometric measurement outcomes. Comprehensive interventions with at least physical activity, dietary intervention and health education may be effective in reducing obesity in Chinese children. The role of grandparents as carers in the one-child society is worth considering further. Current evidence of effective interventions for adults is limited. Publication bias in Chinese databases should be taken into account.


Regulation of bcl-2 family proteins during development and in response to oxidative stress in cardiac myocytes: association with changes in mitochondrial membrane potential.
Cardiac myocyte apoptosis is potentially important in many cardiac disorders. In other cells, Bcl-2 family proteins and mitochondrial dysfunction are probably key regulators of the apoptotic response. In the present study, we characterized the regulation of antiapoptotic (Bcl-2, Bcl-xL) and proapoptotic (Bad, Bax) Bcl-2 family proteins in the rat heart during development and in oxidative stress-induced apoptosis. Bcl-2 and Bcl-xL were expressed at high levels in the neonate, and their expression was sustained during development. In contrast, although Bad and Bax were present at high levels in neonatal hearts, they were barely detectable in adult hearts. We confirmed that H(2)O(2) induced cardiac myocyte cell death, stimulating poly(ADP-ribose) polymerase proteolysis (from 2 hours), caspase-3 proteolysis (from 2 hours), and DNA fragmentation (from 8 hours). In unstimulated neonatal cardiac myocytes, Bcl-2 and Bcl-xL were associated with the mitochondria, but Bad and Bax were predominantly present in a crude cytosolic fraction. Exposure of myocytes to H(2)O(2) stimulated rapid translocation of Bad (<5 minutes) to the mitochondria. This was followed by the subsequent degradation of Bad and Bcl-2 (from approximately 30 minutes). The levels of the mitochondrial membrane marker cytochrome oxidase remained unchanged. H(2)O(2) also induced translocation of cytochrome c from the mitochondria to the cytosol within 15 to 30 minutes, which was indicative of mitochondrial dysfunction. Myocytes exposed to H(2)O(2) showed an early loss of mitochondrial membrane potential (assessed by fluorescence-activated cell sorter analysis) from 15 to 30 minutes, which was partially restored by approximately 1 hour. However, a subsequent irreversible loss of mitochondrial membrane potential occurred that correlated with cell death. These data suggest that the regulation of Bcl-2 and mitochondrial function are important factors in oxidative stress-induced cardiac myocyte apoptosis.


Pch2 acts through Xrs2 and Tel1/ATM to modulate interhomolog bias and checkpoint function during meiosis.
Proper segregation of chromosomes during meiosis requires the formation and repair of double-strand breaks (DSBs) to form crossovers. Repair is biased toward using the homolog as a substrate rather than the sister chromatid. Pch2 is a conserved member of the AAA(+)-ATPase family of proteins and is implicated in a wide range of meiosis-specific processes including the recombination checkpoint, maturation of the chromosome axis, crossover control, and synapsis. We demonstrate a role for Pch2 in promoting and regulating interhomolog bias and the meiotic recombination checkpoint in response to unprocessed DSBs through the activation of axial proteins Hop1 and Mek1 in budding yeast. We show that Pch2 physically interacts with the putative BRCT repeats in the N-terminal region of Xrs2, a member of the MRX complex that acts at sites of unprocessed DSBs. Pch2, Xrs2, and the ATM ortholog Tel1 function in the same pathway leading to the phosphorylation of Hop1, independent of Rad17 and the ATR ortholog Mec1, which respond to the presence of single-stranded DNA. An N-terminal deletion of Xrs2 recapitulates the pch2Δ phenotypes for signaling unresected breaks. We propose that interaction with Xrs2 may enable Pch2 to remodel chromosome structure adjacent to the site of a DSB and thereby promote accessibility of Hop1 to the Tel1 kinase. In addition, Xrs2, like Pch2, is required for checkpoint-mediated delay conferred by the failure to synapse chromosomes.


Acute kidney injury and electrolyte disorders in COVID-19.
Acute kidney injury (AKI) and electrolyte disorders are important complications of hospitalized coronavirus disease 2019 (COVID-19) patients. AKI is thought to occur due to multiple pathophysiological mechanisms, such as multiple organ dysfunction (mainly cardiac and respiratory), direct viral entry in the renal tubules, and cytokine release syndrome. AKI is present in approximately one in every ten hospitalized COVID-19 patients. The incidence rates of AKI increase in patients who are admitted to the intensive care unit (ICU), with levels higher than 50%. Additionally, renal replacement therapy (RRT) is used in 7% of all AKI cases, but in nearly 20% of patients admitted to an ICU. COVID-19 patients with AKI are considered moderate-to-severe cases and are managed with multiple interdisciplinary conducts. AKI acts as a risk factor for mortality in severe acute respiratory syndrome coronavirus 2 infection, especially when RRT is needed. Electrolyte disorders are also common manifestations in hospitalized COVID-19 patients, mainly hyponatremia, hypokalemia, and hypocalcemia. Hyponatremia occurs due to a combination of syndrome of inappropriate secretion of antidiuretic hormone and gastrointestinal fluid loss from vomiting and diarrhea. When it comes to hypokalemia, its mechanism is not fully understood but may derive from hyperaldosteronism due to renin angiotensin aldosterone system overstimulation and gastrointestinal fluid loss as well. The clinical features of hypokalemia in COVID-19 are similar to those in other conditions. Hypocalcemia is the most common electrolyte disorder in COVID-19 and seems to occur because of vitamin D deficiency and parathyroid imbalance. It is also highly associated with longer hospital and ICU stay.


Bacteriophage MX-1: properties of the phage and its structural proteins.
Bacteriophage MX-1 is a virulent DNA phage for Myxococcus. The host range includes strains of Myxococcus xanthus, M. fulvus and M. virescens. The phage has a sedimentation coefficient (S degrees 20,w) of 1145S and a density of 1-531 g/ml. By using SDS-polyacrylamide gel electrophoresis, 23 phage proteins with apparent mol. wt. between 10000 and 150000 were resolved. Gel filtration in the presence of non-ionic detergent partially resolved the proteins. The fraction excluded from Sephadex G-100, fraction 1, contains two glycoproteins. Fraction 1 was resolved into three fractions (1-1, 1-2 and 1-3) by chromatography on Sephadex G-200. The glycoproteins were present in fraction 1-2; all the proteins from this fraction were derived from the phage tail. Comparison of the amino-acid, hexosamine and neutral-sugar compositions of the two glycoproteins showed that they are distinct molecular species; the smaller molecule is not a subunit of the larger. The significance of these findings is discussed and compared with the proteins of the tails of T-even phage of Escherichia coli.


Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis.
The only vaccine available against tuberculosis (TB), the Bacille Calmette-Guerin (BCG), does not provide effective protection against the most common forms of adult TB and in recent years efforts have been made to develop a new and improved vaccine. Among the strategies implemented, the generation of a new live attenuated mycobacterial strain is seen as one of the most promising and feasible, for scientific, ethical and practical reasons. The new understanding of the biology of the tubercle bacilli and of host-pathogen interaction processes, coupled with the possibility to engineer BCG or M. tuberculosis, opened new avenues to design "intelligent" vaccines, capable of eliciting the immune response associated with protection while avoiding the induction of the host immune response associated with immunopathology. The complex and highly immunogenic mycobacterial cell wall can shape the general and antigen specific immune response elicited following immunization, and the possibility to exploit this knowledge may lead to the development of new vaccines that could help conquer this ancient human disease.


Resistance exercise training decreases oxidative damage to DNA and increases cytochrome oxidase activity in older adults.
Regular resistance exercise increases muscle strength and induces muscle fibre hypertrophy in older adults. Although the underlying causes of aging remain unclear, like acute exercise, aging is associated with oxidative stress. In ageing, however, oxidative stress is closely associated with mitochondrial dysfunction as proposed by the mitochondrial theory of aging. The effect of regular resistance exercise upon mitochondrial function and oxidative stress in older adults is unknown. Twenty-eight older men and women (approximately 68.5+/-5.1 yr) performed whole-body resistance exercise training for 14 weeks. Muscle biopsies were taken before and 72 h following the last exercise bout from the vastus lateralis. Urine samples were also taken at the time of tissue collection. Resistance exercise training was associated with a decrease in 8-OHdG (Pre: 10783+/-5856, Post: 8897+/-4030 ng g(-1) creatinine; p<0.05). Protein content for CuZnSOD, MnSOD, and catalase, and enzyme activities for citrate synthase, mitochondrial ETC complex I+III, and complex II+III were not significantly different from baseline. However, complex IV activity was significantly higher after training as compared to before training (Pre: 2.2+/-0.5, Post: 2.9+/-0.9 micromol min(-1) g(-1)ww; p<0.05), as was the ratio of complex IV to complex I (Pre: 11.1+/-9.3, Post: 14.5+/-10.3; p<0.05). There were no apparent changes in normal mtDNA content or visible mtDNA deletion products as a function of training. These data suggest that regular resistance exercise decreases oxidative stress, but does not affect mtDNA. Moreover, increases in complex IV of the electron transport chain may have an indirect antioxidant effect in older adults and may improve function in daily activities.


Therapeutic benefits of pharmacologic and nonpharmacologic treatments for depressive symptoms after traumatic brain injury: a systematic review and network meta-analysis.
Depression is a common morbidity after traumatic brain injury. This network meta-analysis investigated the efficacy and tolerability of pharmacologic and nonpharmacologic interventions for depression after traumatic brain injury. We extracted randomized controlled trials examining pharmacologic or nonpharmacologic interventions with placebo- or active-controlled designs from PubMed, the Cochrane Library and ScienceDirect, from inception to October 30, 2018. We based study selection and extraction of a predefined list of variables on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, and conducted meta-analysis procedures using random effects modelling. Primary outcomes were changes in depressive symptom severity after pharmacologic or nonpharmacologic treatment; the secondary outcome was tolerability, reflected in overall patient dropout rates. Our analysis of 27 randomized controlled trials (10 pharmacologic, total n = 483, mean age = 37.9 yr; 17 nonpharmacologic, total n = 1083, mean age = 38.0 yr) showed that methylphenidate had significantly superior efficacy compared to placebo or control (standardized mean difference -0.91, 95% confidence interval [CI] -1.49 to -0.33). Sertraline was associated with significantly lower tolerability (i.e., a higher dropout rate) compared to placebo or control (odds ratio 2.65, 95% CI 1.27 to 5.54). No nonpharmacologic treatment was more effective than the others, and we found no significant differences in tolerability (i.e., dropout rates) among the nonpharmacologic treatments. Heterogeneity in participant characteristics (e.g., comorbidities), study designs (e.g., trial duration) and psychopathology assessment tools, as well as small trial numbers for some treatment arms, could have been confounders. The present network meta-analysis suggests that methylphenidate might be the best pharmacologic intervention for depressive symptoms related to traumatic brain injury. None of the nonpharmacologic interventions was associated with better improvement in depressive symptoms than the others or than control conditions. None of the pharmacologic or nonpharmacologic treatments had inferior tolerability compared to placebo or controls except for sertraline, which had significantly lower tolerability than placebo.