Pharmacology of alcohol preference in rodents.
In alcoholism research, two fundamental and closely related questions are: "Why do people drink?" and "Why do some people drink too much?" Humans voluntarily drink alcoholic beverages or self-administer alcohol, more often than not, in a social setting. Environmental factors and how individuals react to them can, therefore, have powerful influences on drinking behavior. On the other hand, the neuropsychopharmacological actions of ethanol and how different individuals react to them can be important biological determinants. Ethanol's action is biphasic, i.e., it can be reinforcing (rewarding) in the low concentration range, but aversive at high concentrations. Perception by the individual of the reinforcing actions of ethanol might be expected to maintain alcohol-seeking behavior, whereas aversive effects would be expected to extinguish this behavior. Identification of the environmental and biological variables that promote and maintain alcohol-seeking or alcohol self-administration behavior is key to our understanding of the disorder alcoholism itself.


Beyond ultra-processed: considering the future role of food processing in human health.
Food-based dietary guidelines have been the basis of public health recommendations for over half a century, but more recently, there has been a trend to classify the health properties of food not by its nutrient composition, but by the degree to which it has been processed. This concept has been supported by many association studies, narrative reviews and the findings from one randomised controlled feeding trial, which demonstrated the sustained effect of ultra-processed diets on increasing both energy intake and body weight. This has led to widespread speculation as to specific features of ultra-processed foods that promote increased energy intakes. Rising interest in the ultra-processed topic has led to proposals to include guidance and restrictions on the consumption of processed foods in national dietary guidelines, with some countries encouraging consumers to avoid highly processed foods completely, and only choose minimally processed foods. However, there remains a lack of consensus on the role of processed foods in human health when faced with the challenges of securing the food supply for a growing global population, that is, healthy, affordable and sustainable. There has also been criticism of the subjective nature of definitions used to differentiate foods by their degree of processing, and there is currently a lack of empirical data to support a clear mechanism by which highly processed foods promote greater energy intakes. Recommendations to avoid all highly processed foods are potentially harmful if they remove affordable sources of nutrients and will be impractical for most when an estimated two-thirds of current energy purchased are from processed or ultra-processed foods. The current review highlights some considerations when interpreting the dietary association studies that link processed food intake to health and offers a critique on some of the mechanisms proposed to explain the link between ultra-processed food and poor health. Recent research suggests a combination of higher energy density and faster meal eating rates are likely to influence meal size and energy intakes from processed foods and offers new perspectives on how to manage this in the future. In going beyond the ultra-processed debate, the aim is to summarise some important considerations when interpreting existing data and identify the important gaps for future research on the role of processed food in health.


Preparation, structural characteristics and antioxidant activity of polysaccharide and its metal chelates from the peel of Dioscorea oppositifolia L.
Two metal chelates of Dioscorea oppositifolia L. peel polysaccharides (DTP) were prepared: iron chelate (DTP-Fe) and zinc chelate (DTP-Zn). The physicochemical properties of the polysaccharide and its metal chelates were assessed by UV-Vis absorption spectroscopy, Fourier-transform infra-red spectroscopy, scanning electron microscopy, and thermogravimetric analysis. Antioxidant activities were evaluated by DPPH, ABTS + and hydroxyl radical scavenging assays. According to ICP-MS, the iron content of DTP-Fe was 9.47%, while the zinc content of DTP-Zn was 4.02%. The antioxidant capacity of DTP-Fe increased with the increase of concentration, and its overall activity was higher than that of DTP and DTP-Zn. This polysaccharide-iron chelate can be developed and utilised as an antioxidant and multifunctional iron supplement. DTP-Zn showed the potential to be a natural antioxidant and zinc supplement food.


The impact of neurological performance and volumetrics on overall survival in brain metastasis in colorectal cancer: a retrospective single-center case series.
Brain metastasis (BM) of colorectal cancer is a disease with a poor prognosis of only a few months survival. However, it is difficult to estimate the individual prognosis of each patient due to the lack of definitive prognosis parameters. The number of metastases and the Karnofsky performance score are known predictors for survival. We investigated whether or not the neurological performance score and the tumor volumetrics are equally suitable predictors for survival. All patients with histologically diagnosed BM linked to colorectal cancer between 2012 and March 2020 were reviewed. The Medical Research Council Neurological Performance Score was used to quantify neurological performance. Univariate analysis with Kaplan-Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression. Twenty-five patients were included in our analysis with an overall survival of 4.9 months after surgery of the BM. Survival decreased in the univariate analysis with increasing postoperative neurological performance score, low Karnofsky performance score, absence of radiation therapy and radiation therapy modality. The neurological performance score is a reliable scoring parameter for estimating the prognostic course analogous to the Karnofsky performance score. Neither preoperative nor post resection residual tumor volume had any impact on overall survival in our small cohort. Our data suggest that the postoperative neurological performance is a valuable prognostic factor for colorectal cancer patients with BM. Tumor volumetrics show no correlation to survival. Further investigations with a larger number of cases are mandatory.


Structure-Based Discovery of Mouse Trace Amine-Associated Receptor 5 Antagonists.
Trace amine-associated receptors (TAARs) were discovered in 2001 as new members of class A G protein-coupled receptors (GPCRs). With the only exception of TAAR1, TAAR members (TAAR2-9, also known as noncanonical olfactory receptors) were originally described exclusively in the olfactory epithelium and believed to mediate the innate perception of volatile amines. However, most noncanonical olfactory receptors are still orphan receptors. Given its recently discovered nonolfactory expression and therapeutic potential, TAAR5 has been the focus of deorphanization campaigns that led to the discovery of a few druglike antagonists. Here, we report four novel TAAR5 antagonists identified through high-throughput screening, which, along with the four ligands published in the literature, constituted our starting point to design a computational strategy for the identification of TAAR5 ligands. We developed a structure-based virtual screening protocol that allowed us to identify three new TAAR5 antagonists with a hit rate of 10%. Despite lacking an experimental structure, we accurately modeled the TAAR5 binding site by integrating comparative sequence- and structure-based analyses of serotonin receptors with homology modeling and side-chain optimization. In summary, we have identified seven new TAAR5 antagonists that could serve as lead candidates for the development of new treatments for depression, anxiety, and neurodegenerative diseases.


The matrix domain of the Gag protein from avian sarcoma virus contains a PI(4,5)P2-binding site that targets Gag to the cell periphery.
The Gag protein of avian sarcoma virus (ASV) lacks an N-myristoyl (myr) group, but contains structural domains similar to those of HIV-1 Gag. Similarly to HIV-1, ASV Gag accumulates on the plasma membrane (PM) before egress; however, it is unclear whether the phospholipid PI(4,5)P2 binds directly to the matrix (MA) domain of ASV Gag, as is the case for HIV-1 Gag. Moreover, the role of PI(4,5)P2 in ASV Gag localization and budding has been controversial. Here, we report that substitution of residues that define the PI(4,5)P2-binding site in the ASV MA domain (reported in an accompanying paper) interfere with Gag localization to the cell periphery and inhibit the production of virus-like particles (VLPs). We show that co-expression of Sprouty2 (Spry2) or the pleckstrin homology domain of phospholipase Cδ (PH-PLC), two proteins that bind PI(4,5)P2, affects ASV Gag trafficking to the PM and budding. Replacement of the N-terminal 32 residues of HIV-1 MA, which encode its N-terminal myr signal and its PI(4,5)P2-binding site, with the structurally equivalent N-terminal 24 residues of ASV MA created a chimera that localized at the PM and produced VLPs. In contrast, the homologous PI(4,5)P2-binding signal in ASV MA could target HIV-1 Gag to the PM when substituted, but did not support budding. Collectively, these findings reveal a basic patch in both ASV and HIV-1 Gag capable of mediating PM binding and budding for ASV but not for HIV-1 Gag. We conclude that PI(4,5)P2 is a strong determinant of ASV Gag targeting to the PM and budding.


Tibial plafond fractures treated by articulated external fixation: a randomized trial of postoperative motion versus nonmotion.
Assess whether postoperative ankle motion after fixation of a fracture of the tibial plafond, treated with articulated external fixation, leads to a better outcome when compared with similar treatment without postoperative ankle motion. Multicenter randomized trial. Three Level I trauma centers. Fifty-five patients were enrolled and entered into a Web-based database and randomized into 1 of 2 groups. Forty-one patients were evaluated at a 1-year follow-up visit, and 31 were seen at 2 years or longer after injury. Patients were treated with a hinged external fixator and limited internal fixation of the articular surface. They were divided postoperatively into two groups, 1 of which had a locked hinge and the other had a mobile hinge and a motion protocol. A general health status questionnaire, the SF-36 (short-form 36); a joint-specific ankle questionnaire, the Ankle Osteoarthritis Score (AOS); and range of motion (ROM) of the ankle joint. There were no significant differences between the two groups at either follow-up interval in the ankle ROM measurement, the AOS pain and disability scale, or the SF-36 physical component summary (PCS) and mental component summary (MCS) scales. These results indicate that treatment protocols that use long periods of cross-joint external fixation that immobilizes the ankle as definitive treatment result in similar patient outcomes compared to otherwise identical treatment protocols that incorporate and use an articulated hinge for ankle motion. However, the results should be interpreted with caution because the patient numbers were too small to detect potentially meaningful differences in outcomes and the follow-up was too short to assess for differences in the development of arthrosis.


Acceptability and cost-effectiveness of military telehealth mental health screening.
Telehealth has been touted as one solution to the shortage of mental health providers within the military. Despite developing evidence for the equivalence of telehealth mental health care, there is no research that covers the use of telehealth for population mental health screening, a standard component of postdeployment medical screening. This paper summarizes soldier perceptions of three separate screening events in which telehealth was used and the cost-effectiveness of telehealth versus in-person implementations of the same screening. Soldiers who have not been through telehealth screening report a strong preference for in-person screening. Soldiers who have been through telehealth screening still report preference for in-person screening, but they express more ambivalence about the screening method. Using telehealth-only mental health screening for large numbers of soldiers within a compressed time frame is more expensive than in-person screening. Telehealth resulted in higher referral rates than in-person screening. Government and military leaders should use care when making decisions about telehealth implementation. Although telehealth for small numbers may be sufficiently equivalent and economical, there is no evidence of cost savings or improved acceptability for telehealth mental health post-deployment screening.


Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Spanish Transplantation Infection Study Group, GESITRA.
Tuberculosis is unusual in transplant recipients. The incidence, clinical manifestations, and optimal treatment of this disease in this population has not been adequately defined. The present study was undertaken to assess the incidence, clinical features, and response to therapy of Mycobacterium tuberculosis infection in solid-organ transplant recipients. We evaluated retrospectively the incidence, clinical characteristics, diagnostic procedures, antituberculous treatment, clinical course, and factors influencing mortality in 51 solid-organ transplant recipients who developed tuberculosis after transplantation. We also reviewed the world literature on tuberculosis in solid-organ transplantation. The overall incidence of tuberculosis was 0.8%. The localization was pulmonary in 63% of the cases, disseminated in 25%, and extrapulmonary in 12%. Tuberculosis developed from 15 days to 13 years after surgery (mean, 23 months). In one third of the cases, diagnosis was not suspected initially, and in three cases, diagnosis was made at necropsy. Fever was the most frequent symptom, followed by constitutional symptoms, cough, respiratory insufficiency, and pleuritic pain. Fifteen patients (33%) developed hepatotoxicity during treatment; hepatotoxicity was severe in seven cases. Hepatotoxicity was higher in patients receiving four or more antituberculous drugs (50%) than in patients receiving three drugs (21%; P=0.03). Serum levels of cyclosporine decreased in the 26 patients under the simultaneous use of rifampin. Nine of them (35%) developed acute rejection, and five (56%) died, in comparison with 3 of 17 patients (18%) who did not develop rejection after the use of cyclosporine and rifampin (P=0.03). Although microbiological response was favorable in 94% of the 35 patients who completed 6 or more months of treatment, 16 other patients (31%) died before diagnosis or in the course of treatment. None of the patients treated for more than 9 months died as a consequence of tuberculosis, whereas the mortality rate was 33% among those treated for 6 to 9 months (P=0.03). Use of antilymphocyte antibodies or high doses of steroids for acute rejection before tuberculosis was associated with a higher mortality rate. M tuberculosis causes serious and potentially life-threatening disease in solid-organ transplant recipients. Treatment with at least three drugs during 9 months or more, avoiding the use of rifampin, appears to be appropriate.


[Data from the Bavarian perinatal survey on the problem of the incidence of cesarean section].
Data are presented on caesarean section rates during the first five-year period of the Bavarian Perinatal Study (BPE 1982-1986), comprising 450,000 births. In order to identify long-term trends, statistical studies from the Munich Perinatal Study (MPS) dating back to 1975 were continued in the same Munich hospitals through to 1982-1984. The results may be broken down as follows: 1. The overall rate of caesarean sections has been increasing, steadily, reaching 15% in the 1986 BPE. No clear levelling-off is evident yet. 2. The highest rates of caesarean sections and vaginal operative deliveries were found in university hospitals. Spontaneous deliveries occurred least often in university hospitals (about 70%), and most frequently in the larger country and private hospitals (77-79%). Smaller externally staffed private hospitals had about the same rate of vaginal-operative deliveries as university hospitals. 3. Following caesarean section, postoperative complications prompted a three- to sixfold higher rate of maternal transfer to other hospitals over that following spontaneous delivery. 4. As maternal age increases, so does the rate of caesarean section for primiparae. Nevertheless, recent years have witnessed a levelling-off for women over 34 years of age. No trend toward further increase is evident for this age group.(ABSTRACT TRUNCATED AT 250 WORDS)


Stimulatory effects of Porphyromonas gingivalis GroEL protein on interleukin-6 and interleukin-8 in human osteoblasts.
Porphyromonas gingivalis is an oral pathogen associated with periodontal diseases. P. gingivalis GroEL protein is a stimulator of inflammatory cytokines in macrophages. This study inspected effects of P. gingivalis GroEL protein on production of interleukin (IL)-6 and IL-8 by human osteoblasts. Viability of GroEL-treated osteoblasts was analyzed with 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide. Secretion of IL-6 and IL-8 was analyzed using the enzyme-linked immunosorbent assay. Levels of mRNA were analyzed using the reverse transcription and real-time polymerase chain reaction. The antioxidant (curcumin), the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) and the c-Jun N-terminal kinase (JNK) inhibitor (SP600125) were employed to elucidate possible signaling pathways involved. Treatment with GroEL did not affect morphology and viability of osteoblasts. GroEL significantly induced the secretion of IL-6 and IL-8 by osteoblasts in a concentration-dependent pattern. Moreover, the mRNA levels of IL-6 and IL-8 were stimulated by GroEL. The application of SP600125 (10 μM) significantly suppressed the induction of IL-6 and IL-8 by GroEL-treated cells. However, curcumin (20 μM) and SB203580 (20 μM) only down-regulated the stimulatory effects of GroEL on IL-6. GroEL protein stimulated the inflammatory reaction of osteoblasts, probably through the activation of p38 MAPK or JNK pathway. The findings suggest that P. gingivalis GroEL may influence the immune functions of osteoblasts and endanger the periodontal health.


Unanswered clinical questions in the management of cardiometabolic risk in the elderly: a statement of the Spanish Society of Internal Medicine.
Despite the progressive increase in life expectancy and the relationship between aging with multi-morbidities and the increased use of healthcare resources, current clinical practice guidelines (CPG) on cardiometabolic risk cannot be adequately applied to elderly subjects with multiple chronic conditions. Its management frequently becomes complicated by both, an excessive use of medications that may lead to overtreatment, drug interactions and increased toxicity, and errors in dosage and non-compliance. Concerned by this gap, the Spanish Society of Internal Medicine created a group of independent experts on cardiometabolic risk who discussed what they considered to be unanswered questions in the management of elderly patients. Current guidelines do not specifically address the problem of elderly with multiple chronic conditions. For this reason, the combined use of the limited available evidence, clinical experience and common sense, could all help us to address this unmet need. In very old people, life expectancy and functionality are the most important factors for guiding potential treatments. Their higher propensity to develop serious adverse events and their shorter lifespan could prevent them from obtaining the potential benefits of the interventions administered. In this document, experts on cardiometabolic risk factors have established a number of consensual recommendations that have taken into account international guidelines and clinical experience, and have also considered the more effective use of healthcare resources. This document is intended to provide general recommendations for clinicians and to promote the effective use of procedures and medications.


Cytologic evaluation of inflammation in canine liver aspirates.
Liver aspiration cytology has been used routinely for more than a decade for the evaluation of canine and feline liver disease. However, the value of liver cytology in detecting inflammatory liver disease is poorly defined. We retrospectively reviewed 51 canine liver cytology reports and compared the conclusions with those from concurrent surgical biopsy reports. Overall sensitivity of cytology for diagnosis of inflammatory liver disease was 93% and specificity was 96%. For suppurative hepatitis (n = 14), the sensitivity of cytologic diagnosis was 100% and the specificity was 95%. For chronic active hepatitis (n = 13), the sensitivity of cytologic diagnosis was 100% and the specificity was 93%. For lymphocytic hepatitis (n = 3), the sensitivity of cytologic diagnosis was 33% and the specificity was 100%. We conclude that canine liver aspiration cytology is a highly sensitive test for the detection of suppurative and chronic active inflammation; however, it is insensitive for the detection of lymphocytic hepatitis.


Quality of life after islet transplant: impact of the number of islet infusions and metabolic outcome.
The health-related quality of life (HRQL; Health Utilities Index Mark 2) and the fear of hypoglycemia (Hypoglycemia Fear Survey) were assessed after islet transplant; the impact of a single islet infusion and of the metabolic outcome were determined. A control group included 166 patients with type 1 diabetes. Islet transplant had no impact on overall HRQL. Prior to transplant, islet recipients had more fear of hypoglycemia than controls (P<0.000001), but this improved up to 36 months after transplant (P<0.00001, pretransplant vs. each time point). With a single islet infusion, this fear improved substantially (P<0.00001), but improved further with subsequent islet infusions (P</=0.01). Fear of hypoglycemia correlated with the occurrence of hypoglycemia (r=0.47, P=0.01), and even more so with blood glucose stability (r=0.56, P=0.0007) and insulin requirement (r=0.69, P=0.000002).


Metabolic characterization of a woman homozygous for the Ser113Leu missense mutation in carnitine palmitoyl transferase II.
Carnitine palmitoyl transferase (CPT) II is a key enzyme in transporting FFA into the mitochondrial matrix for beta oxidation. The clinical manifestation of CPT II deficiency is characterized mainly by myopathic symptoms. Conceivably, the inability of skeletal muscle to oxidize (long-chain) FFAs could also have far-reaching metabolic consequences, such as insulin resistance secondary to increased muscle lipids, about which relatively little is known. We therefore performed a series of metabolic studies in a 43-yr-old woman homozygous for the Ser113Leu mutation in the CPT II gene, the single most common genetic cause of CPT II deficiency, and compared the results with data from a male and female control group taken from the Tübingen family study database. The metabolic studies included oral glucose tolerance test (OGTT), euglycemic hyperinsulinemic clamp to measure insulin sensitivity, indirect calorimetry to measure substrate oxidation, stable isotopes for determination of glycerol turnover, and magnetic resonance spectroscopy for measurement of intramyocellular lipids. Compared with the female control group, the patient was normal glucose tolerant but severely insulin resistant, basal lipolysis was markedly reduced, and carbohydrate oxidation was maximally increased in the basal state and did not increase further during insulin stimulation. Conversely, lipid oxidation was virtually absent and did not decrease during insulin stimulation. Surprisingly, intramyocellular lipids were well within the range of the control group. In conclusion, genetic CPT II deficiency is characterized by insulin resistance, which is not explained by increased intramyomellular lipids. However, it may be partially explained by glucose oxidation already maximally increased in the basal state, which cannot be increased any further by insulin. Reduced basal lipolysis may represent a compensatory mechanism for the reduced oxidative FFA disposal characteristic for this disease.


The derring effect: Deliberate errors enhance learning.
How can we strategically and systematically learn from our errors? Over their long history, errors have traditionally been prevented entirely or, at best, permitted to occur spontaneously. Across three experiments, we tested and found evidence for a counterintuitive phenomenon that we termed the derring effect-deliberately committing errors even when one already knows the correct answers produces superior learning than avoiding them, particularly when one's errors are corrected. Learners engaged in an educationally relevant task of learning scientific term-definition concepts via open-book study by deliberately generating conceptually incorrect definitions with or without correction, or copying and underlining them (Experiment 1). On a cued recall test, deliberate erring outperformed errorless copying, with error correction yielding an additional benefit. This advantage of deliberate erring persisted over actively generating alternative conceptually correct answers (Experiment 2), which in turn surpassed copying. Even when errorless generation was given a further boost to involve a higher degree of elaboration by prompting learners to generate a specific real-world example that illustrated or applied each concept, deliberately committing and correcting errors still produced better learning (Experiment 3). Altogether, the derring effect is neither fully attributable to a generation nor an elaboration benefit, but stems at least in part from enhanced target processing specific to having first deliberately produced incorrect responses. Notwithstanding deliberate erring's prowess, learners were largely oblivious to its benefits, misjudging the strategy as less effective. Both theoretical and educational implications of positioning errors as active, systematic, and intentional events in learning are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


[Use of a scanner to register the results of enzyme immunoassay in the standard microplates].
Whether a commercially available scanner might be used as a vertical photometer of 96-well microplates for enzyme immunoassay (EIA) was studied. The analytical characteristics of the scanner in this regard were assessed, by comparing the findings with the respective photometric data obtained by a "VICTOR" EIA analyzer. It is concluded that the scanner registration system in combination with "Expert-Lab EIA" may be used in all types of EIA. The scanner system provides additional possibilities as compared with the conventional photometric analyzers.


Pregnancy termination after detection of fetal chromosomal or metabolic abnormalities.
In 3400 midtrimester amniocenteses, 68 fetuses had abnormal findings. Three women elected to continue their pregnancies and the remainder chose terminations. Of these, 29 were cared for in our hospitals. Pregnancy termination was carried out in gestations averaging 21.6 +/- 2.3 weeks and fetal weights averaging 531 +/- 351 g. Three prostaglandins techniques were used, two of which proved to be effective. Dosages employed were comparable to those used in early second trimester pregnancy terminations. Side effects were similar; one retained placenta occurred. We have used a multidisciplinary counseling approach for these couples and have restricted ourselves to the medical aspects of their problems. Techniques are described for the psychologic support of the couple during this stressful period.


Return on investment imperative: the cost of care calculator for an evidence-based practice program.
The key elements of the evaluation process of an evidence-based practice (EBP) program and the infrastructure needed as identified by a large health care organization. The EBP evaluation program has 2 major elements for measuring success. The first component for evaluation is the impact on the clinical outcomes of care and the second is the fiscal implications of implementing the EBP. This article focuses on the fiscal evaluation component and describes a process to calculate the cost of care compared to before and after implementation of the EBP. The literature to support the care calculations is examined and a cost algorithm is described.


Covalently Linked Heterostructures of Phosphorene with MoS2/MoSe2 and Their Remarkable Hydrogen Evolution Reaction Activity.
Hydrogen production by photochemical and electrochemical means is an important area of research related to renewable energy. 2D nanomaterials such as C3N4 and MoS2 have proven to be active for the hydrogen evolution reaction (HER). Phosphorene, a mono-elemental 2D layer of phosphorus, is known to catalyze the HER, but the activity is marginal. The use of phosphorene is also limited by its ambient instability. We have been able to prepare covalently cross-linked nanocomposites of phosphorene with MoS2 as well as MoSe2. The phosphorene-MoS2 nanocomposite shows excellent photochemical HER activity yielding 26.8 mmol h-1 g-1 of H2, while only a negligible amount is produced by the physical mixture of phosphorene and MoS2. The phosphorene-MoS2 composite also displays high electrochemical HER activity with an onset overpotential of 110 mV, close to that of Pt. The enhanced HER activity of the phosphorene-MoS2 nanocomposite can be attributed to the ordered cross-linking of the 2D sheets, increasing the interfacial area as well as the charge-transfer interaction between phosphorene and MoS2 layers. The phosphorene-MoSe2 nanocomposite also exhibits good photochemical HER activity.


[A comparative pharmacologic study of histamine H-1 antagonists].
In a representative group of 10 conventional antihistaminic agents, a comparison of their H1-antagonistic efficacy was carried out in a series of pharmacological tests. A very good correlation of findings obtained under in vivo conditions in guinea-pigs (tests of detoxication of histamine and histamine aerosol) and a test in rats, which examined the influence on local changes induced by histamine in the dermal region, was demonstrated. No statistically significant correlation of in vivo findings and receptor binding studies on membranes of the rat brain (displacement of (3H)-mepyramine) was found. The tests based on displacement of (3H)-mepyramine are usable primarily for the needs of screening research. The predictive value of pharmacological findings obtained under in vivo conditions is substantially higher.


Holter STAT-ON™ against other tools for detecting MF in advanced Parkinson's disease: an observational study.
Different screening tools to identify advanced Parkinson's disease (APD) have emerged in recent years. Among them, wearable medical devices, such as STAT-ON™, have been proposed to help to objectively detect APD. To analyze the correlation between STAT-ON™ reports and other assessment tools to identify APD and to assess the accuracy of screening tools in APD patients, using the STAT-ON™ as the gold standard. In this retrospective, observational study, data from the University Hospital Complex of Pontevedra database on 44 patients with potential APD who wore STAT-ON™ were extracted. Data were collected according to different sources of tools for identifying APD: (1) STAT-ON™, (2) information provided by the patient, (3) questionnaire for advanced Parkinson's disease (CDEPA), (4) 5-2-1 Criteria, and (5) Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD). Considering STAT-ON™ recordings as a reference, the sensitivity, specificity, and positive and negative predictive values for each tool were calculated. The kappa index assessed the degree of agreement between the gold standard and the other instruments. Although no statistically significant association was found between STAT-ON™ recordings and any screening methods evaluated, the CDEPA questionnaire demonstrated the highest sensitivity and VPN values to detect patients with APD candidates for second-line therapy (SLT). According to the correlation analyses, MANAGE-PD demonstrated the highest degree of concordance with STAT-ON™ recordings to identify the SLT indication and to predict the SLT decision. STAT-ON™ device may be a helpful tool to detect APD and to guide treatment decisions.


Does a minimally invasive approach result in better pulmonary function postoperatively when compared with median sternotomy for coronary artery bypass graft?
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Does a minimally invasive approach result in better pulmonary function postoperatively when compared with median sternotomy for coronary artery bypass graft?'. Procedures such as limited sternotomy and minimally invasive direct coronary artery bypass (MIDCAB) though a minithoracotomy were regarded as minimally invasive. Overall, 681 papers were found, of which eight represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, evidence level, relevant outcomes and results of these papers were tabulated. Three randomized, controlled trials (RCT) were included: One study suggested that ministernotomy dividing the corpus sterni (n = 50) offers no advantage over standard sternotomy (n = 50) during the first 10 postoperative days. Two further studies reported on minithoracotomy: one trial presented data suggesting that minithoracotomy (n = 21) is as safe as standard sternotomy with (n = 18) or without (n = 19) cardiopulmonary bypass, but without the benefit ascribed to the minimally invasive incision. A two-centre report investigated pulmonary function as a secondary outcome and claimed that minithoracotomy worsens FEV1 and FVC. The study was not powered to detect these differences as pulmonary function data were available only for one of the centres. Five non-randomized reports were also included in this analysis: These investigated outcomes after minithoracotomy or limited sternotomy compared with standard sternotomy. Patient groups were small, involving <20 subjects per group. Non-randomized studies suggested a benefit to postoperative lung function in using thoracotomy. One of these reports included only patients with severe chronic obstructive pulmonary disease (COPD) (FEV1 <70% of predicted) and detected benefits in selected patients undergoing MIDCAB. A further study was in agreement with the above statement in patients without COPD. MIDCAB may be more painful initially, but results in quicker recovery of lung function. Demonstrating the benefits of ministernotomy compared with the standard sternal incision was less clear. One paper demonstrates better outcomes when compared with standard sternotomy, while another reports no difference. We conclude that non-randomized studies support the hypothesis that minimally invasive coronary artery bypass benefits postoperative lung function in patients with known respiratory problems.


Secreted frizzled-related protein 2, a novel mechanism to induce myocardial ischemic protection through angiogenesis.
Our hypothesis is that Secreted Frizzled-Related Protein 2 (sFPR2) is an important mechanism mediating ischemic cardioprotection, since it is the most upregulated gene in the third window of ischemic preconditioning. One week after permanent coronary artery occlusion (CAO), sFRP2 TG mice exhibited a 49% higher LV ejection fraction and a 36% reduction in infarct size, p < 0.05, and reduced fibrosis in both adjacent and remote zones, along with an increase in collagen type III and a decrease in the collagen type I/III ratio compared with WTL. The ischemic cardioprotection was associated with increased angiogenesis and arteriogenesis, reflected by increased capillary and arteriolar proliferation in the ischemic zone, thereby preserving blood flow after CAO. The angiogenesis and arteriogenesis were mediated by cross talk between myocytes and endothelial cells. The mechanism for cardioprotection and angiogenesis/arteriogenesis did not involve a traditional vascular growth hormone, e.g., VEGF or FGF, but rather cTGF, and ATF6 through the stress signaling pathway. The ATF6 inhibitor, AEBSF, blocked the upregulation of cTGF and both the angiogenesis and arteriogenesis, resulting in abolition of the reduced infarct size and protection of cardiac function in the sFRP2 TG mouse following permanent CAO. sFRP2 is a novel mechanism to induce angiogenesis/arteriogenesis, mediated through the endoplasmatic reticulum (ER) stress signaling pathway, ATF6 and cTGF, which protects the heart from myocardial ischemia.


[Growth phenomena of jaw ameloblastomas].
Jaw ameloblastomas produce most frequently (62%) multilocular translucences. An unilocular translucence was observed in 28% of the cases. In both forms, secondary cysts were present. This radiomorphologic finding is of pathognomonic value. Conchiform or finger-shaped translucences were seen in 10% of the cases. Such radiographic changes were observed in ameloblastomas arising from the oral mucosa. The border of the radiolucent area was always sharply defined and had a lobulate or wreathed form. The ameloblastoma spreads in an expansive or invasive way. The bone destruction is in all probability caused by the acid phosphatase activity of the tumour. Bone transformation occurs simultaneously with bone destruction and might be regarded as a morphologic sign of the defence mechanism.


Is regular exercise an effective strategy for weight loss maintenance?
Weight regain after weight loss is one of the most significant challenges to successful obesity treatment. Regular exercise has long been touted as a strategy for weight loss maintenance, but the lack of clear evidence in clinical trials has caused some to question its effectiveness. In this review, we present the arguments both questioning and in support of exercise as an obesity therapeutic. Our purpose is to bring clarity to the literature, present a unified perspective, and identify the gaps in knowledge that need to be addressed in future studies. Critical questions remain including sex differences, individual variability and compensatory behaviors in response to exercise, exercise adherence, the role of energy flux and the molecular mechanisms mediating the beneficial effects of exercise after weight loss and during weight regain. Future research should focus on these critical questions to provide a more complete understanding of the potential benefits of exercise on weight loss maintenance.


Second trimester maternal dimeric inhibin-A in the multiple-marker screening test for Down's syndrome.
The aim of this study was to evaluate the additional value of dimeric inhibin-A serum concentration in second trimester multiple-marker screening tests for pregnancies affected by Down's syndrome. We anticipated that second trimester maternal serum dimeric inhibin-A concentrations would be altered in pregnancies complicated by fetal Down's syndrome and that dimeric inhibin-A would perform better than one of the three substances analysed in the multiple-marker screening test currently in use. A total of 1156 serum samples were screened for dimeric inhibin-A in parallel with the routine classic triple test screening programme performed on a random obstetric population. Classic triple test performance was compared with detection rates obtained after substitution of unconjugated oestriol by inhibin-A and with the performance of inhibin-A and alpha-fetoprotein alone. Absolute dimeric inhibin-A maternal serum concentrations of Down's syndrome pregnancies were indeed significantly higher than those of normal pregnancies in our screened population. The performance of dimeric inhibin-A in combination with the multiple-marker screening test, however, is limited because of its strong correlation with intact human chorionic gonadotrophin.


Genetics of metabolic variations between Yersinia pestis biovars and the proposal of a new biovar, microtus.
Yersinia pestis has been historically divided into three biovars: antiqua, mediaevalis, and orientalis. On the basis of this study, strains from Microtus-related plague foci are proposed to constitute a new biovar, microtus. Based on the ability to ferment glycerol and arabinose and to reduce nitrate, Y. pestis strains can be assigned to one of four biovars: antiqua (glycerol positive, arabinose positive, and nitrate positive), mediaevalis (glycerol positive, arabinose positive, and nitrate negative), orientalis (glycerol negative, arabinose positive, and nitrate positive), and microtus (glycerol positive, arabinose negative, and nitrate negative). A 93-bp in-frame deletion in glpD gene results in the glycerol-negative characteristic of biovar orientalis strains. Two kinds of point mutations in the napA gene may cause the nitrate reduction-negative characteristic in biovars mediaevalis and microtus, respectively. A 122-bp frameshift deletion in the araC gene may lead to the arabinose-negative phenotype of biovar microtus strains. Biovar microtus strains have a unique genomic profile of gene loss and pseudogene distribution, which most likely accounts for the human attenuation of this new biovar. Focused, hypothesis-based investigations on these specific genes will help delineate the determinants that enable this deadly pathogen to be virulent to humans and give insight into the evolution of Y. pestis and plague pathogenesis. Moreover, there may be the implications for development of biovar microtus strains as a potential vaccine.


Trading twitter: Amateur recorders and economies of scientific exchange at the Cornell Library of Natural Sounds.
Scientists have long engaged in collaborations with field collectors, but how are such collaborations established and maintained? This article examines structures of collaborative data collection between professional scientists and various field recorders around the Cornell Library of Natural Sounds. The Library collects animal sound recordings for use in education, preservation, and entertainment, but primarily in the scientific field of bio-acoustics. Since 1945, the Library has enlisted academic researchers, commercial recorders and broadcasters (such as the British Broadcasting Corporation), and amateur sound hunters in its expansion. I argue that the Cornell Library of Natural Sounds managed to craft and sustain a crucial network of contributors through creative and strategic brokering with its collection of recordings/data. Drawing on notions from exchange theory, I show that sound recordings were valued not just as scientific data, but also as copyrighted commodities that could be bought, sold, traded, and converted in a range of economic, social, and symbolic capitals within collaborators' respective social fields. Thus, aligning collaborators' interests, these exchange relations enabled the Cornell Library of Natural Sounds to negotiate amateur recorders' reliability, willingness to share work, and commitment to scientific standards, as well as the bonds that solidified their collaboration with the Cornell Library of Natural Sounds. Attending to the micro-economics of data exchange, this article thus brings into perspective the multi-dimensional processes through which data-flows are managed.


A Summary of the Anatomy and Current Regional Anesthesia Practices for Postoperative Pain Management in Total Knee Arthroplasty.
The planning and implementation of an effective postoperative pain management program depend on the surgical technique for total knee arthroplasty (TKA), the type of regional anesthesia, and the multimodal analgesia regimen. It is imperative to understand the surgical anatomy of TKA and the relevant nerve supply of the knee for optimum perioperative patient satisfaction with respect to pain management in the patient undergoing TKA. The commonly used regional techniques have their own specific benefits and limitations. The ideal postoperative pain management should be customized for a patient to achieve the goals of effective pain control, early ambulation, faster recovery, and discharge.


Association Between Diabetes Mellitus and Outcomes of Patients with Sepsis: A Meta-Analysis.
BACKGROUND Diabetes mellitus (DM) is a critical medical problem that can make people more likely to develop infectious complications, even sepsis. However, the influence of DM on the outcomes of septic patients is still controversial. Thus, we conducted the present meta-analysis to investigate whether DM worsens outcomes of septic patients. MATERIAL AND METHODS We searched studies from PubMed, Embase, and Cochrane Library databases from 1966 to July 1, 2016. The primary outcome we chose was 28-day or 30-day mortality or in-hospital mortality. RESULTS Our meta-analysis of 10 enrolled studies performed between 2000 and 2016 shows that the mortality rate of septic patients with DM was slightly lower than that of non-diabetic patients (risk ratio [RR]=0.97, 95% confidence interval [CI]: 0.96 to 0.98, P<0.00001). On the other hand, septic patients with DM had a shorter hospital stay (weighted mean difference (WMD)=-2.27, 95% CI: -4.11 to -0.44, P=0.01), a higher incidence rate of AKI (RR=1.56, 95% CI: 1.25 to 1.95, P<0.001), and a similar incidence of respiratory dysfunction (RR=0.86, 95% CI: 0.71 to 1.04, P=0.11) compared with those without DM. CONCLUSIONS The results from the meta-analysis suggest that DM does not impair the outcome of patients with sepsis, and the incidence of acute kidney injury increases dramatically in septic patients with DM. Due to the limitations of the analysis, more well-designed trials are still necessary.


Relaxation and fluctuations of the number of particles in a membrane channel at arbitrary particle-channel interaction.
We analyze the relaxation of the particle number fluctuations in a membrane channel at arbitrary particle-channel interaction and derive general expressions for the relaxation time and low-frequency limit of the power spectral density. These expressions simplify significantly when the channel is symmetric. For a square-well potential of mean force that occupies the entire channel, we verify the accuracy of the analytical predictions by Brownian dynamics simulations. For such a channel we show that as the depth of the well increases, the familiar scaling of the relaxation time with the channel length squared is transformed into a linear dependence on the length.


Longevity of complete dentures: A systematic review and meta-analysis.
Patients and clinicians are aware of the efficacy and benefits of complete dentures, but evidence regarding their longevity is limited. The purpose of this systematic review was to examine the literature describing the longevity of complete dentures and to review variations in longevity by denture type and duration of follow-up. Four electronic databases were searched by using key terms: MEDLINE, CINAHL (EBSCO), Dentistry and Oral Sciences Databases, and The Cochrane Library. Studies meeting the inclusion criteria were reviewed according to an established protocol and data extracted. Reference lists of identified studies were examined. Risk of bias was assessed by using the AXIS tool. Weighted means and weighted standard deviations were calculated. Pooled complete denture failure proportions were estimated by using random effects models based on the DerSimonian and Laird method. The search yielded 21 607 unique abstracts, of which 273 met the inclusion criteria. Assessment of the full-text articles reduced this number to 42. Of these, 24 studies were rated as having low risk of bias and 18 as very low. The weighted mean ±standard deviation longevity of maxillary complete dentures was 10.3 ±3.8 years, of mandibular dentures was 8.6 ±2.6 years, and of both maxillary and mandibular dentures was 10.8 ±4.7 years. The pooled failure proportion for complete dentures observed for 2 years or less was 0.05 (95% confidence interval [CI]: 0.00-0.10), 5 to 6 years was 0.12 (95% CI: 0.08-0.16), and 10 years or more was 0.41 (95% CI: 0.28-0.53). Complete dentures, fabricated primarily in university settings, were found to have a weighted mean ±standard deviation longevity of 10.1 ±4.0 years. The failure rate of these prostheses increased with denture age, and the longevity of maxillary dentures was greater than that of mandibular dentures.


Human hepatoblast phenotype maintained by hyaluronan hydrogels.
Human hepatoblasts and hepatic stem cells, pluripotent hepatic progenitors that give rise to hepatocytes and biliary cells, were isolated from fetal livers and found to express hyaluronan receptors (CD44) in both the freshly isolated cells and after culture. This implicates an in vivo connection to hyaluronan (HA), an embryonic matrix component, as a candidate 3-dimensional (3-D) scaffold for hepatic progenitor cell expansion and/or differentiation. To assess HAs as scaffolds, hepatoblasts and hepatic stem cells were seeded into HA hydrogels with a serum-free, hormonally defined medium tailored for expansion of hepatic progenitors. Cell aggregates formed within the HA hydrogels and remained viable, proliferative, and demonstrated a stable phenotype intermediate between that of hepatic stem cells and hepatoblasts throughout more than 4 weeks of culturing, with little evidence of lineage restriction towards either hepatocytic or biliary pathways. The phenotype consisted of stable co-expression of both hepatocytic and biliary markers such as biliary-specific cytokeratin, CK19, low levels of expression of albumin, and urea synthesis. HA hydrogels are ideal as 3-D scaffolds for pluripotent hepatic progenitors and should be useful for generating cells to be used in bioartificial livers or tissue engineered liver grafts.


DNA methylation pattern of apoptosis-related genes in ameloblastoma.
DNA methylation is an important mechanism of gene control expression, and it has been poorly addressed in odontogenic tumours. On this basis, we aimed to assess the methylation pattern of 22 apoptosis-related genes in solid ameloblastomas. Ameloblastoma fresh samples (n = 10) and dental follicles (n = 8) were included in the study. The percentage fraction of methylated and unmethylated DNA promoter of 22 apoptosis-related genes was determined using enzymatic restriction digestion and quantitative real-time PCR (qPCR) array. The relative expressions of the genes that showed the most discrepant methylation profile between tumours and controls were analysed by reverse-transcription quantitative PCR (RT-qPCR). Lower methylation percentages of TNFRSF25 (47.2%) and BCL2L11 (33.2%) were observed in ameloblastomas compared with dental follicles (79.3% and 59.5%, respectively). The RT-qPCR analysis showed increased expression of BCL2L11 in ameloblastomas compared with dental follicles, in agreement with the methylation analysis results, while there was no difference between the expression levels of TNFRSF25 between both groups. On the basis of our results, the transcription of the apoptosis-related gene BCL2L11 is possibly regulated by promoter DNA methylation in ameloblastoma. The biological significance of this finding in ameloblastoma pathobiology remains to be clarified.


Effect Sizes in Single-Case Aphasia Studies: A Comparative, Autocorrelation-Oriented Analysis.
Purpose In single-case treatment studies, researchers may compare client performance during a baseline, nontreatment phase(s) to client performance during intervention phases. Autocorrelation in the data series gathered during such studies increases the likelihood that analysts will detect or fail to detect meaningful differences between baseline and treatment phase data. We examined the impact that autocorrelation has on 4 effect size calculation methods when these methods are applied to data generated by people with aphasia during anomia treatment studies. The effect sizes we selected were Busk and Serlin's d, Young's C, nonoverlap of all pairs, and Tau-U. We hypothesized that d and C would be influenced by autocorrelation, whereas nonoverlap of all pairs and Tau-U would not. Method We extracted 173 highly autocorrelated data series from published investigations of treatments for anomia. These data series were then "cleansed" of autocorrelation through the use of an autoregressive integrated moving average (ARIMA) process. The 4 effect size calculation methods were used to derive an effect size for each published and each corresponding ARIMA-tized data series. The published and ARIMA-tized effect sizes associated with each calculation method were then compared. Results For all of the 4 effect sizes, statistically significant differences existed between the published effect sizes and the ARIMA-tized effect sizes. Conclusions All 4 of the methods were influenced by autocorrelation. Further research that develops effect size calculation methods that are not influenced by autocorrelation will help to improve the quality of single-case studies. Supplemental Material https://doi.org/10.23641/asha.8298530.


The role of thiols and disulfides in platelet function.
Disulfide bonds formed in newly synthesized proteins in the endoplasmic reticulum of cells are important for protein structure and stability. Recent research, however, emphasizes a role for thiol-disulfide reactions with disulfide bond rearrangement as a dynamic process in cell and protein function, and in platelet function in particular. Protein disulfide isomerase was found on the platelet surface where it appears to play an important role in the platelet responses of aggregation and secretion, as well as activation of the platelet fibrinogen receptor, the alphaIIbbeta3 integrin. Additionally, sulfhydryl groups in alphaIIbbeta3 have been implicated in the activation of this integrin. Physiologic concentrations of reduced glutathione generate sulfhydryls in alphaIIbbeta3 and potentiate sulfhydryl-dependent reactions in alphaIIbbeta3. Sulfhydryl labeling in alphaIIbbeta3 is inhibited by phenylarsine oxide, a reagent that binds to vicinal thiols. As vicinal thiols are in equilibrium with disulfide bonds, they provide redox-sensitive sites in alphaIIbbeta3 able to respond to external or cytoplasmic reducing equivalents. Furthermore, protein disulfide isomerase and sulfhydryls are now implicated in platelet adhesion by a second platelet integrin, the alpha2beta1 collagen receptor. Most recently, extracellular sulfhydryls in the P2Y12 ADP receptor were found to be required for platelet activation by this receptor. We here provide an overview of this field with a focus on recent developments, and conclude with a working model.


[Acute cerebral sinus-thrombosis due to polyangiitis overlap syndrome with granulomatosis with polyangiitis (Wegener's granulomatosis) and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)].
A brief review of literature is made on the problem of modern classification, diagnosis and treatment of systemic vasculitis. The authors present a clinical case of a 40-YO male, in whom the disease started with focal neurological signs: epileptic seizures, disorder of consciousness, light euphoria, nasolabial fold insufficiency and left upper extremity hypoesthesia. Initial examination revealed upper sagittal sinus together with right lateral sinus thrombosis with forming of bilateral frontal lobe's hemorrhages; development of stable thrombocytopenia and platelet antibodies in blood species as well as hyperhomocysteinemia and a MTHFR gene mutation. Further, the patient was followed-up by the hematologist and treated by steroids. Systemic vasculitis of granulomatosis with polyangiitis (Wegener's granulomatosis) and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) were late diagnosed in this patient, and coexistence of two systemic vasculitis predetermined extremely severe course of the disease with fatal outcome in nearly 5 years after the disease started, and after steroid and rituximab treatment. It is concluded that the diagnosis of cerebral venous thrombosis in a young patient should exclude systemic vasculitis as one of its possible causes.


Inflammation and endothelial dysfunction during aging: role of NF-kappaB.
One of the major conceptual advances in our understanding of the pathogenesis of age-associated cardiovascular diseases has been the insight that age-related oxidative stress may promote vascular inflammation even in the absence of traditional risk factors associated with atherogenesis (e.g., hypertension or metabolic diseases). In the present review we summarize recent experimental data suggesting that mitochondrial production of reactive oxygen species, innate immunity, the local TNF-alpha-converting enzyme (TACE)-TNF-alpha, and the renin-angiotensin system may underlie NF-kappaB induction and endothelial activation in aged arteries. The theme that emerges from this review is that multiple proinflammatory pathways converge on NF-kappaB in the aged arterial wall, and that the transcriptional activity of NF-kappaB is regulated by multiple nuclear factors during aging, including nuclear enzymes poly(ADP-ribose) polymerase (PARP-1) and SIRT-1. We also discuss the possibility that nucleophosmin (NPM or nuclear phosphoprotein B23), a known modulator of the cellular oxidative stress response, may also regulate NF-kappaB activity in endothelial cells.


Biochemical pathogenesis of genetic leukodystrophies: comparison of metachromatic leukodystrophy and globoid cell leukodystrophy (Krabbe's disease).
Among the genetic leukodystrophies known to occur in man, the fundamental genetic defects have been clarified in two disorders, metachromatic leukodystrophy and globoid cell leukodystrophy (Krabbe's disease). Nevertheless, the biochemical sequences with which the underlying genetic defects lead to the clinical and pathological features of the diseases and to disruption of the normal brain function are not well understood. Comparison of the two classical leukodystrophies provides us an opportunity to consider the biochemical pathogenesis of these disorders, some common between them and others apparently unique. That both metachromatic leukodystrophy and globoid cell leukodystrophy manifest themselves almost exclusively as diseases of the myelin sheath is relatively easy to understand because both are caused by genetic abnormalities in the metabolism of the characteristic constituents of myelin, sulfatide and galactosylceramide. The presence of the abnormal and characteristic globoid cells in the white matter of Krabbe's disease patients appears to be due to a unique property of galactosylceramide in that, when present in free form in the brain, it elicits infiltration of macrophages which transform themselves to globoid-like cells. No other lipids, including sulfatide, are known to induce similar tissue reactions. The most conspicuous difference between the two diseases is the presence or absence of abnormal accumulation of the substrates, the degradation of which is genetically blocked in the respective diseases. In metachromatic leukodystrophy, sulfatide accumulates to abnormally high levels, as logically expected for a "lysosomal storage disease". In Krabbe's disease, on the other hand, galactosylceramide is always much less than normal despite the genetic block in its catabolic pathway. This paradoxical finding can be explained by the "psychosine hypothesis".(ABSTRACT TRUNCATED AT 250 WORDS)


Advances in early biomarkers of diabetic nephropathy.
Diabetic nephropathy is the main cause of chronic kidney disease, and represents the most common and serious complication of diabetes. The exact pathogenesis is complex and not elucidated. Several factors and mechanisms contribute to the development and outcome of diabetic nephropathy. An early diagnosis and intervention may slow down disease progression. A variety of biological markers associated with diabetic nephropathy were found in recent years, which was important for predicting the occurrence and development of the disease. Therefore, this article provides an overview of early biomarkers that are associated with diabetic nephropathy.


Origin of circular dichroism of xanthorhodopsin. A study with artificial pigments.
Xanthorhodopsin (xR) is a retinal protein that contains, in addition to the retinal moiety, a salinixanthin chromophore absorbing at 456, 486, and 520 nm [Balashov, S. P.; Science 2005, 309, 2061]. The CD spectrum of xR is very unique with a "conservative" character, containing negative and positive lobes and resembling the first derivative of the absorption spectrum [Balashov, S. P.; Biochemistry 2006, 45, 10998]. It was suggested that the CD spectrum is likely to be composed of several components and that the salinixanthin interacts closely with the retinal chromophore [Balashov, S. P.; Biochemistry 2006, 45, 10998; Imasheva, E. S.; Photochem. Photobiol. 2008, 84, 977; Lanyi, J. K.; Acta Bioenerg. 2008, 1777, 684; Smolensky, E.; Biochemistry 2009, 48, 8179; Smolensky Koganov, E.; Biochemistry 2013, 52, 1290]. In this work, we aim to further explore the nature and origin of the unique CD spectrum of xR. We follow the absorption and CD spectra at different pHs of wild-type (wt) xR and of artificial xR pigments, characterized by a shifted absorption maximum of the retinal chromophore, as well as their corresponding reduced retinal protonated Schiff base pigments. Our results revealed a protein residue (other than the protonated Schiff base counterion), for which protonation affects the CD spectrum by decreasing the negative lobe at ∼530 nm and the positive lobes at 478 and 455 nm, which might be due to elimination of excitonic coupling between the salinixanthin chromophores, although other possibilities cannot be completely excluded. This spectrum change occurs by the pH decreasing, even in artificial pigment where the absorption of the retinal pigment is significantly shifted from 570 to about 450 nm. The possible excitonic coupling between the salinixanthin chromophores and its contribution to the CD spectrum of xR were supported by a good fitting of the CD spectrum to conservative (excitonic) bands [Zsila, F.; Tetrahedron: Asymmetry 2001, 12, 3125; Zsila, F.; Tetrahedron: Asymmetry 2002, 13, 273]. We propose that the CD spectrum of xR consists of contributions from an excitonic coupling interaction between the salinixanthins chromophores located in different subunits of the 3D structure of xR, the chiral conformation of the salinixanthin within its binding site, and the contribution of the retinal chromophore to the negative lobe at around 550 nm.


The Deterioration of the Glycemic Profile during Hormone Replacement Therapy in a Patient with Fulminant Type 1 Diabetes.
Although most women with type 1 diabetes experience the normal transition to menopause, there is little information about the impact of hormone replacement therapy on their glycemic profiles. A 54-year-old postmenopausal woman with fulminant type 1 diabetes was admitted to our hospital due to diabetic ketoacidosis. She was treated with fluid replacement and a continuous insulin infusion. Thereafter, her glycemic profile was well maintained by daily multiple insulin injections. However, her glycemic profiles immediately deteriorated following the administration of progesterone in hormone replacement therapy. This transient deterioration implies that external progesterone can lead to the deterioration of glycemic profiles in postmenopausal women with type 1 diabetes.


Snapshots of Iron Speciation: Tracking the Fate of Iron Nanoparticle Drugs via a Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometric Approach.
Nanomedicines are nanoparticle-based therapeutic or diagnostic agents designed for targeted delivery or enhanced stability. Nanotechnology has been successfully employed to develop various drug formulations with improved pharmacokinetic characteristics, and current research efforts are focused on the development of new innovator and generic nanomedicines. Nanomedicines, which are often denoted as complex or nonbiological complex drugs, have inherently different physicochemical and pharmacokinetic properties than conventional small molecule drugs. The tools necessary to fully evaluate nanomedicines in clinical settings are limited, which can hamper their development. One of the most successful families of nanomedicines are iron-carbohydrate nanoparticles, which are administered intravenously (IV) to treat iron-deficiency anemia. In the U.S., the FDA has approved six distinct iron-carbohydrate nanoparticles but only one generic version (sodium ferric gluconate for Ferrlecit). There is significant interest in approving additional generic iron-carbohydrate drugs; however, the lack of a direct method to monitor the fate of the iron nanoparticles in clinical samples has impeded this approval. Herein we report a novel liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS) method that allows for the direct quantification of the iron-carbohydrate drugs in clinical samples, while simultaneously measuring the speciation of the iron released from the nanoparticles in biological samples. To our knowledge, this is the first time that iron nanoparticles have been observed in clinical samples, opening the door for direct pharmacokinetic studies of this family of drugs. This method has potential applications not only for iron-nanoparticle drugs but also for any nanomedicine with an inorganic component.


The role of dietary supplementation with L-glutamine in inflammatory mediator release and intestinal injury in hypoxia/reoxygenation-induced experimental necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is a multifactorial syndrome in the neonate. Enteral feeding practices are an important component of gastrointestinal injury in neonatal NEC. In the present study, we examined the protective effect of oral supplementation with L-glutamine, an important specific fuel for the enterocytes, against hypoxia-reoxygenation (H/R)-induced NEC in young mice. Young mice were divided into four groups: group 1 mice (untreated) underwent H/R; group 2 mice were supplemented with L-glutamine in drinking water (0.5 g/dl) for 3 days, and group 3 mice were supplemented with L-glutamine (3 g/dl) for 10 days. Group 4 mice served as control. Hypoxia was induced by placing the young mice in a 100% CO(2) chamber for 5 min. After hypoxia, they were reoxygenated for 10 min with 100% oxygen. We examined the intestinal lesions with light microscopy and measured intestinal generation of PAF and TNF-alpha in the H/R-induced model of NEC. In group 3 mice, NEC-induced intestinal tissue damage was greatly attenuated with necrosis limited partially to the mucosa. Both intestinal tissue PAF and TNF-alpha concentrations were significantly higher in the untreated group than in controls (p < 0.001). Group 3 mice (3 g/dl supplemented) showed a significant decrease in intestinal TNF-alpha concentration compared with young group 1 and group 2 mice (p < 0.05 and p < 0.05, respectively). On the other hand, no significant difference was observed in the intestinal generation of PAF between H/R groups (p > 0.05). The present study suggests that H/R plays an important role in the pathogenesis of NEC and supports the hypothesis that especially PAF and TNF-alpha are involved in the pathophysiological mechanism of H/R-induced NEC. This study also demonstrates that dietary supplementation with L-glutamine reduces the histologic evidence of H/R-induced intestinal injury. Based on these findings, beneficial effects of L-glutamine in this model of NEC are mediated via mechanisms inhibiting intestinal cytokine release.


Presence of pesticide residues on produce cultivated in Suriname.
Agricultural pesticides are widely used in Suriname, an upper middle-income Caribbean country located in South America. Suriname imported 1.8 million kg of agricultural pesticides in 2015. So far, however, national monitoring of pesticides in crops is absent. Reports from the Netherlands on imported Surinamese produce from 2010 to 2015 consistently showed that samples exceeded plant-specific pesticide maximum residue limits (MRLs) of the European Union (EU). Consumption of produce containing unsafe levels of pesticide residues can cause neurological disorders, and particularly, pregnant women and children may be vulnerable. This pilot study assessed the presence of pesticide residues in commonly consumed produce items cultivated in Suriname. Thirty-two insecticides (organophosphates, organochlorines, carbamates, and pyrethroids) and 12 fungicides were evaluated for their levels in nine types of produce. Pesticide residue levels exceeding MRLs in this study regarded cypermethrin (0.32 μg/g) in tomatoes (USA MRL 0.20 μg/g), lambda-cyhalothrin (1.08 μg/g) in Chinese cabbage (USA MRL 0.40 μg/g), endosulfan (0.07 μg/g) in tannia (EU MRL 0.05 μg/g), and lindane (0.02 and 0.03 μg/g, respectively) in tannia (EU MRL 0.01 μg/g). While only a few pesticide residues were detected in this small pilot study, these residues included two widely banned pesticides (endosulfan and lindane). There is a need to address environmental policy gaps. A more comprehensive sampling and analysis of produce from Suriname is warranted to better understand the scope of the problem. Preliminary assessments, using intake rate, hazard quotient, and level of concern showed that it is unlikely that daily consumption of tannia leads to adverse health effects.


Identifying U.S. regions with the highest suicide rates and examining differences in suicide methods among Asian American, Native Hawaiian, and Pacific Islander Veterans.
The suicide rate among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) Veterans increased from 2001 to 2020. Identifying regions where suicide rates are elevated and increasing among AANHPI Veterans would inform targeted prevention efforts for members of this cohort. We conducted a population-based retrospective cohort study of 377,833 AANHPI Veterans to examine suicide rates and methods (2005-2019) by United States (US) region and over time (2005-2009, 2010-2014, 2015-2019), using US Veteran Eligibility Trends and Statistics and Joint DoD/VA Mortality Data Repository data. AANHPI Veterans across most regions experienced increases in suicide rates from the earliest to latest period; however, patterns differed by region. Age-adjusted suicide rates increased across all three periods among those in the Northeast and West, but increased, then declined in the Midwest and South. In 2015-2019, the age-adjusted suicide rate among AANHPI Veterans was highest in the Northeast (42.0 per 100,000) and lowest in the West (27.5). However, the highest percentages of AANHPI Veteran suicide deaths in 2005-2019 occurred in the West (39.5%) and South (34.7%), with lower percentages in the Midwest (15.0%) and Northeast (10.8%). Across regions, those ages 18-34 had the highest suicide rates. Firearms were the most frequently used suicide method across regions (44.4%-60.2%), except the Northeast (35.2%), where suffocation was more common (38.3%). Results suggest particular needs for suicide prevention efforts among AANHPI Veterans in the Northeast and to ensure that lethal means safety initiatives for AANHPI Veterans encompass both firearms and suffocation, with some variations in emphasis across regions.


[Event-related potential of working memory on emotional faces in children with autism spectrum disorder].
To investigate the characteristics of working memory ability on emotional faces and related event-related potential (ERP) in children with autism spectrum disorder (ASD). The Chinese Facial Affective Picture System was used as test material, and the event-related potential system was used to record the electroencephalographic data when 16 ASD children aged 6-12 years (ASD group) and 14 normal children matched for age (control group) were completing the facial emotion delayed match-to-sample task. The characteristics of P3b component were analyzed for both groups. Compared with the control group, the ASD group had a significantly longer reaction time (1 527 ms vs 1 060 ms; P<0.05) and a significantly lower accuracy rate (76% vs 88%; P<0.01) in the facial emotion delayed match-to-sample task. There was a difference in the amplitude of P3b component during the encoding stage between the two groups. In the ASD group, the P3b component on the left side electrode had a higher amplitude than that on the right side electrode (P<0.05), while the control group had no such characteristics. There is a difference in P3b component during the encoding stage between school-aged ASD children and normal children. In ASD children, working memory on emotional faces may depend more on the related neural pathway in the left hemisphere.


Histological Pattern Of Endometrial Samples In Postmenopausal Women With Abnormal Uterine Bleeding.
Abnormal uterine bleeding is one of the most common clinical problems in gynaecological practice and is an indicator of various underlying disorders. An endometrial biopsy should be done in all women over 35 years with AUB to rule out endometrial cancer or pre-malignant lesion and to initiate treatment. However, wide range of histological patterns on endometrial biopsy offer a diagnostic challenge to practicing pathologists. The objective of this study was to determine histological patterns of endometrium in postmenopausal women with abnormal uterine bleeding. This cross-sectional study was conducted in the department of obstetrics and gynaecology, Benazir Bhutto Shaheed women and children teaching hospital, Abbottabad from 15/11/2014 to 14/05/2015. This study involved 110 postmenopausal women presenting with abnormal uterine bleeding. A written informed consent was obtained from every patient. The mean age of the patients was 61.60±6.17 years and the mean duration of AUB was 5.20±2.80 years. Most of the patients were para 6 (28.2%) and para 5 (28.2%) followed by para 4 (18.2%) and para 3 (17.3%) while only 8.2% were para 1. The most common histological pattern observed was complex hyperplasia without atypia (30.9%) followed by atrophic endometrium (24.5%), simple hyperplasia (23.6%), malignancy (12.7%), complex hyperplasia with atypia (4.5%) and benign endometrial polyp (3.6%). When stratified the data, there was no significant difference of histological patterns across various age groups (p=.673), duration of AUB (p=.064) and parity (p=.242). The most common histological pattern observed in postmenopausal women with AUB was complex hyperplasia without atypia (30.9%) followed by atrophic endometrium (24.5%), simple hyperplasia (23.6%), malignancy (12.7%), complex hyperplasia with atypia (4.5%) and benign endometrial polyp (3.6%).


You and me versus the rest of the world: the effects of affiliative motivation and ingroup partner status on social tuning.
Bandura argues that individuals are more likely to engage in social learning when they identify with a social model and when they are motivated or rewarded. Therefore, in the present work, we investigate how these two key factors, perceived similarity and affiliative motivation, influence the extent to which individuals engage in social tuning or align their views with an interaction partner-especially if their partner's attitudes differ from the larger social group. Experiment 1 (170 participants) explored the role of perceived similarity through group membership when needing to work collaboratively with a collaboration partner whose climate change beliefs differed from a larger social group. Experiment 2 (115 participants) directly manipulated affiliative motivation (i.e., length of interaction time) along with perceived similarity (i.e., Greek Life membership) to explore if these factors influenced social tuning of drinking attitudes and behaviors. Experiments 3 (69 participants) and 4 (93 participants) replicated Experiment 2 and examined whether tuning occurred for explicit and implicit attitudes towards weight (negative views Experiment 3 and positive views Experiment 4). Results indicate that when individuals experience high affiliative motivation, they are more likely to engage in social tuning of explicit and implicit attitudes when their interaction partner belongs to their ingroup rather than their outgroup. These findings are consistent with the tenets of Social Learning Theory, Shared Reality Theory, and the affiliative social tuning hypothesis.


Interaction between the interstitial fluid and the extracellular matrix in confined indentation.
The Movement of the interstitial fluid in extracellular matrices not only affects the mechanical properties of soft tissues, but also facilitates the transport of nutrients and the removal of waste products. In this study, we aim to quantify interstitial fluid movement and fluid-matrix interaction in a new loading configuration-confined tissue indentation, using a poroelastic theory. The tissue sample sits in a cylindrical chamber and loading is applied on the top central surface of the specimen by a porous indenter that is fixed on the specimen. The interaction between the solid and the fluid is examined using a finite element method under ramp and cyclic loads. Typical compression-relaxation responses of the specimen are observed in a ramp load. Under a cyclic load, the system reaches a dynamic equilibrium after a number of loading cycles. Fluid circulation, with opposite directions in the loading and unloading phases in the extracellular matrix, is observed. The most significant variation in the fluid pressure locates just beneath the indenter. Fluid pressurization arrives at equilibrium much faster than the solid matrix deformation. As the loading frequency increases, the location of the peak pressure oscillation moves closer to the indenter and the magnitude of the pressure oscillation increases. Concomitantly, the axial stress variation of the solid matrix is reduced. It is found that interstitial fluid movement helps to alleviate severe strain of the solid matrix beneath the indenter. This study quantifies the interaction between the interstitial fluid and the extracellular matrix by decomposing the loading response of the specimen into the "transient" and "dynamic equilibrium" phases. Confined indentation in this manuscript gives a better representation of some in vitro and in vivo loading configurations where the indenter covers part of the top surface of the tissue.


[Oriental elements in Byzantine medicine].
Late Byzantine medicine contains numerous oriental elements which were assimilated in two ways: first via translations of important treatises written by eminent physicians, but above all in the form of new medical remedies proposed mainly by Symeon Seth, Nicolaus Myrepsos, Constantinus Meliteniotes, Isaac Taxiotes. As Byzantine - Eastern Roman medicine had solid foundations and enjoyed a development of its own, these influences were rather fragmentary and attributable to the ecumenical disposition of the Empire.


Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration.
Estetrol (E4) is a natural estrogen produced solely during human pregnancy. E4 is suitable for clinical use since it acts as a selective estrogen receptor modulator. In clinical trials E4 has been seen to have little or no effect on coagulation. Hence, it is interesting to investigate whether E4 alters endothelial-dependent fibrinolysis. We studied the effects of E4 on the fibrinolytic system and whether this could influence the ability of endothelial cells to migrate. In addition, we compared the effects of E4 with those of 17β-estradiol (E2). Human umbilical vein endothelial cells (HUVEC) were obtained from healthy women. Expression of plasminogen-activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (u-PA) and tissue plasminogen activator (t-PA) proteins was evaluated by Western blot analysis. Endothelial cell migration was studied by razor-scrape horizontal and multiwell insert systems assays. E4 increased the expression of t-PA, u-PA and PAI-1 in HUVEC, but less so than did equimolar amounts of E2. The effects of E4 on t-PA, u-PA and PAI-1 were mediated by the induction of the early-immediate genes c-Jun and c-Fos. E4 in combination with E2 antagonized the effects induced by pregnancy-like E2 concentrations but did not impair the effects of postmenopausal-like E2 levels. We also found that the increased synthesis of PAI-1, u-PA and t-PA induced by E2 and E4 is important for horizontal and three-dimensional migration of HUVEC. These results support the hypothesis that E4 acts as an endogenous selective estrogen receptor modulator (SERM), controlling the fibrinolytic system and endothelial cell migration.


Posttraumatic stress disorder, depression, alcohol use disorders and quality of life in adolescents.
Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder among adolescents. While the effects of PTSD on quality of life (QOL) have been systematically studied with adults, research on the consequences of PTSD with adolescents has been limited. Among the other psychiatric disorders often associated with PTSD, major depression and alcohol use disorders are prevalent and have their own substantial morbidities. This study was designed to examine and compare the effects of PTSD, major depression, and alcohol use disorders on quality of life during adolescence. The subjects were 540 adolescents (ages 12-18 years old) recruited from clinical and community sources. Psychiatric disorders characterizing the sample included one or more of the three disorders studied (n = 275), other psychiatric disorders (n = 121), or no psychiatric disorders (n = 144). Analysis of covariance was utilized to determine the individual main effects and relative effects sizes of the three primary disorders on QOL variables. PTSD showed significant adverse effects on psychological, physical, and social functioning. Major depression showed a similar pattern. In contrast, alcohol use disorders primarily affected role functioning. While PTSD, major depression, and alcohol use disorders all adversely influenced adolescent QOL, the patterns of their effects differed. Remedial treatment interventions designed to restore QOL for adolescents with these disorders may need to focus on different areas for adolescents with PTSD or major depression than for adolescents with alcohol use disorders.


Meta-analysis of the coral environmental stress response: Acropora corals show opposing responses depending on stress intensity.
As climate change progresses, reef-building corals must contend more often with suboptimal conditions, motivating a need to understand coral stress response. Here, we test the hypothesis that there is a stereotyped transcriptional response that corals enact under all stressful conditions, functionally characterized by downregulation of growth, and activation of cell death, response to reactive oxygen species, immunity, and protein folding and degradation. We analyse RNA-seq and Tag-Seq data from 14 previously published studies and supplement them with four new experiments involving different stressors, totaling over 600 gene expression profiles from the genus Acropora. Contrary to expectations, we found not one, but two distinct types of response. The type A response was observed under all kinds of high-intensity stress, was correlated between independent projects and was functionally consistent with the hypothesized stereotyped response. The consistent correlation between projects, irrespective of stress type, supports the type A response as the general coral environmental stress response (ESR), a blanket solution to severely stressful conditions. The distinct type B response was observed under lower intensity stress and was more variable among studies. Unexpectedly, at the level of individual genes and functional categories, the type B response was broadly opposite the type A response. Finally, taking advantage of the breadth of the data set, we present contextual annotations for previously unannotated genes based on consistent stress-induced differences across independent projects.


Gene Co-occurrence Networks Reflect Bacteriophage Ecology and Evolution.
Bacteriophages are the most abundant and diverse biological entities on the planet, and new phage genomes are being discovered at a rapid pace. As more phage genomes are published, new methods are needed for placing these genomes in an ecological and evolutionary context. Phages are difficult to study by phylogenetic methods, because they exchange genes regularly, and no single gene is conserved across all phages. Here, we demonstrate how gene-level networks can provide a high-resolution view of phage genetic diversity and offer a novel perspective on virus ecology. We focus our analyses on virus host range and show how network topology corresponds to host relatedness, how to find groups of genes with the strongest host-specific signatures, and how this perspective can complement phage host prediction tools. We discuss extensions of gene network analysis to predicting the emergence of phages on new hosts, as well as applications to features of phage biology beyond host range.IMPORTANCE Bacteriophages (phages) are viruses that infect bacteria, and they are critical drivers of bacterial evolution and community structure. It is generally difficult to study phages by using tree-based methods, because gene exchange is common, and no single gene is shared among all phages. Instead, networks offer a means to compare phages while placing them in a broader ecological and evolutionary context. In this work, we build a network that summarizes gene sharing across phages and test how a key constraint on phage ecology, host range, corresponds to the structure of the network. We find that the network reflects the relatedness among phage hosts, and phages with genes that are closer in the network are likelier to infect similar hosts. This approach can also be used to identify genes that affect host range, and we discuss possible extensions to analyze other aspects of viral ecology.


Intermolecular interactions of trifluorohalomethanes with Lewis bases in the gas phase: an ab initio study.
We perform an ab initio computational study of molecular complexes with the general formula CF3X-B that involve one trifluorohalomethane CF3X (X = Cl or Br) and one of a series of Lewis bases B in the gas phase. The Lewis bases are so chosen that they provide a range of electron-donating abilities for comparison. Based on the characteristics of their electron pairs, we consider the Lewis bases with a single n-pair (NH3 and PH3), two n-pairs (H2O and H2S), two n-pairs with an unsaturated bond (H2CO and H2CS), and a single π-pair (C2H4) and two π-pairs (C2H2). The aim is to systematically investigate the influence of the electron pair characteristics and the central atom substitution effects on the geometries and energetics of the formed complexes. The counterpoise-corrected supermolecule MP2 and coupled-cluster single double with perturbative triple [CCSD(T)] levels of theory have been employed, together with a series of basis sets up to aug-cc-pVTZ. The angular and radial configurations, the binding energies, and the electrostatic potentials of the stable complexes have been compared and discussed as the Lewis base varies. For those complexes where halogen bonding plays a significant role, the calculated geometries and energetics are consistent with the σ-hole model. Upon formation of stable complexes, the C-X bond lengths shorten, while the C-X vibrational frequencies increase, thus rendering blueshifting halogen bonds. The central atom substitution usually enlarges the intermolecular bond distances while it reduces the net charge transfers, thus weakening the bond strengths. The analysis based on the σ-hole model is grossly reliable but requires suitable modifications incorporating the central atom substitution effects, in particular, when interaction components other than electrostatic contributions are involved.


[The relationship between physical activity and clustering of metabolic abnormalities in children].
This study was performed to assess the association between physical activity and the clustering of metabolic abnormalities among Korean children. The effect of substituting moderate to vigorous physical activity for the time spent in inactivity was examined as well. The study subjects were comprised of 692 (354 boys, 338 girls) 4th grade elementary school students. We used a modified form of the physical activity questionnaire that was developed in the Five-City Project. The subjects with clustering of metabolic abnormalities were defined as having two or more of the following five characteristics: waist circumference > or =90 %, systolic or diastolic blood pressure > or =90 %, fasting glucose > or =110 mg/dl, triglycerides > or =110 mg/dl and HDL cholesterol < or =40 mg/dl. We calculated the odds ratios to assess the effect of substituting moderate to vigorous physical activity for time spent in inactivity. The risk of clustered metabolic abnormalities was inversely correlated with the increased time spent on moderate to vigorous physical activity, but the correlation was not significant. The odds ratio for clustering of metabolic abnormalities that represented the effect of substituting moderate to vigorous physical activity for 30 minutes of sedentary activity was 0.87 (95% CI=0.76-1.01). These findings suggest that substituting moderate to vigorous physical activity for sedentary activity could decrease the risk of clustered metabolic abnormalities.


[Applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis].
Thrombotic diseases in different forms become a great threat to human health. Such anti-platelet aggregation drugs as aspirin and clopidogrel are common drugs in clinic. However, along with the appearance of resistance and side effects of western anti-platelet aggregation drugs, anti-platelet aggregation traditional Chinese medicines promoting blood circulation to remove blood stasis have gradually become an important study orientation. Platelet is one of major participant in thrombosis, and plays an important role as a bioactive material in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis, mainly involving two aspects--the evaluation for the anti-platelet aggregation activity of traditional Chinese medicines and the screening of their active components. This paper summarized the applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis, so as to provide basis for further studies.


[The fourth horseman: The yellow fever].
Dengue virus three, Chikunguya and Zika have entered the national territory through the south of the country. Cases and outbreaks of yellow fever have now been identified in the Americas where it threatens to expand. Although Mexico has a robust epidemiological surveillance system for vector-borne diseases, our country must be alert in case of its possible introduction into the national territory. This paper presents theoretical assumptions based on factual data on the behavior of yellow fever in the Americas, as well as reflections on the epidemiological surveillance of vector-borne diseases.


[Interaction of sydnocarb with preparations influencing the metabolism of catecholamines].
Changes in the stimulating action of sydnocarbum and d,1-amphetamine on the locomotor activity of mice and conditioned reflexes of rats following introduction of reserpine, alpha-methyl-para-tyrosine (alpha-Mt) and nialamide were studied. The stimulating effect of sydnocarbum is in a great measure suppressed by reserpine, while that of amphetamine--by alpha-MT. Nialamide potentiates the stimulating action of both agents, the strengthening of the sydnocarbum effect, however, was more marked than that of amphetamine. The noted difference in the action of sydnocarbum and amphetamine was, possibly, due to the influence of the former chiefly on the stable, and of the second--on the labile neuronal norepinephrine depot.


Does sleep bruxism affect masticatory muscles volume and occlusal force distribution in young subjects? A preliminary study.
Objective To compare the differences in masticatory muscle volume and occlusal force distribution between patients with sleep bruxism (SB) and healthy individuals. Methods The study was performed on 14 SB patients and 12 controls aged between 20 and 27 years. Magnetic resonance images from a previous clinical trial were used for volumetric measurements of masticatory muscles. Distribution of bite forces was recorded using T-Scan® II. T-tests were used for data comparison. Results The mean age of the subjects was 23 ± 1.85 years. The mean muscle volumes of patients with SB and healthy subjects were 177.3 and 185.9 cm3, respectively. The mean occlusal force areas were 72.4 pixels and 89.8 pixels for patients with SB and healthy subjects, respectively. There was no significant difference in measurements between groups (p > 0.05). Conclusion There was no significant difference in the distribution of masticatory muscles and occlusal force between young patients with SB and healthy subjects.


An Improved Method for the Sensitive Detection of Shiga Toxin 2 in Human Serum.
Shiga toxins (Stx) released by Stx-producing E. coli (STEC) are virulence factors that are most closely 3associated with hemolytic uremic syndrome (HUS), a life-threatening complication of intestinal infections by STEC. Stx have to enter into the circulatory system before they are delivered to target organs and cause damage. The presence of Stx in sera could be a risk indicator for HUS development. However, the detection of Stx, particularly Stx2, has been difficult due to the presence of Stx2-binding components in human serum. Here, we report new ELISA-based methods for the detection of Stx1 and Stx2 in human serum and the effect of guanidinium chloride on enhancing the sensitivity for the detection of Stx2. The recovery rate for Stx2 was 62% when Stx2-spiked serum samples were treated with guanidinium chloride at a concentration of 200 mM, in contrast to 17% without guanidinium chloride treatment. The effectiveness of guanidinium chloride treatment for the detection of Stx2 in human serum was validated using sera from STEC-infected patients. Coimmunoprecipitation results indicated a specific physical interaction between Stx2 and the human serum amyloid P component (HuSAP) in human serum samples. Our in vitro study demonstrated that the inhibition from HuSAP alone for the detection of Stx2 was only 20%, much less than 69.6% from human serum at Stx2 level 10 ng/mL, suggesting that there may be other factors that bind Stx2 in human serum. This study indicates that treatment of serum samples with guanidinium chloride may be useful for the early and sensitive detection of Stx2 in sera of STEC-infected patients, so preventive measures can be adopted in a timely manner.


Impairing DNA methylation obstructs memory enhancement for at least 24 hours in Lymnaea.
Stressor-induced memory enhancement has previously been shown to involve DNA methylation in the mollusc Lymnaea stagnalis. Specifically, injection of the DNA methylation inhibitor 5-AZA one hour before exposure to a memory-enhancing stressor obstructs memory augmentation. However, the duration of the influence of 5-AZA on this memory enhancement has not yet been examined. In this study, 2 memory-enhancing stressors (a thermal stress and exposure to the scent of a predator) were used to examine whether injection of the DNA methylation inhibitor 5-AZA 24 hours before stress exposure would still impair memory enhancement. Indeed, it was observed that memory is still obstructed when 5-AZA is injected 24 hours before exposure to either of these stressors in Lymnaea. Understanding that 5-AZA still effectively impairs memory enhancement after a period of 24 hours is valuable because it indicates that experimental manipulations do not need to be made within one hour after the injection of this DNA methylation inhibitor and can instead be made within one day (i.e. 24 hours). These results will allow for a future examination of the possible involvement of DNA methylation in memory enhancement related to longer-term stressors or environmental changes. This study further elucidates the involvement of epigenetic changes in memory enhancement in Lymnaea, providing insight into the process of memory formation in this mollusc.


Growth pattern of skinfold thicknesses in term symmetric & asymmetric small for gestational age infants.
A etiologically symmetric and asymmetric small for gestational age (SGA) infants are two distinct entities. In view of absence of longitudinal information on growth pattern of skinfold thicknesses (SFTs) among Indian infants, this study was conducted to assess the auxological dynamics of SFTs (sub-cutaneous fat) of symmetric and asymmetric SGA infants. Triceps, sub-scapular, biceps, mid-axillary and anterior thigh SFTs among full-term, 100 symmetric SGA, 100 asymmetric SGA and 100 appropriate for gestational age (AGA) infants were measured at one, three, six, nine and 12 months. Ponderal Index (PI) was used to categorize infants into symmetric SGA (PI ≥2.2 g/cm3) and asymmetric SGA (PI <2.2 g/cm3). Intra-group (symmetric vs. asymmetric), inter-group (SGA vs. AGA) and gender differences were quantified. SFTs among symmetric, asymmetric SGA infants increased to attain peak by six months. Maximum fat deposition in SGA infants was noticed for triceps, minimum for mid-axillary SFT. Mean triceps and sub-scapular skinfolds were measured higher in symmetric SGA than in asymmetric infants. SGA infants had significantly (P≤0.05) thinner SFTs than AGA. Growth velocity for SFTs, among symmetric and asymmetric SGA, was measured maximum between one and three months, threreafter it declined and relatively, steepness of fall was maximum for mid-axillary SFT followed by sub-scapular SFT. Thinner SFTs obtained for symmetric and asymmetric SGA as compared to AGA infants reveal their compromised adiposity and nutritional status. Comparatively, higher SFTs in symmetric than in asymmetric SGA infants appear to suggest that the former have a tendency to accumulate more fat, than the latter during infancy.