Intrapartum monitoring and management of the low birth weight fetus.
All physicians responsible for the care of gravidae at high risk for preterm labor and delivery must be expert in the management of these pregnancies. Only a fraction of women who present in labor remote from term are candidates for long-term tocolysis. Whatever treatment regimen is utilized, the clinician must be familiar with their risks as well as their benefits. The majority of women who present with preterm labor will require delivery or will deliver despite efforts to the contrary. If delivery is imminent or indicated, intensive intrapartum monitoring of these fetuses, especially those weighing less than 1500 gm, is mandatory. The mother should be transferred to a facility that contains both expert obstetric care and a neonatal intensive care unit staffed with individuals experienced in the management of these very low birth weight infants. Attempts at pharmacologic induction of lung maturation should be reserved for those situations in which: (1) the fetal membranes are intact, (2) the fetal lungs are likely to be immature, (3) delivery of the infant may be delayed without undue risk for 48 hours following initiation of therapy, and finally, (4) the informed consent of the parents has been obtained. (By the same token, the probable efficacy of glucocorticoids should not serve as license to deliver the preterm infant.) Preterm infants are viable, even at 25 to 26 weeks of gestation, provided that labor and delivery are managed expertly. When vaginal delivery is contemplated, labor, if induced, should not be forceful. Fetal heart rate and uterine contractions should be monitored continuously. Evidence of fetal jeopardy must be dealt with expeditiously. Nontraumatic delivery, including the liberal use of cesarean section, into the hands of an experienced neonatologist will reduce the number of asphyxiated premature infants and, therefore, the risk of hyaline membrane disease. For the very low birth weight infant presenting as a breech, abdominal delivery is recommended. It is important that the uterine incision, regardless of type, be large enough to allow for nontraumatic delivery of the infant. If greater improvements in the survival and outcome of low birth weight infants are to continue, it is mandatory that there be close collaboration not only between obstetrician and pediatrician, but also between all physicians and nursing staff who care for this group of high-risk patients.


New approaches to the classification of the lymphomata.
Our recently proposed functional approach to and classification of the malignant lymphomata based upon the T and B cell systems, lymphocyte transformation and their development as blocks or a "switch on" in lymphocyte transformation has been reviewed. This functional classification contains 5 major groups: (a) U cell or undefined for those proliferations without specific markers; (b) T cell; (c) B cell; (d) histiocytes as macrophages; (e) unclassifiable for those technically insufficient for specific cytological classification. Retrospective study of several case populations indicates that the majority of non-Hodgkin's lymphomata exhibit features of follicular centre cell (FCC) lymphomata of either cleaved or non-cleaved types. The prognostically favourable status of nodular lymphomata seems to result from the retained capability of follicle formation by FCC types with limited abnormality. Lymphomata of large cell types previously classified as histiocytic lymphoma or reticulum cell sarcoma predominantly resemble transformed lymphocytes and rarely exhibit features of histiocytes as macrophages. They are designated "immunoblastic sarcoma" when they occur as large transformed lymphocytes and may have either T or B cell immunological markers. Immunoblastic sarcoma has been observed to develop in individuals with chronic abnormal immune states, Sjögren's syndrome, alpha chain disease, in patients on immunosuppression therapy for graft rejection and in senescence. There is accumulating evidence of lymphomata of T cells but none are firmly established. These include Sézary's syndrome, mycosis fungoides and the convoluted lymphocyte type, prev-ously included designated as acute lymphocytic leukaemia with mediatinal mass. The results of initial functional studies provide support for the proposed classification and indicate that the modern pathological investigative approach requires the collection of fresh lymphomatous tissue and an integrated immunocytochemical and morphological approach for the precise characterization of human lymphoma cell types.


Geographic range of vector-borne infections and their vectors: the role of African wildlife.
The role of African wildlife in the occurrence of vector-borne infections in domestic animals has gained renewed interest as emerging and re-emerging infections occur worldwide at an increasing rate. In Africa, biodiversity conservation and the expansion of livestock production have increased the risk of transmitting vector-borne infections between wildlife and livestock. The indigenous African pathogens with transboundary potential, such as Rift Valley fever virus, African horse sickness virus, bluetongue virus, lumpy skin disease virus, African swine fever virus, and blood-borne parasites have received the most attention. There is no evidence for persistent vector-borne viral infections in African wildlife. For some viral infections, wildlife may act as a reservoir through the inter-epidemic circulation of viruses with mild or subclinical manifestations. Wildlife may also act as introductory or transporting hosts when moved to new regions, e.g. for lumpy skin disease virus, Rift Valley fever virus and West Nile virus. Wildlife may also act as amplifying hosts when exposed to viruses in the early part of the warm season when vectors are active, with spillover to domestic animals later in the season, e.g. with bluetongue and African horse sickness. Some tick species found on domestic animals are more abundant on wildlife hosts; some depend on wildlife hosts to complete their life cycle. Since the endemic stability of a disease depends on a sufficiently large tick population to ensure that domestic animals become infected at an early age, the presence of wildlife hosts that augment tick numbers may be beneficial. Many wild ungulate species are reservoirs of Anaplasma spp., while the role of wildlife in the epidemiology of heartwater (Ehrlichia ruminantium infection) has not been elucidated. Wild ungulates are not usually reservoirs of piroplasms that affect livestock; however, there are two exceptions: zebra, which are reservoirs of Babesia caballi and Theileria equi, and buffalo, which are reservoirs of Theileria parva. The latter causes Corridor disease when transmitted from buffaloto cattle, butthis appearsto be a self-limiting condition, at least in southern Africa. Wild animals are important reservoirs of tsetse-transmitted Trypanosoma spp. infection. The distribution and abundance of some tsetse species, e.g. Glossina morsitans and G. pallidipes, are closely related to the occurrence of their preferred wildlife hosts.


Protein kinase C-alpha and -delta are required for FcalphaR (CD89) trafficking to MHC class II compartments and FcalphaR-mediated antigen presentation.
Studies have demonstrated that receptor-mediated signaling, receptor/antigen complex trafficking, and major histocompatibility complex class II compartments (MIIC) are critically related to antigen presentation to CD4+ T cells. In this study, we investigated the role of protein kinase C (PKC) in FcalphaR/gammagamma (CD89, human IgA receptor)-mediated internalization of immune complexes and subsequent antigen presentation. The classical and novel PKC inhibitor, Calphostin C, inhibits FcalphaR-mediated antigen presentation and interaction of MIIC and cargo vesicle (receptor and antigen). PKC-alpha, PKC-delta, and PKC-epsilon were recruited to lipid rafts following FcalphaR crosslinking, the extent of which was determined by the phenotype of the gamma chain. Mutant gamma chain with an FcgammaRIIA ITAM (immunoreceptor tyrosine-based activation motif) insert was less able to recruit PKC and trigger antigen presentation. Both PKC isoform-specific peptide inhibitors and short interfering RNA (siRNA) showed that PKC-alpha and PKC-delta, but not PKC-epsilon, were required for association of cargo vesicle and MIIC and for FcalphaR-mediated and soluble antigen presentation. Inhibition of PKC (classical and novel) did not alter major histocompatibility class II biosynthesis, assembly, transport, or plasma membrane stability. PKC's role in facilitating interaction of cargo vesicle and MIIC is likely due to regulation of vesicle biology required for fusion of cargo vesicles to MIIC.


Hospital care and capacity in the tri-state region of Indiana, Kentucky, and Ohio: analysis and insights.
Hospitals are a significant part of the burgeoning healthcare sector in the United States (U.S.) economy. Despite the availability of what some describe as the world's best healthcare, the U.S. suffers from wide discrepancies in healthcare provision across hospitals and regions of the country. Specifically, capacity, utilization, quality, and even financial performance of hospitals vary widely. Based on secondary data from 533 hospitals in the adjoining states of Indiana, Kentucky, and Ohio, this study develops several comparative metrics that enable benchmarking, which, in turn, leads to several inferences and implications for hospital administrators. The paper concludes with implications for hospital administrators and suggestions for future research.


The reduction of 176Lu background in Lu-based PET scanners using optimized classification.
Positron emission tomography (PET) using scanners incorporating lutetium-based (Lu-based) scintillators are widely used in nuclear medicine. However their application in imaging very low (<100 kBq) activity distributions is quite limited due to the intrinsic 176Lu radiation emitted from the scintillators. To visualize very low activities, 176Lu background needs to be reduced or removed. This study proposes a classification method to select background coincidences from true coincidences arising from the source by supervised learning using the optimal classifier as determined by investigating 5 different classifiers: logistic regression, support vector machine, random forest, extreme gradient boosting (XGBoost) and deep neural network. Five energy and time-of-flight (TOF) related features from each coincidence event are extracted to form the training and test set in the classification. The proposed method was verified on a pair of TOF-PET detector modules. Since the measured source coincidences cannot be differentiated from the background events experimentally, simulated source coincidences are used to train the classification model. The simulated feature spectra are therefore compared with those obtained from measurement to verify the feasibility of classifying measured coincidences using a model learned by simulation. XGBoost classifier performed most effectively in classifying the coincidences and provided impressively high classification accuracy (>99%). It was subsequently tested by imaging point-like source, planar Derenzo and bar phantoms with the pair of TOF-PET detectors. An 89.4% image contrast enhancement for the Derenzo phantom at an activity concentration of 100 Bq mm-2, and a 52.4% peak-to-valley ratio improvement across the area of bar phantom at a concentration of 25 Bq mm-2, were observed on the reconstructed images with XGBoost classification applied. The proposed method could extend the usage of Lu-based PET scanners to very low activity detection and imaging and has the potential to be used in a variety of molecular imaging tasks to detect low-level signals.


Positive social interdependence and classroom climate.
We explored the relationship between student perceptions of social interdependence and social support. Attitudinal responses to the Classroom Life Instrument (Johnson & Johnson, 1983; Johnson, Johnson, & Anderson, 1983; Johnson, Johnson, Buckman, & Richards, 1985) were gathered in Canada from four classes totaling 123 eighth-grade students learning geometry in cooperative groups. We extended previous findings by examining the relationships among the classroom climate variables, causal attributions, and achievement, and explored the consistency among the four classroom climate studies using statistical methods for meta-analysis to determine overall effect magnitudes and the degree of study-to-study variability. Social support from the teacher and fellow students was moderately related to perceptions of positive interdependence, but social interdependence factors were less important predictors of student learning than was student self-esteem.


Synthesis of the tube-brush-shaped SiC nanowire array on carbon fiber and its photoluminescence properties.
Tube-brush-shaped nanostructure of SiC nanowires was synthesized on polyacrylonitrile-based carbon fibers. The morphology and microstructure of the nanowires were characterized by X-ray powder diffraction, field emission scanning electron microscopy and high-resolution transmission electron microscopy. A quasi-periodically twin structure with (111) plane as the boundary along the SiC nanowires was observed. The vapor-solid growth mechanism of the SiC nanowire brush is also discussed. Moreover, some separated blue-shifted photoluminescence peaks around 469 nm were measured. The separated blue-shifted emission peaks are attributed to the quantum confinement of nanoscaled twin segments along each nanowire rather than the apparent diameters of the nanowires. The SiC nanowire brushes hopefully can find potential applications in nanotechnology.


Contrast-enhanced magnetic resonance imaging estimation of altered capillary permeability in experimental mammary carcinomas after X-irradiation.
Dynamic magnetic resonance imaging (MRI) enhanced with a macromolecular contrast medium, albumin-(Gd-DTPA)35, was used to detect changes in microvascular characteristics in R3230 mammary adenocarcinomas induced by x-irradiation. Tumors were implanted in either flank in nine rats. One of the tumors was exposed to single-dose x-irradiation (30 Gy) 3 days before MRI. The contralateral control tumor was shielded from irradiation. Capillary permeability to macromolecular contrast medium in irradiated tumors was elevated significantly (P < .05) compared to the control nonirradiated tumors. The mean estimated permeability surface area product for the irradiated tumors increased more than three-fold; 0.511 +/- .046 mL hr-1 cm-3 compared with 0.121 +/- .011 mL hr-1 cm-3 for the nonirradiated tumors. This radiation-induced increase in permeability was corroborated using a macromolecular Evans blue-protein complex measured in the same tumors using an invasive spectrophotometric technique. Dynamic MRI-enhanced with macromolecular contrast medium permits noninvasive quantitative estimates of capillary permeability in tumors, with and without x-irradiation. Because the transendothelial permeability for macromolecular solutes likely influences tumoral accumulation of macromolecular chemotherapeutic agents, this noninvasive technique may prove to be clinically useful in tailoring tumor treatment programs which combine radiation and chemotherapy.


Use of Tachosil® in bariatric surgery: preliminary experience in control of bleeding after sleeve gastrectomy.
Laparoscopic sleeve gastrectomy (LSG) is one of the most common procedures of bariatric surgery. Nevertheless complications after LSG are common, the most frequent is bleeding. Our purpose was to reduce bleeding after gastric resection, thus reducing the risk of anemia. The study took part in our Multidisciplinary Obesity Treatment Centre, between May 2008 and January 2010. Thirty patients were candidates to SG. They were enrolled in this prospective, parallel group, single-blind randomized trial, to proof the effectiveness and safety of the use of hemostatic-sealant drug Tachosil® as a reinforcement of the suture line in sleeve gastrectomy. Patients were enrolled in Group A when TachoSil® was used and Group B if not. We collected data about weight loss every month, RBC, Hb, PLT, ESR, CRP, WBC in the first week daily and at 2, 4 and 6 months on follow-up. Two groups did not significantly differ for mean age, mean of body weight (118.5 vs. 121.9 kg), BMI (48.4 vs. 49.6 kg/m2), operation time (108 vs. 102 min), hospitalization duration (6.5 vs. 7 days). In group B mean drainage fluid collection was 120, 80 and 60 mL on 1st, 2nd and 3rd postoperative day. Tube removal occurred on average on 5th postoperaive day. In group A (no drainage) control echogram ruled out any fluid collection. RBC, Hb and PLT decreased from 2nd postoperative day. Decrease of PLT was non-significantly different. Decrease of RBC and Hb was significantly different (-0.4 x 106/mL vs. -1.7 x 106/mL; -0.5 g/dL vs. -1.2 g/dL). All other values were not different between groups. In this prospective experience the hemostatic-sealant drug Tachosil®, that contains a collagen sponge coated by human fibrinogen and thrombin was shown to reduce post-operatory bleeding and probably promote optimal wound healing.


Relationship between rate and free energy difference for electron transfer from cytochrome c2 to the reaction center in Rhodobacter sphaeroides.
The rate of electron transfer from cytochrome c2 to the bacteriochlorophyll dimer of the reaction center from the photosynthetic bacterium Rhodobacter sphaeroides has been investigated using time-resolved optical spectroscopy. Measurements were performed on a series of mutant reaction centers in which the midpoint potentials of the bacteriochlorophyll dimer vary over a range of 350 mV. Dramatic changes in the characteristic time of electron transfer were observed, with the measured values ranging from 7730 to 80 ns compared to 960 ns for wild type. The binding constants (0.15 to 0.25 microM-1) and the second-order rate constants for the slow component (5.5 x 10(8) to 9.4 x 10(8) M-1 s-1) for the mutants are similar to the corresponding values for wild type (0.35 microM-1 and 11 x 10(8) M-1 s-1), indicating that the binding of the cytochrome to the reaction center is not changed in the mutants. In the mutants with the fastest rates, an additional minor component was resolved that is probably due to formation of a reaction center-cytochrome complex in an unfavorable configuration with a binding constant an order of magnitude weaker than the major component. The altered midpoint potentials in the mutants result in values for the free energy difference for this electron transfer reaction ranging from -65 to -420 meV compared to -160 meV for wild type. The relationship between the rate and free energy difference was well fit by a Marcus equation using a reorganization energy of 500 meV.(ABSTRACT TRUNCATED AT 250 WORDS)


Nutritional modulation of age-related changes in the immune system and risk of infection.
The immune system undergoes some adverse alterations during aging, many of which have been implicated in the increased morbidity and mortality associated with infection in the elderly. In addition to intrinsic changes to the immune system with aging, the elderly are more likely to have poor nutritional status, which further impacts the already impaired immune function. Although the elderly often have low zinc serum levels, several manifestations commonly observed during zinc deficiency are similar to the changes in immune function with aging. In the case of vitamin E, although its deficiency is rare, the intake above recommended levels is shown to enhance immune functions in the elderly and to reduce the risk of acquiring upper respiratory infections in nursing home residents. Vitamin D is a critical vitamin in bone metabolism, and its deficiency is far more common, which has been linked to increased risk of infection as demonstrated in a number of observational studies including those in the elderly. In this review, we focus on zinc, vitamin E, and vitamin D, the 3 nutrients which are relatively well documented for their roles in impacting immune function and infection in the elderly, to discuss the findings in this context reported in both the observational studies and interventional clinical trials. A perspective will be provided based on the analysis of information under review.


Method development and measurements of endogenous serine/threonine Akt phosphorylation using capillary electrophoresis for systems biology.
Signal transduction studies have indicated that Akt is essential for transducing the signals originating from extracellular stimuli. An exploration of the Akt signal transduction mechanism depends on the ability to assay its activation states by determining the ability of Akt to phosphorylate various substrates. This paper describes a CE-based kinase assay for Akt using a UV detection method. The RPRAATF peptide was used as the specific substrate to determine the Akt activity. Under the CE separation conditions used, the phosphorylated and nonphosphorylated forms of the RPRAATF peptide were rapidly resolved in the Akt reaction mixture within 20 min. Using this method for measuring the Akt activity, the incubation time for the Akt reactions as well as the kinetic parameters (KM) were examined. Furthermore, the developed method was applied to a PC12 cell system to assess the dynamics of the Akt activity by examining the effectiveness of the RPRAATF peptide substrate under various cytokine-stimulated environments. These results highlight the feasibility of the CE method, which is a simple and reliable technique for determining and characterizing various enzyme reactions particularly kinase enzymes.


Maternal hypertensive disorder of pregnancy and mortality in offspring from birth to young adulthood: national population based cohort study.
To examine the association of maternal hypertensive disorder of pregnancy (HDP) with overall and cause specific mortality in offspring from birth to young adulthood. Nationwide population based cohort study. Danish national health registers. All 2 437 718 individuals live born in Denmark, 1978-2018, with follow-up from date of birth until date of death, emigration, or 31 December 2018, whichever came first. The primary outcome was all cause mortality. Secondary outcomes were 13 specific causes of death in offspring from birth to young adulthood (age 41 years). Cox regression was used to assess the association, taking into consideration several potential confounders. The role of timing of onset and severity of pre-eclampsia, maternal history of diabetes, and maternal education were also studied. 102 095 mothers had HDP: 67 683 with pre-eclampsia, 679 with eclampsia, and 33 733 with hypertension. During follow-up to 41 years (median 19.4 (interquartile range 9.7-28.7) years), deaths occurred in 781 (58.94 per 100 000 person years) offspring born to mothers with pre-eclampsia, 17 (133.73 per 100 000 person years) born to mothers with eclampsia, 223 (44.38 per 100 000 person years) born to mothers with hypertension, and 19 119 (41.99 per 100 000 person years) born to mothers with no HDP. The difference in cumulative incidence in overall mortality between cohorts exposed and unexposed to maternal HDP was 0.37% (95% confidence interval 0.11% to 0.64%), and the population attributable fraction for maternal HDP was estimated as 1.09% (95% confidence interval 0.77% to 1.41%). Maternal HDP was associated with a 26% (hazard ratio 1.26, 95% confidence interval 1.18 to 1.34) higher risk of all cause mortality in offspring. The corresponding estimates for maternal pre-eclampsia, eclampsia, and hypertension were 1.29 (1.20 to 1.38), 2.88 (1.79 to 4.63), and 1.12 (0.98 to 1.28). Increased risks were also observed for several cause specific mortalities, such as deaths from conditions originating in the perinatal period (2.04, 1.81 to 2.30), cardiovascular diseases (1.52, 1.08 to 2.13), digestive system diseases (2.09, 1.27 to 3.43), and endocrine, nutritional, and metabolic diseases (1.56, 1.08 to 2.27). The increased risks were more pronounced among offspring of mothers with early onset and severe pre-eclampsia (6.06, 5.35 to 6.86) or with both HDP and diabetes history (1.57, 1.16 to 2.14) or HDP and low education level (1.49, 1.34 to 1.66). Maternal HDP, particularly eclampsia and severe pre-eclampsia, is associated with increased risks of overall mortality and various cause specific mortalities in offspring from birth to young adulthood.


Assessment of pro-oxidant activity of foods by kinetic analysis of crocin bleaching.
The pro-oxidant activity of potent oxidants and foods was determined using the kinetic analysis of crocin bleaching. In its reduced form, crocin has an absorption band at 443 nm, which disappears upon oxidation by a generic radical species. Hydroxyl radicals generated by hydrogen peroxide, peroxyl radicals from ABAP, and the stable free radical DPPH(*) were allowed to react with crocin in an aqueous solution at 40 degrees C. Pro-oxidant activity was taken as the ratio between the decrease in crocin absorbance at 5 min and the relevant oxidant concentration. The test proposed was used to evaluate the pro-oxidant activity of widely consumed foods such as pasteurized skim milk and bread. They both exerted significant pro-oxidant activities, which were attributed to the early nonenzymatic browning products formed upon heat treatment.


Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis.
The authors reported a mutation, P1158S, of the human skeletal muscle sodium channel gene (SCN4A) in a family with cold-induced hypokalemic periodic paralysis (hypoKPP) and myotonia. To identify mechanisms of temperature dependency in this channelopathy. Using the amphotericin B perforated patch clamp method, sodium currents were recorded at 22 and 32 degrees C from the wild-type (WT) and P1158S mutant SCN4A expressed in tsA201 cells. Computer simulation was performed, incorporating the gating parameters of the P1158S mutant SCN4A. P1158S mutant SCN4A exhibited hyperpolarizing shifts in voltage dependence of both activation and inactivation curves at a cold temperature and a slower rate of inactivation than the WT. Computer simulation reproduced the abnormal skeletal muscle electrical activities of both paralysis at a low potassium concentration in the cold and myotonia at a normal potassium concentration. Both paralysis and myotonia are attributable to the biophysical properties of the SCN4A mutation associated with hypoKPP. This is the first report of an SCN4A mutation that exhibits temperature-dependent shifts of voltage dependence in sodium channel gating.


An Approach to Automated Fusion System Design and Adaptation.
Industrial applications are in transition towards modular and flexible architectures that are capable of self-configuration and -optimisation. This is due to the demand of mass customisation and the increasing complexity of industrial systems. The conversion to modular systems is related to challenges in all disciplines. Consequently, diverse tasks such as information processing, extensive networking, or system monitoring using sensor and information fusion systems need to be reconsidered. The focus of this contribution is on distributed sensor and information fusion systems for system monitoring, which must reflect the increasing flexibility of fusion systems. This contribution thus proposes an approach, which relies on a network of self-descriptive intelligent sensor nodes, for the automatic design and update of sensor and information fusion systems. This article encompasses the fusion system configuration and adaptation as well as communication aspects. Manual interaction with the flexibly changing system is reduced to a minimum.


Traditional Uses, Chemical Constituents and Biological Activities of Plants from the Genus Sanguisorba L.
Plants from the genus Sanguisorba have been treated as medicinal ingredients for over 2000 years. This paper reviews advances in the botanical, phytochemical and pharmacological studies of the genus. To date, more than 120 chemical constituents have been isolated and identified from these plants, especially from S. officinalis and S. minor. Among these compounds, triterpenoids, phenols and flavonoids are the primary biologically active constituents. Triterpenoids can be used as quality control markers to determine the quality of medicinal materials and their preparations. In vivo and in vitro studies have shown that plants from the genus Sanguisorba exhibit a wide range of pharmacological properties, including hemostatic, antibacterial, antitumor, neuroprotective and hypoglycemic activities. In Chinese medical practice, many drugs (e.g., tablets and powders) that contain S. officinalis roots have been used to treat leukopenia, hemorrhaging and burns. However, there is still a multitude of Sanguisorba species that have garnered little or no attention. Indeed, there are few reports concerning the clinical use and toxic effects of these plants. Further attention should be focused on the study of these species in order to gather information on their respective toxicology data, any relevant quality-control measures, and the clinical value of the crude extracts, active compounds, and bioactive metabolites from Genus Sanguisorba.


[Staying fit after fifty].
It is common knowledge that when women reach the menopause, they put on weight and change body shape. The menopause is particularly feared as a sign of aging. The deficiency in estrogen at the menopause is responsible for the change from a gynoid fat pattern to an android one (i.e. fat accumulates on the upper portion of the abdomen instead of on the hips). In addition, women are no longer protected against CardioVascular Diseases (CVD), and will rapidly share the same risks as men. The menopause is marked by an increase in the prevalence of various CVD risk factors: elevated blood pressure, hypertriglyceridemia, Diabetes, etc. This phenomenon may be explained by an increase in the occurrence of the polymetabolic (PM) syndrome at this time of life. In the IDF ((International Diabetics Federation) 2005 definition, waist circumference becomes the main criterion of PM syndrome. Keeping a slim waist can no longer be considered a woman's vain obsession but a justified health concern, since the waist to height ratio is a better predictor of CVD than BMI (Body Mass Index). A diet and healthcare program is now available which, if followed from the age of 35, can help women live 'in good shape' and for longer.


Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity.
The discovery of novel acyclic amide cannabinoid-1 receptor inverse agonists is described. They are potent, selective, orally bioavailable, and active in rodent models of food intake and body weight reduction. A major focus of the optimization process was to increase in vivo efficacy and to reduce the potential for formation of reactive metabolites. These efforts led to the identification of compound 48 for development as a clinical candidate for the treatment of obesity.


After the pandemic: perspectives on the future trajectory of COVID-19.
There is a realistic expectation that the global effort in vaccination will bring the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) under control. Nonetheless, uncertainties remain about the type of long-term association that the virus will establish with the human population and, in particular, whether coronavirus disease 2019 (COVID-19) will become an endemic disease. Although the trajectory is difficult to predict, the conditions, concepts and variables that influence this transition can be anticipated. Persistence of SARS-CoV-2 as an endemic virus, perhaps with seasonal epidemic peaks, may be fuelled by pockets of susceptible individuals and waning immunity after infection or vaccination, changes in the virus through antigenic drift that diminish protection and re-entries from zoonotic reservoirs. Here we review relevant observations from previous epidemics and discuss the potential evolution of SARS-CoV-2 as it adapts during persistent transmission in the presence of a level of population immunity. Lack of effective surveillance or adequate response could enable the emergence of new epidemic or pandemic patterns from an endemic infection of SARS-CoV-2. There are key pieces of data that are urgently needed in order to make good decisions; we outline these and propose a way forward.


Evaluation of the interactions of serotonergic and adrenergic drugs with mu, delta, and kappa opioid binding sites.
Several serotonergic and adrenergic agents were tested for an ability to interact with mu, delta, and kappa opioid binding sites. Spiroxatrine interacted nearly equipotently with all three opioid subtypes, yielding Ki values near 110 nM. A number of other serotonergic and adrenergic agents interacted with affinities in the 1-50 microM range. Most of the other compounds tested in this study were found to compete for opioid binding to some degree, though not achieving a 50% inhibition of binding at concentrations up to 100 microM. If this interaction between monoaminergic agents and opioid receptors is found to have functional significance, it must be considered in the interpretation of results from studies using these agents to evaluate the contribution of monoaminergic systems to opioid-mediated events.


Evaluation of the self-sampling for cervical cancer screening in Bolivia.
Incidence and mortality rates of cervical cancer in Bolivia are the highest in Latin America. Vaginal cell self-sampling can improve screening coverage. Information on common reasons for low screening coverage and preferences for future screening are essential to reduce cervical cancer incidence. We aimed to evaluate the knowledge about human papillomavirus (HPV) and cervical cancer of Bolivian women from urban, peri-urban and rural areas of Cochabamba and to determine their degree of acceptability and confidence towards vaginal HPV self-sampling. In addition, we assessed the impact of self-sampling on cervical cancer screening coverage in a selected peri-urban area. We gathered information from women living in urban, peri-urban and rural areas of Cochabamba province in Bolivia using two different structured questionnaires. In Survey1, we collected information from 222 women about their knowledge on HPV and cervical cancer. In Survey 2, the acceptance and confidence towards vaginal HPV self-sampling compared to the physician-sampling was assessed in 221 women. A non-probabilistic stratified sampling by areas was carried out for the two questionnaires. In the third phase of the study, we determined the impact of HPV self-sampling collection on screening coverage in a peri-urban area of Cochabamba. Bolivian women knew little or nothing about cervical cancer and HPV infection in all areas. They all found self-sampling collection easier to perform (86.9 to 93.2%) and more comfortable (79.4 to 83.3%) compared to physician sampling. Sampling accuracy to detect cervical cancer was probably higher in their point of view when it was taken by physician (35.1 to 63.5%). However in rural areas women preferred self-sampling. Accordingly, the campaign of vaginal HPV self-sampling in this peri-urban area increased screening coverage, reaching in three months the annual rate average. The knowledge about cervical cancer and HPV infection is poor in Bolivia. Despite greater acceptance of the vaginal HPV self-sampling in all areas, women kept greater confidence in the screening performed by the gynecologist although HPV self-sampling improved coverage rate.


Clinical observations on enzyme replacement therapy in patients with Fabry disease and the switch from agalsidase beta to agalsidase alfa.
Fabry disease is an X-linked inherited lysosomal storage disease that can be treated with the enzymes of agalsidase beta (Fabrazyme) and agalsidase alfa (Replagal). Since June 2009, viral contamination of Genzyme's production facility has resulted in a worldwide shortage of agalsidase beta, leading to the switch to agalsidase alfa for patients with Fabry disease in Taiwan. The medical records were retrospectively reviewed for nine male patients with Fabry disease from the start of agalsidase beta treatment until the switch to agalsidase alfa for at least 1 year. After 12-112 months of enzyme replacement therapy (ERT), decreased plasma globotriaosylsphingosine (lyso-Gb3) was found in five out of seven patients, indicating improvement in disease severity. Among the six patients with available echocardiographic data at baseline and after ERT, all six experienced reductions of left ventricular mass index. Renal function, including microalbuminuria and estimated glomerular filtration rate, showed stability after ERT. Mainz Severity Score Index scores revealed that all nine patients remained stable at 12 months after switching to agalsidase alfa. ERT improved or stabilized cardiac status and stabilized renal function, while reducing plasma lyso-Gb3. ERT was well tolerated, even among the three patients who had hypersensitivity reactions. The switch of ERT from agalsidase beta to agalsidase alfa appears to be safe after 1 year of follow-up for Taiwanese patients with Fabry disease.


Anterior prefrontal cortex and the recollection of contextual information.
Recollective memory can involve the retrieval of many different kinds of contextual information, including where and when an event took place, as well as our thoughts and feelings at the time. The brain regions associated with this ability were examined in an event-related fMRI experiment, where participants made decisions about words or famous faces which were presented either on the left or right of a monitor screen. Subsequently, the studied words and faces were again presented and participants underwent fMRI brain scanning while recollecting either which of the decisions they had made on each item ("task memory"), or whether it had been presented on the left or right of the screen ("position memory"). A functional dissociation was observed within anterior prefrontal cortex (principally Brodmann's area 10), with activation in lateral regions associated with remembering either type of information (relative to baseline), and a medial anterior PFC region showing significantly greater activation during the "task memory" conditions. These results suggest different roles for lateral and medial anterior prefrontal cortex in recollection.


The Role of Endostatin in Rheumatoid Arthritis.
Endostatin by its therapeutic value against rheumatoid arthritis has recently gained significant interest in biomedical science. A recent study revealed that various approaches have been made to prevent rheumatoid arthritis by either controlling or inhibiting the progression of angiogenesis. The main objective of the current manuscript is to enumerate the intrinsic role of endostatin in rheumatoid arthritis. A thorough and detailed review of literature from the papers published from the year 1997-2019 was studied for the preparation of the current article. Endostatin is one such agent of the subfamily of ECM called as multiplexins obtained from proteolytic cleavage of XVIII and its carboxylic terminal fragments and is known for its antiangiogenic and antiproliferative property. The exact mechanism of endostatin is still unclear, but it acts by downregulating or inhibiting the responses of various factors, including Id1, Id3, matrix metalloproteinase, and Nuclear factor Kappa B that are liable for angiogenesis. The mutual effects on adipogenesis and angiogenesis, endostatin inhibits dietary-induced obesity and its related metabolic disorders, such as insulin resistance, glucose intolerance, and hepatic steatosis. The present review demonstrates the intrinsic usage of endostatin as a novel molecule in rheumatoid arthritis. It focuses on the status of the therapeutic potential of endostatin in inhibiting the activity of angiogenesis is also very well explored.


Deep screening of proximal and distal splicing-regulatory elements in a native sequence context.
Pre-mRNA splicing, a key process in gene expression, can be therapeutically modulated using various drug modalities, including antisense oligonucleotides (ASOs). However, determining promising targets is impeded by the challenge of systematically mapping splicing-regulatory elements (SREs) in their native sequence context. Here, we use the catalytically dead CRISPR-RfxCas13d RNA-targeting system (dCas13d/gRNA) as a programmable platform to bind SREs and modulate splicing by competing against endogenous splicing factors. SpliceRUSH, a high-throughput screening method, was developed to map SREs in any gene of interest using a lentivirus gRNA library that tiles the genetic region, including distal intronic sequences. When applied to SMN2, a therapeutic target for spinal muscular atrophy, SpliceRUSH robustly identified not only known SREs, but also a novel distal intronic splicing enhancer, which can be targeted to alter exon 7 splicing using either dCas13d/gRNA or ASOs. This technology enables a deeper understanding of splicing regulation with applications for RNA-based drug discovery.


Rice bran protein hydrolysates prevented interleukin-6- and high glucose-induced insulin resistance in HepG2 cells.
Rice bran, which is a byproduct of rice milling process, contains various nutrients and biologically active compounds. Rice bran protein hydrolysates have various pharmacological activities such as antidiabetic and antidyslipidemic effects. However, there are limited studies about the mechanisms of rice bran protein hydrolysates (RBP) on insulin resistance and lipid metabolism. RBP used in this study were prepared from Thai Jasmine rice. When HepG2 cells were treated with IL-6, the IRS-1 expression and Akt phosphorylation were suppressed. This effect of IL-6 was prevented by RBP in association with inhibition of STAT3 phosphorylation and SOCS3 expression. RBP could increase the phospho-AMPK levels and inhibit IL-6- or high glucose-induced suppression of AMPK and Akt activation. High glucose-induced dysregulation of the expression of lipogenic genes, including SREBP-1c, FASN and CPT-1, was normalized by RBP treatment. Moreover, impaired glucose utilization in insulin resistant HepG2 cells was significantly alleviated by concurrent treatment with RBP. Our results suggested that RBP suppresses inflammatory cytokine signaling and activates AMPK, and thereby these effects may underlie the insulin sensitizing effect.


The effects of acupuncture on operative pain and the hormonal responses to stress.
Variations in study results presented in this chapter may be attributed to a number of factors, including the population studied and type of hormonal assay used. Some researchers selected experimental groups from a population different from that used for the control group. It is unclear from the animal studies using nonacupunctured controls whether the controls received physical contacts with the experimenters comparable to those experienced by the experimental animals. The choice of acupuncture points used may also contribute to the inconsistency between experiments, since according to traditional acupuncture theory, points are not equivalent in their mediation of systemic effects. Duration of the acupuncture treatment, frequency of sampling, and time from treatment to last sample were not standardized. There is little consistency between studies even after adjustment for sampling time. Most of the statistically significant changes have been seen with electroacupuncture, and they appear to occur soon after onset of treatment, then disappear within 30 minutes of needle removal. However, the subjective changes in pain threshold have lasted several hours following needle removal. As an analgesic technique or adjuvant, acupuncture has been used most successfully in dental procedures and relatively superficial operations such as thyroidectomy; however, it has also been employed in more complex operations. The blood pressure and heart rate stability that have been observed with acupuncture analgesia have not been sufficiently explained and warrant further investigation, as does the possibility that acupuncture may be helpful in shock states characterized by increased stress hormone concentrations.


[Chemoradiotherapy with S-1 for Recurrence Cases of Colorectal Cancer].
Although chemotherapy is the main treatment for recurrent colorectal cancer, the utility of radiotherapy as a local treatment has been widely reported. We performed chemoradiotherapy with S-1 for cases with recurrence after surgery, and the outcomes are reported herein. Chemoradiotherapy with S-1 was performed in 4 cases. S-1 was administered for 2 weeks during the irradiation period, and the off period provided was 1 week. X-ray irradiation was performed in 2 cases and proton beam irradiation in the other 2. The progression free periods of the 2 cases receiving proton beam irradiation were 31 months and 36 months. In contrast, the progression free periods of the 2 cases given X-ray irradiation were 24 months and 21 months. It is known that S-1 not only achieves a high anticancer effect via dihydropyrimidine dehydrogenase(DPD)inhibition, which is a major metabolic pathway of 5-FU, but also increases the radiation susceptibility of malignancies. S-1 is regarded as an ideal anticancer agent when used in combination with radiation therapy. Since the local control achieved in our 4 cases was good, chemoradiotherapy with S-1 was considered to be a useful treatment.


Apert syndrome: temporal lobe abnormalities on fetal brain imaging.
Apert syndrome is characterized by craniosynostosis and complex hand and foot syndactyly, and an increased risk of brain, palate, heart, and visceral malformations, and intellectual disability. This study aims to describe the structural brain abnormalities detected by dedicated neuroimaging of fetuses with Apert syndrome. Retrospective review of ultrasound and magnetic resonance imaging brain imaging obtained in six fetuses with a diagnosis of Apert syndrome. Five fetuses had attenuation of the septal leaflets, and two had corpus callosum dysgenesis. All six had temporal lobe expansion and overconvolution and temporal lobe clefts. The temporal lobe abnormalities preceded the development of cranial deformity in two fetuses. Overexpansion and overconvolution of the temporal lobe is evident antenatally and is particularly conspicuous in the fetus when the normal brain is still relatively smooth (approximately 24 to 28 weeks of gestation).


Draft Genome Sequence of the Organophosphorus Compound-Degrading Burkholderia zhejiangensis Strain CEIB S4-3.
Burkholderia species are widely distributed in the environment. A Burkholderia zhejiangensis strain was isolated from pesticide-contaminated soil from an agricultural field in Mexico and identified as an organophosphorus compound-degrading bacterium. In this study, we report the draft genome sequence of Burkholderia zhejiangensis strain CEIB S4-3.


Impact of Family History of Diabetes on Diabetes Control and Complications.
Our aim was to assess the impact of parental and sibling history of type 2 diabetes (T2D) on patient characteristics, glycemic control, and T2D complications. This cross-sectional study included adults with T2D. Type 1 diabetes and gestational diabetes patients were excluded. The laboratory data were retrieved from the patients' electronic files, and baseline measurements were obtained by the researchers. The study included a total of 511 T2D patients, with a mean age of 60.1 ± 10.9 years and mean hemoglobin A1c of 8.94 ± 2.1% (74.2 ± 22.9 mmol/mol). Of these patients, 54% were male and 49.7% had a parental history of T2D. The patients with parental history of T2D were diagnosed at a younger age and had a higher body mass index (BMI) ( P = .035) and higher waist circumference (WC) ( P = .013) than those T2D patients with no parental history. Approximately 60% of the participants had siblings with a history of T2D, and in comparison with those with no sibling history, they had higher prevalence of cerebrovascular accidents ( P = .02). Having a parental history of T2D is significantly associated with diagnosis at a younger age and a higher BMI and WC. Having a sibling history of T2D is significantly associated with worse cerebrovascular outcome. ACR = albumin to creatinine ratio; BMI = body mass index; DBP = diastolic blood pressure; DM = diabetes mellitus; FBG = fasting blood glucose; GFR = glomerular filtration rate; HbA1c = hemoglobin A1c; LDL = low-density lipoprotein; SBP = systolic blood pressure; T2D = type 2 diabetes; TG = triglyceride; WC = waist circumference.


Quantitative analysis of seminiferous epithelium in subfertile carriers of chromosomal translocations.
In order to study the effect of structural chromosomal aberrations on spermatogenesis, quantitative analysis of the germinal epithelium was performed on testicular specimens from 12 carriers of balanced chromosomal translocations diagnosed at male infertility clinics: a Y-autosome translocation, eight reciprocal translocations, and three D/D Robertsonian translocations. Spermatogenic arrest at the spermatocyte stage was revealed in the Y-autosome translocation and four of the reciprocal translocations. The number of spermatids was selectively reduced in three carriers, while normal spermatogenesis was found in three. Thus, the majority of carriers with impaired semen quality showed a complete or partial reduction in the number of spermatids, suggesting that the effect of chromosomal aberrations is to arrest the spermatogenic process at the spermatocyte stage.


Scaling and universality of inherent structure simulations.
In this paper we explore the inherent structures (IS) approach to the dynamics of the East constrained kinetic Ising model. The inherent structures do not capture the nature of the dynamics of many quantities, including the spin autocorrelation function. Simply monitoring the quenched energy fluctuations, i.e., IS energy, results in an oversimplified single order-parameter description of the system's dynamics, but examining other features, such as domain dynamics or normal modes, may give a more complete and useful picture of the dynamics. The universality in the behavior of the IS energy of this model does not reveal nonuniversal features of the kinetics that determine long-time relaxation of the system. As a result, popular functional forms, such as the stretched exponential relaxation or Gaussian distribution of energies, may be a numerical fit to data with little physical justification. Filtering data can be shown to erase features of the system and the resulting quantities resemble more universal functional forms that lack physical insight. These results for the East model have implications for IS simulations of realistic systems and suggest careful analysis including the examination of other potential order parameters is necessary to evaluate the validity of applications of universal and scaling arguments to IS simulations.


The impact of genetic modification of human foods in the 21st century: a review.
Genetic engineering of food is the science which involves deliberate modification of the genetic material of plants or animals. It is an old agricultural practice carried on by farmers since early historical times, but recently it has been improved by technology. Many foods consumed today are either genetically modified (GM) whole foods, or contain ingredients derived from gene modification technology. Billions of dollars in U.S. food exports are realized from sales of GM seeds and crops. Despite the potential benefits of genetic engineering of foods, the technology is surrounded by controversy. Critics of GM technology include consumer and health groups, grain importers from European Union (EU) countries, organic farmers, environmentalists, concerned scientists, ethicists, religious rights groups, food advocacy groups, some politicians and trade protectionists. Some of the specific fears expressed by opponents of GM technology include alteration in nutritional quality of foods, potential toxicity, possible antibiotic resistance from GM crops, potential allergenicity and carcinogenicity from consuming GM foods. In addition, some more general concerns include environmental pollution, unintentional gene transfer to wild plants, possible creation of new viruses and toxins, limited access to seeds due to patenting of GM food plants, threat to crop genetic diversity, religious, cultural and ethical concerns, as well as fear of the unknown. Supporters of GM technology include private industries, research scientists, some consumers, U.S. farmers and regulatory agencies. Benefits presented by proponents of GM technology include improvement in fruit and vegetable shelf-life and organoleptic quality, improved nutritional quality and health benefits in foods, improved protein and carbohydrate content of foods, improved fat quality, improved quality and quantity of meat, milk and livestock. Other potential benefits are: the use of GM livestock to grow organs for transplant into humans, increased crop yield, improvement in agriculture through breeding insect, pest, disease, and weather resistant crops and herbicide tolerant crops, use of GM plants as bio-factories to yield raw materials for industrial uses, use of GM organisms in drug manufacture, in recycling and/or removal of toxic industrial wastes. The potential risks and benefits of the new technology to man and the environment are reviewed. Ways of minimizing potential risks and maximizing the benefits of GM foods are suggested. Because the benefits of GM foods apparently far outweigh the risks, regulatory agencies and industries involved in GM food business should increase public awareness in this technology to enhance worldwide acceptability of GM foods. This can be achieved through openness, education, and research.


Protective impacts of Withania somnifera leaf extract from Taif area against diclofenac induced hepato-renal toxicity: role of antioxidants, inflammation, apoptosis, and anti-oxidative stress biomarkers.
Current study examined the boosting impacts of Withania somnifera leaf extract from Taif area (high-altitude area) against hepatic and renal toxicity induced by diclofenac in experimental rats. Withania is highly grown on Taif area as environmental herb with multiple functions. Diclofenac is non-steroidal medication used for treatment of pain but over dose has severe side effects. Thirty-two adult Wistar rats of male type were subdivided into 4 groups. The control rats (group 1) received saline. Second group received diclofenac (50 mg/kg BW intraperitoneally) at days 4 and 5. Third group received W. somnifera leaf extract (250 mg /kg body weight) for 6 days. The fourth protective group, received W. somnifera leaf extract plus diclofenac for 6 days as shown in groups 2 and 3. Diclofenac significantly increased serum AST, ALT, and decreased albumin and total proteins levels. It also increased serum concentrations of uric acid and creatinine. In addition, it increased lipid peroxidation, and decreased reduced glutathione and superoxide dismutase levels. Diclofenac increased inflammatory cytokines secretion and up-regulated hepatic oxidative stress genes (HO-1; hemoxygenase-1 and Nrf2nuclear factor erythroid 2-related factor 2 (Nrf2) and renal inflammatory transcriptional markers (TGF-β1; transforming growth factor-beta1 and COX-2; cycloxygenas-2). In parallel, hepatic caspase-3 expression was up-regulated as an apoptotic marker, while Bcl2; (B-cell lymphoma 2) mRNA expression was down regulated as anti-apoptotic marker. W. somnifera pre-administration in the protective group ameliorated the altered parameters induced by diclofenac. In conclusion, W. somnifera leaf extract has the potential to antagonize side effects of diclofenac by regulating the pathways of oxidative stress, inflammation, and apoptosis/antiapoptosis.


Genome Sequences of Three Colombian Helicobacter pylori Strains Isolated from Tolimense Patients.
We present the complete genome sequences of three Helicobacter pylori strains isolated from patients who resided in Tolima Department, Colombia, diagnosed with chronic gastritis. The genomes present an average length of 1.6 Mbp and 1,546 genes and correspond to different H. pylori subpopulations.


Sfh1p, a component of a novel chromatin-remodeling complex, is required for cell cycle progression.
Several eukaryotic multiprotein complexes, including the Saccharomyces cerevisiae Snf/Swi complex, remodel chromatin for transcription. In contrast to the Snf/Swi proteins, Sfh1p, a new Snf5p paralog, is essential for viability. The evolutionarily conserved domain of Sfh1p is sufficient for normal function, and Sfh1p interacts functionally and physically with an essential Snf2p paralog in a novel nucleosome-restructuring complex called RSC (for remodels the structure of chromatin). A temperature-sensitive sfh1 allele arrests cells in the G2/M phase of the cell cycle, and the Sfh1 protein is specifically phosphorylated in the G1 phase. Together, these results demonstrate a link between chromatin remodeling and progression through the cell division cycle, providing genetic clues to possible targets for RSC function.


Silencing of Two Vitellogenin Genes Inhibits Oviposition in the Chagas Disease Vector Triatoma infestans (Hemiptera: Reduviidae).
RNA interference caused by exogenous double-stranded RNA (dsRNA) is used to downregulate crucial genes to control insects. The reproductive success of all oviparous species depends on vitellogenin (Vg) biosynthesis and its accumulation in the developing oocytes. Adult females of Triatoma infestans were independently injected with two Vg dsRNAs (Vg1 dsRNA or Vg2 dsRNA) or nuclease-free water (control) 24 hours before feeding, and a group of adult females not injected was also analyzed (control). Vg1 and Vg2 messenger RNAs silencing was verified by reverse transcription quantitative polymerase chain reaction. The transcript levels of the Vg1 and Vg2 genes were significantly reduced after dsRNA treatment in fat body and ovary of T. infestans in relation to those detected in individuals injected with nuclease-free water and not injected (controls). Moreover, the present study demonstrated that the silencing of the Vg1 or Vg2 genes inhibits oviposition in the Chagas disease vector T. infestans. These findings may have important implications for the development of novel vector control strategies.


Human subcutaneous dirofilariasis. 1. Two new cases in Venice. Identification of the causal agent as Dirofilaria repens Raillet and Henry, 1911.
Two human cases of subcutaneous dirofilariasis are described in a 41 year-old woman and in a 14 year-old boy living in Venice Lido. In the first case, the development of a nodule at the left forearm had been preceded by generalized symptoms such as pruriginous urticarioid patches in various regions of the body, transitory swellings and 8% eosinophilia. From the nodule, an adult female of Dirofilaria repens was recovered with embryos visible in the uterus. In the second case, the parasite was localized in the scrotum, where it had caused an extensive oedema with the formation of a nodule having the size of a nut. An immature female specimen of D. repens was found. In both cases, the serological tests (Indirect Haemoagglutination and Bentonite Flocculation) gave significant titres specific for filariasis (1:256 and 1:20 in the first case, 1:128 and 1:5 in the second, respectively). A parasitological survey of blood samples from 145 stray dogs captured in the territory of the Venice municipality revealed the presence of D. repens in 8.3% of cases, D. immitis in 4.8% and Dipetalonema reconditum in 0.7%. This is the first time that the aetiological agent of human subcutaneous dirofilariasis was identified as D. repens in Italy.


Fiber liquid-pressure sensor with high sensitivity and a wide measurement range using photopolymer.
This paper presents a novel fiber liquid-pressure sensor that uses photopolymer glue to generate Fabry-Perot (F-P) interference, resulting in high sensitivity and a wide measurement range. The sensor comprises a single-mode fiber and photopolymer glue; the latter adheres to the fiber's end face and is decomposed by a 405-nm laser to create an air channel with a diameter of 5.9 µm and a length of 50 µm. When the air channel is placed underwater, a 17.5-µm air cavity forms between the fiber core and the air-liquid boundary due to the pressure balance, creating an F-P interferometer. Based on experimental results, the sensor has an average pressure sensitivity of 5.68 nm/kPa over 0.49-2.94 kPa. The sensitivity can be maintained at this level across different pressure measurement ranges (up to about 500 kPa) by using a 980-nm laser's radiation pressure to reset the air-liquid boundary. Besides its high sensitivity and wide measurement range, the sensor's straightforward structure, durability, affordability, compactness, and simple construction make it an appealing choice for liquid pressure measurement applications in various fields.


Monocyte and neutrophil activity after minor surgical stress.
Surgical stress produces changes in the immune status of patients. In adults, major surgery causes immunosuppression, whereas minor operations stimulate immune responses. In children, the immunologic response to surgery has not been elucidated completely. The authors investigated the effects of minor surgery on immune response by analyzing neutrophil and monocyte phagocytosis and oxidative burst activity. Sixteen children undergoing elective minor surgery were enrolled. Blood samples were collected before the operation (at time of induction of anesthesia), at the end of operation, and 72 hours after surgery. Neutrophil and monocyte phagocytosis and oxidative burst activity were studied using a flow cytometric method. Phagocytosis and oxidative burst increased significantly at the end of the operation, both in neutrophils (7.4% and 14.3%, respectively) and monocytes (11.6% and 27%, respectively). The increase was only significant for monocytes (17.5%) 72 hours after surgery. White cell count did not show any significant changes. There was no significant correlation between phagocytosis, oxidative burst activity, and white cell count or neutrophil and monocyte count. This study shows that minor surgery in children induces immune activation by increasing neutrophil and monocyte phagocytosis and oxidative burst activity. Further studies are required to understand the molecular basis of these findings.


Characterization of an interaction between insulin receptor substrate 1 and the insulin receptor by using the two-hybrid system.
Insulin receptor substrate 1 (IRS-1) is a major substrate of the insulin receptor and has been implicated in insulin signaling. Although IRS-1 is thought to interact with the insulin receptor, the nature of the interaction has not been defined. In this study, we used the two-hybrid assay of protein-protein interaction in the yeast Saccharomyces cerevisiae to study the interaction between human IRS-1 and the insulin receptor. We demonstrate that IRS-1 forms a specific complex with the cytoplasmic domain of the insulin receptor when both are expressed as hybrid proteins in yeast cells. We show that the interaction is strictly dependent upon receptor tyrosine kinase activity, since IRS-1 shows no interaction with a kinase-inactive receptor hybrid containing a mutated ATP-binding site. Furthermore, mutation of receptor tyrosine 960 to phenylalanine eliminates IRS-1 interaction in the two-hybrid assay. These data suggest that the interaction between IRS-1 and the receptor is direct and provide evidence that the juxtamembrane domain of the receptor is involved. Furthermore, we show that a 356-amino-acid region encompassed by amino acids 160 through 516 of IRS-1 is sufficient for interaction with the receptor in the two-hybrid assay. Lastly, in agreement with our findings for yeast cells, we show that the insulin receptor is unable to phosphorylate an IRS-1 protein containing a deletion of amino acids 45 to 516 when expressed in COS cells. The two-hybrid assay should provide a facile means by which to pursue a detailed understanding of this interaction.


Predictive model for high-frequency microsatellite instability in colorectal cancer patients over 50 years of age.
Microsatellite instability (MSI) is an important biomarker for screening for Lynch syndrome, and also of response to immune checkpoint inhibitors. The aim of this study is to create a predictive model to determine which elderly patients with colorectal cancer (CRC) should undergo MSI and/or immunohistochemistry testing on the basis of clinicopathological data. We analyzed a test cohort of CRC patients aged ≥50 years (n = 2219) by multivariate logistic regression analyses to identify predictors of high-frequency MSI (MSI-H). The created prediction model was validated in an external cohort (n = 992). The frequency of MSI-H was 5.5% among CRC patients aged ≥ 50 years. The following five predictors of MSI-H were identified in the test cohort: female (1 point), mucinous component (2 points), tumor size ≥ 60 mm (2 points), location in proximal colon (3 points), and BRAF mutation (6 points). The area under curve (AUC) in the receiver-operating characteristic (ROC) analysis of this prediction model was 0.832 (95% confidence interval: 0.790-0.874). The sensitivity and specificity were 74.4% and 77.7%, respectively, for a cut-off score of 4 points. The receiver-operating characteristic curve of the validation cohort also showed an AUC of 0.856 (95% CI: 0.806-0.905). This prediction model is useful to select elderly CRC patients who should undergo MSI testing, and who may benefit from treatment with 5-FU-based adjuvant chemotherapy and cancer immunotherapy.


Topoisomerase expression in oral squamous cell carcinoma: relationship with cancer stem cells profiles and lymph node metastasis.
The relationship between predictive proteins and tumors presenting cancer stem cells (CSCs) profiles in oral tumors is still poorly understood. This study aims to identify the relationship between topoisomerases I, IIα, and IIIα and putative CSCs immunophenotype in oral squamous cell carcinoma (OSCC) and determine its influence on prognosis. The following data were retrieved from 127 patients: age, gender, primary anatomic site, smoking and alcohol intake, recurrence, metastases, histologic classification, treatment, and survival. An immunohistochemical study for topoisomerases I, IIα, and IIIα was performed in a tissue microarray containing 127 paraffin blocks of OSCCs. In univariate analysis, topoisomerases expression showed significant differences according to CSCs profiles and p53 immunoexpression, but not with survival. Topoisomerases IIα and IIIα also showed significant relationship with lymph node metastasis. The multivariate test confirmed these associations. The results that all topoisomerases correlates with OSCC CSCs may indicate a role for topoisomerases in head and neck carcinogenesis. Notwithstanding, it is plausible that other members of topoisomerases family could represent novel therapeutical targets in oral squamous cell carcinoma.


Evaluation of Novel Routes for NOx Formation in Remote Regions.
Photochemical cycling of nitrogen oxides (NOx) produces tropospheric ozone (O3), and NOx is traditionally considered to be directly emitted. The inability of current global models to accurately calculate NOx levels, and concurrently, difficulties in performing direct NOx measurements in low-NOx regimes (several pptv or several tens of pptv) globally introduce a large uncertainty in the modeling of O3 formation. Here, we use the near-explicit Master Chemical Mechanism (MCM v3.2) within a 0D box-model framework, to describe the chemistry of NOx and O3 in the remote marine boundary layer at Cape Verde. We explore the impact of a recently discovered NOx recycling route, namely photolysis of particulate nitrate, on the modeling of NOx abundance and O3 formation. The model is constrained to observations of long-lived species, meteorological parameters, and photolysis frequencies. Only a model with this novel NOx recycling route reproduces levels of gaseous nitrous acid, NO, and NO2 within the model and measurement uncertainty. O3 formation from NO oxidation is several times more efficient than previously considered. This study highlights the need for the inclusion of particulate nitrate photolysis in future models for O3 and for the photolysis rate of particulate nitrate to be quantified under variable atmospheric conditions.


Theoretical Antecedents of Standing at Work: An Experience Sampling Approach Using the Theory of Planned Behavior.
Time spent sitting has been associated with an increased risk of diabetes, cancer, obesity, and mental health impairments. However, 75% of Americans spend most of their days sitting, with work-sitting accounting for 63% of total daily sitting time. Little research examining theory-based antecedents of standing or sitting has been conducted. This lack of solid groundwork makes it difficult to design effective intervention strategies to decrease sitting behaviors. Using the Theory of Planned Behavior (TPB) as our theoretical lens to better understand factors related with beneficial standing behaviors already being practiced, we examined relationships between TPB constructs and time spent standing at work among "positive deviants" (those successful in behavior change). Experience sampling methodology (ESM), 4 times a day (midmorning, before lunch, afternoon, and before leaving work) for 5 consecutive workdays (Monday to Friday), was used to assess employees' standing time. TPB scales assessing attitude (α = 0.81-0.84), norms (α = 0.83), perceived behavioral control (α = 0.77), and intention (α = 0.78) were developed using recommended methods and collected once on the Friday before the ESM surveys started. ESM data are hierarchically nested, therefore we tested our hypotheses using multilevel structural equation modeling with Mplus. Hourly full-time university employees (n = 50; 70.6% female, 84.3% white, mean age = 44 (SD = 11), 88.2% in full-time staff positions) with sedentary occupation types (time at desk while working ≥6 hours/day) participated. A total of 871 daily surveys were completed. Only perceived behavioral control (β = 0.45, p < 0.05) was related with work-standing at the event-level (model fit: just fit); mediation through intention was not supported. This is the first study to examine theoretical antecedents of real-time work-standing in a naturalistic field setting among positive deviants. These relationships should be further examined, and behavioral intervention strategies should be guided by information obtained through this positive deviance approach to enhance perceived behavioral control, in addition to implementing environmental changes like installing standing desks.


Bacterial communities in the rhizosphere of Vitis vinifera L. cultivated under distinct agricultural practices in Argentina.
Plants interact with a myriad of microbial cells in the rhizosphere, an environment that is considered to be important for plant development. However, the differential structuring of rhizosphere microbial communities due to plant cultivation under differential agricultural practices remains to be described for most plant species. Here we describe the rhizosphere microbiome of grapevine cultivated under conventional and organic practices, using a combination of cultivation-independent approaches. The quantification of bacterial 16S rRNA and nifH genes, by quantitative PCR (qPCR), revealed similar amounts of these genes in the rhizosphere in both vineyards. PCR-DGGE was used to detect differences in the structure of bacterial communities, including both the complete whole communities and specific fractions, such as Alphaproteobacteria, Betaproteobacteria, Actinobacteria, and those harboring the nitrogen-fixing related gene nifH. When analyzed by a multivariate approach (redundancy analysis), the shifts observed in the bacterial communities were poorly explained by variations in the physical and chemical characteristics of the rhizosphere. These approaches were complemented by high-throughput sequencing (67,830 sequences) based on the V6 region of the 16S rRNA gene, identifying the major bacterial groups present in the rhizosphere of grapevines: Proteobacteria, Actinobacteria, Firmicutes, Bacteriodetes, Acidobacteria, Cloroflexi, Verrucomicrobia and Planctomycetes, which occur in distinct proportions in the rhizosphere from each vineyard. The differences might be related to the selection of plant metabolism upon distinct reservoirs of microbial cells found in each vineyard. The results fill a gap in the knowledge of the rhizosphere of grapevines and also show distinctions in these bacterial communities due to agricultural practices.


AMP deaminase isozymes in human blood cells.
Column chromatographic, electrophoretic and immunological studies showed the distribution of AMP deaminase isozymes in human blood cells as follows: isozyme E1 in erythrocyte, E2 in granulocyte, L in mononuclear cells, platelets and T-lymphoblast, and probably E1-L hybrid sets in B-lymphoblast.


Mathematical modeling to predict residential solid waste generation.
One of the challenges faced by waste management authorities is determining the amount of waste generated by households in order to establish waste management systems, as well as trying to charge rates compatible with the principle applied worldwide, and design a fair payment system for households according to the amount of residential solid waste (RSW) they generate. The goal of this research work was to establish mathematical models that correlate the generation of RSW per capita to the following variables: education, income per household, and number of residents. This work was based on data from a study on generation, quantification and composition of residential waste in a Mexican city in three stages. In order to define prediction models, five variables were identified and included in the model. For each waste sampling stage a different mathematical model was developed, in order to find the model that showed the best linear relation to predict residential solid waste generation. Later on, models to explore the combination of included variables and select those which showed a higher R(2) were established. The tests applied were normality, multicolinearity and heteroskedasticity. Another model, formulated with four variables, was generated and the Durban-Watson test was applied to it. Finally, a general mathematical model is proposed to predict residential waste generation, which accounts for 51% of the total.


Spontaneous rhythm discrimination in a mammalian vocal learner.
Rhythm and vocal production learning are building blocks of human music and speech. Vocal learning has been hypothesized as a prerequisite for rhythmic capacities. Yet, no mammalian vocal learner but humans have shown the capacity to flexibly and spontaneously discriminate rhythmic patterns. Here we tested untrained rhythm discrimination in a mammalian vocal learning species, the harbour seal (Phoca vitulina). Twenty wild-born seals were exposed to music-like playbacks of conspecific call sequences varying in basic rhythmic properties. These properties were called length, sequence regularity, and overall tempo. All three features significantly influenced seals' reaction (number of looks and their duration), demonstrating spontaneous rhythm discrimination in a vocal learning mammal. This finding supports the rhythm-vocal learning hypothesis and showcases pinnipeds as promising models for comparative research on rhythmic phylogenies.


Efficacy of 1% terbinafine cream in comparison with 0.75% metronidazole gel for the treatment of papulopustular rosacea.
Topical antifungals comprising imidazole derivatives have been used for the treatment of rosacea previously, owing to their anti-inflammatory activities. Terbinafine, an antifungal agent belongs to allylamine group, has also anti-inflammatory effects. Currently, there are only a few unpublished studies, in which terbinafine has been used systemically for rosacea treatment. In this single-blind, 8-week study, we investigated the potential efficacy and safety of terbinafine 1% cream for the treatment of mild and moderate papulopustular rosacea, and compared the results with those of 0.75% metronidazole gel. Forty patients, 30 females and 10 males, with papulopustular rosacea were enrolled into the study between 2006 and 2007 years. Twenty of the patients were instructed to apply 1% terbinafine cream, whereas others patients of the study population were instructed to use 0.75% metronidazole gel. A total of 32 patients completed the study. Pre-treatment and post-treatment total severity score (TSS) of the disease were determined by assessing the severity of erythema/telangiectasia, and the number of papules/pustules of the whole face. The overall response rates, differences of pre-/post-treatment scores of each criterium and the percentages of the decrease in TSS of the study groups were compared statistically. There was no statistically significant difference between the groups in terms of age, sex, and disease duration (P = 0.937, 1.000, and 0.055, respectively). No significant difference was found between the mean post-treatment TSSs of the two groups (P = 0.605). The percentage of clearance assessed by the differences between pre-treatment and post-treatment TSSs was 55% in terbinafine group, although the percentage was 45% in metronidazole group, with no statistically significant difference between the groups (P = 0.496). Local side effects including erythema, pruritus, and burning were mild and transient in both groups, with similar frequencies (P = 0.101). This preliminary study suggests that 1% terbinafine cream is an effective and safe treatment for papulopustular rosacea, and can be an option for patients who cannot tolerate other modalities.


Epithelioid sarcoma with diffuse bone marrow metastases and associated leukemoid reaction. A case report and brief literature review.
A patient with a recurrent epithelioid sarcoma of the hand was observed for five years with a diagnosis of nodular fasciitis. Eventually, the patient had a pulmonary metastasis and diffuse bone marrow spread, which was associated with a leukemoid reaction. Bone marrow dissemination by sarcoma is unusual, and its production of a leukemoid reaction very rare; this is its first reported occurrence in epithelioid sarcoma that the authors have been able to identify in the literature.


Candida albicans skin abscesses.
Two neonates who developed Candida albicans skin abscesses are described. One developed disseminated infection. In the newborn abscesses cannot be assumed to be of bacterial origin.


Determination of the microscopic equilibrium dissociation constants for risedronate and its analogues reveals two distinct roles for the nitrogen atom in nitrogen-containing bisphosphonate drugs.
Microscopic equilibrium dissociation constants, k as, were determined for four nitrogen-containing bisphosphonates (N-BP): risedronate and its analogues 2-(2-aminophenyl)-1-hydroxyethylidene-1,1-bisphosphonate, NE 11807, and NE 97220. The proportion of each and of analogues 2-(3'-( N-ethyl)pyridinium)-ethylidenebisphosphonate and 2-(3-piperinidyl)-1-hydroxyethylidene-1,1-bisphosphonate, having a positively charged nitrogen and three negative charges on the bisphosphonate group ("carbocation analogue") at pH 7.5, was calculated. When set in order of increasing potency at inhibiting farnesyl diphosphate (FDP) synthase (their intracellular target), the N-BPs are also ranked in order of decreasing mole fraction of carbocation analogue. However, only a weak correlation exists between potency for inhibiting FDP synthase and potency for inhibiting Dictyostelium discoideum growth. It is concluded that, although high potency for inhibiting FDP synthase is favored when the nitrogen atom in a N-BP is uncharged, N-BPs having a positively charged nitrogen can still be potent inhibitors of Dictyostelium growth owing to favorable interaction with a second, unidentified target.


Does more "appropriateness" explain higher rates of cardiac procedures among patients hospitalized with coronary heart disease?
There have been few studies of the extent to which differences in the pool of patients being managed might account for geographic variations in treatment rates. For two cardiac procedures, cardiac catheterization and revascularization, we evaluate the hypothesis that differences in "the percentage of patients for whom the procedure is appropriate" is a factor explaining variations in use rates among those hospitalized with coronary heart disease (CHD). Based on hospital utilization patterns in Massachusetts in 1990, we created 70 small geographic areas. Using 1992 Massachusetts Peer Review Organization data, areas were ranked from highest to lowest based on (empirical-Bayes-adjusted) hospitalization rates for each procedure. One thousand seven hundred four cases from 43 hospitals were sampled, roughly half each from high and low use areas. Half had a procedure and half were candidates for the same procedure but did not have it. For each procedure, medical records were reviewed to determine whether the procedure was (or, for those not having it, would have been) appropriate, based on criteria developed using a modified Delphi approach. Among those having either procedure, appropriateness rates were similar in high and low rate areas (P = 0.59 for catheterization and P = 0.30 for revascularization). However, among candidates for either procedure who did not have it, appropriateness for performing the procedure was greater in high-rate areas (41.4% vs. 32.1%, P = 0.05 for catheterization; 71.2% vs. 57.2%, P = 0.003, for revascularization). Among those hospitalized with CHD, appropriateness rates for two cardiac procedures are higher in areas with higher use rates.


Estimation of cardiodepressant potency of nadolol, alprenolol, propranolol and pindolol, beta-blocking agents, in heart-lung preparation and blood-perfused excised papillary muscle preparation of the dog.
Direct cardiodepressant potency of nadolol was determined by comparing its effect with those of alprenolol, propranolol and pindolol, in both heart-lung preparation and blood-perfused papillary muscle preparation of the dog. In the heart-lung preparation, mean 50% beta-blocking doses of the beta-blockers to inhibit the positive chronotropic action of isoproterenol were 3.75 micrograms for nadolol, 12.5 micrograms for alprenolol, 9.6 micrograms for propranolol and 1.6 micrograms for pindolol. Alprenolol and propranolol in a dose of 10 mg shifted the cardiac function curves rightward and downward, while nadolol and pindolol in the dose of 10 mg did not shift the cardiac function curves. In the blood-perfused papillary muscle preparation, mean 50% beta-blocking doses of the beta-blockers, administered i.v. to the donor dog, to inhibit the positive inotropic action of isoproterenol were 9.1 micrograms/kg for nadolol, 56.6 micrograms/kg for alprenolol, 68.3 micrograms/kg for propranolol and 8.1 micrograms/kg for pindolol. Nadolol did not depress the contractile force in doses up to 1 mg/kg given i.v. or doses up to 10 mg given intra-arterially (i.a.) close to the preparation. Alprenolol and propranolol exerted the dose-related negative inotropic effects, when larger doses (30-300 micrograms) were injected i.a. Thus, it is confirmed that nadolol virtually possesses no direct cardiodepressant activity and also that the depressant activity is exerted only by large doses of the other beta-blockers.


Emancipatory practices of nurses in primary health care: the home visit as an instrument of health needs assessment.
Objective Identify nurses' emancipatory practices in primary care, to contribute to the improvement of health care. Method A case study type social research of qualitative nature, in which nurses of a primary health care service unit in São Paulo were interviewed. Results The home visit was identified as a nursing practice possible to be expanded in order to identify social determinants of health, triggering emancipatory practices in the service. This expansion occurred because the design of health care labour intended by the service team changed its focus from the traditional object of health services, the disease. Conclusion First, it is advocated that social policies lead projects with the purpose of improving health needs. On the other hand, the daily labour needs to provide opportunities for reflection and discussion of healthcare projects, leading workers to propose labour-processes targeted to both the social determinants of health and people's illness.


Honeycomb-ring hybrid random mesh design with electromagnetic interference (EMI) shielding for low stray light.
A honeycomb-ring hybrid random mesh structure is designed to achieve low stray light performance. The honeycomb-ring hybrid random mesh comprises the random honeycomb and random ring, achieving two random superpositions in the structure distribution. The stray light distribution is very low by the combination design with different random hybrid structures. In order to illustrate the advantages of the hybrid random structure, we design a random honeycomb network by randomly offsetting vertices. At the same time, for the random honeycomb structure, we replace each vertex with the ring structure with the size of the ring randomly controlled. Thus, the corresponding honeycomb-ring hybrid random structure is obtained. Compared with the random honeycomb, the maximal normalized high-order diffraction energy of the honeycomb-ring hybrid random mesh is about a 62.85% drop, and the shielding performance is increased by about 50%. At the same time, the optical transmittance remains nearly unchanged. Due to the enjoyable property of the designed honeycomb-ring hybrid random mesh, a sample was prepared for performance verification. The measurement results show that it achieves eminent diffraction pattern distribution with the maximal normalized high-order diffraction energy of about -31.8 dB. At the same time, the average optical transmittance exceeds 86%, and the electromagnetic shielding effectiveness (SE) in the Ku band is greater than 26 dB. Based on the fine photoelectric performance of the honeycomb-ring hybrid random mesh structure, it has great application potential for high-quality optical windows.


Do organisms living around hydrothermal vent sites contain specific metallothioneins? The case of the genus Bathymodiolus (Bivalvia, Mytilidae).
The unusual characteristics of the hydrothermal vent environment (high pressure and metal concentrations, low pH, etc.) leads us to wonder how species living in this particular biotope have adjusted to these severe living conditions. To investigate the consequences of high metal concentrations, filter-feeding organisms are commonly used in ecotoxicological studies. Metallothioneins (MTs) are proteins conserved throughout the animal kingdom and involved in intracellular metal regulation. Therefore, we tried here to find out whether the metallothioneins of hydrothermal bivalves are different from those of coastal bivalves. The characterization of DNA sequences coding MTs from some of the most common hydrothermal bivalves, belonging to the genus Bathymodiolus (Mytilidae) was performed by reverse transcription polymerase chain reactions (RT-PCRs). The complementary DNAs (cDNAs) of MT-10 and MT-20 isoforms were obtained for the Atlantic and Pacific hydrothermal mussels (Bathymodiolus azoricus and Bathymodiolus thermophilus). The MT-10 transcripts were 222 nucleotides long and the MT-20 transcripts, 207 nucleotides. The polymorphism of the MT cDNAs in these two hydrothermal species is discussed. The comparison between metallothionein cDNA sequences of the Mytilus and the Bathymodiolus genera shows strong homologies among metallothioneins of coastal and hydrothermal mussels.


An assessment of orthotopic liver transplantation in acute liver failure.
Mortality of fulminant hepatic failure with standard supportive therapy is high (80 to 85%), but unfortunately most patients present to hospital already in Grade IV encephalopathy with severe liver dysfunction, and many have secondary organ damage. If seen earlier, during Grade III encephalopathy, recent experience with charcoal hemoperfusion can give good results (65% survival). Transplantation has a place in those patients who do not respond, and in cases with early Grade IV encephalopathy. Transplantation should also be considered in patients with subacute hepatic failure in whom mortality is equally high and progression to cirrhosis may occur in those who recover. In both groups, the ability to correct the hemorrhagic diathesis and an adequate supply of donor organs are essential to achievement of a successful transplant at this critical time.


catena-Poly[[[diaqua-(2-fluoro-benzoato-κO,O')strontium]-μ(3)-2-fluoro-benzoato-κO:O,O':O',F] monohydrate].
In the title compound, {[Sr(C(7)H(4)FO(2))(2)(H(2)O)(2)]·H(2)O}(n), the Sr(II) atom is coordinated by six O atoms and one F atom from four 2-fluoro-benzoate ligands and two water mol-ecules, resulting in an irregular SrFO(8) coordination environment. The μ(3)-2-fluoro-benzoate ligand bridges three symmetry-related Sr(II) atoms, giving rise to a chain structure extending along [010]. The polymeric chains are connected via O-H⋯O hydrogen bonds into a two-dimensional supra-molecular structure parallel to (100).


Why Quorum Sensing Controls Private Goods.
Cell-cell communication, also termed quorum sensing (QS), is a widespread process that coordinates gene expression in bacterial populations. The generally accepted view is that QS optimizes the cell density-dependent benefit attained from cooperative behaviors, often in the form of secreted products referred to as "public goods." This view is challenged by an increasing number of cell-associated products or "private goods" reported to be under QS-control for which a collective benefit is not apparent. A prominent example is nucleoside hydrolase from Pseudomonas aeruginosa, a periplasmic enzyme that catabolizes adenosine. Several recent studies have shown that private goods can function to stabilize cooperation by co-regulated public goods, seemingly explaining their control by QS. Here we argue that this property is a by-product of selection for other benefits rather than an adaptation. Emphasizing ecophysiological context, we propose alternative explanations for the QS control of private goods. We suggest that the benefit attained from private goods is associated with high cell density, either because a relevant ecological condition correlates with density, or because the private good is, directly or indirectly, involved in cooperative behavior. Our analysis helps guide a systems approach to QS, with implications for antivirulence drug design and synthetic biology.


A new numerical concept for modeling hydroxyapatite in human cortical bone.
This research presents a new modelling procedure which allows the computation of the physical properties of the human cortical bone, considered as a strongly heterogeneous medium consisting of bony architecture and the physical properties of the two basic components: the collagen and the hydroxyapatite (Hap). The numerical simulations are based on the homogenisation theory, however, since the size of the Hap crystals are small compared to the size of a collagen stick, a new entity (the elementary volume of mineral content (EVMC)) is defined at the nanoscopic scale. This model permits the testing of all the possible structural configurations that may be present and suggests that the anisotropy of the bone is not only induced by the haversian structure but by the properties of the Hap crystals and their special organisation.


Artificial intelligence-driven shimming for parallel high field nuclear magnetic resonance.
Rapid drug development requires a high throughput screening technology. NMR could benefit from parallel detection but is hampered by technical obstacles. Detection sites must be magnetically shimmed to ppb uniformity, which for parallel detection is precluded by commercial shimming technology. Here we show that, by centering a separate shim system over each detector and employing deep learning to cope with overlapping non-orthogonal shimming fields, parallel detectors can be rapidly calibrated. Our implementation also reports the smallest NMR stripline detectors to date, based on an origami technique, facilitating further upscaling in the number of detection sites within the magnet bore.


Human Activity Recognition Using Hybrid Coronavirus Disease Optimization Algorithm for Internet of Medical Things.
In our current digital world, smartphones are no longer limited to communication but are used in various real-world applications. In the healthcare industry, smartphones have sensors that can record data about our daily activities. Such data can be used for many healthcare purposes, such as elderly healthcare services, early disease diagnoses, and archiving patient data for further use. However, the data collected from the various sensors involve high dimensional features, which are not equally helpful in human activity recognition (HAR). This paper proposes an algorithm for selecting the most relevant subset of features that will contribute efficiently to the HAR process. The proposed method is based on a hybrid version of the recent Coronavirus Disease Optimization Algorithm (COVIDOA) with Simulated Annealing (SA). SA algorithm is merged with COVIDOA to improve its performance and help escape the local optima problem. The UCI-HAR dataset from the UCI machine learning repository assesses the proposed algorithm's performance. A comparison is conducted with seven well-known feature selection algorithms, including the Arithmetic Optimization Algorithm (AOA), Gray Wolf Optimizer (GWO), Whale Optimization Algorithm (WOA), Reptile Search Algorithm (RSA), Zebra Optimization Algorithm (ZOA), Gradient-Based Optimizer (GBO), Seagull Optimization Algorithm (SOA), and Coyote Optimization Algorithm (COA) regarding fitness, STD, accuracy, size of selected subset, and processing time. The results proved that the proposed approach outperforms state-of-the-art HAR techniques, achieving an average performance of 97.82% in accuracy and a reduction ratio in feature selection of 52.7%.


Ex-vivo nephron-sparing surgery and autotransplantation for renal tumours: Revisited.
We studied the feasibility of ex-vivo nephron-sparing surgery and autotransplantation for complex renal tumours. We also studied the role of laparoscopy in these situations. All patients who underwent renal autotransplantation for renal tumour at our centre were included in this retrospective study. Patient profiles were recorded in detail. Operative and postoperative details were also recorded. Our series includes 3 patients. Two patients had complex renal cell carcinoma and 1 patient had bilateral large angiomyolipoma. In first 2 patients, laparoscopic approach was used for nephrectomy. Operative time for case 1, 2 and 3 was 5.5, 4.5, 8 (right side) and 6 (left side) hours, respectively. Cold ischemia time was 110, 90, 150 and 125 minutes, respectively. One patient required temporary postoperative hemodialysis. Ex-vivo nephron-sparing surgery and autotransplantation still remain a viable option for complex renal tumours. It offers satisfactory renal functional outcome with acceptable morbidity. The laparoscopic approach should be used whenever possible to reduce morbidity.


Sexually Transmitted Infection Review for the Acute Care Pharmacist.
Review selected sexually transmitted infections (STIs) and treatment recommendations for pharmacists and providers practicing in the acute care setting. In 2015, the Centers for Disease Control and Prevention (CDC) published an updated guideline on the treatment of STIs with an emphasis on prevention and new diagnostic strategies to combat the growing problem of STIs in the United States. Despite this guidance, the incidence of infection has continued to grow. In October 2016, an in-depth analysis reported that 20 million new infections occur annually in the United States. With this growing burden of disease, it is pertinent that health-care providers optimize their treatment strategies to improve upon the management of STIs. Focusing on identification of asymptomatic- and symptomatic-infected persons, treatment, education, effective follow-up, and counseling for patients and sexual partners, emergency medicine pharmacists and providers can help minimize the negative long-term health consequences of STIs. In the emergency department setting, clinical pharmacists and providers can play a crucial role in preventing and treating STIs and should continue to expand and keep current their knowledge of this topic.


Evaluation of digestive tolerance of a soluble corn fibre.
To assess consumers' acceptance of a new fibre, it is essential to evaluate its digestive tolerance after ingestion. We aimed to determine the tolerance of increasing dosages of Promitor™ Soluble Gluco Fibre (SGF; Tate&Lyle, Hoffman Estates, IL, USA) up to 70 g fibre per day using a validated gastrointestinal composite score. A composite score of gastrointestinal tolerance integrating gastrointestinal symptoms, stool frequency and consistency was applied. To statistically validate this composite score, the gastrointestinal tolerance of inulin (10 g versus 20 g containing, respectively, 9 g versus 18 g of fibre) was assessed in 18 healthy volunteers in a randomised double-blind placebo-controlled cross-over study. Second, in a double-blind placebo-controlled cross-over study with 20 healthy volunteers, the gastrointestinal tolerance of SGF in both acute and 'spread over the day' conditions of consumption was assessed. By contrast to 10 g, 20 g of inulin demonstrated a significant difference in composite score compared to placebo [P < 0.001, difference = 7.6; 95% confidence interval (CI) = 3.8-11.3]. These values were considered as reference during the second study. In acute conditions, 40 g of SGF fibre was the highest (threshold) dose tested that indicates the digestive tolerance criteria (difference from placebo on the composite score <7.6 and upper limit of the 95% CI <11.3); this is twice the amount tolerated for inulin. In 'spread over the day' conditions, 65 g of SGF fibre was the threshold dose (P < 0.001, difference = 6.5; 95% CI = 3.4-9.5). The results of the present study demonstrate that 40 g of SGF fibre, when consumed as a single dose, and 65 g of SGF fibre, when consumed in multiple-doses, across the day are well-tolerated by healthy volunteers.