Expression of a mutant alpha-zein creates the floury2 phenotype in transgenic maize.
The maize floury2 mutation results in the formation of a soft, starchy endosperm with a reduced amount of prolamin (zein) proteins and twice the lysine content of the wild type. The mutation is semidominant and is associated with small, irregularly shaped protein bodies, elevated levels of a 70-kDa chaperone in the endoplasmic reticulum, and a novel 24-kDa polypeptide in the zein fraction. The 24-kDa polypeptide is a precursor of a 22-kDa alpha-zein protein that is not properly processed. The defect is due to an alanine-to-valine substitution at the C-terminal position of the signal peptide, which causes the protein to be anchored to the endoplasmic reticulum. We postulated that the phenotype associated with the floury2 mutation is caused by the accumulation of the 24-kDa alpha-zein protein. To test this hypothesis, we created transgenic maize plants that produce the mutant protein. We found that endosperm in seeds of these plants manifests the floury2 phenotype, thereby confirming that the mutant alpha-zein is the molecular basis of this mutation.


The impact of local government investment on the carbon emissions reduction effect: An empirical analysis of panel data from 30 provinces and municipalities in China.
Among studies of the factors that influence carbon emissions and related regulations, economic aggregates, industrial structures, energy structures, population levels, and energy prices have been extensively explored, whereas studies from the perspective of fiscal leverage, particularly of local government investment (LGI), are rare. Of the limited number of studies on the effect of LGI on carbon emissions, most focus on its direct effect. Few studies consider regulatory effects, and there is a lack of emphasis on local areas. Using a cointegration test, a panel data model and clustering analysis based on Chinese data between 2000 and 2013, this study measures the direct role of LGI in carbon dioxide (CO2) emissions reduction. First, overall, within the sample time period, a 1% increase in LGI inhibits carbon emissions by 0.8906% and 0.5851% through its influence on the industrial structure and energy efficiency, respectively, with the industrial structure path playing a greater role than the efficiency path. Second, carbon emissions to some extent exhibit inertia. The previous year's carbon emissions impact the following year's carbon emissions by 0.5375%. Thus, if a reduction in carbon emissions in the previous year has a positive effect, then the carbon emissions reduction effect generated by LGI in the following year will be magnified. Third, LGI can effectively reduce carbon emissions, but there are significant regional differences in its impact. For example, in some provinces, such as Sichuan and Anhui, economic growth has not been decoupled from carbon emissions. Fourth, the carbon emissions reduction effect in the 30 provinces and municipalities sampled in this study can be classified into five categories-strong, relatively strong, medium, relatively weak and weak-based on the degree of local governments' regulation of carbon emissions. The carbon emissions reduction effect of LGI is significant in the western and central regions of China but not in the eastern and northeast regions. This study helps overcome the limitations of previous studies on the regulatory effects of LGI on carbon emissions, and the constructed model may more closely reflect actual economic conditions. Moreover, the current study can benefit countries similar to China that aim to objectively identify the impacts of their LGI on carbon emissions, and such countries can use it as a reference in the formulation of investment policies based on their economic and industrial characteristics.


Trigger point dry needling increases masseter muscle oxygenation in patients with temporomandibular disorder.
Temporomandibular disorder (TMD) is an umbrella term encompassing various clinical complaints involving the temporomandibular joints, masticatory muscles, and/or associated orofacial structures. Myogenous TMDs are the most frequent cause of chronic orofacial pain. Musculoskeletal pain is commonly associated with myofascial trigger points (MTPs), for which dry needling (DN) is a routine treatment. To investigate muscle oxygenation and pain immediately after DN application on an MTP in the masseter muscle of patients with myogenous TMDs. Masseter muscle oxygen tissue saturation indices (TSI%) were assessed by near-infrared spectroscopy (NIRS) pre- and post-interventions by a randomized, controlled, double-blind, crossover DN/Sham clinical trial (primary outcome). Pain was investigated by the visual analog scale (VAS). In total, 32 individuals aged from 18 to 37 years who were diagnosed with myogenous TMD and myofascial trigger points in their masseter muscles participated in this study. Relative deltas for the studied variables were calculated. Data normality was tested using the Shapiro-Wilk test. According to their distribution, data were analyzed by two-way ANOVA and the Student's t-, and Mann-Whitney tests. Statistical analyses were performed using Prism® 5.0 (GraphPad, USA). We found a significant difference (2,108% vs. 0,142%) between masseter muscle TSI% deltas after the DN and Sham interventions, respectively (n=24). We only evaluated women since men refused to follow NIRS procedures. Pain increased immediately after DN (n=32, 8 men), in comparison to Sham delta VAS. These findings show an increase in tissue oxygen saturation in the evaluated sample immediately after the DN intervention on the MTP of patients' masseter muscle. Pain may have increased immediately after DN due to the needling procedure.


Early Exposure to Cardiac Treatment and Distress Among Patients and Their Caregiving Partners.
Background: The experience of an acute coronary event (ACE), including early care and evaluation, can be a distressing and traumatic experience for patients and their romantic partners, who also act as caregivers. We hypothesized that, among partners who were present during the ACE, those who were also present during (1) transportation to the hospital and (2) initial medical treatment would experience greater (a) anxiety early post-event and (b) posttraumatic stress symptoms (PSS) related to the event 4 months later. The associations between partner presence with patient anxiety and PSS were also explored. Methods: Participants were ACE patients and their partners recruited between March 2015 and December 2016 from the Intensive Cardiac Care Unit (ICCU) of the Sheba Medical Center in Israel (N = 143; all patients were males and partners were females). Partners self-reported whether or not they were present during the cardiac event, the hospital drive, and initial care. Patients and partners self-reported anxiety in-hospital and PSS, keyed to the ACE, an average of 4 months later. Data were analyzed using General Estimating Equations (GEE) and Multilevel Modeling. Results: Neither patient anxiety nor PSS differed according to partner presence during the drive to the hospital. In contrast, partners had higher anxiety when they were not present at all (difference = 3.65, p = 0.019) and when present during the event and during the drive (difference = 2.93, p = 0.029) as compared to when they were present for the event but not for the drive. Partners who were present during the event, but not the drive, had lower PSS than those who were present for both the event and the drive (difference = -4.64, p = 0.026). Conclusions: Partners who accompany patients on the drive to the hospital may inadvertently put themselves at risk for greater distress following their loved one's cardiac event. Future research should enroll couples in an acute care context to inform couple-targeted tailored interventions to reduce distress in patients and their caregiving partners.


Multidimensional analysis of actin depolymerising factor family in pigeon pea under different environmental stress revealed specific response genes in each subgroup.
Actin depolymerising factor (ADF) is an actin binding protein that is ubiquitous in animal and plant cells. It plays an important role in plant growth and development, as well as resistance to biotic and abiotic stress. The research of plant ADF family has been restricted to Arabidopsis thaliana (L.) Heynh. and some herb crops, but no woody cash crops have been reported to date. All members of the Cajanus cajan (L.) Millsp. ADF (CcADF) family were identified from the pigeon pea genome, and distributed among the four subfamilies by phylogenetic analysis. CcADFs were relatively conservative in gene structure evolution, protein structure and functional expression, and different CcADFs showed specific expression patterns under different treatments. The expression characteristics of several key CcADFs were revealed by analysing the stress response pattern of CcADFs and the time series RNA-seq of aluminium stress. Among them, CcADF9 in the first subgroup specifically responded to aluminium stress in the roots; CcADF3 in the second subgroup intensively responded to fungal infection in the leaves; and CcADF2 in the fourth subgroup positively responded to various stress treatments in different tissues. This study extended the relationship between plant ADF family and aluminium tolerance, as well as adding to the understanding of CcADF family in woody crops.


Combination immunomodulator and antibiotic treatment in patients with inflammatory bowel disease and clostridium difficile infection.
Management of Clostridium difficile infection in patients with flaring inflammatory bowel disease (IBD) has not been optimized. We investigated the effects of combination therapy with antibiotics and immunomodulators in patients with IBD and C difficile infection. We analyzed data from 155 patients (59% with ulcerative colitis [UC]) from a retrospective, European Crohn's and Colitis organization, multi-center study comparing outcome of hospitalized IBD patients with C difficile infection who were treated with antibiotics (n = 51) or antibiotics and immunomodulators (n = 104). The primary composite outcome was death or colectomy within 3 months of admission, in-hospital megacolon, bowel perforation, hemodynamic shock, or respiratory failure. The primary outcome occurred in 12% of patients given the combination treatment vs none of the patients given antibiotics alone (P = .01). UC, abdominal tenderness, or severe bloody diarrhea was more common among patients that received the combined therapy. However, multivariate analysis revealed that only the combination therapy maintained a trend for an independent association with the primary outcome (likelihood ratio = 11.9; CI, 0.9-157; P = .06). Treatment with 2 or 3 immunomodulators was correlated with the primary outcome, independent of disease severity at presentation (odds ratio [OR] = 17; CI, 3.2-91; P < .01). Acid-suppressing medications increased the risk of C difficile relapse (OR = 3.8; CI, 1.1-12.9; P = .03), whereas recent hospitalization correlated with increased rate of C difficile persistence (OR = 8; CI, 2.1-29; P = .002). Patients with IBD that also have C difficile infection are frequently treated with a combination of antibiotics and immunomodulators. However, this combination tends to associate with a worse outcome than antibiotic therapy alone. Prospective controlled trials are urgently needed to optimize the management of these challenging patients.


Doubles Connected Moments Expansion: A Tractable Approximate Horn-Weinstein Approach for Quantum Chemistry.
Ab initio methods based on the second-order and higher connected moments, or cumulants, of a reference function have seen limited use in the determination of correlation energies of chemical systems over the years. Moment-based methods have remained unattractive relative to more ubiquitous methods, such as perturbation theory and coupled cluster theory, due in part to the intractable cost of assembling moments of high-order and poor performance of low-order expansions. Many of the traditional quantum chemical methodologies can be recast as a selective summation of perturbative contributions to their energy; using this familiar structure as a guide in selecting terms, we develop a scheme to approximate connected moments limited to double excitations. The tractable Doubles Connected Moments [DCM(N)] approximation is developed and tested against a multitude of common single-reference methods to determine its efficacy in the determination of the correlation energy of model systems and small molecules. The DCM(N) sequence of energies exhibits smooth convergence toward limiting values in the range of N = 11-14, with compute costs that scale as a noniterative O(M6) with molecule size, M. Numerical tests on correlation energy recovery for 55 small molecules comprising the G1 test set in the cc-pVDZ basis show that DCM(N) strongly outperforms MP2 and even CCD with a Hartree-Fock reference. When using an approximate Brueckner reference from orbital-optimized (oo) MP2, the resulting oo:DCM(N) energies converge to values more accurate than CCSD for 49 of 55 molecules. The qualitative success of the method in regions where strong correlation effects begin to dominate, even while maintaining spin purity, suggests this may be a good starting point in the development of methodologies for the description of strongly correlated or spin-contaminated systems while maintaining a tractable single-reference formalism.


Preparation and Visible-Light Driven Photocatalytic Properties of CuS/Reduced Graphene Oxide Composites.
The CuS/RGO composites were prepared using a facile one-step solvothermal method. The asobtained samples were characterized by X-ray diffraction (XRD), Raman spectra, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), Brunner-Emmet-Teller (BET) measurements and UV-Vis spectrophotometry. The results showed that the CuS particles were uniformly dispersed on the surface of RGO and electronic migration effect existed between RGO and CuS. The photocatalytic activity of CuS/RGO composites was evaluated by the degradation of Cationic blue SD-BL, Cationic red X-5GN, Direct blue 86, Reactive blue KN-R, Methylene blue and Rhodamine B under visible light irradiation. The photocatalytic experiments showed that the CuS/RGO composites exhibited a better photocatalytic performance for organic dyes with absence of hydrogen peroxide (H2O2) due to the inhibition of recombination of electron-hole pair induced on the surface of CuS. The photodegradation ratio of Cationic blue SD-BL, Cationic red X-5GN, Direct blue 86, Reactive blue KN-R, Methylene blue and Rhodamine B increased to 100%, 95.8%, 99.5%, 87.8%, 100%, 81% after 75 min of irradiation, respectively. Moreover, no significant decline of CuS/RGO photocatalyst for photodegradation of dyes was observed after five cycles, indicating better photostability of the samples. Thus, the CuS/RGO composites could have a promising application in wastewater treatment.


Circular dichroism and superdiffusive transport at the surface of BiTeI.
We investigate the electronic states of BiTeI after the optical pumping with circularly polarized photons. Our data show that photoexcited electrons reach an internal thermalization within 300 fs of the arrival of the pump pulse. Instead, the dichroic contrast generated by the circularly polarized light relaxes on a time scale shorter than 80 fs. This result implies that orbital and spin polarization created by the circular pump pulse rapidly decays via manybody interaction. The persistent dichroism at longer delay times is due to the helicity dependence of superdiffussive transport. We ascribe it to the lack of inversion symmetry in an electronic system far from equilibrium conditions.


Reduction of Vibrio vulnificus in pure culture, half shell and whole shell oysters (Crassostrea virginica) by X-ray.
The purpose of this investigation was to study the inactivation effect of X-ray treatments on inoculated Vibrio vulnificus in pure culture, half shell and whole shell oysters to achieve a 5.0 log reduction, which is recommended by the Interstate Shellfish Sanitation Conference and the Food and Drug Administration. A mixed culture of three V. vulnificus strains was used to prepare the pure culture and inoculated oysters. The pure culture and inoculated oysters were treated with 0.0, 0.1, 0.5, 0.75, 1.0, 1.5, 2.0, and 3.0 kGy X-ray at 22 degrees C and 50-60% relative humidity. Surviving bacterial populations in the pure culture and inoculated oysters were enumerated using overlay-plating method [with a non-selective media (trypticase soy agar) followed by a selective medium (Modified Cellobiose-Polymyxin B-Colistin) and most probable number (MPN) method. Greater than a 6-log reduction of V. vulnificus was achieved with 0.75, 1.0 3.0 kGy X-ray in pure culture, half shell and whole shell oysters, respectively. Treatment with 0.75 kGy X-ray significantly (p<0.05) reduced the inherent microorganisms in half shell oysters, to less than the detectable limit (<1 log CFU/g). The maximum dose (3.0 kGy) of X-ray treatment did not affect the survivability of live oysters.


Aggregation properties of amide bearing cleavable gemini surfactants by small angle neutron scattering and conductivity studies.
The micellar aggregation of different amide bearing cleavable gemini surfactants with varying methylene spacer chain length (m = 2, 4, 6, 8, and 12) along with the corresponding monomeric surfactant in aqueous media has been investigated by conductometric and small angle neutron scattering (SANS) studies. The critical micellar concentration (CMC) values of gemini surfactants were found to be very low (CMC = 0.08-0.19 mM) and were 23-55 times lesser than the corresponding monomeric analogue (CMC = 4.4 mM). With increase in the spacer chain length, CMC was found to decrease whereas the degree of ionization was found to increase. SANS data have been analyzed by considering the screened coulombic interactions between the micelles to compute the interparticle structure factor S(Q). The extent of micellar growth and the variation of shapes of the micelles formed by these new surfactants in aqueous solution have been found to depend strongly on the spacer chain length. It was observed that the extent of micellar growth and variation of micellar shapes are more pronounced for surfactants with short spacer chain length (m ≤ 4), whereas the surfactants with a long spacer chain length (m ≥ 6) showed slight variation of these properties in aqueous solution. The effects of the variation of the concentration and temperature on the SANS spectra (and hence on the microstructure) of the gemini surfactant (m = 4) were also examined. With an increase in concentration the aggregation number (N) and size of the micelles (the ratio of semimajor axis (a) to semiminor axis (b = c)) increased whereas opposite phenomena was observed with an increase in temperature.


Migraine and the benign partial epilepsies of childhood: evidence for an association.
There is an increasing body of evidence to suggest that benign rolandic epilepsy and benign occipital epilepsy of childhood are frequently associated with migraine. This however has not been universally recognized. Clearly further investigation of this association is required. The purpose of this report is to examine the varied diagnostic criteria for common migraine utilized by epileptologists and other neurologists, to review clinical migraine epilepsy relationships, EEG abnormalities in migraine and epilepsy, and the association of seizures with vascular headache in patients with various forms of epilepsy. Hopefully, this will stimulate further research into this intriguing association of two conditions which though they have different pathophysiology frequently coexist.


Potential energy surface for high-energy N + N2 collisions.
Potential energy surface calculations yield physical insight into the structure of intermediates and the dynamics of molecular collisions, and they are the first step toward molecular simulations that provide physical insight into energy transfer, reaction, and dissociation probabilities. The potential energy surface for high-energy collisions of N2 with N can be used for modeling chemical dynamics and energy transfer in atmospheric shock waves. Here we present an analytic ground-state. (4A'') potential energy surface for N3 that governs electronically adiabatic collisions of N2(1Σ+g) with N(4S). The fitted surface consists of a pairwise potential based on an accurate diatomic potential energy curve plus a connected permutationally invariant polynomial (PIP) in mixed-exponential-Gaussian bond order variables (MEGs) for the three-body part. The three-body fit is based on multireference complete active space second order perturbation theory (CASPT2) calculations. The quality of the quartet N3 fit is comparable to that for a previous fit of the NO2 potential. We characterize two local minima of N3, two tight transition structures, two van der Waals geometries, and the noncollinear reaction path for the symmetric exchange reaction. The nonreactive approach of an N atom to N2 along the perpendicular bisector is more repulsive than the collinear reproach, but plots of the force on the bond versus the potential energy at the distance of closest approach allow us to infer that vibrational energy transfer should occur much more readily in high-energy collinear collisions than in high-energy perpendicular-bisector collisions.


Global genetic variation of HIV-1 infection.
Variability, both at the population (interhost) as well as at the individual (intrahost) level is a key property of HIV that stems mainly from the inherent infidelity of the reverse transcriptase enzyme that the virus uses to transcribe its RNA genome into DNA so that it may be integrated into the human genetic material and propagated along with it. The lack of proofreading mechanisms, high turnover of virions, and propensity for recombination also contribute to the extensive variability of HIV. These parameters provide the virus quasispecies with an impressive capacity to adapt to immunologic, pharmacologic or other selection pressures and have important implications for the diagnosis of new infections, the monitoring of antiretroviral treatment response, and effective vaccine(s) design. Herein, we discuss in detail the global genetic variation of HIV-1 infection.


Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusion in dogs.
During the acute phase of myocardial ischemia, adenine nucleotides are degraded to nucleosides and bases, especially inosine and hypoxanthine. Simultaneously, xanthine dehydrogenase is converted to xanthine oxidase, an enzyme that converts hypoxanthine to xanthine, and xanthine to uric acid, producing a superoxide anion for each molecule of hypoxanthine or xanthine oxidized. To determine if free radicals via this enzymatic source contribute to cell death in myocardial ischemia, we determined whether allopurinol, an inhibitor of xanthine oxidase, could limit infarct size in a reperfusion preparation of myocardial infarction. The circumflex coronary artery of each of 34 dogs was occluded for 40 min, followed by reperfusion for 4 days. Infarct size then was measured by histologic methods and was related to major baseline predictors of infarct size, including anatomic area at risk and collateral blood flow. Infarct size was larger (NS) in the allopurinol (n = 8) than in the control (n = 11) group, a trend that was related to slightly higher (NS) collateral blood flow in the control group. We conclude that allopurinol has no beneficial effect in this preparation of experimental myocardial infarction. The results oppose the hypothesis that free radicals, produced via the xanthine oxidase reaction, are an important contributing factor in myocardial ischemic cell death.


A Web-based Multimedia Program Before Colonoscopy Increased Knowledge and Decreased Anxiety, Sedation Requirement, and Procedure Time.
Assess the impact of a web-based multimedia patient engagement program on patient anxiety, perception and knowledge about the colonoscopy in addition to procedure outcomes. The success of patients coming for a colonoscopy for colorectal cancer screening is dependent in part on patients' understanding of the preparation and of the procedure. Patients were randomized to use either our institution's standard preprocedure colonoscopy packet or a web-based multimedia patient engagement program (Emmi Solutions) before their scheduled procedure. On the day of colonoscopy, all participants completed a survey including questions to assess knowledge and perception of colonoscopy, in addition to the State Trait Anxiety Inventory. We also collected procedure data including medication doses and procedure time. Patients in the experimental group correctly answered knowledge questions (82%) more often than the control group (74%) (P=0.0003). More than half (58%) of patients in the experimental group felt this intervention reduced their anxiety about the procedure, and the State Trait Anxiety Inventory anxiety score was lower in the experimental group (P=0.026). Patients who viewed the program required less midazolam (3.66 vs. 4.46 mg, P=0.0035) and total procedure time was shorter (24.8 vs. 29 min, P=0.024). A web-based multimedia patient engagement program watched before colonoscopy decreased patient anxiety, medication requirements, and procedure time while increasing knowledge. This intervention could help patients understand and feel more comfortable about colonoscopy leading to increased screening rates while increasing efficiency and decreasing recovery time.


cAMP-dependent induction of fatty acid cyclooxygenase mRNA in mouse osteoblastic cells (MC3T3-E1).
In an osteoblastic cell line, MC3T3-E1, cloned from mouse calvaria, epinephrine stimulated the production of prostaglandin E2 as an essentially sole arachidonate metabolite (Kusaka, M., Oshima, T., Yokota, K., Yamamoto, S., and Kumegawa, M. (1988) Biochim. Biophys. Acta. 972, 339-346). Western and Northern blot analyses showed increases in the enzyme protein and mRNA of fatty acid cyclooxygenase in the epinephrine-treated cells. A rapid cAMP production caused by epinephrine was followed by increases in the activity and mRNA of cyclooxygenase. Both dibutyryl cAMP and 8-bromo-cAMP also increased the level of the cyclooxygenase activity and mRNA. These results suggest that cAMP produced by beta-adrenergic stimulation was responsible for the increased cyclooxygenase mRNA level leading to induction of the cyclooxygenase enzyme. Furthermore, the addition of prostaglandin E2 (the final arachidonate metabolite in the MC3T3-E1 cells) brought about a rapid synthesis of intracellular cAMP followed by increases in the enzyme protein and mRNA of cyclooxygenase.


Sunlight-induced propagation of the lysogenic phage encoding cholera toxin.
In toxigenic Vibrio cholerae, the cholera enterotoxin (CT) is encoded by CTXPhi, a lysogenic bacteriophage. The propagation of this filamentous phage can result in the origination of new toxigenic strains. To understand the nature of possible environmental factors associated with the propagation of CTXPhi, we examined the effects of temperature, pH, salinity, and exposure to direct sunlight on the induction of the CTX prophage and studied the transmission of the phage to potential recipient strains. Exposure of cultures of CTXPhi lysogens to direct sunlight resulted in approximately 10,000-fold increases in phage titers. Variation in temperature, pH, or salinity of the culture did not have a substantial effect on the induction of the prophage, but these factors influenced the stability of CTXPhi particles. Exposure of mixed cultures of CTXPhi lysogens and potential recipient strains to sunlight significantly increased both the in vitro and in vivo (in rabbit ileal loops) transduction of the recipient strains by CTXPhi. Included in these transduction experiments were two environmental nontoxigenic (CTXPhi(-)) strains of V. cholerae O139. These two O139 strains were transduced at high efficiency by CTXPhi, and the phage genome integrated into the O139 host chromosome. The resulting CTXPhi lysogens produced biologically active CT both in vitro and in rabbit ileal loops. This finding suggests a possible mechanism explaining the origination of toxigenic V. cholerae O139 strains from nontoxigenic progenitors. This study indicates that sunlight is a significant inducer of the CTX prophage and suggests that sunlight-induced transmission of CTXPhi may constitute part of a natural mechanism for the origination of new toxigenic strains of V. cholerae.


Cytokine dysregulation in activated cystic fibrosis (CF) peripheral lymphocytes.
Recent studies demonstrate in vivo and in vitro cytokine dysregulation in CF epithelial cells. To see if these abnormalities may be generalized to other cells expressing cystic fibrosis transmembrane conductance regulator (CFTR) but not directly exposed to local inflammation, we studied mRNA transcription, intracellular protein production and extracellular secretion of IL-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-gamma) from freshly isolated blood mononuclear and CD4+ T cells from CF patients and controls. Cells were activated by phorbol myristate acetate (PMA) and anti-CD3, PMA-ionomycin, or lipopolysaccharide (LPS) and assessed for cytokine mRNA transcription by semiquantitative reverse transcriptase-polymerase chain reaction, intracellular protein production by flow cytometry, and secretion by supernatant ELISA. Cytokine expression was highly stimulus-dependent. CF cells showed higher IL-10 transcription than control cells after maximal activation by LPS (P = 0.01); despite this, cytokine production and secretion were equivalent to controls. CF cells showed lower cellular IL-10 production after PMA-anti-CD3 activation (P = 0.002). CF cells secreted less IFN-gamma than control cells after maximal activation by PMA-anti-CD3 (1836 +/- 273 pg/ml versus 9635 +/- 3437 pg/ml, P = 0.04). IL-2, IL-4 and IL-5 regulation was similar to controls. We conclude that CF mononuclear cells show selective cytokine dysregulation after maximal activation, namely reduced IFN-gamma secretion and increased IL-10 mRNA without increased production or secretion. These findings extend defects described in respiratory epithelial cells to circulating immunoregulatory cells, suggesting a link between CF genotype and cytokine dysregulation.


A Forensic Genomics Approach for the Identification of Sister Marija Crucifiksa Kozulić.
Sister Marija Krucifiksa Kozulić (1852-1922) was a Croatian nun who is in consideration for beatification by the Vatican, which is facilitated by the identification of her 20th-century remains. Sister Marija was buried in a tomb in Rijeka, Croatia, along with other nuns including her biological sister, Tereza Kozulić (1861-1933). When the remains were exhumed in 2011, they were found in a deteriorated state and commingled with several other sets of remains. Thus, mitochondrial genome sequencing of the long bones was performed to sort the remains by mitochondrial haplotype. Two similar but unique haplotypes belonging to haplogroup H1bu were identified, and samples from these bones were subjected to autosomal short tandem repeat (STR) and single nucleotide polymorphism (SNP) sequencing. Although only partial profiles were obtained, the data were sufficient for kinship analysis with the profile of a paternal niece of Sister Marija (Fides Kozulić). The data indicate that it is 574,195-fold more likely that the two sets of skeletal remains represent 2nd-degree relatives of Fides than sisters who are unrelated to Fides. Although it is impossible to discern which set of remains belongs to Marija and which belongs to Tereza, forensic genomics methods have enabled identification of the sisters.


Cyclic AMP regulation of myosin isozymes in mammalian cardiac muscle.
Hyperpermeable cells from rat heart contain a cAMP-dependent system that can increase the maximum Ca-activated force (contractility) of the contractile proteins. In two different conditions where the relative concentration of the myosin isozymes changes, i.e., hypothyroidism and aging, the size of the increase in contractility from activation of the cAMP-regulated system varies closely with the relative concentration of V1, the isozyme of myosin with the greatest Ca- and actin-activated ATPase activity. The existence of another system for the regulation of the slow isozyme V3 has been demonstrated, and it may be inhibited by beta-adrenergic activity. The possibility of cAMP-dependent myosin regulation of contraction in addition to Ca regulation of troponin is considered. Phosphorylation of the contractile proteins themselves is not required for the increased contractility.


Topologically non-linked circular duplex DNA.
The discovery of circular DNA, over 30 years ago, introduced an element of uneasiness in what had been, up to that point, the almost picture-perfect story of the elucidation of the molecular biology of heredity. If DNA indeed has the Watson-Crick right-handed helical secondary structure, then in circular DNA, thousands, or perhaps even millions of twists must be removed in each generation, and re-wound in the next generation. Although enzyme systems adequate for this task have long since been found and characterized, there have nevertheless arisen a number of proposals for alternative DNA structures in which the strands are topologically non-linked, so that they might separate during replication without having to be unwound. These structures have generally been put forth as theory only, and have been largely unaccompanied by experimental evidence to support their applicability to native DNA from living systems. Recently, however, a report has emerged suggesting that it might be possible to separate, intact, the individual single-stranded circular half-chromosomes which constitute the double-stranded circular chromosomes of certain plasmids. This would not be possible unless the chromosomes had one of the alternative, topologically non-linked structures. It is widely believed that after a half-century of worldwide DNA research, any significant change to the Watson-Crick structure is unlikely to stand up to scrutiny. Nevertheless, the present author has found that in many instances in which the behavior of circular duplex DNA is considered to be explicable only in terms of the topologically linked helical model, it is also possible to explain that same behavior in terms of a topologically non-linked model. It is necessary, in these instances, to make certain logical assumptions which cannot be conclusively proven at the present time. The author herein offers an example of one such instance, namely an examination of the behavior of circular duplex DNA in an alkaline titration experiment, where conformational changes in DNA are deduced from changes in its buoyant density at pH's between 7 and 14. These data have been explained in terms of topological linkage between the DNA strands, but they can also be explained without invoking any such topological linkage, provided that the above-mentioned logical assumptions can be accepted. The principles which emerge from this are applicable to other settings in which knowledge of the topology of DNA is critical to the understanding of observed phenomena.


Oxidative Stress and the ER Stress Response in a Murine Model for Early-Stage Alcoholic Liver Disease.
Alcoholic liver disease (ALD) is a primary cause of morbidity and mortality in the United States and constitutes a significant socioeconomic burden. Previous work has implicated oxidative stress and endoplasmic reticulum (ER) stress in the etiology of ALD; however, the complex and interrelated nature of these cellular responses presently confounds our understanding of ethanol-induced hepatopathy. In this paper, we assessed the pathological contribution of oxidative stress and ER stress in a time-course mouse model of early-stage ALD. Ethanol-treated mice exhibited significant hepatic panlobular steatosis and elevated plasma ALT values compared to isocaloric controls. Oxidative stress was observed in the ethanol-treated animals through a significant increase in hepatic TBARS and immunohistochemical staining of 4-HNE-modified proteins. Hepatic glutathione (GSH) levels were significantly decreased as a consequence of decreased CBS activity, increased GSH utilization, and increased protein glutathionylation. At the same time, immunoblot analysis of the PERK, IRE1α, ATF6, and SREBP pathways reveals no significant role for these UPR pathways in the etiology of hepatic steatosis associated with early-stage ALD. Collectively, our results indicate a primary pathogenic role for oxidative stress in the early initiating stages of ALD that precedes the involvement of the ER stress response.


Intestinal perforation after radical cystectomy due to drain: case report.
The current standard treatment for nonmetastatic invasive bladder cancer is radical cystectomy with urinary diversion. Radical cystectomy surgery carries a serious potential risk of complications. In this case report, an intestinal perforation which was thought to be occurred due to a Foley catheter placed as a drain after the cystectomy is presented.


[Effects of treatments (heat and fermentation by Rhizopus oligosporus sp-T3) of sweet white lupin seeds on certain factors of its nutritional use].
For improving the nutritional value and functional properties of sweet white lupin (SWL), a solid fermentation process using Rhizopus oligosporus was developed for the preparation of lupin products. A comparison of the effects of soaking + thermal treatment and fermentation was made from 3 lupin products: non-treated lupin seeds (SWLnt), heated lupin seeds (steamed at 100 degrees C for 30 min) (SWLh), and fermented lupin products (SWLf) from SWLh on chemical characteristics and protein efficiency ratio (PER) in rats. The major effect of soaking and thermal treatment is a loss of protein solubility and available lysine (from 3.02 +/- 0.18 g/16 g N to 2.3 +/- 0.25). Fermentation leads to a modification, of amino acid composition and to an increase in available lysine compared to heating (2.90 +/- 0.12 g/16 g N). The nutritional quality of SWLnt is low (PER = 0.83 +/- 0.09), thermal treatment decreases it (0.58 +/- 0.18) and fermentation compensates heating effect (0.74 +/- 0.25). It is suggested that the modifications of nutritional quality depends on the availability of lysine rather than on the variations of the levels of other amino acids.


Impact and characteristics of quality of life in Japanese patients with multiple sclerosis.
To evaluate health-related quality of life (HRQOL) in Japanese patients with multiple sclerosis (MS) and investigate associations between the results of these QOL assessments and disease severity. One-hundred sixty-three Japanese MS patients completed a questionnaire battery comprising the Functional Assessment of MS (FAMS), the Nottingham Adjustment Scale-Japanese version (NAS-J), and the European QOL scale (EQ-5D). Additional five factors affecting QOL as identified by MS patients in a focus group interview were also investigated: employment status, change of income, availability of disease information, communication with medical staff, and care received. Disease severity was determined using the Expanded Disability Status Scale (EDSS). There was a strong negative correlation of the subscale scores for mobility, symptoms, emotional well-being, thinking and fatigue, and additional concerns on the FAMS with EDSS score. For the NAS-J, only acceptance of the condition was correlated with disease severity. Among the five additional aspects of the condition identified by patients, employment status, income, and disease information were shown to be important for maintaining QOL in patients with MS. Support for finding employment and having increased or maintained household income and readily available information about the disease contribute to improving QOL in Japanese MS patients.


Activity-induced patterns of dental abrasion in prehistoric Pakistan: evidence from Mehrgarh and Harappa.
A detailed investigation of worn teeth should reveal a record of past activity patterns including information regarding diet, food preparation methods, and craft or occupational activities. Anthropological studies of the extensive dental samples from Neolithic (MR 3) and Chalcolithic (MR 2) levels at Mehrgarh, Baluchistan, and Bronze Age Harappa, Punjab, yielded several interesting examples of unusual dental abrasion. This paper provides macro- and microscopic (scanning electron microscope) descriptions of three types of activity-induced dental abrasion: 1) interproximal tooth grooving and interproximal abrasion patches, 2) facial abrasion of maxillary anterior teeth, and 3) lingual abrasion of maxillary incisors in association with rounded wear of lower incisors. The gross size and shape of abrasion features, the orientation of microscopic wear striae, and ethnographic parallels are employed in inferring causal factors involved in their formation. Behavioral activities and dietary explanations possibly associated with each type of dental wear are considered and their implications for reconstructing prehistoric activity patterns discussed. The need for extensive ethno-anthropology research into variations of tooth use among living people with different diets, subsistence bases, and craft specializations is essential to further progress in this field.


A methoxylated fatty acid isolated from the brown seaweed Ishige okamurae inhibits bacterial phospholipase A2.
A methoxylated fatty acid that inhibits phospholipase A(2) (PLA(2); EC 188.8.131.52) was purified from the brown seaweed Ishige okamurae. Approximately 8.1 mg of the inhibitory compound, 7-methoxy-9-methylhexadeca-4,8-dienoic acid, was isolated from 1 kg of I. okamurae powder. Recombinant PLA(2) derived from the pathogenic bacterium Vibrio mimicus was used as the target enzyme. The methoxylated fatty acid compound competitively inhibited PLA(2) with a Ki value of 3.9 microg/mL. The concentrations required for 50% inhibition of PLA(2), oedema and erythema were 1.0 microg/mL, 3.6 mg/mL and 4.6 mg/mL, respectively. The compound strongly inhibited PLA(2) activity in vitro and had potent antiinflammatory activity in vivo.


In Vivo [18F]GE-179 Brain Signal Does Not Show NMDA-Specific Modulation with Drug Challenges in Rodents and Nonhuman Primates.
As one of the major excitatory ion channels in the brain, NMDA receptors have been a leading research target for neuroscientists, physicians, medicinal chemists, and pharmaceutical companies for decades. Molecular imaging of NMDA receptors by means of positron emission tomography (PET) with [18F]GE-179 quickly progressed to clinical PET studies, but a thorough understanding of its binding specificity has been missing and has thus limited signal interpretation. Here a preclinical study with [18F]GE-179 in rodents and nonhuman primates (NHPs) is presented in an attempt to characterize [18F]GE-179 signal specificity. Rodent PET/CT was used to study drug occupancy and functional manipulation in rats by pretreating animals with NMDA targeted blocking/modulating drug doses followed by a single bolus of [18F]GE-179. Binding competition with GE-179, MK801, PCP, and ketamine, allosteric inhibition by ifenprodil, and brain activation with methamphetamine did not alter the [18F]GE-179 brain signal in rats. In addition, multimodal imaging with PET/MRI in NHPs was used to evaluate changes in radiotracer binding as a function of pharmacological challenges. Drug-induced hemodynamic changes were monitored simultaneously using functional MRI (fMRI). Comparisons of baseline and signal after drug challenge in NHPs demonstrated that the [18F]GE-179 signal cannot be manipulated in a predictable fashion in vivo. fMRI data acquired simultaneously with PET data supported this finding and provided evidence that radiotracer delivery is not altered by blood flow changes. In conclusion, the [18F]GE-179 brain signal is not readily interpretable in the context of NMDA receptor binding on the basis of the results shown in this study.


Association of Transforming Growth Factor-β1 rs1982073 Polymorphism with Susceptibility to Acute Renal Rejection: a Systematic Review and Meta-Analysis.
The association of rs1982073 (codon 10) polymorphism at Transforming Growth Factor- β1 (TGF-β1) gene with acute renal rejection (ARR) has been reported by several studies. However, the results were controversial. To derive a more precise estimation of this association, a meta-analysis was performed. The eligible literatures were identified through PubMed, Scopus, Web of Science, EMBASE, SciELO, WanFang, and CNKI databases up to July 01, 2019. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to calculate the strength of the association. A total of 23 case-control studies with 795 ARR cases and 1,562 non-AR controls were selected. Pooled data revealed that there was no significant association between TGF-β1 codon 10 polymorphism and an increased risk of ARR in the overall population (C vs. T: OR=0.908, 95% CI 0.750-1.099, p = 0.322; CT vs. TT: OR=1.074, 95% CI 0.869-1.328, p = 0.507; CC vs.TT: OR=0.509, 95% CI=0.738-1.253, p = 0.770; CC+CT vs. TT: OR = 0.917, 95% CI 0.756-1.112, p = 0.376, and CC vs. CT+TT: OR=0.995, 95% CI 0.809-1.223, p = 0.959). Moreover, stratified analysis revealed no significant association between the TGF-β1 rs1982073 polymorphism and ARR risk by ethnicity and cases type (recipient and donor). The current meta-analysis demonstrated that the TGF-β1 rs1982073 polymorphism was not significantly associated with increased risk of ARR. However, studies with a larger number of subjects among different ethnic groups are needed to further validate the results.


Fatty acyl donor selectivity in membrane bound O-acyltransferases and communal cell fate decision-making.
The post-translational modification of proteins with lipid moieties confers spatial and temporal control of protein function by restricting their subcellular distribution or movement in the extracellular milieu. Yet, little is known about the significance of lipid selectivity to the activity of proteins targeted for such modifications. Membrane bound O-acyl transferases (MBOATs) are a superfamily of multipass enzymes that transfer fatty acids on to lipid or protein substrates. Three MBOATs constitute a subfamily with secreted signalling molecules for substrates, the Wnt, Hedgehog (Hh) and Ghrelin proteins. Given their important roles in adult tissue homoeostasis, all three molecules and their respective associated acyltransferases provide a framework for interrogating the role of extracellular acylation events in cell-to-cell communication. Here, we discuss how the preference for a fatty acyl donor in the Wnt acyltransferase porcupine (Porcn) and possibly in other protein lipidation enzymes may provide a means for coupling metabolic health at the single cell level to communal cell fate decision-making in complex multicellular organisms.


Enhancing Quality of Provider Practices for Older Adults in the Emergency Department (EQUiPPED).
EQUiPPED is a multicomponent quality improvement initiative combining education, electronic clinical decision support, and individual provider feedback to influence prescribing and improve medication safety for older adults. The objective here was to evaluate the effectiveness and sustainability of EQUiPPED to reduce the use of potentially inappropriate medications (PIMs), as defined by the American Geriatrics Society 2012 Beers Criteria, prescribed to older Veterans at the time of emergency department (ED) discharge. This evaluation represents a pre- and post-intervention comparison of PIM prescriptions at 4 urban Veteran Affairs (VA) Medical Center EDs. Poisson regression was used to compare the number of PIMs prescribed to Veterans 65 years or older discharged from the ED for at least 6 months prior to the first EQUiPPED intervention at each site and for at least 12 months following the final EQUiPPED intervention. The implementation timeline varied by site depending on local resources. All 4 sites showed a significant and sustained reduction in use of PIMs. The proportion of PIMs at site one decreased from 11.9% (SD 1.8) pre-EQUiPPED to 5.1% (SD 1.4) post-EQUiPPED (P < .0001); site 2 from 8.2% (SD 0.8) pre to 4.5% (SD 1.0) post (P < .0001); site 3 from 8.9% (SD 1.9) pre to 6.1% (SD 1.7) post (P = .0007); and site 4 from 7.4% (SD 1.7) pre to 5.7% (SD 0.8) post (P = .04). These results suggest a multicomponent program to influence provider prescribing behavior leads to safer prescribing for older adults discharged from the ED and is sustainable across multiple VA ED sites.


Malignant nephroblastoma in Macaca fascicularis.
A case of malignant nephroblastoma was identified in a 4.5-month-old female Macaca fascicularis. The age of onset, clinical history, gross and microscopic pathology, and the pulmonary metastasis were analogous to this condition as seen in man.


The Role of Zinc in Selected Female Reproductive System Disorders.
Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response and reproduction. This review focuses on its importance in the reproductive system of women of reproductive and postmenopausal ages, not including its well described role in pregnancy. Only recently, attention has been drawn to the potential role of zinc in polycystic ovary syndrome (PCOS), dysmenorrhea, or endometriosis. This review is mainly based on 36 randomized, controlled studies on reproductive, pre- and post-menopausal populations of women and on research trying to explain the potential impact of zinc and its supplementation in the etiology of selected female reproductive system disorders. In women with PCOS, zinc supplementation has a positive effect on many parameters, especially those related to insulin resistance and lipid balance. In primary dysmenorrhea, zinc supplementation before and during each menstrual cycle seems to be an important factor reducing the intensity of menstrual pain. On the other hand, little is known of the role of zinc in endometriosis and in postmenopausal women. Therefore, further studies explaining the potential impact of zinc and its supplementation on female reproductive system would be highly advisable and valuable.


The origins of stone tool technology in Africa: a historical perspective.
The search for the earliest stone tools is a topic that has received much attention in studies on the archaeology of human origins. New evidence could position the oldest traces of stone tool-use before 3.39 Myr, substantially earlier than previously documented. Nonetheless, the first unmistakable evidence of tool-making dates to 2.6 Ma, the period in which Oldowan assemblages first appear in the East African record. However, this is not an unchangeable time boundary, and considerations about the tempo and modo of tool-making emergence have varied through time. This paper summarizes the history of research on the origins of stone knapping in Africa and places the current evidence in a historical perspective.


Hepatoprotective effects of the water extract from adzuki bean hulls on acetaminophen-induced damage in rat liver.
We examined the hepatoprotective effect of water-extract from adzuki bean (Vigna angularis) hulls on acetaminophen (AAP)-induced damage in rat liver. F344/DuCrj rats of 8 weeks of age were fed diets without and with 0.5% AAP or besides it 5% adzuki extract (lyophilized) on a daily basis over a period of 4 wk. At that time, serum aspartate aminotransferase activity in only AAP-treated group was higher than in both control and AAP plus adzuki extract (AAPA)-treated groups, while hepatic glutathione content and hepatic glutathione reductase and catalase activities in the AAP-treated group were lower than in the control group in contrast to the reverse in the AAPA-treated group. Hepatic phosphatidylcholine hydroperoxide and phosphatidylethanolamine hydroperoxide concentrations were higher in the AAP-treated group than in the control group, and were lower in the AAPA-treated group than in the AAP-treated group. Hepatic glutathione peroxidase activity was higher in the AAP-treated group than in the control group, although there was no significant difference between both AAP- and AAPA-treated groups in this respect. These findings suggest that the adzuki extract will serve as a prophylactic against oxidative damage to the liver.


Clinical effectiveness of cognitive therapy v. interpersonal psychotherapy for depression: results of a randomized controlled trial.
Although both cognitive therapy (CT) and interpersonal psychotherapy (IPT) have been shown to be effective treatments for major depressive disorder (MDD), it is not clear yet whether one therapy outperforms the other with regard to severity and course of the disorder. This study examined the clinical effectiveness of CT v. IPT in a large sample of depressed patients seeking treatment in a Dutch outpatient mental health clinic. We tested whether one of the treatments was superior to the other at post-treatment and at 5 months follow-up. Furthermore, we tested whether active treatment was superior to no treatment. We also assessed whether initial depression severity moderated the effect of time and condition and tested for therapist differences. Depressed adults (n = 182) were randomized to either CT (n = 76), IPT (n = 75) or a 2-month waiting list control (WLC) condition (n = 31). Main outcome was depression severity, measured with the Beck Depression Inventory - II (BDI-II), assessed at baseline, 2, 3, and 7 months (treatment phase) and monthly up to 5 months follow-up (8-12 months). No differential effects between CT and IPT were found. Both treatments exceeded response in the WLC condition, and led to considerable improvement in depression severity that was sustained up to 1 year. Baseline depression severity did not moderate the effect of time and condition. Within our power and time ranges, CT and IPT appeared not to differ in the treatment of depression in the acute phase and beyond.


Perturbations induced by synthetic peptides from hepatitis G virus structural proteins in lipid model membranes: a fluorescent approach.
The name HGV/GBV-C remains as an acronym for hepatitis G virus (HGV) and GB virus-C (GBV-C), strain variants of this enveloped RNA virus independently but simultaneously discovered in 1995. Nowadays there is no evidence that it causes hepatitis in humans either during initial infection or after long-term carriage, but it has been recently related with HIV regarding the inhibition of progression to AIDS. The overall genomic organization of HGV/GBV-C is similar to that of hepatitis C virus (HCV) and other members of the Flavivirus family in Hepacivirus genus. Although a stretch of conserved, hydrophobic amino acids within the envelop glycoprotein of HCV has been proposed as the virus fusion peptide, the mode of entry of GBV-C/HGV into target cells is at present unknown. In the present work, sequences derived from the structural E2-protein of HGV/GBV-C have been selected by means of semiempirical methods and then synthesized manually following solid-phase methodologies. Their ability to induce perturbations in model membranes has been analysed by measuring the penetration of such peptides in lipid monolayers and by a series of experiments based on tryptophan peptide fluorescence emission spectra. Besides, release of vesicular contents to the medium was monitored by the ANTS/DPX assay. The membrane destabilization properties of these peptides was found very related with the length of the sequence.


Effect of mating delay on the reproductive performance of Cnephasia jactatana (Lepidoptera: Tortricidae).
The leafroller species, Cnephasia jactatana Walker, is an important pest of kiwifruit in New Zealand. The effect of mating delay on its reproductive performance was investigated in the laboratory to provide information for the development of pheromonal pest control measures such as mating disruption. Reproductive performance of both sexes is adversely affected by mating delay. Females are more severely affected by mating delay than males in terms of reproductive potential. Delaying mating in females for 3 and 4 d reduced the reproductive potential by 29 and 88%, respectively. It is suggested that mating disruption may have potential for the control of this species.


An alternative tandem affinity purification strategy applied to Arabidopsis protein complex isolation.
Tandem affinity purification (TAP) strategies constitute an efficient approach for protein complex purification from many different organisms. However, the application of such strategies for purifying endogenous Arabidopsis multi-protein complexes has not yet been reported. Here, we describe an alternative TAP (TAPa) system that successfully allows protein complex purification from Arabidopsis. In our newly generated TAPa tag we have replaced the tobacco etch virus (TEV) protease cleavage site with the more specific and low-temperature active rhinovirus 3C protease site. In addition, the second purification step can now be performed through two different affinity tags: a six His repeat or nine copies of a myc repeat. To examine our purification procedure we generated a C-terminal fusion between the TAPa tag and CSN3, a component of the multi-protein COP9 signalosome (CSN) complex. Subsequent analysis showed that CSN3-TAPa could rescue a csn3 mutant, and that the components of the CSN complex could be co-purified with CSN3-TAPa. As part of our long running interest in light signaling in Arabidopsis we have generated Arabidopsis transgenic lines harboring, both N-terminal and C-terminal TAPa fusions of many different light signaling pathway regulators. Molecular characterization of these transgenic lines showed fusion expression in 88% of the genes analyzed and that this expression is largely independent of the fusion orientation. Mutant complementation analysis showed that most of the TAPa fusions analyzed retained function of the wild-type proteins. Taken together, the data demonstrate the suitability of the TAPa system to allow efficient multi-protein complex isolation from stably transformed Arabidopsis.


SGLT2 Inhibitors as Add-On Therapy to Metformin for People with Type 2 Diabetes: A Review of Placebo-Controlled Trials in Asian versus Non-Asian Patients.
Metformin remains the first pharmacological choice for treating hyperglycemia in type 2 diabetes (T2DM) in most international guidelines. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are increasingly used as add-on therapy. T2DM pathophysiology is different in Asian and non-Asian (mainly Caucasian) patients. The aim of this systematic review is to compare the efficacy of SGLT2is vs placebo added to metformin in randomized controlled trials (RCTs: range 12-52 weeks) in Asian versus non-Asian patients with T2DM. The primary endpoint is the reduction in glycated hemoglobin (HbA1c) from baseline and key secondary endpoints are reductions in fasting plasma glucose (FPG), body weight (BW) and systolic blood pressure (SBP). Systematic literature search collected 7 RCTs (3 with 2 doses) in Asian patients (10 analyses, n=1164, iSGLT2: canagliflozin, dapagliflozin, ertugliflozin, ipragliflozin, tofogliflozin)) and 10 RCTs (6 with two doses) in non-Asian patients (16 analyses, n=2482, iSGLT2: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin). Baseline values of HbA1c (7.98±0.19 vs 7.89±0.27%), FPG (8.80 ±0.46 vs 9.11±0.49 mmol/l) and SBP (128.4±1.6 vs 130.2±3.1 mmHg) were not significantly different in Asian vs non-Asian patients, but BW was lower in Asian patients (71.6±4.8 vs 88.0±2.5 kg, p<0.001). The placebo-adjusted weighed mean differences (WMD, 95% CI) were similar in Asian versus non-Asian patients regarding the reductions in HbA1c -0.60 (-0.68, -0.53) % versus -0.54 (-0.59, -0.49) % (p=0.568), FPG -1.37 (-1.53, -1.22) mmol/l vs -1.37 (-1.47, -1.27) mmol/l (p=0.627), BW when expressed in percentage of baseline BW -2.23 (-2.55, -1.90) % vs -2.16 (-2.37, -1.96) % (p=0.324), and SBP -4.53 (-5.53, -3.53) mmHg vs -4.06 (-4.83, -3.29) mmHg) (p=0.223). In conclusion, clinical efficacy of SGLT2i, as an add-on treatment to metformin monotherapy in patients with T2DM, is similar in Asian versus non-Asian patients, despite known ethnic differences in phenotype and pathophysiology of T2DM.


[Respiratory symptoms and lung function in children aged 6-14 years and their relationship with particulate matter PM10 in Santa Marta, Colombia].
The effects of particulate matter (PM10) on respiratory health are a public health interest because of the high risk of disease and death in the exposed population, more so when it comes to children. The goal was to identify the relationship between concentrations of PM10 and presence of respiratory symptoms and impaired lung function in children aged 6-14 years in the city of Santa Marta. A cross sectional study was developed. The sample consisted of 305 randomly selected school children enrolled in schools in the areas. Two surveys were carried out: (i) the survey of the International Study of Asthma Allergies in Childhood (ISAAC), to identify symptoms of allergic rhinitis and asthma, and (ii) the survey to identify co-variates in the home environment. Spirometry was performed to assess lung function. To characterize exposure defined four areas of the city where they were located fmrOMNI low volume samplers to measure PM10 concentrations. EpiInfo 3.5.3 was used for bivariate analysis (Chi²) and multivariate (logistic regression) and epidemiological measures (OR). The prevalence of respiratory symptoms in the study population was 39.3%. Living in exposed areas increases the risk of suffer respiratory symptoms in upper tract (ORa=2,19 p=0,0015) and having cats (ORa=1,79 p=0,0389). In children aged 6-14 years exposed to PM10 concentrations higher than 70 µg/m³ the risk of upper respiratory tract symptoms increases and lung function is altered.


Developmental differences in stress responding after repeated underwater trauma exposures in rats.
Adolescence is a distinct developmental period characterized by behavioral and physiological maturation. Rapid ongoing changes during neurodevelopment in particular present potential opportunities for stress to have lasting effects on longitudinal outcomes of behavioral and neuroendocrine function. While adult stress effects on outcomes during adulthood have been characterized, little is known about the lasting effects of adolescent repeated stressor exposure on outcomes during adolescence. We have previously reported different stress responses in adolescent rats relative to adult rats, including a blunted fear response outcome in adulthood in rats stressed during adolescence. The present study characterized the ontogeny of behavioral and neuroendocrine responses to eight underwater trauma (UWT) exposures in rats over a two week poststress time period during adolescence (P34) or adulthood (P83) relative to age-matched control groups that underwent eight swimming episodes without UWT. Repeated UWT exposures starting in adolescence, but not adulthood, resulted in adverse behavioral responses on the elevated plus maze 1 day post-stress. Corticosterone responses did not differ between UWT-exposed and controls for either age group at 1 day or at 7 days poststress, although there was an effect of age on corticosterone levels. We conclude that repeated UWT stress events have a lasting, negative behavioral effect on adolescent rats that is not observed in adult rats after the two-week exposure window. These results suggest that neurophysiological mechanisms underlying recovery from a repeated stressor are immature in adolescence relative to adulthood in rats.


Enhanced expression of manganese-dependent superoxide dismutase in human and sheep CLN6 tissues.
Neuronal ceroid lipofuscinosis type 6 and its sheep model (OCL6) are lysosomal storage disorders caused by mutations in the CLN6 gene product of unknown function. It has been proposed that mitochondrial dysfunction, including defects in mitochondrial protein degradation, organelle enlargement and functional changes in oxidative phosphorylation, may contribute to the disease pathology. To further explore the disease mechanisms underlying CLN6, protein expression was compared between normal and affected tissues. Using two-dimensional electrophoretic separation of proteins, MS and immunoblotting, MnSOD (manganese-dependent superoxide dismutase) was found to be significantly and specifically increased in fibroblasts and brain extracts of both human and sheep affected with CLN6. Both the activity and expression of MnSOD mRNA were enhanced in affected fibroblasts. Confocal fluorescence microscopy and immunohistochemical studies revealed the presence of MnSOD in mitochondria of CLN6 fibroblasts and in CLN6 brain sections within both neurons and hypertrophic astrocytes. These data suggest that oxidative stress and/or the production of pro-inflammatory cytokines are characteristic features of human and sheep CLN6, resulting in elevated expression of MnSOD, which may be important for diagnostic purposes.


Transfusion Transmissible Infections Among Walk-In Blood Donors at Kisumu Regional Blood Transfusion Centre, Kisumu County, Kenya, 2015.
Transfusion transmissible infections (TTIs) are threats to blood safety. This study investigated TTIs among volunteer blood donors at the Kisumu Regional Blood Transfusion Centre (KRBTC) in Kenya. We performed a retrospective record review of blood donor registers at KRBTC, 2015. Walk-in donors accepted for donation were analyzed to determine prevalence of human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV), and syphilis. Descriptive and associative statistics were calculated using Microsoft Excel and Open-Epi software. The records of a total of 3690 walk-in donors were reviewed, and 2046 were included in the analysis. Mean age was 30 ± 9.6 years, 76% male, 51% married, and 80% were Kisumu residents. Seroprevalence of HIV, HBV, HCV, and syphilis was 2.4%, 3.1%, 2.3%, and 1%, respectively. HBV was the most common TTI among the volunteers. KRBTC should be proactive and address issues of donor self-exclusion, strict adherence to donor selection criteria, and vaccination.


Mapping QTLs for enhancing early biomass derived from Aegilops tauschii in synthetic hexaploid wheat.
Strong early vigour plays a crucial role in wheat yield improvement by enhancing resource utilization efficiency. Synthetic hexaploid wheat (SHW) combines the elite genes of tetraploid wheat with Aegilops tauschii and has been widely used in wheat genetic improvement for its abundant genetic variation. The two SHWs Syn79 and Syn80 were derived from the crossing of the same tetraploid wheat DOY1 with two different Ae. tauschii accessions, AT333 and AT428, respectively. The Syn80 possessed better early vigour traits than Syn79, theretically caused by their D genome from Ae. tauschii. To dissect their genetic basis in a hexaploid background, 203 recombinant inbred lines (RILs) derived from the cross of Syn79 x Syn80 were developed to detect quantitative trait loci (QTL) for four early biomass related traits: plant height (PH), tiller number (TN), shoot fresh weight (SFW) and shoot dry weight (SDW) per plant, under five different environmental conditions. Determined from the data of SNP markers, two genome regions on 1DS and 7D were stably associated with the four early biomass related traits showing pleiotropic effects. Four stable QTLs QPh.saas-1DS, QTn.saas-1DS, QSfw.saas-1DS and QSdw.saas-1DS explaining 7.92, 15.34, 9.64 and 10.15% of the phenotypic variation, respectively, were clustered in the region of 1DS from AX-94812958 to AX-110910133. Meanwhile, QPh.saas-7D, QTn.saas-7D, QSfw.saas-7D and QSdw.saas-7D were flanked by AX-109917900 and AX-110605376 on 7D, explaining 16.12, 24.35, 15.25 and 13.37% of the phenotypic variation on average, respectively. Moreover, these genomic QTLs on 1DS and 7D enhancing biomass in the parent Syn80 were from Ae. tauschii AT428. These findings suggest that these two QTLs from Ae. tauschii can be expressed stably in a hexaploid background at the jointing stage and be used for wheat improvement.


Microaerobic conditions enhance type III secretion and adherence of enterohaemorrhagic Escherichia coli to polarized human intestinal epithelial cells.
Advances in the understanding of the pathogenesis of enterohaemorrhagic Escherichia coli (EHEC) have greatly benefited from the use of human epithelial cell lines under aerobic conditions. However, in the target site of EHEC infection, the human intestine, conditions are microaerobic. In our study we used polarized human colon carcinoma cells in a vertical diffusion chamber system to investigate the influence of reduced apical oxygen levels on EHEC colonization. While apical microaerobiosis did not affect cell integrity and barrier function, numbers of adherent bacteria were significantly increased under low compared with high apical oxygen concentrations. In addition, expression and translocation of EHEC type III secreted (T3S) effector proteins was considerably enhanced under microaerobic conditions and dependent on the presence of host cells. Increased colonization was mainly mediated via EspA as adherence levels of an isogenic deletion mutant were not influenced by low oxygen levels. Other potential adherence factors (E. coli common pilus and flagella) were only minimally expressed under high and low oxygen levels. Addition of nitrate and trimethylamine N-oxide as terminal electron acceptors for anaerobic respiration failed to further increase bacterial colonization or T3S under microaerobiosis. This study indicates that EHEC T3S and colonization are enhanced by the microaerobic environment in the gut and therefore might be underestimated in conventional aerobic cell culture systems.


Differential effects of systemic prostaglandin E2 on bone mass in rat long bones and calvariae.
Prostaglandin E2 (PGE2) has been shown to possess anabolic properties when administered systemically. All the experiments performed so far examined long bones from animals of varying age and bone status. In this study we compared the changes in bone mass of long bones (femur, tibia and humerus) to those in calvariae after a 3-week daily administration of 6 mg/kg PGE2 into 3-week-old rats. This regimen inhibited body weight gain (by 14.1%) as well as longitudinal growth of long bones (by 2.2-3.5%) but increased their mass. Ash weight (measuring both cancellous and compact bone) increased by 10.1-14.1% but tibial cancellous bone area was elevated by 54%. Radial growth was slightly reduced due to transient inhibition of mineral apposition rate at the periosteal envelope but the expansion of the marrow cavity was inhibited to a greater extent, resulting in an 8.1% increase in the relative compact bone area. The increased bone mass was associated with greater mechanical strength of the femoral neck (24.2% increase in fracture load and 19% in stiffness). In contrast, PGE2 administration did not affect calvarial thickness or mineral apposition rate but increased its density, i.e. reduced the area of marrow spaces due to stimulation of endocortical bone formation at this site. The pattern of bone mass changes documented in this study closely correlates with that of the induced expression of early-response genes following a single dose of PGE2 as we recently reported. These data, therefore, support the hypothesis that in vivo administration of an anabolic dose of PGE2 increases bone formation and augments bone mass largely by stimulating the recruitment of new osteoblasts via induction of the proliferation and/or differentiation of bone marrow osteogenic precursors.


[Can telemedicine re-establish geographic equity in the treatment of acute stroke?].
In acute stroke patients, urgent expert neurologic evaluation and thrombolytic treatment within the first hours alter onset are the only proven effective therapeutic measures. Patients living far from large hospitals do not have access to these measures. Implementing a telemedicine system allows that patients with suspected acute stroke admitted to a community hospital could be urgently evaluated by a specialized vascular neurologist located in a Reference Stroke Center. This paper reviews the best care access geographic equity imbalances created after the approval of acute stroke treatments and the solutions offered by the new telecommunication technologies. Telemedicine systems allow around the clock specialized urgent evaluation of those patients arriving to hospitals lacking a neurologist on call. This may lead to the use of thrombolytic treatments in community hospitals under the supervision of an expert physician, reducing time to treatment and the number of unnecessary patient transfers to referral Stroke Centers.


Metacommunity theory explains the emergence of food web complexity.
Food webs are highly complex ecological networks, dynamic in both space and time. Metacommunity models are now at the core of unified theories of biodiversity, but to date they have not addressed food web complexity. Here we show that metacommunity theory can explain the emergence of species-rich food webs with complex network topologies. Our analysis shows that network branching in the food web is maximized at intermediate colonization rates and limited dispersal scales, which also leads to concomitant peaks in species diversity. Increased food web complexity and species diversity are made possible by the structural role played by network branches that are supported by omnivore and generalist feeding links. Thus, in contrast to traditional food web theory, which emphasizes the destabilizing effect of omnivory feeding in closed systems, metacommunity theory predicts that these feeding links, which are commonly observed in empirical food webs, play a critical structural role as food webs assemble in space. As this mechanism functions at the metacommunity level, evidence for its operation in nature will be obtained through multiscale surveys of food web structure. Finally, we apply our theory to reveal the effects of habitat destruction on network complexity and metacommunity diversity.


[Malunited juvenile upper and lower leg fractures. Spontaneous correction, complications, indication for corrective intervention].
If malunion occurs after shaft fractures of the femur or tibia, it often corrects itself spontaneously. If the remaining growth period is +/- 2 years, side to side dislocations, shortening and varus deformities (up to 15 degrees) are equalized. Valgus, recurvation and antecurvation equalize much more slowly and rotation deformities only at the femur. The indication to perform a corrective osteotomy before the end of growth is therefore rare, and the remaining axis deviations have a good long-term prognosis as far as arthritic changes are concerned. Exceptions of this rule are rotation deformities in the lower leg and progressive valgus after high tibial fractures. Contractures instabilities and overuse of neighbouring joints represent another indication for early correction osteotomies. Risk of damage to the growth plate limits the possibilities for performing corrective osteotomies in young children. On the other hand, stable fixation is of less importance. At the end of growth, the procedures are the same as for adults.


Social knowledge and signals in primates.
Primates are notable for having a rich and detailed understanding of their social environment and there has been great interest in the evolution and function of social knowledge in primates. Indeed, primates have been shown to have impressive understandings of not only other group members but also the complex relationships among them. To be useful, however, social knowledge requires memories from previous encounters and observations about individual traits that are stable. Here, we argue that social systems or traits that make social knowledge more costly or less accurate will favor signals that either supplement or replace social knowledge. Thus, the relationship between signals and social knowledge can be complementary or antagonistic depending on the type of signal. Our goal in this review is to elucidate the relationships between signals and social knowledge in primates. We categorize signals into three types, each with different relationships to social knowledge. (1) Identity signals directly facilitate social knowledge, (2) current-state signals supplement information gained through social knowledge, and (3) badges of status replace social knowledge. Primates rely extensively on identity information, but it remains to be determined to what extent this is based on receiver perception of individual variation or senders using identity signals. Primates frequently utilize current-state signals including signals of intent to augment their interactions with familiar individuals. Badges of status are rare in primates, and the cases where they are used point to a functional and evolutionary trade-off between badges of status and social knowledge. However, the nature of this relationship needs further exploration.


Incorporating scientific knowledge into phenotype development: penalized latent class regression.
The field of psychiatric genetics is hampered by the lack of a clear taxonomy for disorders. Building on the work of Houseman and colleagues (Feature-specific penalized latent class analysis for genomic data. Harvard University Biostatistics Working Paper Series, Working Paper 22, 2005), we describe a penalized latent class regression aimed at allowing additional scientific information to influence the estimation of the measurement model, while retaining the standard assumption of non-differential measurement. In simulation studies, ridge and LASSO penalty functions improved the precision of estimates and, in some cases of differential measurement, also reduced bias. Class-specific penalization enhanced separation of latent classes with respect to covariates, but only in scenarios where there was a true separation. Penalization proved to be less computationally intensive than an analogous Bayesian analysis by a factor of 37. This methodology was then applied to data from normal elderly subjects from the Cache County Study on Memory and Aging. Addition of APO-E genotype and a number of baseline clinical covariates improved the dementia prediction utility of the latent classes; application of class-specific penalization improved precision while retaining that prediction utility. This methodology may be useful in scenarios with large numbers of collinear covariates or in certain cases where latent class model assumptions are violated. Investigation of novel penalty functions may prove fruitful in further refining psychiatric phenotypes.


Preconditioning and postresuscitation injury.
A major challenge in improving cardiac arrest survival is organ injury that occurs after the return of spontaneous circulation. This postresuscitation injury may result in as many as 90% of such patients not surviving to hospital discharge. Preconditioning, an adaptive physiologic response found in multiple organs and species, may help protect against such injury of ischemic tissue when reperfused at the return of spontaneous circulation. A better understanding of how preconditioning may alter postresuscitation injury is important for two major reasons. First, it is one of the most protective adaptations currently known in nature that attenuates ischemia-reperfusion injury. Pharmacologic and nonpharmacologic means to quickly trigger and perhaps augment this response have the potential to greatly improve survival from the global ischemia of cardiac arrest. Second, potential targets of preconditioning-such as the adenosine triphosphate-sensitive potassium channel and NAD(P)H oxidases-likely play important roles in the postresuscitation phase of cardiac arrest, and their modification may be important components of future treatment for patients with return of spontaneous circulation. The evidence for postresuscitation injury at the cellular level and its modification by preconditioning are discussed.


[Medicine and medical concepts].
Any discussion on the future of medicine has to deal with the healer's art based on cultural values and with the individual situation of the patients, their perception and concept of health and disease, their hopes, intentions and life projects. Medicine and health care are of fundamental importance in all societies, so their task goes far beyond the traditional academic discipline. As well as repairing localized damage with the usual technical and chemical instruments one may also use the regulatory measures of complementary medicine to stimulate the system's self-organization. Over and above this, healing means changing the patient's self-concepts, his concepts of health and disease, changing his behavior, and adapting his life projects and targets. The treatment, therefore, should be experienced by the patient as part of his life, and therapeutic interventions as well as the diagnostic interpretation are to be seen as structuring elements of the healing process, besides, of course, being helpful in the overcoming of the disease. Healing does not happen in a void, but within a therapeutic setting, a sort of subcultural unit which includes the therapist, and is based on a common understanding of the illness and a common will to overcome it. The therapeutic setting is an integrative part of regulatory treatment, and evaluation procedure must be designed in a way that the questions asked are consistent with the specific individual reality of the setting and the evaluation has no impact on the setting as such. Therefore, research cannot be done by the therapist since he is part of the setting, but must be undertaken by independent observation of the setting as a whole from outside. The projects of the Nationales Forschungsprogramm 34 (NFP34) provide an overview of adequate and inadequate concepts and methods for future structured evaluation of complementary medicine. Whether or not the results of the NFP34 will be helpful in advancing medicine depends on the possibility of creating an appropriate research mentality in this new field within the medical community and to establish ongoing projects. Some important concepts of approaching complementary medicine have not been evaluated, e. g. historical, ethnological, sociological and pragmatic methods. As some methods of complementary medicine actually have been integrated into the official curricula, ongoing re-evaluation is mandatory to assure the conherence in teaching and practice. Research into complementary medicine which often has its roots in other times and in other cultures must be designed in such a way that it covers the method's specific cultural concepts as well as the thinking patterns of public medicine today.


Energy Availability in Athletics: Health, Performance, and Physique.
The reported prevalence of low energy availability (LEA) in female and male track and field athletes is between 18% and 58% with the highest prevalence among athletes in endurance and jump events. In male athletes, LEA may result in reduced testosterone levels and libido along with impaired training capacity. In female track and field athletes, functional hypothalamic amenorrhea as consequence of LEA has been reported among 60% of elite middle- and long-distance athletes and 23% among elite sprinters. Health concerns with functional hypothalamic amenorrhea include impaired bone health, elevated risk for bone stress injury, and cardiovascular disease. Furthermore, LEA negatively affects recovery, muscle mass, neuromuscular function, and increases the risk of injuries and illness that may affect performance negatively. LEA in track and field athletes may occur due to intentional alterations in body mass or body composition, appetite changes, time constraints, or disordered eating behavior. Long-term LEA causes metabolic and physiological adaptations to prevent further weight loss, and athletes may therefore be weight stable yet have impaired physiological function secondary to LEA. Achieving or maintaining a lower body mass or fat levels through long-term LEA may therefore result in impaired health and performance as proposed in the Relative Energy Deficiency in Sport model. Preventive educational programs and screening to identify athletes with LEA are important for early intervention to prevent long-term secondary health consequences. Treatment for athletes is primarily to increase energy availability and often requires a team approach including a sport physician, sports dietitian, physiologist, and psychologist.


Dietary treatment for regurgitation--recommendations from a working party.
Regurgitation is a common manifestation in infants below the age of 1 y, and is a frequent reason for counselling of general practitioners and paediatricians. Current recommended therapeutic management starts with parental reassurance and dietary measures, followed by prokinetics. In this paper, the efficacy, safety and nutritional implications of the dietary treatment of regurgitation are evaluated. Industrially prepared thickened feeds may contain cereals of fibres; some have a low lipid content and are casein-predominant. Milk-thickened agents can also be added to regular infant feeding. Formulae claimed as "anti-regurgitation formulae", or positioned as such, should be considered as medical foods or therapeutic diets, and only be available on medical prescription. It is proposed to limit the "anti-regurgitation" (AR) label to those diets which have been proven clinically effective on regurgitation and which are nutritionally safe.


HOST-PARASITE RELATIONSHIPS AMONG GROUP A STREPTOCOCCI. II. INFLUENCE OF SEX ON THE SUSCEPTIBILITY OF INBRED MICE TOWARD STREPTOCOCCAL INFECTION.
Willoughby, Donald S. (University of Minnesota, Minneapolis), and Dennis W. Watson. Host-parasite relationships among group A streptococci. II. Influence of sex on the susceptibility of inbred mice toward streptococcal infection. J. Bacteriol. 87:1457-1461. 1964-BALB/Sy mice showed marked sex differences in susceptibility to a strain of Streptococcus pyogenes type 18. Castration of the highly susceptible normal adult male increased their resistance 1,000-fold, which approximated that of normal female mice. Treatment of male mice with estrogen and stilbestrol did not affect their resistance significantly. Young, sexually immature male mice, 4 weeks old, were more resistant than mature males. Susceptibility of the resistant females was not affected by age or bilateral ovariectomy, but testosterone injections caused an increase in susceptibility. Treatment of male mice with estrogen and stilbestrol did not modify their resistance. Smears of peritoneal exudates from normal male mice after intraperitoneal injection of streptococci revealed rapid multiplication of the organisms. There was no evidence of multiplication in the resistant normal female and castrated male mice.


Estimating HIV-1 Genetic Diversity in Brazil Through Next-Generation Sequencing.
Approximately 36.7 million people were living with the human immunodeficiency virus (HIV) at the end of 2016 according to UNAIDS, representing a global prevalence rate of 0.8%. In Brazil, an HIV prevalence of 0.24% has been estimated, which represents approximately 830,000 individuals living with the virus. As a touristic and commercial hub in Latin America, Brazil harbors an elevated HIV genetic variability, further contributed by the selective pressure exerted by the host immune system and by antiretroviral treatment. Through the progress of the next-generation sequencing (NGS) techniques, it has been possible to expand the study of HIV genetic diversity, evolutionary, and epidemic processes, allowing the generation of HIV complete or near full-length genomes (NFLG) and improving the characterization of intra- and interhost diversity of viral populations. Greater sensitivity in the detection of viral recombinant forms represents one of the major improvements associated with this development. It is possible to identify unique or circulating recombinant forms using the near full-length viral genomes with increasing accuracy. It also permits the characterization of multiple viral infections within individual hosts. Previous Brazilian studies using NGS to analyze HIV diversity were able to identify several distinct unique and circulating recombinant forms and evidenced dual infections. These data unveiled unprecedented high rates of viral recombination and highlighted that novel recombinants are continually arising in the Brazilian epidemic. In the pooled analysis depicted in this report, HIV subtypes have been determined from HIV-positive patients in five states of Brazil with some of the highest HIV prevalence, three in the Southeast (Rio de Janeiro, São Paulo, and Minas Gerais), one in the Northeast (Pernambuco) and one in the South (Rio Grande do Sul). Combined data analysis showed a significant prevalence of recombinant forms (29%; 101/350), and a similar 26% when only NFLGs were considered. Moreover, the analysis was able to evidence the occurrence of multiple infections in some individuals. Our data highlight the great HIV genetic diversity found in Brazil and unveils a more accurate scenario of the HIV evolutionary dynamics in the region.


Stimulation of 1,25-dihydroxyvitamin D3 production by 1,25-dihydroxyvitamin D3 in the hypocalcaemic rat.
Serum 1,25-dihydroxyvitamin D3 concentration and renal 25-hydroxyvitamin D 1 alpha-hydroxylase activity were measured in rats fed various levels of calcium, phosphorus and vitamin D3. Both calcium deprivation and phosphorus deprivation greatly increased circulating levels of 1,25-dihydroxyvitamin D3. The circulating level of 1,25-dihydroxyvitamin D3 in rats on a low-calcium diet increased with increasing doses of vitamin D3, whereas it did not change in rats on a low-phosphorus diet given increasing doses of vitamin D3. In concert with these results, the 25-hydroxyvitamin D 1 alpha-hydroxylase activity was markedly increased by vitamin D3 administration to rats on a low-calcium diet, whereas the same treatment of rats on a low-phosphorus diet had no effect and actually suppressed the 1 alpha-hydroxylase in rats fed an adequate-calcium/adequate-phosphorus diet. The administration of 1,25-dihydroxyvitamin D3 to vitamin D-deficient rats on a low-calcium diet also increased the renal 25-hydroxy-vitamin D 1 alpha-hydroxylase activity. These results demonstrate that the regulatory action of 1,25-dihydroxyvitamin D3 on the renal 25-hydroxyvitamin D3 1 alpha-hydroxylase is complex and not simply a suppressant of this system.


Pulmonary resection for metastasis from renal cell carcinoma.
The treatment of metastatic renal cell carcinoma still represents a widely debated issue due to the introduction of several immunotherapies. To confirm again a role for resection of pulmonary metastases for such tumors, we reviewed our institutional experience. Between 1992 and 2007, eight patients with pulmonary metastases from renal cell carcinoma underwent complete pulmonary resection. All patients had undergone curative resection of their primary renal cell carcinomas and also had obtained or had obtainable locoregional control of their primaries. Various perioperative variables were investigated retrospectively. Disease-free interval varied from 25 to 156 months, with a median of 73 months. In three patients, lung metastases were found to be unilateral and solitary. Four patients presented two metastases in the unilateral lungs. One patient showed five metastases in the bilateral lungs. Six patients underwent wedge resection or segmentectomy, while two patients underwent more than lobectomy. Five patients showed recurrence after pulmonary metastasectomy. Five-year and 10-year overall survival rate was 83.3% and 41.7%, respectively, while 3-year and 5-year disease-free survival rate was 35.0% and 17.5%, respectively. Our study suggested that pulmonary metastasectomy for renal cell carcinoma might be well justified.


An unusual high-spin ground state of Co3+ in octahedral coordination in brownmillerite-type cobalt oxide.
The crystal and magnetic structures of brownmillerite-like Sr(2)Co(1.2)Ga(0.8)O(5) with a stable Co(3+) oxidation state at both octahedral and tetrahedral sites are refined using neutron powder diffraction data collected at 2 K (S.G. Icmm, a = 5.6148(6) Å, b = 15.702(2) Å, c = 5.4543(6) Å; R(wp) = 0.0339, R(p) = 0.0443, χ(2) = 0.775). The very large tetragonal distortion of CoO(6) octahedra (1.9591(4) Å for Co-O(eq) and 2.257(6) Å for Co-O(ax)) could be beneficial for the stabilization of the long-sought intermediate-spin state of Co(3+) in perovskite-type oxides. However, the large magnetic moment of octahedral Co(3+) (3.82(7)μ(B)) indicates the conventional high-spin state of Co(3+) ions, which is further supported by the results of a combined theoretical and experimental soft X-ray absorption spectroscopy study at the Co-L(2,3) edges on Sr(2)Co(1.2)Ga(0.8)O(5). A high-spin ground state of Co(3+) in Sr(2)Co(1.2)Ga(0.8)O(5) resulted in much lower in comparison with a LaCoO(3) linear thermal expansion coefficient of 13.1 ppm K(-1) (298-1073 K) determined from high-temperature X-ray powder diffraction data collected in air.


Neglected Comorbidity of Chronic Heart Failure: Iron Deficiency.
Iron deficiency is a significant comorbidity of heart failure (HF), defined as the inability of the myocardium to provide sufficient blood flow. However, iron deficiency remains insufficiently detected. Iron-deficiency anemia, defined as a decrease in hemoglobin caused by iron deficiency, is a late consequence of iron deficiency, and the symptoms of iron deficiency, which are not specific, are often confused with those of HF or comorbidities. HF patients with iron deficiency are often rehospitalized and present reduced survival. The correction of iron deficiency in HF patients is associated with improved functional capacity, quality of life, and rehospitalization rates. Because of the inflammation associated with chronic HF, which complicates the picture of nutritional deficiency, only the parenteral route can bypass the tissue sequestration of iron and the inhibition of intestinal iron absorption. Given the negative impact of iron deficiency on HF progression, the frequency and financial implications of rehospitalizations due to decompensation episodes, and the efficacy of this supplementation, screening for this frequent comorbidity should be part of routine testing in all HF patients. Indeed, recent European guidelines recommend screening for iron deficiency (serum ferritin and transferrin saturation coefficient) in all patients with suspected HF, regular iron parameters assessment in all patients with HF, and intravenous iron supplementation in symptomatic patients with proven deficiency. We thus aim to summarize all currently available data regarding this common and easily improvable comorbidity.


Impaired processing speed and attention in first-episode drug naive schizophrenia with deficit syndrome.
Although first-episode drug naive patients with schizophrenia are known to show cognitive impairment, the cognitive performances of these patients, who suffer deficit syndrome, compared with those who suffer non-deficit syndrome is undetermined. The aim of this study was to compare cognitive performances in first-episode drug-naive schizophrenia with deficit syndrome or non-deficit syndrome. First-episode drug naive patients (n=49) and medicated patients (n=108) with schizophrenia, and age, sex, and education matched healthy controls (n=57 for the first-episode group, and n=128 for the medicated group) were enrolled. Patients were divided into deficit or non-deficit syndrome groups, using the Schedule for Deficit Syndrome. Cognitive performance was assessed using the CogState computerized cognitive battery. All cognitive domains in first-episode drug naive and medicated patients showed significant impairment compared with their respective control groups. Furthermore, cognitive performance in first-episode drug naive patients was significantly worse than in medicated patients. Interestingly, the cognitive performance markers of processing speed and attention, in first-episode drug naive patients with deficit syndrome, were both significantly worse than in equivalent patients without deficit syndrome. In contrast, no differences in cognitive performance were found between the two groups of medicated patients. In conclusion, this study found that first-episode drug naive schizophrenia with deficit syndrome showed significantly impaired processing speed and attention, compared with patients with non-deficit syndrome. These findings highlight processing speed and attention as potential targets for pharmacological and psychosocial interventions in first-episode schizophrenia with deficit syndrome, since these domains are associated with social outcomes.


Classes and functions of Listeria monocytogenes surface proteins.
Listeria monocytogenes is an opportunistic pathogen that causes infections collectively termed listeriosis, which are related to the ingestion of food contaminated with these gram-positive rods. The pathogenicity of L. monocytogenes is determined by the following virulence factors: listeriolysin O, protein ActA, two phospholipases C, internalins (In1A and In1B), protein CwhA and a metalloprotease. The bacterium is a model organism in studies on the pathogenesis of intracellular parasites. It is able to penetrate, multiply and propagate in various types of eukaryotic cells and is also able to overcome the three main barriers encountered in the host: the intestinal barrier, the blood-brain barrier and the placenta. Based on L. monocytogenes genome sequence analysis 133 surface proteins have been identified. In particular, the large number of proteins covalently bound to murein sets L. monocytogenes apart from other gram-positive bacteria. The ability of this pathogen to multiply in various environments as well as the possibility of its interaction with many kinds of eukaryotic cells is, in fact, made possible by the large number of surface proteins.