Spatial working memory as a cognitive endophenotype of schizophrenia: assessing risk for pathophysiological dysfunction.
Research suggests that first-degree relatives and individuals with schizophrenia spectrum personality disorders (SSPD) may represent nonpenetrant carriers of the genetic diathesis for schizophrenia. This study examined visuospatial working memory (SWM) as a cognitive endophenotype of schizophrenia by expanding the concept of risk for pathophysiological dysfunction beyond overt psychosis. Risk was thus defined by familial status and the presence or absence of SSPD. SWM was assessed in the following groups, in order of decreasing likelihood of genetic vulnerability: 23 patients with schizophrenia, 17 SSPD relatives of patients with schizophrenia, 23 non-SSPD relatives of patients with schizophrenia, 14 SSPD community members with no family history of psychosis, and 36 non-SSPD community members. SWM performance during a computer task was quantified by A-Prime. Relative risk ratios for SWM deficits were compared among the groups. Compared with community non-SSPD volunteers, relative risk (RR) of SWM deficits was significantly elevated in patients with schizophrenia (RR = 3.76, p = .002) and SSPD family members (RR = 2.97, p = .027), but not in the family non-SSPD (RR = 1.88, p = .241) or community SSPD (RR = 1.03, p = .971) groups. The pattern of SWM performance deficits reflected the proposed model of latent genetic liability, upholding SWM as a viable cognitive endophenotype. The results underscore the importance of including both familial liability and the schizophrenia spectrum when considering risk for schizophrenia and schizophrenia-related traits. This is particularly relevant for research efforts to identify pathophysiological components of the disease.


Malpositioned implants in the anterior maxilla: a novel restorative approach to reestablish peri-implant tissue health and acceptable esthetics. Part I. Case presentation and treatment options.
This two-part case presentation describes the prosthetic challenge of managing complications after inadequate esthetic risk assessment, treatment planning, and implant positioning in the anterior maxilla. Here, the case report of a 50-year-old woman, referred after inappropriate execution of immediate implant placement, is presented. Different restorative treatment alternatives are proposed, excluding major surgical procedures. In the next part of the article, the advantages and shortcomings of the various prosthetic options will be discussed and the selected treatment revealed. The aim of this part of the article is to illustrate the importance of treatment planning, emphasizing that the correction of esthetic implant failures consistently leads to compromised results when compared to what could have been achieved first time round.


Artificial Host Molecules to Covalently Capture 8-Nitro-cGMP in Neutral Aqueous Solutions and in Cells.
New 1,3-diazaphenoxazine derivatives (nitroG-Grasp-Guanidine, NGG) have been developed to covalently capture 8-nitro-cGMP in neutral aqueous solutions, which furnish a thiol reactive group to displace the 8-nitro group and a guanidine unit for interaction with the cyclic phosphate. The thiol group was introduced to the 1,3-diazaphenoxazine skeleton through a 2-aminobenzylthiol group (NGG-H) and its 4-methyl (NGG-pMe) and 6-methyl (NGG-oMe) substituted derivatives. The covalent adducts were formed between the NGG derivatives and 8-nitro-cGMP in neutral aqueous solutions. Among the NGG derivatives, the one with the 6-methyl group (NGG-oMe) exhibited the most efficient capture reaction. Furthermore, NGG-H showed a cell permeability into HEK-293 and RAW 264.7 cells and reduced the intracellular 8-nitro-cGMP level. The NGG derivatives developed in this study would become a valuable tool to study the intracellular role of 8-nitro-cGMP.


[Increased levels of beta 2-microglobulin in peripheral blood mononuclear cells and hepatocytes in patients with chronic hepatitis type B].
The levels of beta 2-microglobulin (beta 2m) in peripheral blood mononuclear cells (PBMC) and livers from patients with chronic liver diseases type B were measured. Beta 2m of liver and PBMC in chronic active hepatitis was higher than those of controls (p less than 0.01, p less than 0.01). beta 2m of PBMC are directly proportional to those of livers (r = 0.746), beta 2m levels of PBMC in patients with chronic active hepatitis during the exacerbation of hepatitis was higher than those of remission of hepatitis. The levels of beta 2m in PBMC in vivo, was significantly increased during either interferon alpha or beta administration. Interferon-gamma positive cells in the liver were exacted in the beta 2m increased group of chronic hepatitis type B. INF-gamma production in the lymphocyte of livers, may play an important role in the occurrence of liver injury in patients with chronic hepatitis type B.


Anaerobic Performance after a Low-Carbohydrate Diet (LCD) Followed by 7 Days of Carbohydrate Loading in Male Basketball Players.
Despite increasing interest among athletes and scientists on the influence of different dietary interventions on sport performance, the association between a low-carbohydrate, high-fat diet and anaerobic capacity has not been studied extensively. The aim of this study was to evaluate the effects of a low-carbohydrate diet (LCD) followed by seven days of carbohydrate loading (Carbo-L) on anaerobic performance in male basketball players. Fifteen competitive basketball players took part in the experiment. They performed the Wingate test on three occasions: after the conventional diet (CD), following 4 weeks of the LCD, and after the weekly Carbo-L, to evaluate changes in peak power (PP), total work (TW), time to peak power (TTP), blood lactate concentration (LA), blood pH, and bicarbonate (HCO₃-). Additionally, the concentrations of testosterone, growth hormone, cortisol, and insulin were measured after each dietary intervention. The low-carbohydrate diet procedure significantly decreased total work, resting values of pH, and blood lactate concentration. After the low-carbohydrate diet, testosterone and growth hormone concentrations increased, while the level of insulin decreased. After the Carbo-L, total work, resting values of pH, bicarbonate, and lactate increased significantly compared with the results obtained after the low-carbohydrate diet. Significant differences after the low-carbohydrate diet and Carbo-L procedures, in values of blood lactate concentration, pH, and bicarbonate, between baseline and post exercise values were also observed. Four weeks of the low-carbohydrate diet decreased total work capacity, which returned to baseline values after the carbohydrate loading procedure. Moreover, neither the low-carbohydrate feeding nor carbohydrate loading affected peak power.


Malignant melanoma of the vagina: report of two cases and review of the literature.
Vaginal melanoma (VM) is a rare disease comprising <1% of all melanomas among women, and about 3% of all vaginal malignancies. Patients experience a poor prognosis, showing <15% 5-year survival. The report concerns two premenopausal patients with VM treated by surgery with radical intent. The first patient presented with a large lesion also infiltrating the proximal paracolpium and the bladder. The second patient had a persistent lesion of the lower third of the vagina. However, in the absence of any evidence-based guidelines or even clear suggestions from the literature, it is reasonable to believe that an appropriate management of primary malignant VM should address the radical tumor resection with wide tumor-free surgical margins and symptom relief.


Complete unloading alone may not adequately protect the left ventricle.
The benefit of left ventricular (LV) unloading for preserving LV function is commonly accepted, but its efficacy remains incompletely defined. We studied the influence of complete LV unloading on LV systolic and diastolic mechanics using an in situ isovolumic preparation with two different coronary perfusion pressures (CPPs) in 12 dogs during prolonged normothermic cardiopulmonary bypass. Multivariate analysis of covariance with time as a covariate revealed that a high CPP (143 +/- 36 mm Hg; n = 6) was associated with better preservation of systolic LV function over time as assessed by LV end-systolic elastance (p < 0.001) and the end-systolic pressure-volume relation physiologic intercept (p < 0.001) compared with a moderate CPP (107 +/- 18 mm Hg; p < 0.005 versus a high CPP by t-test; n = 6). Dobutamine (2 micrograms.kg-1.min-1) improved LV end-systolic elastance (p < 0.005) and LV physiologic intercept (p < 0.01) only in the high-CPP group. Conversely, impaired LV diastolic function (as measured by LV stiffness) was observed (p < 0.001) with a high CPP, but did not change with a moderate CPP. These observations in canine hearts suggest that complete LV unloading may not preserve LV systolic function adequately over time when CPP is maintained in the accepted clinical range. A higher CPP is required to prevent deterioration over prolonged cardiopulmonary bypass times, but diastolic dysfunction still occurs.


Cochlea-scaled spectral entropy predicts rate-invariant intelligibility of temporally distorted sentences.
Some evidence, mostly drawn from experiments using only a single moderate rate of speech, suggests that low-frequency amplitude modulations may be particularly important for intelligibility. Here, two experiments investigated intelligibility of temporally distorted sentences across a wide range of simulated speaking rates, and two metrics were used to predict results. Sentence intelligibility was assessed when successive segments of fixed duration were temporally reversed (exp. 1), and when sentences were processed through four third-octave-band filters, the outputs of which were desynchronized (exp. 2). For both experiments, intelligibility decreased with increasing distortion. However, in exp. 2, intelligibility recovered modestly with longer desynchronization. Across conditions, performances measured as a function of proportion of utterance distorted converged to a common function. Estimates of intelligibility derived from modulation transfer functions predict a substantial proportion of the variance in listeners' responses in exp. 1, but fail to predict performance in exp. 2. By contrast, a metric of potential information, quantified as relative dissimilarity (change) between successive cochlear-scaled spectra, is introduced. This metric reliably predicts listeners' intelligibility across the full range of speaking rates in both experiments. Results support an information-theoretic approach to speech perception and the significance of spectral change rather than physical units of time.


Molecular Doping Increases the Semitransparent Photovoltaic Performance of Dilute Bulk Heterojunction Film with Discontinuous Polymer Donor Networks.
The semitransparent and colorful properties of organic solar cells (OSCs) attract intensive academic interests due to their potential application in building integrated photovoltaics, wearable electronics, and so forth. The most straightforward and effective method to tune these optical properties is varying the componential ratio in the blend film. However, the increase in device transmittance inevitably sacrifices the photovoltaic performance because of severe carrier recombination that originates from discontinuous charge-transport networks in the blend film. Herein, a strategy is proposed via the molecular-doping strategy to overcome these shortcomings. It is discovered that p-doping is able to release the trapped holes in segregated polymer domains leading to short-circuit current enhancement, while n-doping is more effective to fill the bandgap states producing a higher fill factor. More importantly, either type of doping improves the photovoltaic performance in the semitransparent photovoltaic devices. These discoveries provide a new pathway to breaking the compromise between the photovoltaic performance and optical transmittance in semitransparent OSCs, and hold promise for their future commercialization.


Investigating endothelial invasion and sprouting behavior in three-dimensional collagen matrices.
Seeding a monolayer of primary human endothelial cells on the surface of a polymerized three-dimensional collagen matrix in the presence of pro-angiogenic stimuli allows manipulation and analysis of rapid sprouting responses. This protocol is useful for elucidating incompletely defined intracellular mechanisms downstream of pro-angiogenic factors that regulate sprout formation and initiation, and can also be used to test the efficacy of pro-and anti-angiogenic compounds. We present protocols to culture endothelial cells, prepare three-dimensional collagen matrices and quantify and image rapid endothelial sprouting responses (24 h). This protocol can be carried out using either type I or type II collagen matrices with primary endothelial cells isolated from macrovascular and microvascular sources of varying species.


U.S. cannabis laws projected to cost generic and brand pharmaceutical firms billions.
Legalization of cannabis by U.S. states is likely increasing the use of cannabis as an alternative to conventional pharmaceutical drugs. We examined how cannabis legalization between 1996 and 2019 affected stock market returns for listed generic and brand pharmaceutical companies and found that returns were 1.5-2% lower at 10 days after legalization. Returns decreased in response to both medical and recreational legalization, for both generic and brand drugmakers. Investors anticipate a single legalization event to reduce drugmaker annual sales by $3B on average.


Tunable Electrocatalytic Annulations of o-Arylalkynylanilines: Green and Switchable Syntheses of Skeletally Diverse Indoles.
Tunable electrocatalytic annulation reactions of o-arylalkynylanilines have been established, leading to green and divergent syntheses of skeletally diverse indoles by adjusting the electrolytes and the solvents. The presence of ammonium halides as the electrolytes enabled the halogenation of o-arylalkynylanilines to give C3-halogenated indoles whereas naphtho[1',2':4,5]furo[3,2-b]indoles could be obtained by changing the electrolyte from ammonium halides to KI. Interestingly, by combining acetone as the solvent and both NH4I and NH4Cl as the electrolytes, the reaction worked through an intramolecular annulation and [5 + 1] cyclization cascade to form naphtho[1',2':5,6][1,3]oxazino[3,4-a]indoles.


[Management of panfacial fractures--also an intubation problem].
Conventional oro- or nasotracheal intubation represents an obstacle in cases of panfacial fractures or elective operations of the facial skeleton above the Le Fort I level because of the intermaxillary fixation that often becomes necessary. Until recently, protection of the airway required tracheotomy with its well-known disadvantages of the usual intubations, which could compromise surgical strategies. A useful alternative method for protecting the airway involves the submental route for intubation and was first described in 1986 by Altemir. We present our experience with submandibular transmylohoid intubation in 14 patients. The technique is relatively simple and includes only a small risk potential. The cosmetic result of the extraoral incision required is good to excellent.


Distinct patterns of mitochondrial genome diversity in bonobos (Pan paniscus) and humans.
We have analyzed the complete mitochondrial genomes of 22 Pan paniscus (bonobo, pygmy chimpanzee) individuals to assess the detailed mitochondrial DNA (mtDNA) phylogeny of this close relative of Homo sapiens. We identified three major clades among bonobos that separated approximately 540,000 years ago, as suggested by Bayesian analysis. Incidentally, we discovered that the current reference sequence for bonobo likely is a hybrid of the mitochondrial genomes of two distant individuals. When comparing spectra of polymorphic mtDNA sites in bonobos and humans, we observed two major differences: (i) Of all 31 bonobo mtDNA homoplasies, i.e. nucleotide changes that occurred independently on separate branches of the phylogenetic tree, 13 were not homoplasic in humans. This indicates that at least a part of the unstable sites of the mitochondrial genome is species-specific and difficult to be explained on the basis of a mutational hotspot concept. (ii) A comparison of the ratios of non-synonymous to synonymous changes (dN/dS) among polymorphic positions in bonobos and in 4902 Homo sapiens mitochondrial genomes revealed a remarkable difference in the strength of purifying selection in the mitochondrial genes of the F0F1-ATPase complex. While in bonobos this complex showed a similar low value as complexes I and IV, human haplogroups displayed 2.2 to 7.6 times increased dN/dS ratios when compared to bonobos. Some variants of mitochondrially encoded subunits of the ATPase complex in humans very likely decrease the efficiency of energy conversion leading to production of extra heat. Thus, we hypothesize that the species-specific release of evolutionary constraints for the mitochondrial genes of the proton-translocating ATPase is a consequence of altered heat homeostasis in modern humans.


Free amino acids present in commercially available seedlings sold for human consumption. A potential hazard for consumers.
The importance of fresh seedlings for human consumption on European markets continues to increase. Although the contents of free amino acids and potentially toxic free nonprotein amino acids in these fresh and supposedly healthy seedlings is very different from those of the seeds, the crude composition is never mentioned on commercial packages. A commercial product containing seven different kinds of fresh seedlings including kamut, adzuki bean, chickpea, mungbean, pinto bean, garden pea, and lentil has been analyzed by HPLC. Per 100 g of fresh product, 548.2 mg of total free amino acids was found, of which 56.7 mg is free nonprotein amino acids including beta-(isoxazolin-5-on-2-yl)alanine, homoserine, and isowillardiine and the plant hormone trigonelline (N-methylnicotinic acid). The highest amounts of free nonprotein amino acids and trigonelline are found in garden pea (28.3 mg/100 g), mungbean (9.59 mg/100 g), and lentil (7.50 mg/100 g) seedlings. Trigonelline is present in all legume seedlings examined.


Report: seroprevalence of corynebacterium diphtheriae among vaccinated population of Rawalpindi/Islamabad, Pakistan.
Diphtheria is a communicable disease of global significance, and its outbreaks have to be reported to the world community under the International Health Regulations (IHR). A pilot seroepidemiological survey was conducted to assess immunity status of diphtheria among healthy individuals of Rawalpindi/Islamabad (Pakistan), who had been administered at least one dose of the vaccine against the disease, as part of childhood vaccination. The study group comprised of 128 healthy subjects, grouped according to the decade representing their age. Antidiphtheria IgG levels were measured by Enzyme Linked Immunosorbent Assay (ELISA) method. The studied sample showed 100% prevalence of diphtheria antitoxin, confirming prior vaccination; however 49.2% exhibited only minimal protection against diphtheria. Full protection was observed in a significantly higher (p=0.013) percentage of males (54.45%) as compared to female subjects (33.33%). Maximum level of serum antibodies were seen in 1-10 year age group (0.195+0.031 IU/mL), which was significantly higher than that recorded in the age group of 11-20 (p=0.024) and above 30 years (p=0.0064). The present results emphasize the need for periodical booster immunization in adolescents and adults, after primary childhood immunization.


Component and state separation in DMPC/DSPC lipid bilayers: a Monte Carlo simulation study.
In this paper a two-state, two-component, Ising-type model is used to simulate the lateral distribution of the components and gel/fluid state acyl chains in dimyristoylphosphatidylcholine/distearoylphosphatidylcholine (DMPC/DSPC) lipid bilayers. The same model has been successful in calculating the excess heat capacity curves, the fluorescence recovery after photobleaching (FRAP) threshold temperatures, the most frequent center-to-center distances between DSPC clusters, and the fractal dimensions of gel clusters (Sugar, I. P., T. E. Thompson, and R. L. Biltonen, 1999. Biophys. J. 76:2099-2110). Depending on the temperature and mole fraction the population of the cluster size is either homogeneous or inhomogeneous. In the inhomogeneous population the size of the largest cluster scales with the size of the system, while the rest of the clusters remain small with increasing system size. In a homogeneous population, however, every cluster remains small with increasing system size. For both compositional and fluid/gel state clusters, threshold temperatures-the so-called percolation threshold temperatures-are determined where change in the type of the population takes place. At a given mole fraction, the number of percolation threshold temperatures can be 0, 1, 2, or 3. By plotting these percolation threshold temperatures on the temperature/mole fraction plane, the diagrams of component and state separation of DMPC/DSPC bilayers are constructed. In agreement with the small-angle neutron scattering measurements, the component separation diagram shows nonrandom lateral distribution of the components not only in the gel-fluid mixed phase region, but also in the pure gel and pure fluid regions. A combined diagram of component and state separation is constructed to characterize the lateral distribution of lipid components and gel/fluid state acyl chains in DMPC/DSPC mixtures. While theoretical phase diagrams of two component mixtures can be constructed only in the case of first-order transitions, state and component separation diagrams can be constructed whether or not the system is involved in first-order transition. The effects of interchain interactions on the component and state separation diagrams are demonstrated on three different models. The influences of state and component separation on the in-plane and off-plane membrane reactions are discussed.


Pharmacists as Frontline Responders During COVID-19: Roles and Responsibilities Need to be Revisited.
The ongoing pandemic has disrupted the health care system, creating challenges for health care workers and patients alike. As workflows and job responsibilities have been adapted to provide care to coronavirus-infected patients, many primary care services have been postponed. This change has led to significant financial impacts that will be difficult to overcome. Ambulatory care pharmacists can help fill gaps both in access to primary care services and in the financial deficit, if given the opportunity to practice at the top of their skillset and bill for their face-to-face and telehealth services both during and after the pandemic.


Renal function in jaundiced patients: a prospective analysis.
A prospective analysis was undertaken to assess renal function in patients with obstructive jaundice. A total of 59 jaundiced patients (serum bilirubin > 100 mumol/l) undergoing biliary decompression by surgical, endoscopic or radiological means received prophylactic fluid volume expansion (3 litres crystalloid fluid intravenously) during the 24 hours before intervention. Renal function (urea and electrolytes, creatinine, creatinine clearance, urinary output) was assessed preoperatively and on days 1-7 and on day 28 postoperatively. Two jaundiced patients (3.4%) developed renal failure (urinary output < 400 ml in 24 hours in the presence of an increased serum urea and/or creatinine) and subsequently died. The overall incidence of post-procedural renal impairment (urinary output < 800 ml in 24 hours) was 10.2%. It is concluded that, with vigilant control of fluid and electrolyte balance and pre-procedural intravenous volume expansion, the incidence of renal dysfunction in patients with obstructive jaundice is not as high as previously reported.


[Prevention of complications: a forgotten aspect of therapy? Thromboembolic complications].
In Heart Failure (HF) there is a prothrombotic state or hypercoagulation by changing of the blood flow, and by endothelial vessels or blood viscosity changes. Although these alterations in HF, the indication for an anticoagulant therapy is not precise, generally being done an empirical therapy, being still as a forgotten aspect in preventing the complications of this syndrome. When anticoagulant therapy is implemented the hemorrhagic complications risk must be carefully observed, for a significant quantity of patients may need hospital care. In spite of the existence of guidelines of the European Society of Cardiology and of the American Society of Heart Failure the decision of hypocoagulation treatment must be studied case by case, considering multiple facts, as the social state of the patient, because this therapy needs a good follow-up, a clinical surveillance and a frequent laboratory control.


Competition between disordered iron sulfide and natural organic matter associated thiols for mercury(II)-an EXAFS study.
Knowledge about the chemical speciation of Hg(II) is a prerequisite for a proper understanding of biogeochemical processes in control of the transformation of Hg(II) into toxic and bioaccumulating monomethyl mercury. Of critical importance are structures and the stability of Hg(II)-complexes with inorganic and organic sulfur ligands in aqueous and solid phases of soils and sediments. On the basis of Hg L(III)-edge EXAFS experiments, we report Hg(II) to form a four-coordinated metacinnabar [beta-HgS(s)] phase when reacted with disordered FeS(s) (mackinawite), at pH 9.0 and a Hg(II) to FeS(s) molar ratio of 0.002-0.012. When Hg(II) (1000-20,000 microg Hg g(-1)) was added to mixtures of <5 days of aged FeS(s) (2-20%) and an organic soil at pH 5.7-6.1, a mixture of Hg(II) coordinated with two organic thiols [Hg(SR)(2)] and Hg(II) coordinated with four inorganic sulfides in a metacinnabar-like phase was formed. Surface complex formation between Hg(II) and FeS(s), or substitution of Hg(II) for Fe(II) in FeS(s), was not observed. Quantities of beta-HgS(s) and Hg(SR)(2) formed (as determined by EXAFS) were in fair agreement with theoretical thermodynamic calculations, as described by the reaction: Hg(SR)(2) + FeS(s) = HgS(s) + Fe(2+) + 2RS(-). The calculated stability constant for this reaction (log K = -16.1 - -15.4) supports a strong bonding of Hg(II) to organic thiols, corresponding to a log beta(2) for the formation of Hg(SR)(2) on the order of 42 or greater.


Inflammatory Cytokines in Nonpathological States.
During infection, inflammatory cytokines induce regulated changes in the host's internal milieu that create a hostile environment to an invading pathogen. Recent evidence indicates that these cytokines are constitutively produced, their production is increased by environmental stressors other than microbes, and they modulate "normal" physiological processes.


[Cura sui--selfcare and its relationship to nursing].
Self care is an answer to the response of finiteness, which is given through the fact of the human body. The article demonstrates in reference to the Selfcaredeficit-Theory (Orem, 2006) how self care in everyday life, ancient roman called it cura sui, is related to nursing practice, specially to acutecare. Self care turns out as an category of ambivalence between ethics and power.


Identification of and Associations among Low, Middle, and High Body Composition Trajectories from Age 5- to 17-Years.
Our objective was to identify sex-specific age 5- to 17-year body composition (body mass index (BMI), % body fat, fat mass index, fat-free mass index) trajectories, compare trajectories assigned using age 5 (AGE5) data to those assigned using all available (ALL) data, and compare BMI assignments to other body composition assignments. Cluster analysis was used to identify low, medium, and high trajectories from body composition measures obtained from dual energy x-ray absorptiometry (DXA) scans at 5, 9, 11, 13, 15, and 17 years in a birth cohort followed longitudinally (n = 469). Moderate agreement was observed for comparisons between AGE5 data and ALL data cluster assignments for each body composition measure. Agreement between cluster assignments for BMI and other body composition measures was stronger using ALL data than using AGE5 data. Our results suggest that BMI, % body fat, fat mass index, and fat free mass index trajectories are established during early childhood, and that BMI is a reasonable predictor of body composition appropriate to track obesity in public health and clinical settings.


Effect of mibefradil on voltage-dependent gating and kinetics of T-type Ca(2+) channels in cortisol-secreting cells.
We have studied the effect of the Ca(2+) antagonist mibefradil on low voltage-activated T-type Ca(2+) channels in whole-cell patch clamp recordings from bovine adrenal zona fasciculata (AZF) cells. AZF cells are distinctive in expressing only T-type Ca(2+) channels, allowing the mechanism of pharmacological agents to be explored without interference from other Ca(2+) channels. The inhibition of T-type Ca(2+) channels by mibefradil was voltage- and use-dependent. When Ca(2+) currents were activated from holding potentials of -80 and -60 mV, mibefradil inhibited currents with IC(50) values of 1.0 and 0.17 microM, respectively. When T-type Ca(2+) current (I(T)) was activated from a holding potential of -90 mV in the presence of 2 microM mibefradil, a single voltage step to -10 mV inhibited I(T) by 16.2% +/- 2.9% (n = 10). With subsequent voltage steps, applied at 10-s intervals, block reached a steady-state value of 51.9% +/- 5.0% (n = 5). Mibefradil (1 microM) produced a leftward shift of 5.7 mV (n = 4) in the voltage-dependent steady-state availability curve such that T-type Ca(2+) channels inactivated at more negative potentials, but this drug did not change the voltage-dependence of T channel opening. Mibefradil failed to alter the kinetics of T channel activation, inactivation, or deactivation, but markedly slowed T channel recovery following an inactivating prepulse. Mibefradil inhibited adrenocorticotropin-stimulated cortisol secretion from AZF cells with an IC(50) value of 3.5 microM. These results show that mibefradil is a relatively potent antagonist of T-type Ca(2+) channels in cortisol-secreting cells. The enhanced potency of mibefradil with sustained or repetitive depolarizations, its shifting of the steady-state inactivation curve, and its slowing of recovery all indicate that this drug preferentially interacts with Ca(2+) channels in the open or inactivated state. The inhibition of cortisol secretion by mibefradil at concentrations similar to those that block I(T) is consistent with a requirement for these channels in corticosteroidogenesis.


Markers of vulnerability in schizophrenia.
Vulnerability in schizophrenia is an integrative concept, which tries to explain the development of schizophrenia as an interaction between different individual susceptibility factors and environmental risk factors. Vulnerability markers used in genetic studies include biochemical indicators, neuroanatomical, neurophysiologic, and cognitive abnormalities. Among those, the most extensive studied markers were: evoked potentials, smooth pursuit eye movements, and attentional deficits. Some of the potential indicators presented in this paper satisfy most of the criteria necessary for a vulnerability marker, but none meets all of them. Nevertheless, they represent important markers of risk to schizophrenia.


Stability of the visual world during eye drift.
We are normally not aware of the microscopic eye movements that keep the retinal image in motion during visual fixation. In principle, perceptual cancellation of the displacements of the retinal stimulus caused by fixational eye movements could be achieved either by means of motor/proprioceptive information or by inferring eye movements directly from the retinal stimulus. In this study, we examined the mechanisms underlying visual stability during ocular drift, the primary source of retinal image motion during fixation on a stationary scene. By using an accurate system for gaze-contingent display control, we decoupled the eye movements of human observers from the changes in visual input that they normally cause. We show that the visual system relies on the spatiotemporal stimulus on the retina, rather than on extraretinal information, to discard the motion signals resulting from ocular drift. These results have important implications for the establishment of stable visual representations in the brain and argue that failure to visually determine eye drift contributes to well known motion illusions such as autokinesis and induced movement.


Impaired mouse fertilization by low chronic alcohol treatment.
Little is known about the effects of low chronic alcohol intake on fertility, particularly in females. Recently, we have shown that chronic 10% (w/v) ethanol treatment affects in-vitro fertilization of mouse female gamete. The aim of this study was to solve questions concerning the lowest dose and duration of ethanol treatment required to alter the fertility of immature and adult female and adult male mouse. Mice were treated with 5% and 2.5% (w/v) ethanol in drinking water for 4 weeks. The in-vitro fertilization rates were significantly decreased with the 5% ethanol when oocytes from prepubertal and pubertal ethanol-treated females were inseminated with spermatozoa from adult control males. The in-vitro fertilization rates were not diminished when oocytes from control females were inseminated with spermatozoa from adult ethanol-treated males. Haploid oocytes were increased when oocytes came from immature females treated with ethanol. The in-vitro fertilization rates were not decreased in adult treated females. The in-vivo fertilization rates were not modified when prepubertal ethanol-treated females were mated with adult control males. Fragmented oocytes, in the in-vitro fertilization experiments, were significantly increased when they came from prepubertal and adult treated females inseminated with ethanol-treated males. These results show that there is a threshold of the ethanol dose to produce an effect. Chronic low ethanol ingestion by immature female mice has a deleterious effect on their in-vitro fertilization. Furthermore, acute ethanol ingestion by adult females during the induction of ovulation resulted in high parthenogenetic activation and fragmentation of mouse oocytes.


Acute Myocardial Infarction among Young Adult Men in a Region with Warm Climate: Clinical Characteristics and Seasonal Distribution.
The aim of this cross sectional study was to investigate the influence of the seasons on acute myocardial infarction (AMI) among young adult among young adults aged <45 years compared to old adults aged ≥45 years. The seasonal distribution of AMI hospital admissions among young adult men in eastern Taiwan was assessed. Data were extracted from 1413 male AMI patients from January 1994 to December 2015, including onset date, the average temperature (Tave) on the date of AMI hospitalization (AMI-Tave), and conventional risk factors, notably smoking, diabetes, hypertension, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index (BMI). The 1413 cases were divided into two groups: the young group (n = 138, <45 y/o) and the older group (n = 1275, ≥45 y/o). The differences between groups were examined. Logistic regression analyses were used to evaluate the associations between the seasons and the AMI hospitalization among the young group. The young group showed significantly higher percentage of smokers, BMI, total cholesterol levels, and triglycerides levels but lower percentage of diabetes and hypertension than the older group (p < 0.05). AMI hospitalization in winter was significantly greater compared to the other seasons among the young group (p < 0.05). Winter hospitalization was significantly associated with the young group relative to the older group (adjusted OR 1.750; 95% CI 1.151 to 2.259), while winter AMI-Tave in the young group was similar to that in the older group. Young adult men diagnosed with AMI are more likely than older adult men to be smokers, obese, and show an onset dependent on winter but not low-temperature in a region with a warm climate.


[Expressions of E-cadherin and N-cadherin in prostate cancer and their implications].
To investigate the differences in the expressions of E-cadherin and N-cadherin between high-risk prostate cancer and low- and medium-risk prostate cancer, and analyze their correlation with the age, serum PSA level, and Gleason score of the patients. We retrospectively analyzed the clinical data of 42 cases of prostate cancer, which were divided into a low- and medium-risk group (group A, n = 15) and a high-risk group (group B, n = 27). We measured the expressions of E-cadherin and N-cadherin by immunohistochemical staining, compared their differences between the two groups, and analyzed their correlation with the age, serum PSA level, and Gleason score of the patients. Immunohistochemical staining showed that the expression of E-cadherin was significantly higher in group A than in B (6.1 +/- 0.51 vs 4.2 +/- 0.37, P < 0.01), and so was its positive rate (73.3% vs 25.9%, P < 0.05). The positive rate of E-cadherin was also markedly higher in the patients with serum PSA < 20 microg/L than in those with serum PSA > or = 20 microg/L (66.7% vs 29.6%, P < 0.05), and so was it in the patients with the Gleason score 5-7 than in those with 8-10 (60.9% vs 21.1%, P < 0.05). On the contrary, the N-cadherin expression was significantly lower in group A than in B (3.7 +/- 0.32 vs 7.5 +/- 0.58, P < 0.01), and so was its positive rate (13.3% vs 59.3%, P < 0.01). The positive rate of N-cadherin was also remarkably lower in the patients with the Gleason score 5-7 than in those with 8-10 (26.1% vs 63.2%, P < 0.05). However, there were no statistically significant differences in the N-cadherin expression between the patients with serum PSA < 20 microg/L and those with serum PSA > or = 20 microg/L (P > 0.05), nor in the expressions of E-cadherin and N-cadherin between the patients aged > or = 70 years and those aged < 70 years (P > 0.05). The expressions of E-cadherin and N-cadherin are significantly different between high-risk prostate cancer and low- and medium-risk prostate cancer, which suggests that both may correlate with the invasion and metastasis of prostate cancer as well as with the serum PSA level and Gleason score of the patients.


Dynamic turnover of centromeres drives karyotype evolution in Drosophila.
Centromeres are the basic unit for chromosome inheritance, but their evolutionary dynamics is poorly understood. We generate high-quality reference genomes for multiple Drosophila obscura group species to reconstruct karyotype evolution. All chromosomes in this lineage were ancestrally telocentric and the creation of metacentric chromosomes in some species was driven by de novo seeding of new centromeres at ancestrally gene-rich regions, independently of chromosomal rearrangements. The emergence of centromeres resulted in a drastic size increase due to repeat accumulation, and dozens of genes previously located in euchromatin are now embedded in pericentromeric heterochromatin. Metacentric chromosomes secondarily became telocentric in the pseudoobscura subgroup through centromere repositioning and a pericentric inversion. The former (peri)centric sequences left behind shrunk dramatically in size after their inactivation, yet contain remnants of their evolutionary past, including increased repeat-content and heterochromatic environment. Centromere movements are accompanied by rapid turnover of the major satellite DNA detected in (peri)centromeric regions.


A perspective on Councils on Chiropractic Education accreditation standards and processes from the inside: a narrative description of expert opinion: Part 2: Analyses of particular responses to research findings.
This is the second article reporting on a study that sought the views of people with extensive experience in Councils on Chiropractic Education (CCEs) on research that has raised concerns about variability in accreditation standards and processes for chiropractic programs (CPs) and chiropractic practice in general. This qualitative study employed in-depth semi-structured interviews that consisted of open-ended questions asking experts about their thoughts and views on a range of issues surrounding accreditation, graduate competency standards and processes. The interviews were audio-recorded, and transcribed verbatim in June and July of 2018. The transcripts were reviewed to develop codes and themes. The study followed the COREQ guidelines for qualitative studies. The interviews revealed that these CCE experts were able to discern positive and negative elements of the accreditation standards and processes. They were, in general, satisfied with CCEs accreditation standards, graduating competencies, and site inspection processes. Most respondents believed that it was not possible to implement an identical set of international accreditation standards because of cultural and jurisdictional differences. This was thought more likely to be achieved if based on the notion of equivalence. Also, they expressed positive views toward an evidence-based CP curriculum and an outcomes-based assessment of student learning. However, they expressed concerns that an evidence-based approach may result in the overlooking of the clinician's experience. Diverse views were found on the presence of vitalism in CPs. These ranged from thinking vitalism should only be taught in an historical context, it was only a minority who held this view and therefore an insignificant issue. Finally, that CCEs should not regulate these personal beliefs, as this was potentially censorship. The notable absence was that the participants omitted any mention of the implications for patient safety, values and outcomes. Expert opinions lead us to conclude that CCEs should embrace and pursue the widely accepted mainstream healthcare standards of an evidence-based approach and place the interests of the patient above that of the profession. Recommendations are made to this end with the intent of improving CCE standards and processes of accreditation.


Self-concept of college students with ADHD: discordance between self- and parent-reports.
To investigate the self-concept of college students with ADHD. College students with ADHD and their parents completed self-report and observer-report measures of self-concept, respectively. Results indicated that college students with ADHD did not report problems with self-concept but their parents did for them. This difference was statistically significant and large in magnitude (d = .84). Perceptions of the self-concept of college students with ADHD appear to vary by informant source. Hypotheses for the discordance between self- and parent-reports are discussed. Multi-informant assessment is recommended as a way to obtain a more complete clinical picture than reliance on self- or parent-report alone.


The neglected burden of stroke in Sub-Saharan Africa.
The looming epidemic of stroke and other chronic non-communicable diseases associated with lifestyle and demographic transitions occurring all over the world is increasingly being acknowledged. However, the significance of these trends in the relatively young populations of the countries comprising Sub-Saharan Africa (SSA) is less certain and considerably overshadowed by attention given to the impact of human immunodeficiency virus and other infectious diseases. We undertook a literature review of the burden of stroke in SSA and provide recommendations for future research. Despite the paucity of high quality studies, the mostly hospital-based data and limited community surveys indicate there to be high and increasing rates of stroke affecting people at much younger ages in SSA than in developed countries. In general, awareness, diagnosis and management of stroke are poor, and the associated case fatality and residual disability are high. As elsewhere, elevated blood pressure is the major determinant of stroke but there are also high rates of strokes related to the complications of rheumatic heart disease and other infections. Given high attributable risks exposures in association with rapid ageing and urbanisation in SSA, the future is not bright. Population-based incidence studies are urgently needed to map the profile and outcome of stroke. Such data would provide the necessary evidence base to improve prevention and treatments for stroke alongside current efforts to bring infectious diseases under control in SSA.


Total Synthesis of Beshanzuenone D and Its Epimers and Abiespiroside A.
A unified and protecting-group-free six-step total synthesis of bisabolane-type sesquiterpenoid beshanzuenone D and its stereoisomers and abiespiroside A using S-(+)-carvone as a common chiral-pool building block is disclosed. This synthetic route features chemoselective allylic chlorination of carvone, Au(I)-catalyzed cycloisomerization induced construction of furan from homopropargylic diol, substrate-controlled selective hydroxylation using Davis-oxaziridine, and dye-sensitized photo-oxidation (through 1O2) of hydroxyalkyl tethered furan to access oxaspirolactone as key transformations. A comprehensive set of NMR data along with DFT calculations, ECD spectra, and optical rotation measurements of the synthesized beshanzuenone D and its epimers were obtained to confirm absolute configurations.


Solubility enhancement of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) using polypolypropylene oxide core PAMAM dendrimers.
The aim of the present study was to evaluate the aqueous solubility enhancement properties of polypropylene oxide cored PAMAM (PPO@PAMAM) dendrimers. The solubility of NSAIDs (Ketoprofen, Ibuprofen and Diflunisal) was investigated in the presence of PPO@PAMAM dendrimers at room temperature in buffer solution. The effects of dendrimer concentration, generation and core size on the solubility of NSAIDs have been investigated. The experimental results showed that the solubility of the NSAIDs was approximately proportional to dendrimer concentration and generation. In addition, the effect of core size on the solubility of NSAIDs in constant generation and concentration of PPO@PAMAM dendrimer was Ketoprofen>Diflunisal>Ibuprofen. Under optimized conditions, PPO@PAMAM dendrimers are highly effective solubility enhancer for NSAIDs due to its new polypropylene oxide core.


Accurate Measurement Calculation Method for Interferometric Radar Altimeter-Based Terrain Referenced Navigation.
In order to improve the performance of Terrain Referenced Navigation (TRN), an Interferometric Radar Altimeter (IRA) has been developed as a more accurate altimeter. The IRA outputs not only the relative distance (slant range, R) but also the cross-track angle (look angle, θ) of the closest point on the zero Doppler line by using the principle of interferometry and two or more antennas. To perform TRN using the IRA, the 3D relative position of the closest point should be calculated. There is a formula to calculate the relative position of the closest point using the Euler angles. However, in an actual flight environment in which the influence of wind exists, the angle of attack, the side slip angle and "the effective look angle" should be used rather than the Euler angles. In this paper, a new formula for calculating the relative position of the closest point is proposed and mathematically derived. The proposed formula was verified with real data from actual flight. The flight test results show that the positions of the closest points calculated using the conventional method and the proposed method are different because of the wind effect. The TRN simulation results indicate that the proposed formula calculates the closest points more accurately than the conventional formula.


Metabolic priming by a secreted fungal effector.
Maize smut caused by the fungus Ustilago maydis is a widespread disease characterized by the development of large plant tumours. U. maydis is a biotrophic pathogen that requires living plant tissue for its development and establishes an intimate interaction zone between fungal hyphae and the plant plasma membrane. U. maydis actively suppresses plant defence responses by secreted protein effectors. Its effector repertoire comprises at least 386 genes mostly encoding proteins of unknown function and expressed exclusively during the biotrophic stage. The U. maydis secretome also contains about 150 proteins with probable roles in fungal nutrition, fungal cell wall modification and host penetration as well as proteins unlikely to act in the fungal-host interface like a chorismate mutase. Chorismate mutases are key enzymes of the shikimate pathway and catalyse the conversion of chorismate to prephenate, the precursor for tyrosine and phenylalanine synthesis. Root-knot nematodes inject a secreted chorismate mutase into plant cells likely to affect development. Here we show that the chorismate mutase Cmu1 secreted by U. maydis is a virulence factor. The enzyme is taken up by plant cells, can spread to neighbouring cells and changes the metabolic status of these cells through metabolic priming. Secreted chorismate mutases are found in many plant-associated microbes and might serve as general tools for host manipulation.


Pediatric Digit Replantation Following Traumatic Amputation: Nationwide Analysis of Patient Selection, Outcomes, and Cost.
Background: Indications for replantation following traumatic digit amputations are more liberal in the pediatric population than in adults, but delineation of patient selection within pediatrics and their outcomes have yet to be elucidated. This study uses a national pediatric database to evaluate patient characteristics and injury patterns involved in replantation and their outcomes. Methods: The Healthcare Cost and Utilization Project Kid's Inpatient Database was queried for traumatic amputations of the thumb and finger from 2000 to 2012. Participants were separated into those who underwent replantation and those who underwent amputation. Patients undergoing replantation were further divided into those requiring revision amputation and/or microvascular revision. Patient age, sex, insurance, digit(s) affected, charges, length of stay, and complications were extracted for each patient. Results: Traumatic digit amputations occurred in 3090 patients, with 1950 (63.1%) undergoing revision amputation and 1140 (36.9%) undergoing replantation. Younger patients, those with thumb injuries, females, and those covered under private insurance were significantly more likely to undergo replantation. Cost, length of stay, and in-hospital complications were significantly greater in replantation patients than in those who had undergone amputation. Following replantation, 237 patients (20.8%) underwent revision amputation and 209 (18.3%) underwent vascular revision, after which 58 required revision amputation. Risk of revision following replantation involved older patients, males, and procedures done recently. Conclusions: Pediatric patients who underwent replantation were significantly younger, female, had thumb injuries, and were covered by private insurance. Our findings demonstrate that in addition to injury factors, demographics play a significant role in the decision for finger replantation and its outcomes.


Growth of in-doped ZnO hollow spheres composed of nanosheets networks and nanocones: structural and optical properties.
This work reports the facile growth and characterizations of In-doped ZnO hollow spheres composed of nanosheets networks and nanocones. The In-doped ZnO hollow spheres composed of nanosheets networks and nanocones were grown on Si (100) substrate by simple and non-catalytic thermal evaporation process using metallic zinc and indium powders in the presence of oxygen. The prepared materials were examined in terms of their morphological, compositional, structural and optical properties. The detailed morphological studies revealed that the synthesized products are hollow spheres composed of nanosheet networks and nanocones and grown in high-density. The observed structural properties exhibited well-crystallinity and wurtzite hexagonal phase for the grown materials. The room-temperature photoluminescence (PL) spectrum showed a broad band in the visible region with a suppressed UV emission and hence due the enhancement in the green emission, the prepared materials exhibits a great interest in the area of ZnO phosphors, such as field emissive display technology, etc.


Epidermal growth factor inhibits glycylsarcosine transport and hPepT1 expression in a human intestinal cell line.
The human intestinal cell line Caco-2 was used as a model system to study the effects of epidermal growth factor (EGF) on peptide transport. EGF decreased apical-to-basolateral fluxes of [(14)C]glycylsarcosine ([(14)C]Gly-Sar) up to 50.2 +/- 3.6% (n = 6) of control values. Kinetic analysis of the fluxes showed that maximal flux (V(max)) of transepithelial transport decreased from 3.00 +/- 0.17 nmol x cm(-2) x min(-1) in control cells to 0.50 +/- 0.07 nmol x cm(-2) x min(-1) in cells treated with 5 ng/ml EGF (n = 6, P < 0.01). The apparent Michaelis-Menten constant (K(m)) was 2.71 +/- 0.31 mM (n = 6) in control cells and 1.89 +/- 0.28 mM (n = 6, not significantly different from control) in EGF-treated cells. Similarly, apical uptake of [(14)C]Gly-Sar decreased in cells treated with EGF, with an ED(50) value of 0.36 +/- 0.06 ng/ml (n = 6) EGF and a maximal inhibition of 80 +/- 0.02% (n = 6). V(max) decreased from 2.61 +/- 0.4 to 1.06 +/- 0.1 nmol x cm(-2) x min(-1) (n = 3, P < 0.05), whereas K(m) remained constant. Basolateral Gly-Sar uptake showed no changes in V(max) or K(m) after EGF treatment (n = 3). RT-PCR showed a decrease in hPepT1 mRNA (using glucose-6-phosphate dehydrogenase mRNA as control) in cells treated with EGF. Western blotting indicated a decrease in hPepT1 protein in cell lysates. We conclude that EGF treatment decreases Gly-Sar transport in Caco-2 cells by decreasing the number of peptide transporter molecules in the apical membrane.


SK Current, Expressed During the Development and Regeneration of Chick Hair Cells, Contributes to the Patterning of Spontaneous Action Potentials.
Chick hair cells display calcium (Ca2+)-sensitive spontaneous action potentials during development and regeneration. The role of this activity is unclear but thought to be involved in establishing proper synaptic connections and tonotopic maps, both of which are instrumental to normal hearing. Using an electrophysiological approach, this work investigated the functional expression of Ca2+-sensitive potassium [IK(Ca)] currents and their role in spontaneous electrical activity in the developing and regenerating hair cells (HCs) in the chick basilar papilla. The main IK(Ca) in developing and regenerating chick HCs is an SK current, based on its sensitivity to apamin. Analysis of the functional expression of SK current showed that most dramatic changes occurred between E8 and E16. Specifically, there is a developmental downregulation of the SK current after E16. The SK current gating was very sensitive to the availability of intracellular Ca2+ but showed very little sensitivity to T-type voltage-gated Ca2+ channels, which are one of the hallmarks of developing and regenerating hair cells. Additionally, apamin reduced the frequency of spontaneous electrical activity in HCs, suggesting that SK current participates in patterning the spontaneous electrical activity of HCs.


Complex Inclusion Bodies and Defective Proteome Hubs in Neurodegenerative Disease: New Clues, New Challenges.
A healthy physiological environment of cells represents the dynamic homeostasis of crowded molecules. A subset of cellular proteome forms protein quality control (PQC) machinery to maintain an uninterrupted synthesis of new polypeptides and targeted elimination of old or defective proteins. The process of PQC may get overwhelmed under specific genetic mutations, environmental stress conditions, and aging-associated perturbances. Many of these conditions may lead to the generation of various types of aberrant protein species that may or may not accumulate as large cellular inclusions. These proteinaceous formations, referred to as inclusion bodies (IBs), could be membrane-bound or membrane-less, cytoplasmic, or nuclear. Most importantly, they could either be toxic or protective. Under acute stress conditions, the formation of aggregates may cause proteostasis failure, leading to large-scale changes in the cellular proteome compositions. However, the large insoluble IBs may act as reservoirs for many soluble proteins with high aggregation propensities, which can overwhelm the cellular chaperoning capacity and protein degradation machinery. The kinetic equilibrium between folding and unfolding, misfolding, and refolding; aggregation and degradation is perturbed in one or many neurodegenerative disorders (NDDs) associated with dementia, cognitive impairments, movement, and behavioural losses. However, a detailed interplay of IBs into the manifestation of the NDDs is unknown, and a very primitive knowledge of structural compositions of amyloid inclusions is present. The present article presents a brief evolutionary background of IBs; their functional relevance for prokaryotes, plants, and animals; and associated involvement in neuronal proteostasis.


Effect of Omega-3 Polyunsaturated Fatty Acids on Lipid Metabolism in Patients With Metabolic Syndrome and NAFLD.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. n-3 polyunsaturated fatty acids (n-3-PUFAs) have been reported to ameliorate the progression of NAFLD in experimental studies; however, clinical trials have yielded contradictory results. The aim of our study was to assess the effects of n-3-PUFA administration on lipid metabolism and the progression of NAFLD in patients with metabolic syndrome. Sixty patients with metabolic syndrome and NAFLD were randomized in a double-blind placebo-controlled trial (3.6 g/day n-3-PUFA vs. placebo). During the 1-year follow-up, the patients underwent periodic clinical and laboratory examinations, liver stiffness measurements, magnetic resonance spectroscopy of the liver, and plasma lipidomic analyses. After 12 months of n-3-PUFA administration, a significant decrease in serum GGT activity was recorded compared with the placebo group (2.03 ± 2.8 vs. 1.43 ± 1.6; P < 0.05). Although no significant changes in anthropometric parameters were recorded, a significant correlation between the reduction of liver fat after 12 months of treatment-and weight reduction-was observed; furthermore, this effect was clearly potentiated by n-3-PUFA treatment (P < 0.005). In addition, n-3-PUFA treatment resulted in substantial changes in the plasma lipidome, with n-3-PUFA-enriched triacylglycerols and phospholipids being the most expressed lipid signatures. Conclusion: Twelve months of n-3-PUFA treatment of patients with NAFLD patients was associated with a significant decrease in GGT activity, the liver fat reduction in those who reduced their weight, and beneficial changes in the plasma lipid profile.


Short-term outcomes after cryosurgical ablation of the prostate in men with recurrent prostate carcinoma following radiation therapy.
Cryosurgical ablation of the prostate represents a possibly efficacious method of treating prostate carcinoma in men failing radiation therapy. In addition to eradicating the disease, cryosurgery has the potential to avoid some of the morbidity associated with other treatment modalities. Therefore, a prospective Phase II trial was conducted to determine the safety and efficacy of cryosurgery following radiation therapy in men with local recurrence. Cryosurgical ablation of the prostate was performed in men with prostate cancer previously treated by radiation therapy. All patients had biopsy-proven recurrent disease and no evidence of metastases. Initial follow-up occurred at approximately 3 months and included repeat biopsy and serum prostate-specific antigen (PSA) determinations. Biochemical disease-free survival defined as a PSA value less than 0.3 ng/mL was assessed using the Kaplan-Meier method. Thus far, 23 patients have been treated with cryosurgery with follow-up ranging between 12 and 23 months. Approximately 3 months after treatment, sextant biopsies revealed no cancer in 19 of 22 (86%) of the specimens; however, 10 of 22 (45%) showed small amounts of benign glandular tissue. The PSA at 3 months postoperatively declined in 18 of 22 (82%) patients but reached female levels in only 8 men (36%). Nineteen of 22 (86%) patients followed up a minimum of 1 year after cryotherapy have a PSA level equal to or greater than 0.3 ng/mL. Complications occurred in 100% of the patients with 12 of 22 (55%) requiring at least one transurethral resection of sloughed, necrotic tissue. Our preliminary results suggest that the current cryosurgical technique used in men failing radiation therapy has a low probability of biochemical cure and a high complication rate. Until more data are available, cryosurgery for men with locally recurrent disease after radiation therapy should be considered strictly experimental.


Porous poly (L-lactic acid) scaffolds are optimal substrates for internal colonization by A6 mesoangioblasts and immunocytochemical analyses.
In this study, mouse mesoangioblasts were seeded onto bidimensional matrices within three-dimensional porous scaffolds of poly (L-lactic acid) (PLLA), in the presence or absence of a type I collagen coating. The cells were observed under a scanning electron microscope and tested for their adhesion, survival and proliferation. Immunolocalization of heat shock protein (Hsp) 70, an abundant and ubiquitous intracellular protein in these cells, was also performed in sectioned cell-containing scaffolds under a confocal fluorescence microscope to determine if in situ analysis of intracellular constituents was feasible. The data show that PLLA films allow direct cell adhesion and represent an optimal support for cell growth, and that the internal surfaces of PLLA polymeric sponges can be colonized by mesoangioblasts, which can be submitted for in situ confocal microscopic analyses for possible monitoring of timedependent expression of differentiation markers.


Distribution and growth of aerobic anoxygenic phototrophs in the Mediterranean Sea.
The distribution of aerobic anoxygenic phototrophs (AAPs) was surveyed in various regions of the Mediterranean Sea in spring and summer. These phototrophic bacteria were present within the euphotic layer at all sampled stations. The AAP abundances increased with increasing trophic status ranging from 2.5 × 10(3) cells per ml in oligotrophic Eastern Mediterranean up to 90 × 10(3) cells per ml in the Bay of Villefranche. Aerobic anoxygenic phototrophs made up on average 1-4% of total prokaryotes in low nutrient areas, whereas in coastal and more productive stations these organisms represented 3-11% of total prokaryotes. Diel bacteriochlorophyll a decay measurements showed that AAP community in the Western Mediterranean grew rapidly, at rates from 1.13 to 1.42 day(-1). The lower AAP abundances registered in the most oligotrophic waters suggest that they are relatively poor competitors under nutrient limiting conditions. Instead, AAPs appear to be metabolically active organisms, which thrive better in more eutrophic environments providing the necessary substrates to maintain high growth rates.


Easy-To-Perform Dual Immunohistochemistry Can Solve Problems in Hematopathology.
Immunohistochemical analysis has become an integral component in the diagnostic work up of hematopoietic neoplasms. It is not uncommon that visualization of single protein expression by immunohistochemistry among cells of interest may become a difficult task. Common scenarios of such include extensive colonization of germinal centers in the differential diagnosis of marginal zone lymphoma and follicular lymphoma, low-level bone marrow involvement by lymphoma and paucity of neoplastic lymphocytes in the setting of numerous background reactive lymphocytes, among others. For this reason, we have developed a variety of easy-to-employ dual-color dual-antibody immunohistochemical assays to aid in solving these diagnostic dilemmas. Herein, we share examples of our use of dual immunohistochemistry to illustrate its beneficial and practical objective.


Twenty-four or four-and-twenty: Language modulates cross-modal matching for multidigit numbers in children and adults.
Does number-word structure have a long-lasting impact on transcoding? Contrary to English, German number words comprise decade-unit inversion (e.g., vierundzwanzig is literally translated as four-and-twenty). To investigate the mental representation of numbers, we tested the effect of visual and linguistic-morphological characteristics on the development of verbal-visual transcoding. In a longitudinal cross-linguistic design, response times (RTs) in a number-matching experiment were analyzed in Grade 2 (119 German-speaking and 179 English-speaking children) and in Grade 3 (131 German-speaking and 160 English-speaking children). To test for long-term effects, the same experiment was given to 38 German-speaking and 42 English-speaking adults. Participants needed to decide whether a spoken number matched a subsequent visual Arabic number. Systematic variation of digits in the nonmatching distractors allowed comparison of three different transcoding accounts (lexicalization, visual, and linguistic-morphological). German speakers were generally slower in rejecting inverted number distractors than English speakers. Across age groups, German speakers were more distracted by Arabic numbers that included the correct unit digit, whereas English speakers showed stronger distraction when the correct decade digit was included. These RT patterns reflect differences in number-word morphology. The individual cost of rejecting an inverted distractor (inversion effect) predicted arithmetic skills in German-speaking second-graders only. The moderate relationship between the efficiency to identify a matching number and arithmetic performance could be observed cross-linguistically in all age groups but was not significant in German-speaking adults. Thus, findings provide consistent evidence of a persistent impact of number-word structure on number processing, whereas the relationship with arithmetic performance was particularly pronounced in young children.


The diagnostic value of positron emission tomography (PET) with radiolabelled fluorodeoxyglucose (18F-FDG) in head and neck cancer.
Positron emission tomography (PET) scanning has recently been introduced into clinical practice but its usefulness in the management of head and neck cancer is not well defined. The aim of this prospective preliminary study was to examine the clinical value of fluorodeoxyglucose (FDG)--PET in patients with head and neck cancer treated by radiotherapy with surgery in reserve by (i) relating quantitative uptake of isotope to tumour type and histological grade and (ii) comparing the imaging findings of PET and magnetic resonance imaging (MRI) in post-radiotherapy assessment of tumour response. Twenty-one patients had pre-treatment PET and MRI scans and these were repeated four and eight months after treatment if there was no clinical relapse. Pre-treatment uptake of FDG using tumour to cerebellar ratio parameters was significantly related to the histological grade of squamous cancer (p = 0.04) but not to tumour type. Discordance of post-treatment PET/MRI findings in one case indicates a possible role for PET in the early detection of tumour recurrence. Other potential uses of PET scanning in the management of head and neck cancer are discussed.


Activation of the human diaphragm during a repetitive postural task.
The co-ordination between respiratory and postural functions of the diaphragm was investigated during repetitive upper limb movement. It was hypothesised that diaphragm activity would occur either tonically or phasically in association with the forces from each movement and that this activity would combine with phasic respiratory activity. Movements of the upper limb and ribcage were measured while standing subjects performed repetitive upper limb movements 'as fast as possible'. Electromyographic (EMG) recordings of the costal diaphragm were made using intramuscular electrodes in four subjects. Surface electrodes were placed over the deltoid and erector spinae muscles. In contrast to standing at rest, diaphragm activity was present throughout expiration at 78 +/- 17% (mean +/- s.d.) of its peak inspiratory magnitude during repeated upper limb movement. Bursts of deltoid and erector spinae EMG activity occurred at the limb movement frequency (approximately 2.9 Hz). Although the majority of diaphragm EMG power was at the respiratory frequency (approximately 0.4 Hz), a peak was also present at the movement frequency. This finding was corroborated by averaged EMG activity triggered from upper limb movement. In addition, diaphragm EMG activity was coherent with ribcage motion at the respiratory frequency and with upper limb movement at the movement frequency. The diaphragm response was similar when movement was performed while sitting. In addition, when subjects moved with increasing frequency the peak upper limb acceleration correlated with diaphragm EMG amplitude. These findings support the argument that diaphragm contraction is related to trunk control. The results indicate that activity of human phrenic motoneurones is organised such that it contributes to both posture and respiration during a task which repetitively challenges trunk posture.


A New Data-Driven Control System for MEMSs Gyroscopes: Dynamics Estimation by Type-3 Fuzzy Systems.
In this study, a novel data-driven control scheme is presented for MEMS gyroscopes (MEMS-Gs). The uncertainties are tackled by suggested type-3 fuzzy system with non-singleton fuzzification (NT3FS). Besides the dynamics uncertainties, the suggested NT3FS can also handle the input measurement errors. The rules of NT3FS are online tuned to better compensate the disturbances. By the input-output data set a data-driven scheme is designed, and a new LMI set is presented to ensure the stability. By several simulations and comparisons the superiority of the introduced control scheme is demonstrated.


Role of lone pair electrons in n-type thermoelectric properties of tin oxides.
Oxide materials have shown promising thermoelectric applications due to their availability, tunability, and thermal stability. Among oxide materials, the layered tin oxides (SnO) attract raising attention in the electronic and optoelectronic field owing to their lone pair electrons. We have investigated the thermoelectric properties of layered SnO structures through first-principle calculations. SnO exhibits superior n-type thermoelectric properties and the metallicity of SnO becomes stronger with the number of layers increasing. The lone pair electrons around Sn atoms are the key factor to n-type properties and they will get bonded and anti-bonded in the case of interlayer interaction. Monolayer SnO exhibits the best thermoelectric performances and the average n-type ZT value of monolayer SnO can achieve 0.90 at 500-700 K. Our results demonstrate that layered SnO will be the potential n-type two-dimensional oxide thermoelectric material.


[Experimental study on uptake of fluoride by dentin after pulsed Nd:YAG laser irradiation].
The purpose of this study was to determine the uptake of fluoride by dentin after pulsed Nd:YAG laser irradiation. Under SEM examination dentin lased by pulsed Nd:YAG laser appeared to be melted; there were no changes of calcium and phosphorus levels. Dentin irradiated by pulsed Nd:YAG laser and treated with 38% Ag(NH3)2F showed greater uptake and deep penetration of fluoride than topical application of fluoride alone, SEM examination revealed that CaF2-like and Ag3PO4-like deposits were formed on the dentin surface. These results suggested that pulsed Nd:YAG laser irradition could improve the absorption of fluoride in dentin.


Initiation of respiratory support for extremely preterm infants at birth.
Neonatal resuscitation algorithms recommend assessing breathing and heart rate (HR) of newborns and giving respiratory support when one or both are unsatisfactory. Recommendations also state that preterm infants may be supported with continuous positive airway pressure rather than routinely intubated for positive pressure ventilation (PPV). We wished to describe the prevalence and time of initiation of respiratory support of extremely preterm and extremely low birthweight (ELBW) infants at our hospital. We reviewed videos of 55 infants. Although most were breathing, practically all newly born extremely preterm ELBW infants were given respiratory support soon after arrival to the resuscitation cot. For the majority, this was done without knowing the HR. The majority received PPV; again, this was often done without knowing the HR. A quarter of infants were managed without any PPV.


Diet and disease.
In this era of evidence based medicine information about diet and diseases is less certain than information about drugs and diseases. Drug treatment is less complex. Dietary change can't usually be incorporated in a double blind trial. There is much more funding for pharmaceutical trials than for dietary trials. The following notes concentrate on newer, developing concepts.


Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats.
As demonstrated by increased hippocampal insulin receptor density following learning in animal models and decreased insulin signaling, receptor density, and memory decline in aging and Alzheimer's diseases, numerous studies have emphasized the importance of insulin in learning and memory processes. This has been further supported by work showing that intranasal delivery of insulin can enhance insulin receptor signaling, alter cerebral blood flow, and improve memory recall. Additionally, inhibition of insulin receptor function or expression using molecular techniques has been associated with reduced learning. Here, we sought a different approach to increase insulin receptor activity without the need for administering the ligand. A constitutively active, modified human insulin receptor (IRβ) was delivered to the hippocampus of young (2 months) and aged (18 months) male Fischer 344 rats in vivo. The impact of increasing hippocampal insulin receptor expression was investigated using several outcome measures, including Morris water maze and ambulatory gait performance, immunofluorescence, immunohistochemistry, and Western immunoblotting. In aged animals, the IRβ construct was associated with enhanced performance on the Morris water maze task, suggesting that this receptor was able to improve memory recall. Additionally, in both age-groups, a reduced stride length was noted in IRβ-treated animals along with elevated hippocampal insulin receptor levels. These results provide new insights into the potential impact of increasing neuronal insulin signaling in the hippocampus of aged animals and support the efficacy of molecularly elevating insulin receptor activity in vivo in the absence of the ligand to directly study this process.


Immediate and Sustained Decrease in Smoking Urges After Acute Insular Cortex Damage.
Smoking urges are fundamental aspects of nicotine dependence that contribute significantly to drug use and postquit relapse. Recent evidence has indicated that damage to the insular cortex disrupts smoking behaviors and claims to reduce urges associated with nicotine use, although tools that assess urge have yet to be used to validate these findings. We examined the effect of insular versus non-insular damage on urge using a well-accepted urge scale. This 3-month observational prospective cohort study consisted of 156 current smokers hospitalized for acute ischemic stroke (38 with insular infarctions, 118 with non-insular infarctions). During hospitalization, the Questionnaire of Smoking Urges (QSU)-brief was assessed retrospectively based on experiences before the stroke (baseline, T0), prospectively immediately following the stroke (T1) and once more via telephone at 3-month follow-up (T2), with higher scores indicating greater urge. Bivariate statistics and multivariable linear regression were used to evaluate differences in QSU-brief scores, relative to baseline, between exposure groups, controlling for age, baseline dependence, stroke severity, use of nicotine replacement, and damage to other mesocorticolimbic regions. A greater reduction in QSU-brief score was seen in the insular group compared to the non-insular group from T0 to T1 (covariate-adjusted difference in means of -1.15, 95% CI: -1.85, -0.44) and similarly from T0 to T2 (covariate-adjusted difference in means of -0.93, 95% CI: -1.79, -0.07). These findings confirm the potential role of the insula in regulating nicotine-induced urges and support the growing evidence of its novelty as a key target for smoking cessation interventions. Human lesioning studies that evaluate the insula's involvement in maintaining nicotine addiction make inferences of the insula's role in decreasing urge, but do not use validated instruments that directly assess urges. This study corroborates prior findings using the continuous Questionnaire of Smoking Urges to quantify changes in urge from before lesion onset to immediate and 3-month follow-up time points.


Tobacco-related risk perceptions, social influences and public smoke-free policies in relation to smoke-free home restrictions: findings from a baseline cross-sectional survey of Armenian and Georgian adults in a community randomised trial.
Given high prevalence of smoking and secondhand smoke exposure in Armenia and Georgia and quicker implementation of tobacco legislation in Georgia versus Armenia, we examined correlates of having no/partial versus complete smoke-free home (SFH) restrictions across countries, particularly smoking characteristics, risk perceptions, social influences and public smoking restrictions. Cross-sectional survey study design. 28 communities in Armenia and Georgia surveyed in 2018. 1456 adults ages 18-64 in Armenia (n=705) and Georgia (n=751). We used binary logistic regression to examine aforementioned correlates of no/partial versus complete SFH among non-smokers and smokers in Armenia and Georgia, respectively. Participants were an average age of 43.35, 60.5% women and 27.3% smokers. In Armenia, among non-smokers, having no/partial SFHs correlated with being men (OR=2.63, p=0.001) and having more friend smokers (OR=1.23, p=0.002); among smokers, having no/partial SFHs correlated with being unmarried (OR=10.00, p=0.001), lower quitting importance (OR=0.82, p=0.010) and less favourable smoking attitudes among friends/family/public (OR=0.48, p=0.034). In Georgia, among non-smokers, having no/partial SFHs correlated with older age (OR=1.04, p=0.002), being men (OR=5.56, p<0.001), lower SHS risk perception (OR=0.43, p<0.001), more friend smokers (OR=1.49, p=0.002) and fewer workplace (indoor) restrictions (OR=0.51, p=0.026); among smokers, having no/partial SFHs correlated with being men (OR=50.00, p<0.001), without children (OR=5.88, p<0.001), daily smoking (OR=4.30, p=0.050), lower quitting confidence (OR=0.81, p=0.004), more friend smokers (OR=1.62, p=0.038) and fewer community restrictions (OR=0.68, p=0.026). Private settings continue to lack smoking restrictions in Armenia and Georgia. Findings highlight the importance of social influences and comprehensive tobacco legislation, particularly smoke-free policies, in changing household smoking restrictions and behaviours. NCT03447912.


The peripheral branching pattern of identified dorsal unpaired median (DUM) neurones of the locust
Identified dorsal unpaired median (DUM) neurones of the locust Locusta migratoria were stained intracellularly with large amounts of cobalt to reveal their extensive peripheral branching patterns. Two neurones of the suboesophageal ganglion were studied as well as several neurones of thoracic ganglia. The peripheral branching pattern of all these neurones is described completely. As expected, the prevalent target organs of all DUM neurones are skeletal muscles. In addition several, but not all DUM neurones studied here form neurohaemal release sites on the surface of peripheral nerves and thus represent potential sources for octopamine acting as a neurohormone.


The Crosstalk Between Long Non-Coding RNAs and Various Types of Death in Cancer Cells.
With the increasing aging population, cancer has become one of the leading causes of death worldwide, and the number of cancer cases and deaths is only anticipated to grow further. Long non-coding RNAs (lncRNAs), which are closely associated with the expression level of downstream genes and various types of bioactivity, are regarded as one of the key regulators of cancer cell proliferation and death. Cell death, including apoptosis, necrosis, autophagy, pyroptosis, and ferroptosis, plays a vital role in the progression of cancer. A better understanding of the regulatory relationships between lncRNAs and these various types of cancer cell death is therefore urgently required. The occurrence and development of tumors can be controlled by increasing or decreasing the expression of lncRNAs, a method which confers broad prospects for cancer treatment. Therefore, it is urgent for us to understand the influence of lncRNAs on the development of different modes of tumor death, and to evaluate whether lncRNAs have the potential to be used as biological targets for inducing cell death and predicting prognosis and recurrence of chemotherapy. The purpose of this review is to provide an overview of the various forms of cancer cell death, including apoptosis, necrosis, autophagy, pyroptosis, and ferroptosis, and to describe the mechanisms of different types of cancer cell death that are regulated by lncRNAs in order to explore potential targets for cancer therapy.


Studies on the photoactivation of the water-oxidizing enzyme : I. Processes limiting photoactivation in hydroxylamine-extracted leaf segments.
In weak yet optimal light intensity, complete photoactivation of the water-oxidizing enzyme in NH(2)OH-extracted wheat (Triticum aestivum, var Oasis) leaf segments could be obtained only after long dark preincubation. Photoactivation was not affected by ethylenediaminetetraacetate or inhibitors of photophosphorylation and protein synthesis, but was partially inhibited by a divalent cation ionophore. Complete photoactivation required ligation of approximately 4 Mn by the water oxidizing enzyme.WITHOUT DARK PREINCUBATION, PHOTOSYSTEM II (PSII) WAS SUSCEPTIBLE TO WEAK LIGHT PHOTOINHIBITION RESULTING IN: (a) 50% maximum decrease in photooxidation of artificial electron donors by PSII: (b) increased times for the variable fluorescence rise (with 3-(3,4-dichlorophenyl)-1,1-dimethyl urea): (c) abolishment of photoactivation: and (d) the imposition of sensitivity to inhibitors of photophosphorylation and 70S but not 80S protein synthesis on subsequent light-dependent recovery from photoinhibition and recovery of O(2) evolution. Decrease in susceptibility to photoinhibition and increase in rates of photoactivation resulting from dark preincubations proved closely correlated. Neither protein synthesis nor increases in abundances of thylakoid Mn(2+) and Ca(2+) were required for escape from photoinhibition. However, photoactivation of the wateroxidizing enzyme in NH(2)OH-extracted Chlamydomonas occurred in absence of dark preincubation and protein synthesis. Results are discussed in the context of disassembly/reassembly/resynthesis of specific PSII polypeptides.


DNA microarrays for assessing ovarian cancer gene expression.
Although DNA microarray analysis is presented as a revolution in gene expression studies, it is in fact based on the classic technique of Southern DNA hybridisation where a labelled DNA probe is hybridised to single stranded DNA that is bound to a solid support matrix. The truly revolutionary aspect of microarray analysis lies in the fact that, within a given cell population, the expression of tens of thousands of genes, and ultimately the entire genome, can be assayed simultaneously. This capability, when coupled with powerful data analysis software, allows researchers to rapidly compare gene expression between two cell populations. In the cancer field, this enables researchers to compare gene expression between normal and malignant cells and to identify genes that are differentially regulated during cancer development. Microarray data can also be used to categorize tumours on the basis of their molecular profile, which may provide important biological, diagnostic and prognostic information. As little as 5 years ago identifying even a few differentially expressed genes may have taken several years and cost tens of thousands of dollars. Today microarrays can identify ten times the number of candidate genes in just a few months and at a tenth of the cost. Even so, microarray analysis is still in its infancy and the technology is advancing rapidly. There is little doubt that microarrays will revolutionize our ability to quantify the complex changes that occur in gene expression during cancer development. The greatest challenge that lies ahead is how to translate this knowledge into clinically useful diagnostic and therapeutic tools. In this review, we describe the technical aspects of DNA microarray analysis and some of the current and future applications of this technology for analysing gene expression in ovarian cancer.


Routines, Time Dedication and Habit Changes in Spanish Homes during the COVID-19 Lockdown. A Large Cross-Sectional Survey.
Many countries chose to establish social distancing as lockdowns after the COVID-19 outbreak. Households had to adapt their day-to-day lifestyles to new circumstances, affecting routines and time dedication to tasks. This national study was carried out to find out how the confinement by COVID-19 affected Spanish households on the perceived habit changes during this period, in relation to their socio-demographic characteristics and household composition. An online questionnaire was launched during the COVID-19 lockdown, from 30 April to 22 June 2020. Descriptive statistics were analyzed, stratified by gender, on time dedication, routine, home leaving, and habit change variables. Chi-square tests were used to explore the relations of significance with socio-demographic characteristics and home composition. All contrast analyses were performed for a 95% confidence level (significance considered for p < 0.05). In total, 1673 respondents participated from different age groups, educational level, employment status and household composition. Sixty percent of respondents maintained their routines. A third tried to establish a new one, being related to women, young people, not a university student, and living with others, including minors. Regarding dedication to tasks, adults aged 35-54 years, with more cohabitants, especially women, devoted themselves intensively to the home or to care, while those under 35 were dedicated more to rest, leisure, television or reading. People with university studies were more related to teleworking. The frequency of going outside was related to gender, age, educational level and living with elders, specifically for grocery shopping and taking out garbage. Changes in habits, routines and time dedication in confinement were strongly linked to the sociodemographic and coexistence conditions in Spanish homes. The greatest impacts were suffered by women, people with children, and adults between 35-54 years of age, especially on care and domestic chores.


Bacterial Response to Oxidative Stress and RNA Oxidation.
Bacteria have to cope with oxidative stress caused by distinct Reactive Oxygen Species (ROS), derived not only from normal aerobic metabolism but also from oxidants present in their environments. The major ROS include superoxide O2 -, hydrogen peroxide H2O2 and radical hydroxide HO•. To protect cells under oxidative stress, bacteria induce the expression of several genes, namely the SoxRS, OxyR and PerR regulons. Cells are able to tolerate a certain number of free radicals, but high levels of ROS result in the oxidation of several biomolecules. Strikingly, RNA is particularly susceptible to this common chemical damage. Oxidation of RNA causes the formation of strand breaks, elimination of bases or insertion of mutagenic lesions in the nucleobases. The most common modification is 8-hydroxyguanosine (8-oxo-G), an oxidized form of guanosine. The structure and function of virtually all RNA species (mRNA, rRNA, tRNA, sRNA) can be affected by RNA oxidation, leading to translational defects with harmful consequences for cell survival. However, bacteria have evolved RNA quality control pathways to eliminate oxidized RNA, involving RNA-binding proteins like the members of the MutT/Nudix family and the ribonuclease PNPase. Here we summarize the current knowledge on the bacterial stress response to RNA oxidation, namely we present the different ROS responsible for this chemical damage and describe the main strategies employed by bacteria to fight oxidative stress and control RNA damage.


Radiological prediction of pulmonary hypertension in chronic obstructive pulmonary disease.
A study was undertaken to determine whether measurements of radiological indices from postero-anterior chest X-rays were useful in predicting pulmonary artery hypertension. Measurements of the transhilar (THD) and pulmonary lobar distances (PLD) as well as the width of the descending branch of the right pulmonary artery (DB) were made from X-rays of 100 patients with chronic obstructive pulmonary disease. For these patients the forced expiratory volume in 1 s was 1.2 +/- 0.6 l (group mean +/- SD), the arterial PO2 was 62.2 +/- 14.5 mmHg and the mean pulmonary artery pressure (PAP) was 26.7 +/- 11.9 mmHg. Considerable differences in the measurement of THD and PLD were found between and within observers whereas the measurement of DB was more reproducible. DB was better correlated (r = 0.59, P less than 0.001) with PAP than were THD and PLD. Using a stepwise multiple regression procedure including other physiological variables, it was found that DB and arterial PO2 were the only significant (P less than 0.05) predictors of PAP, together accounting for 48% of the variation in PAP, with DB being the more important predictor.


Abnormal Spontaneous Brain Activity in Left-Onset Parkinson Disease: A Resting-State Functional MRI Study.
Objective: Motor asymmetry is characteristic in Parkinson disease (PD). This phenomenon is originated from uneven degeneration of bilateral substantia nigra. However, this asymmetry may not restrict to substantia nigra or striatum. We aimed to determine the effect of asymmetry on spontaneous brain activity across the whole brain. Methods: We consecutively recruited 71 patients with PD, as well as 35 healthy controls, and collected relevant demographic, clinical, and neuropsychological information. The PD patients were divided into two groups according to the side of motor symptom onset. All the participants underwent resting-state functional magnetic resonance imaging, and spontaneous brain activity was assessed using amplitude of low-frequency fluctuation (ALFF). The associations between areas showing significant group differences and various clinical and neuropsychological measures were analyzed. Results: Finally, the data of 30 PD patients with left-onset (LPD), 27 PD patients with right-onset (RPD), and 32 healthy controls were obtained. The three groups had similar age and gender ratios. Our results demonstrated that LPD patients had increased ALFF in the left inferior temporal gyrus and decreased ALFF in bilateral thalamus and cerebellum anterior lobes than the control group. The value of ALFF of the left inferior temporal gyrus was correlated with motor function, and ALFF value of the thalamus was associated with cognition. Comparisons between LPD and RPD patients and between RPD patients and the controls did not yield significant difference. Conclusions: The present study provides new insights into the distinct characteristics of spontaneous brain activity in LPD, which may be associated with motor and cognitive function.


Hepatic metabolism and biliary excretion of silymarin flavonolignans in isolated perfused rat livers: role of multidrug resistance-associated protein 2 (Abcc2).
Silymarin, an extract from seeds of Silybum marianum, is used by 8 to 33% of patients to self-treat chronic viral hepatitis C in the United States. Studies in humans and rodents suggest that biliary excretion of glucuronide and sulfate conjugates is the major route for silymarin's elimination. To determine the role of multidrug resistance-associated protein 2 (Mrp2) (Abcc2) in the biliary excretion of silymarin, the hepatobiliary disposition of the six major silymarin flavonolignans was studied using isolated perfused livers (IPRLs) from wild-type (WT) and Mrp2-deficient (TR(-)) Wistar rats. For all the flavonolignans, approximately 96% of the dose was cleared from perfusate within 30 min in both WT and TR(-) livers, and <5% of parent was recovered in bile or perfusate by the end of the perfusion. In WT livers, the percentage of dose excreted as conjugates into bile varied for each flavonolignan (silychristin, 51.6 +/- 9.3%; silydianin, 101.5 +/- 28.3%; silybin A, 21.0 +/- 8.3%; silybin B, 31.7 +/- 13.2%; isosilybin A, 50.5 +/- 23.6%; isosilybin B, 42.8 +/- 19.3%). Among the flavonolignans, only silydianin was primarily glucuronidated and almost completely recovered in bile. In TR(-) livers, biliary excretion of flavonolignan conjugates was reduced 80 to 92%, with 30 to 83% of each flavonolignan conjugate recovered in perfusate compared with only 5 to 30% at 90 min. Biliary excretion of glucuronide and sulfate conjugates of all the flavonolignans were reduced by 94 to 98% and 73 to 84%, respectively, in TR(-) IPRLs. These data indicate a primary role for Mrp2 in the biliary elimination of silymarin flavonolignan conjugates.


Facile synthesis of azaarene-substituted 3-hydroxy-2-oxindoles via Brønsted acid catalyzed sp3 C-H functionalization.
Brønsted acid catalyzed functionalization of sp(3) C-H bonds in 2-methyl azaarenes has been achieved in the reaction with isatins. This method provides facile synthesis of biologically important azaarene-substituted 3-hydroxy-2-oxindoles in one step in moderate to good yields.


Pattern of electrical activity of the ovine uterus and cervix from mating to parturition.
The electrical activity of the uterus, greater curvature and lesser curvature, and of the cervix were recorded throughout several oestrous cycles, matings and the entire course of pregnancy in a set of ewes. In cyclic ewes, all electrode sites were active during the periovulatory period, but during the luteal phase only the cervix and lesser curvature continued to present regular activity, i.e. episodes of 6-8 min duration. Matings failed to disrupt the oestrous activity pattern in 5 out of 6 ewes. During the subsequent pregnancy in 4 ewes, activity, when present, consisted of the cyclic occurrence of regular activity episodes in the gravid horn(s) (greater curvature) and in the cervix (and lesser curvature in 1 ewe). Three phases were recognized on the basis of the activity of the greater curvature of the gravid horn(s). The first phase corresponded to quiescence of the horn from Day 5 (Day 0 = mating) to about Day 41. The second phase was marked by the sudden onset of regular activity of the uterus; frequency rapidly increased and maximal values were reached around Day 49, after which frequency progressively decreased until around Day 66. The third phase was characterized by a steady state in genital tract activity until the peripartum period. The cervix and lesser curvature activity followed an almost similar development of regular activity episodes with only slight time differences.


Structure, Oligomerization and Activity Modulation in N-Ribohydrolases.
Enzymes catalyzing the hydrolysis of the N-glycosidic bond in nucleosides and other ribosides (N-ribohydrolases, NHs) with diverse substrate specificities are found in all kingdoms of life. While the overall NH fold is highly conserved, limited substitutions and insertions can account for differences in substrate selection, catalytic efficiency, and distinct structural features. The NH structural module is also employed in monomeric proteins devoid of enzymatic activity with different physiological roles. The homo-oligomeric quaternary structure of active NHs parallels the different catalytic strategies used by each isozyme, while providing a buttressing effect to maintain the active site geometry and allow the conformational changes required for catalysis. The unique features of the NH catalytic strategy and structure make these proteins attractive targets for diverse therapeutic goals in different diseases.


Where the education system and women's bodies collide: The social and health impact of girls' experiences of menstruation and schooling in Tanzania.
The global development community has focused in recent decades on closing the gender gap in education, but has given insufficient attention to the specific needs of pre- and post-pubescent girls as they transition to young womanhood within the educational institution. This study explored the social context of girls' experiences of menses and schooling in northern Tanzania, with data collection focused on capturing girls' voiced concerns and recommendations. Results indicated that pubescent girls are confronted with numerous challenges to managing menses within the school environment. Many are transitioning through puberty without adequate guidance on puberty and menses management, and pursuing education in environments that lack adequate facilities, supplies, and gender sensitivity. Girls have pragmatic and realistic recommendations for how to improve school environments, ideas that should be incorporated as effective methods for improving girls' academic experiences and their healthy transitions to womanhood.