Regulation of synaptic timing in the olfactory bulb by an A-type potassium current.
Although rapid synaptic transmission confers signal fidelity, the activity of some neuronal circuits depends on prolonged excitation or inhibition. Here we demonstrate that GABAergic granule cells in the rat olfactory bulb produce prolonged inhibition of mitral cells through a precise kinetic matching between transmitter-gated and voltage-gated channels in their dendritic membrane. A transient A-type potassium current (IA) specifically attenuated dendrodendritic inputs mediated by fast-acting AMPA receptors such that the excitation and subsequent inhibitory output of granule cells followed the prolonged kinetics of their NMDA receptors. Altering the weights of the AMPA and NMDA receptor-mediated inputs by modulating IA provides a mechanism to regulate the timing of inhibition according to the demands on the bulb network.


Till Surgery do us Part: Unexpected Bilateral Kissing Molars.
The occurrence impacted teeth, single or multiple is very common. But, phenomenon of kissing molars is an extremely rare phenomenon. Mandibular third molars are the most common impacted teeth. Mandibular first or second molars does not share the same frequency of occurrence. But, there are rare cases in which the occlusal surfaces of impacted molars are united by the same follicular space and the roots point in the opposite direction, and are termed as kissing molars. Sometimes, these teeth will be associated with pathologies. This article reports a rare case of mandibular bilateral kissing molars.


Can Post-Exercise Hemodynamic Response Be Influenced by Different Recovery Methods in Paraplegic Sportsmen?
Post-exercise hypotension is of great clinical relevance and also in sports training settings, as recovery speed is important. The aim of this study was to compare the influence of different recovery methods on post-exercise hemodynamic response. Twelve male paraplegic sportsmen (25.40 ± 3.30 years) performed a strength training (ST) session using the bench press exercise. After the ST, three recovery methods were randomly performed over a 15-min period: passive recovery (PR), cold-water (CW) and dry needle (DN). Blood pressure (BP), heart rate (HR) and myocardial oxygen were measured before and post ST, as well as post the recovery method. Results: Dry needling induced lower systolic blood pressure (SBP) immediately after the treatment when compared with the other recovery methods, but the contrary was observed at 50 and 60-min post recovery, where records with DN exhibit higher mean values (η2p = 0.330). There were no differences in post-exercise diastolic BP and mean BP between recovery methods. There was a significantly higher HR after the PR method, when compared with CW and with DN (η2p = 0.426). The same was observed for double product and for myocardial oxygen, though with a larger effect size (η2p = 0.446). We conclude that dry needling seems to induce a faster SBP lowering immediately after the procedure but at 50-min post procedure the cold-water method showed better result. As for HR, both procedures (DN and CW) showed a better recovery when compared with passive recovery, along the several moments of measurement.


Recessions and Health: The Long-Term Health Consequences of Responses to the Coronavirus.
The lockdown measures that were implemented in the spring of 2020 to stop the spread of COVID-19 are having a huge impact on economies in the UK and around the world. In addition to the direct impact of COVID-19 on health, the following recession will have an impact on people's health outcomes. This paper reviews economic literature on the longer-run health impacts of business-cycle fluctuations and recessions. Previous studies show that an economic downturn, which affects people through increased unemployment, lower incomes and increased uncertainty, will have significant consequences on people's health outcomes both in the short and longer term. The health effects caused by these adverse macroeconomic conditions will be complex and will differ across generations, regions and socio-economic groups. Groups that are vulnerable to poor health are likely to be hit hardest even if the crisis hit all individuals equally, and we already see that some groups such as young workers and women are worse hit by the recession than others. Government policies during and after the pandemic will play an important role in determining the eventual health consequences.


Epidemiology of foodborne diseases: a worldwide review.
Acute foodborne disease infections and intoxications are much more of a concern to governments and the food industry today than a few decades ago. Some of the factors that have led to this include the identification of new agents that have caused life-threatening conditions; the finding that traditional agents are being associated with foods that were of no concern previously: an increasing number of large outbreaks being reported; the impact of foodborne disease on children, the aging population and the immunocompromised; migrant populations demanding their traditional foods in the countries of settlement; the ease of worldwide shipment of fresh and frozen food; and the development of new food industries, including aquaculture. However, to meaningfully monitor increases or decreases in foodborne disease requires an effective surveillance system at the local, national and international levels. To date, resources have been limited for most countries and regions to do this, and our current knowledge is based, for the most part, on passive reporting mechanisms. Laboratory isolation data and reports of notifiable diseases have some value in observing timely changes in case numbers of some enteric diseases, but they usually do not indicate the reasons for these trends. Special epidemiological studies are useful for the area covered, but it is often questionable whether they can be extrapolated to other areas or countries. Outbreak investigations tell us that a certain set of circumstances led to illness and that another outbreak may occur under similar but not necessarily identical conditions. Control programmes have often been triggered by the conclusions from investigations of specific outbreaks. Unfortunately, the agent/ food combination leading to illness in many of the reported incidents were not predicted from existing databases, and no doubt foodborne agents will continue to surprise food control agencies in the foreseeable future. Nevertheless, data from around the world do show some common elements. Salmonella is still the most important agent causing acute foodborne disease, with Salmonella enteritidis and S. typhimurium being of most concern. Foods of animal origin, particularly, meat and eggs, were most often implicated. Desserts, ice cream and confectionery items were products also mentioned, but some of these would have egg as a raw or incompletely cooked ingredient. Incidents most frequently occurred in homes or restaurants, and the main factors contributing to outbreaks were poor temperature control in preparing, cooking and storing food. Clostridium botulinum, Salmonella and VTEC are more frequently documented in industrialized than in developing countries. ETEC, EPEC, Shigella, Vibrio cholerae and parasites are the main scourges in developing countries, but it is uncertain how many cases are attributed to food, to water or to person-to-person transmission. The apparent decrease of S. aureus and C. perfringens outbreaks in industrialized countries may be related to improved temperature control in the kitchen. An increasing number of illnesses are international in scope, with contamination in a commercial product occurring in one country and affecting persons in several other countries, or tourists being infected abroad and possibly transmitting the pathogen to others at home. For Salmonella, a rapid alert and response coordination is being encouraged through Salm-Net and other international programs. However, unless such a network is worldwide, tracking clusters of illnesses is going to fall on the countries where the first cases occur, and some of these have very limited resources for investigation and control. It was heartening to see funds recently being allocated to foodborne disease surveillance and control in several industrialized countries, but the same commitment is required by the World Health Organization for the international community.


Photosensitization and redox signaling.
The effect of light in combination with a chemical or a natural compound is termed photosensitization, and is known to have multiple cellular effects. Among them, modulation of gene expression is one of the most important, because it directly influences cell adaptation to novel environmental conditions. In previous years, the cis- and trans-acting genetic elements responsible for gene regulation by radiation and photosensitization, in particular, have been well characterized. The molecular mechanisms involved in the cell response revealed that an important control occurs at the transcriptional level and is coordinated by various transcription factors. The extracellular or intracellular changes mediated by photosensitization are detected by several signal transduction networks, allowing cells to mount an appropriated response in term of gene regulation. Mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinases (PI3-K) are among the most thoroughly studied of signal transduction systems and have been shown to participate in a diverse array of cellular programs. In this review, we will show how these cascades can be activated by photosensitization. A third signal type of transduction machinery, which has been shown to be activated by photosensitization, is the one leading to the activation of the Rel/NF-kappaB family of transcription factors. This family includes many members, most of which can form DNA-binding homo- or heterodimers. We will show that molecular mechanisms leading to NF-kappaB activation by photosensitization are initiated by oxidative damage. While the exact nature of the transduction intermediates is still unknown, NF-kappaB activation by radiation followed different pathways from those used by pro-inflammatory cytokines.


Conjunctival squamous cell carcinoma: prognostic factors for the recurrence and metastasis and clinicopathological characteristics at an oncological hospital in Peru.
Conjunctival squamous cell carcinoma (CSCC) is the most frequent malignant tumour of the conjunctiva, with scarce recurrence and infrequent metastasis. The purpose of this study is to describe the clinical and pathological characteristics of this neoplasm and to identify the prognostic factors for recurrence and metastasis in a cancer hospital in Peru. A longitudinal, retrospective study of 176 consecutive patients diagnosed with SCC of the conjunctiva. Sociodemographic and clinical characteristics were evaluated. In addition, Kaplan-Meier curves were performed, and Cox regression was used to determine prognostic factors for recurrence and metastasis over time. Only 12.5% presented tumour size ≤5 mm. The highest proportion according to the histopathological type was the well-differentiated infiltrative forms (40.9%), and according to tumour, node, metastases (TNM), stage T3 was the most frequent (31.3%). The most performed initial treatment was orbital exenteration (38.6%). The proportion of recurrence was 6.8% and 8.0% for metastasis. The annual survival rate was 7% and the annual metastasis rate was 6%; for recurrence after 5 years, the survival rate was 11% and the metastasis rate was 14%. No prognostic factor evaluated was significant. This is the most extensive patient study in Latin America with CSCC, with a high proportion of advanced histopathological grade, TNM stages, and radical treatments such as exenteration. Recurrence rates on average are similar to other reported studies, and it describes the rates of metastasis that have been poorly described in the literature.


Collection and cultivation of and phagocytosis by pulmonary macrophages obtained from hysterectomy-derived pigs.
Methods were developed for procuring phagocytically active macrophages from porcine lung with minimal damage to respiratory tissues. Procedures included anesthetizing, surgically introducing a T-shaped tracheal catheter, and repeatedly flushing the respiratory tract. Macrophages collected in this manner were characterized as to numbers, types, and phagocytic activity, nonselective lavage of the pulmonary airways of unstimulated and stimulated (evoking agent: thioglycolate medium) animals yielded 5 X 10(7) and 11 X 10(7) respiratory cells per pig, respectively. Because sufficient quantities (300 to 600 cells/test) of unstimulated cells were collected, stimulated cells contaminated with thioglycolate were not further tested. Morphologically, unstimulated macrophages were mainly spherical and mononucleated by variable in size, ranging from 9 to 30 micrometer. Culturally, macrophages adhered to plastic or glass surfaces and readily phagocytized fungal spores, staphylococci, and latex particles in an enrichment medium containing greater than or equal to 20% bovine fetal serum. Macrophages failed to replicate during a 3-week maintenance period. The data suggest that porcine phagocytes of the pulmonary system comprise a free-cell population that is a major surface-constitutive part of the luminal surface of the airways.


Design of a micro-opto-electro-mechanical-system-based near-infrared hyperspectral imager.
We present the development of an imaging spectrometer for the near infrared (NIR) using a micro-opto-electromechanical system. A diffraction grating has been etched into the surface of a micromechanical scanning mirror made of silicon and is used to scan the object space and to disperse the NIR radiation simultaneously. Beginning with the specific requirements of NIR hyperspectral imaging, a detailed analysis of the system approach resulting in an all-reflective optical design for the hyperspectral imager is presented. The investigation includes a thorough consideration of spectral and spatial distortion occurring by scanning the scene with a grating. Minimization of these aberrations leads to an improved spectrometer design.


Distinct population and single-neuron selectivity for executive and episodic processing in human dorsal posterior cingulate.
Posterior cingulate cortex (PCC) is an enigmatic region implicated in psychiatric and neurological disease, yet its role in cognition remains unclear. Human studies link PCC to episodic memory and default mode network (DMN), while findings from the non-human primate emphasize executive processes more associated with the cognitive control network (CCN) in humans. We hypothesized this difference reflects an important functional division between dorsal (executive) and ventral (episodic) PCC. To test this, we utilized human intracranial recordings of population and single unit activity targeting dorsal PCC during an alternated executive/episodic processing task. Dorsal PCC population responses were significantly enhanced for executive, compared to episodic, task conditions, consistent with the CCN. Single unit recordings, however, revealed four distinct functional types with unique executive (CCN) or episodic (DMN) response profiles. Our findings provide critical electrophysiological data from human PCC, bridging incongruent views within and across species, furthering our understanding of PCC function.


Diclofenac and ketorolac in the treatment of pain after photorefractive keratectomy.
Photorefractive keratectomy (PRK) can produce significant ocular pain. Topical diclofenac, a non-steroidal anti-inflammatory drug (NSAID), is effective in the reduction of this pain. This study compares a second NSAID, ketorolac, to diclofenac. This prospective matched-control study involved 102 eyes of 102 patients. Prior to PRK, patients were randomly assigned to receive ketorolac or diclofenac drops. At the first postoperative visit, a standardized questionnaire was used to assess the patient's average and peak levels of discomfort. In addition, the quantities of acetaminophen and codeine consumed were recorded. The overall level of discomfort was 1.53 +/- 0.64 for diclofenac and 1.88 +/- 0.55 for ketorolac (scale: 0 to 4) (P = 0.004). The diclofenac group reported a peak discomfort level of 2.0 +/- 0.75 and the ketorolac group reported 2.3 +/- 0.62 (P > 0.05). The diclofenac group consumed 2000 +/- 1150 mg of acetaminophen and 92 +/- 54 mg of codeine whereas the ketorolac group consumed 2150 +/- 940 of acetaminophen and 98 +/- 50 mg of codeine (P > 0.05). The differences in levels of peak discomfort, acetaminophen ingestion, and codeine ingestion, were not statistically significant. As compared to ketorolac, diclofenac resulted in a statistically significant lower mean overall discomfort.


Bias in Radiology Resident Selection: Do We Discriminate Against the Obese and Unattractive?
To evaluate for appearance-based discrimination in the selection of radiology residents. A deception study simulating the resident selection process examined the impact of attractiveness and obesity on resident selection. Seventy-four core faculty from 5 academic radiology departments reviewed mock residency applications in September and October 2017. Each application included demographic information and a photograph, representing a prespecified distribution of facial attractiveness and obesity, combined with randomized academic and supporting variables. Reviewers independently scored applications for interview desirability. Reviewer scores and application variables were compared using linear mixed fixed- and random-effects models. Reviewers evaluated 5,447 applications (mean: 74 applications per reviewer). United States Medical Licensing Examination Step 1 scores were the strongest predictor of reviewer rating (B = 0.35 [standard error (SE) = 0.029]). Applicant facial attractiveness strongly predicted rating (attractive vs unattractive, B = 0.30 [SE = 0.056]; neutral vs unattractive, B = 0.13 [SE = 0.028]). Less influential but still significant predictors included race/ethnicity (B = 0.25 [SE = 0.059]), preclinical class rank (B = 0.25 [SE = 0.040]), clinical clerkship grades (B = 0.23 [SE = 0.034]), Alpha Omega Alpha membership (B = 0.21 [SE = 0.032]), and obesity (vs not obese) (B = -0.14 [SE = 0.024]). Findings provide preliminary evidence of discrimination against facially unattractive and obese applicants in radiology resident selection. Obesity and attractiveness were as influential in applicant selection for interview as traditional medical school performance metrics. Selection committees should invoke strategies to detect and manage appearance-based bias.


Psychological perspectives of inflammatory bowel disease patients undergoing surgery: rightful concerns and preconceptions.
Surgery has been associated with variable effect on the quality of life of inflammatory bowel disease (IBD) patients, depending on clinical patterns and baseline disease characteristics. However, surgical treatment is often conceived by these patients with distress and considered as the failure of their therapies. Lack of control, risk of complications, defacement of the body image, need of ostomy and hospitalization may be triggering concerns leading to anguish and anxiety. Even though the quality of life in most cases generally improves after surgery, some particular aspects such as sexual activity, bowel movements and the ability to deal with a possible stoma may present a slower amelioration trend. These problems represent common causes of distress and may lead to an heightened risk of depression and anxiety with respect to background population. The psychological impact and apprehension surrounding surgery will be discussed in this review. Pros and cons of the surgical treatment in various IBD populations and its long-term sequelae in terms of quality of life and psychological well-being will be highlighted. Furthermore the tools to encompass these issues such as complete patient information, gastroenterologist/surgeon synergy and psychological counseling will be explored analyzing their respective roles.


Image Analysis Technique for Material Behavior Evaluation in Civil Structures.
The article presents a hybrid monitoring technique for the measurement of the deformation field. The goal is to obtain information about crack propagation in existing structures, for the purpose of monitoring their state of health. The measurement technique is based on the capture and analysis of a digital image set. Special markers were used on the surface of the structures that can be removed without damaging existing structures as the historical masonry. The digital image analysis was done using software specifically designed in Matlab to follow the tracking of the markers and determine the evolution of the deformation state. The method can be used in any type of structure but is particularly suitable when it is necessary not to damage the surface of structures. A series of experiments carried out on masonry walls of the Oliverian Museum (Pesaro, Italy) and Palazzo Silvi (Perugia, Italy) have allowed the validation of the procedure elaborated by comparing the results with those derived from traditional measuring techniques.


Regulation of ribosomal protein synthesis in Escherichia coli B/r.
The differential synthesis rate of ribosomal protein (r-protein), alpha-r (synthesis rate of r-protein divided by synthesis rate of total protein), was measured during the cell division cycle. It was observed that alpha-r remained essentially constant and was not measurably affected by duplication of the r-protein gene cluster (i.e., str-spc region) during the process of chromosome replication. It was further observed that the rate of total protein synthesis and r-protein synthesis increased continuously and uniformly during the entire cell cycle. This gene dosage independence of the synthesis rate of r-protein was similar to that observed earlier for the synthesis of ribosomal ribonucleic acid (rRNA). These observations indicate that the synthesis rates of the protein and RNA components of the ribosome are coordinately balanced during the entire cell division cycle and are not significantly perturbed by duplication of the r-protein or rRNA genes. Furthermore, this balanced synthesis insures that neither free rRNA nor free r-protein accumulate in appreciable amounts during balanced growth.


Anti-Thy 1.2 monoclonal antibody linked to ricin is a potent cell-type-specific toxin.
The cell-type specificity of the toxin ricin, which ordinarily binds, enters, and kills cells through receptors containing galactose, has been altered by covalently binding it to a monoclonal antibody and by reversibly binding it to lactose. The antibody, a monoclonal rat IgG2b directed against the Thy 1.2 antigen, provides ricin with a new binding site for the murine thymus cell surface. Addition of lactose saturates the galactose-binding site on ricin and inhibits ricin from binding and killing cells via the galactose-containing receptors. The antibody-ricin hybrid protein, anti-Thy 1.2-ricin, formed with a thioether linkage, has been purified by size exclusion and affinity chromatography. When assayed by inhibition of protein synthesis of EL-4 cells, which express the Thy 1.2 antigen anti-Thy 1.2-ricin is equally as toxic as ricin on a molar basis. The hybrid protein toxicity is unchanged in the presence of 100 mM lactose, whereas unmodified ricin toxicity is reduced to 1% of its toxicity in the absence of lactose. This demonstrates the altered receptor specificity of the ricin hybrid. The cell-type specificity of the anti-Thy 1.2-ricin inhibition of protein synthesis correlates with the presence of the Thy 1.2 antigen. Anti-Thy 1.2-ricin at 4 microgram/ml in the presence of lactose inhibits protein synthesis within 3.5 hr by 60-80% in EL-4 cells but does not affect Thy 1.1 alloantigen and HeLa cells that lack the Thy 1 antigen. Anti-Thy 1.2-ricin in the presence of lactose selectively kills EL-4 cells at concentrations that do not kill AKR-K36 cells. This selectivity, expressed as the ratio of anti-Thy 1.2-ricin concentrations required to kill 40% of both cell types, is 700. Ricin-monoclonal antibody hybrids of this type combine a high degree of cell-type selectivity and toxicity and may have pharmacologic utility as antitumor reagents.


Discoidin domain receptor 1 (DDR1) kinase as target for structure-based drug discovery.
Discoidin domain receptor (DDR) 1 and 2 are transmembrane receptors that belong to the family of receptor tyrosine kinases (RTK). Upon collagen binding, DDRs transduce cellular signaling involved in various cell functions, including cell adhesion, proliferation, differentiation, migration, and matrix homeostasis. Altered DDR function resulting from either mutations or overexpression has been implicated in several types of disease, including atherosclerosis, inflammation, cancer, and tissue fibrosis. Several established inhibitors, such as imatinib, dasatinib, and nilotinib, originally developed as Abelson murine leukemia (Abl) kinase inhibitors, have been found to inhibit DDR kinase activity. As we review here, recent discoveries of novel inhibitors and their co-crystal structure with the DDR1 kinase domain have made structure-based drug discovery for DDR1 amenable.


Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature.
Precise localization of sulco-gyral structures of the human cerebral cortex is important for the interpretation of morpho-functional data, but requires anatomical expertise and is time consuming because of the brain's geometric complexity. Software developed to automatically identify sulco-gyral structures has improved substantially as a result of techniques providing topologically correct reconstructions permitting inflated views of the human brain. Here we describe a complete parcellation of the cortical surface using standard internationally accepted nomenclature and criteria. This parcellation is available in the FreeSurfer package. First, a computer-assisted hand parcellation classified each vertex as sulcal or gyral, and these were then subparcellated into 74 labels per hemisphere. Twelve datasets were used to develop rules and algorithms (reported here) that produced labels consistent with anatomical rules as well as automated computational parcellation. The final parcellation was used to build an atlas for automatically labeling the whole cerebral cortex. This atlas was used to label an additional 12 datasets, which were found to have good concordance with manual labels. This paper presents a precisely defined method for automatically labeling the cortical surface in standard terminology.


Betamethasone valerate dressing is non-inferior to calcipotriol-betamethasone dipropionate ointment in the treatment of patients with mild-to-moderate chronic plaque psoriasis: results of a randomized assessor-blinded multicentre trial.
A ready-to-use betamethasone valerate 0.1% (BMV) dressing was found to be superior to placebo dressing and a reference 0.1% BMV cream in the treatment of patients with chronic plaque psoriasis (CPP). This multicentre, prospective, randomized, investigator-blinded, controlled, non-inferiority trial compared the efficacy and safety of the BMV dressing to the calcipotriol-betamethasone dipropionate (CBD) ointment during a 4-week treatment of patients with mild to moderate CPP. The primary efficacy endpoint was the 4-item psoriasis total severity score (TSS-4) at week 4, and the associated non-inferiority margin was 1 point. Secondary outcome measures included the psoriasis global assessment (PGA) score and patients' quality of life (QoL). Safety was assessed through adverse events (AE) reporting in each treatment group. Of 325 screened patients, 324 were randomized to BMV (N = 165) or CBD (N = 159), and were considered evaluable for the safety and intention-to-treat (ITT) efficacy analyses. Per protocol (PP) populations included 133 and 131 patients in the BMV and CBD groups respectively. The mean adjusted TSS-4 significantly decreased through the study from baseline in both groups. The PP (primary) analysis of week 4 data revealed a -0.288 (95% CI: -0.610 to 0.034) not significant between-group difference in adjusted means, demonstrating non-inferiority of BMV to CBD. Non-inferiority was also demonstrated in the ITT analysis. The PGA and other secondary outcomes were significantly improved from baseline in both groups at week 4. The QoL score was slightly better in the CBD group at week 4, but no difference was observed at follow-up. No safety or tolerability concerns were observed in either group. BMV dressing is non-inferior to CBD ointment in patients with mild to moderate CPP. Both treatments significantly improve patients' psoriasis and QoL.


Complementary probes reveal that phosphatidylserine is required for the proper transbilayer distribution of cholesterol.
Cholesterol is an essential component of metazoan cellular membranes and it helps to maintain the structural integrity and fluidity of the plasma membrane. Here, we developed a cholesterol biosensor, termed D4H, based on the fourth domain of Clostridium perfringens theta-toxin, which recognizes cholesterol in the cytosolic leaflet of the plasma membrane and organelles. The D4H probe disassociates from the plasma membrane upon cholesterol extraction and after perturbations in cellular cholesterol trafficking. When used in combination with a recombinant version of the biosensor, we show that plasmalemmal phosphatidylserine is essential for retaining cholesterol in the cytosolic leaflet of the plasma membrane. In vitro experiments reveal that 1-stearoy-2-oleoyl phosphatidylserine can induce phase separation in cholesterol-containing lipid bilayers and shield cholesterol from cholesterol oxidase. Finally, the altered transbilayer distribution of cholesterol causes flotillin-1 to relocalize to endocytic organelles. This probe should be useful in the future to study pools of cholesterol in the cytosolic leaflet of the plasma membrane and organelles.


Effect of acid on the ultraviolet-visible absorption and emission properties of curcumin.
Steady-state and time-resolved emission techniques were employed to study the acid-base effects on the UV-vis spectrum of curcumin in several organic solvents. The fluorescence-decay rate of curcumin increases with increasing acid concentration in all of the solvents studied. In methanol and ethanol solutions containing about 1 M HCl, the short-wavelength fluorescence (λ < 560 nm) decreases by more than an order of magnitude. (The peak fluorescence intensity of curcumin in these solvents is at 540 nm.) At longer wavelengths (λ ≥ 560 nm) the fluorescence quenching is smaller by a factor of ∼3. A new fluorescence band with a peak at about 620 nm appears at an acid concentration of about 0.2 M in both methanol and ethanol. The 620 nm/530 nm band intensity ratio increases with an increase in the acid concentration. In trifluoroethanol and also in acetic acid in the presence of formic acid, the steady-state emission of curcumin shows an emission band at 620 nm. We attribute this new emission band in hydrogen-bond-donating solvents to a protonated curcumin ROH2(+) form. At high acid concentrations in acetic acid and in trifluoroethanol, the ground state of curcumin is also transformed to ROH2(+) which absorbs at longer wavelengths with a band peak at ∼530 nm compared to 420 nm in neutral-pH samples or 480 nm in basic solutions. In hydrogen-bond-accepting solvents such as dimethyl sulfoxide and also in methanol and ethanol, curcumin does not accept a proton to form the ground-state ROH2(+)


Novel Skeletal Rearrangements of the Tigliane Diterpenoid Core.
To investigate the role of the secondary 5-hydroxy group in the activity of the anticancer drug tigilanol tiglate (2b) (Stelfonta), oxidation of this epoxytigliane diterpenoid from the Australian rainforest plant Fontainea picrosperma was attempted. Eventually, 5-dehydrotigilanol tiglate (3a) proved too unstable to be characterized in terms of biological activity and, therefore, was not a suitable tool compound for bioactivity studies. On the other hand, a series of remarkable skeletal rearrangements associated with the presence of a 5-keto group were discovered during its synthesis, including a dismutative ring expansion of ring A and a mechanistically unprecedented dyotropic substituent swap around the C-4/C-10 bond. Taken together, these observations highlight the propensity of the α-hydroxy-β-diketone system to trigger complex skeletal rearrangements and pave the way to new areas of the natural products chemical space.


Partnering with Fishing Fleets to Monitor Ocean Conditions.
Engaging ocean users, including fishing fleets, in oceanographic and ecological research is a valuable method for collecting high-quality data, improving cost efficiency, and increasing societal appreciation for scientific research. As research partners, fishing fleets provide broad access to and knowledge of the ocean, and fishers are highly motivated to use the data collected to better understand the ecosystems in which they harvest. Here, we discuss recent trends in collaborative research that have increased the capacity of and access to scientific data collection. We also describe common elements of successful collaborative research programs, including definition of a scientific problem and goals, choice of technology, data collection and sampling design, data management and dissemination, and data analysis and communication. Finally, we review four case studies that demonstrate the general principles of effective collaborative research as well as the utility of citizen-collected data for academic research and fisheries management. We also discuss the challenge of funding, particularly as it relates to maintaining collaborative research programs in the long term. We conclude with a discussion of likely future trends. Ultimately, we predict that collaborative research will continue to grow in importance as climate change increasingly impacts ocean ecosystems, commercial fisheries, and the global food supply.


A joint Bayesian framework for missing data and measurement error using integrated nested Laplace approximations.
Measurement error (ME) and missing values in covariates are often unavoidable in disciplines that deal with data, and both problems have separately received considerable attention during the past decades. However, while most researchers are familiar with methods for treating missing data, accounting for ME in covariates of regression models is less common. In addition, ME and missing data are typically treated as two separate problems, despite practical and theoretical similarities. Here, we exploit the fact that missing data in a continuous covariate is an extreme case of classical ME, allowing us to use existing methodology that accounts for ME via a Bayesian framework that employs integrated nested Laplace approximations (INLA) and thus to simultaneously account for both ME and missing data in the same covariate. As a useful by-product, we present an approach to handle missing data in INLA since this corresponds to the special case when no ME is present. In addition, we show how to account for Berkson ME in the same framework. In its broadest generality, the proposed joint Bayesian framework can thus account for Berkson ME, classical ME, and missing data, or any combination of these in the same or different continuous covariates of the family of regression models that are feasible with INLA. The approach is exemplified using both simulated and real data. We provide extensive and fully reproducible Supporting Information with thoroughly documented examples using R-INLA and inlabru.


Calculated Versus Measured Urine Osmolarity: Accuracy of Estimated Urine Density.
Urine osmolarity (OsmU) is the gold standard for the evaluation of the kidney's urine concentration capacity; nevertheless, urinary density (UD) is often used as a surrogate for its estimation. The objective of this study was to analyze the accuracy of UD in estimating OsmU. A transversal study including patients with simultaneous determination of UD measured with refractometry and OsmU measured by osmometer (OsmUm). We multiplied the last two digits of the UD by 35, 30, 32, 33.5, and 40 to estimate OsmU; the estimates were considered precise if the value was ± 30 mOsm/kg from the OsmUm. A Bland-Altman analysis was conducted. Among 205 patients, there was no difference between OsmUm and the estimated form when using a factor of 33.5 (p = 0.578). When analyzing by the absence or presence of proteinuria and/or glycosuria, there were no differences when using the factors 35 (p = 0.844) and 32 with adjusted UD (p = 0.898). In the linear correlation analysis, values for Pearson's r = 0.788 and r2 = 0.621 were obtained (p < 0.001). The areas under the curve obtained by the receiver operating characteristics curves to estimate urine osmolarity values < 100 and > 600 mOsm/kg were > 0.90. The estimation of the OsmU from UD showed adequate performance. If an osmometer is unavailable, we recommend using the factor 35 for clean samples and 32 with adjusted UD for samples with proteinuria and/or glycosuria.


Toward globalization of a profession.
The International Federation of Nurse Anesthetists [IFNA] has been striving to promote quality education and practice standards since it began in 1989. Many organizations throughout the world have recognized these efforts including the International Council of Nurses. This Guest Editorial summarizes IFNA's achievements and introduces IFNA's new initiative to enhance the quality of anesthesia care worldwide through an approval process for education programs.


An integrated genetic linkage map for white clover (Trifolium repens L.) with alignment to Medicago.
White clover (Trifolium repens L.) is a temperate forage legume with an allotetraploid genome (2n=4×=32) estimated at 1093 Mb. Several linkage maps of various sizes, marker sources and completeness are available, however, no integrated map and marker set has explored consistency of linkage analysis among unrelated mapping populations. Such integrative analysis requires tools for homoeologue matching among populations. Development of these tools provides for a consistent framework map of the white clover genome, and facilitates in silico alignment with the model forage legume, Medicago truncatula. This is the first report of integration of independent linkage maps in white clover, and adds to the literature on methyl filtered GeneThresher®-derived microsatellite (simple sequence repeat; SSR) markers for linkage mapping. Gene-targeted SSR markers were discovered in a GeneThresher® (TrGT) methyl-filtered database of 364,539 sequences, which yielded 15,647 SSR arrays. Primers were designed for 4,038 arrays and of these, 465 TrGT-SSR markers were used for parental consensus genetic linkage analysis in an F1 mapping population (MP2). This was merged with an EST-SSR consensus genetic map of an independent population (MP1), using markers to match homoeologues and develop a multi-population integrated map of the white clover genome. This integrated map (IM) includes 1109 loci based on 804 SSRs over 1274 cM, covering 97% of the genome at a moderate density of one locus per 1.2 cM. Eighteen candidate genes and one morphological marker were also placed on the IM. Despite being derived from disparate populations and marker sources, the component maps and the derived IM had consistent representations of the white clover genome for marker order and genetic length. In silico analysis at an E-value threshold of 1e-20 revealed substantial co-linearity with the Medicago truncatula genome, and indicates a translocation between T. repens groups 2 and 6 relative to M. truncatula. This integrated genetic linkage analysis provides a consistent and comprehensive linkage analysis of the white clover genome, with alignment to a model forage legume. Associated marker locus information, particularly the homoeologue-specific markers, offers a new resource for forage legume research to enable genetic analysis and improvement of this forage and grassland species.


Kinin effects on electrogenic ion transport in primary cultures of pig renal papillary collecting tubule cells.
Confluent monolayers of pig renal papillary collecting tubule (RPCT) cells were formed on Millipore filters coated with collagen. They were clamped in Ussing-type chambers and used to measure short-circuit current (SCC). The monolayers had low potentials (0.1 mV) with the basolateral side positive. Small inward currents flowed under short-circuit conditions. Increases in SCC were obtained following addition of a number of agents. Receptors associated with SCC changes were disposed as follows: for kinins (e.g., lysyl-bradykinin) they were present on both sides of the tissue, while those for arginine vasopressin and norepinephrine were present on the basolateral side only. Epithelia responded to PGE2 added to the apical or basolateral face of the tissue; application to one side prevented the response from the contralateral side. The tissues also responded to forskolin, an activator of adenylate cyclase, with a sustained inward current that was sensitive to furosemide. Similar sustained inward currents were recorded following exposure to 8-bromoadenosine-3',5'-cyclic monophosphate (BrcAMP). Responses to kinins were attenuated by inhibition of fatty acid cyclooxygenase with either indomethacin or piroxicam or by replacing chloride with impermeant ions. If the SCC was first increased with forskolin, BrcAMP, or norepinephrine, the kinin effects on SCC were either abolished or reversed. It is concluded that kinin can cause chloride secretion in RPCT monolayers, possibly via a prostaglandin or a prostaglandin-adenylate cyclase mechanism. Secondary effects of kinin, exposed by first raising tissue cAMP levels, are not precluded.


Streptomyces coelicolor A3(2) lacks a genomic island present in the chromosome of Streptomyces lividans 66.
Streptomyces lividans ZX1 has become a preferred host for DNA cloning in Streptomyces species over its progenitor, the wild-type strain 66 (stock number 1326 from the John Innes Center collection), especially when stable DNA is crucial for in vitro electrophoresis, because DNA from strain 66 contains a novel modification that makes it sensitive to oxidative double-strand cleavage during electrophoresis. Detailed analysis of this modification-deficient mutant (ZX1) revealed that it has several additional phenotypic traits associated with a chromosomal deletion of ca. 90 kb, which was cloned and mapped by using a cosmid library. Comparative sequence analysis of two clones containing the left and right deletion ends originating from strain 66 and one clone with the deletion and fused sequence cloned from strain ZX1 revealed a perfect 15-bp direct repeat, which may have mediated deletion and fusion to yield strain ZX1 by site-specific recombination. Analysis of AseI linking clones in the deleted region in relation to the published AseI map of strain ZX1 yielded a complete AseI map for the S. lividans 66 genome, on which the relative positions of a cloned phage phiHAU3 resistance (phiHAU3r) gene and the dnd gene cluster were precisely localized. Comparison of S. lividans ZX1 and its progenitor 66, as well as the sequenced genome of its close relative, Streptomyces coelicolor M145, reveals that the ca. 90-kb deletion in strain ZX1 may have originated from an insertion from an unknown source.


[Leisure among university students in the healthcare area: a review of the literature].
This article set out to analyze studies on leisure activities among university students in the healthcare area. It conducted a search using the following key words: leisure and students, and their corresponding terms in Spanish and English in the Bireme database, which resulted in 32 articles at the end of the review. In the articles analyzed there was a predominance of the following leisure interests: sports, social, intellectual and artistic activities, with a greater number of articles presenting experiences in sports. It was also noted that the intake of alcohol in the leisure context is often mentioned by this population group. There was a predilection for physical exercised/sport during leisure time, compared to other leisure interests and little knowledge about any other possibilities for leisure. This article also discusses the need to develop strategies that promote leisure among these students, seeking to improve their quality of life. It is noteworthy that they are health professionals in the training phase and it is quite possible that their future orientations might be influenced by their personal practices.


Binding conformation of 2-oxoamide inhibitors to group IVA cytosolic phospholipase A2 determined by molecular docking combined with molecular dynamics.
The group IVA cytosolic phospholipase A(2) (GIVA cPLA(2)) plays a central role in inflammation. Long chain 2-oxoamides constitute a class of potent GIVA cPLA(2) inhibitors that exhibit potent in vivo anti-inflammatory and analgesic activity. We have now gained insight into the binding of 2-oxoamide inhibitors in the GIVA cPLA(2) active site through a combination of molecular docking calculations and molecular dynamics simulations. Recently, the location of the 2-oxoamide inhibitor AX007 within the active site of the GIVA cPLA(2) was determined using a combination of deuterium exchange mass spectrometry followed by molecular dynamics simulations. After the optimization of the AX007-GIVA cPLA(2) complex using the docking algorithm Surflex-Dock, a series of additional 2-oxoamide inhibitors have been docked in the enzyme active site. The calculated binding affinity presents a good statistical correlation with the experimental inhibitory activity (r(2) = 0.76, N = 11). A molecular dynamics simulation of the docking complex of the most active compound has revealed persistent interactions of the inhibitor with the enzyme active site and proves the stability of the docking complex and the validity of the binding suggested by the docking calculations. The combination of molecular docking calculations and molecular dynamics simulations is useful in defining the binding of small-molecule inhibitors and provides a valuable tool for the design of new compounds with improved inhibitory activity against GIVA cPLA(2).


Long-term kinetics of T cell production in HIV-infected subjects treated with highly active antiretroviral therapy.
The long-term kinetics of T cell production following highly active antiretroviral therapy (HAART) were investigated in blood and lymph node in a group of HIV-infected subjects at early stage of established infection and prospectively studied for 72 wk. Before HAART, CD4 and CD8 T cell turnover was increased. However, the total number of proliferating CD4(+) T lymphocytes, i.e., CD4(+)Ki67(+) T lymphocytes, was not significantly different in HIV-infected (n = 73) and HIV-negative (n = 15) subjects, whereas proliferating CD8(+)Ki67(+) T lymphocytes were significantly higher in HIV-infected subjects. After HAART, the total body number of proliferating CD4(+)Ki67(+) T lymphocytes increased over time and was associated with an increase of both naive and memory CD4(+) T cells. The maximal increase (2-fold) was observed at week 36, whereas at week 72 the number of proliferating CD4(+) T cells dropped to baseline levels, i.e., before HAART. The kinetics of the fraction of proliferating CD4 and CD8 T cells were significantly correlated with the changes in the total body number of these T cell subsets. These results demonstrate a direct relationship between ex vivo measures of T cell production and quantitative changes in total body T lymphocyte populations. This study provides advances in the delineation of the kinetics of T cell production in HIV infection in the presence and/or in the absence of HAART.


Effects of self-efficacy, body mass, and cardiorespiratory fitness on exercise motives in Chinese college students.
Researchers have studied exercise determinants primarily from cognitive and social psychology perspectives, which typically give minimal attention to the body as a physical and biological entity. With the belief that tapping into multidimensional variables would potentially help us better understand motivation in exercise, we designed this study to examine the influences of self-efficacy, body mass, and cardiorespiratory fitness level on Chinese college students' leisure-time exercise motives. 208 college students completed measures of self-efficacy and exercise motives during regular physical education classes. Their body mass and cardiorespiratory fitness level data were derived from the latest annual physical training test. Multiple regression analyses were conducted to investigate the effects of self-efficacy, body mass, and cardiorespiratory fitness on exercise motives. Cardiorespiratory fitness level and self-efficacy in exercise significantly contributed to both psychological and interpersonal motives. Body mass was the only significant predictor for body-related motives. However, analyses of health and fitness motives did not result in any significant predictors. Physical and psychological variables have both independent and specialized functions on exercise motives. Future motivational studies in exercise should pay greater attention to ecological approaches that account for physical, psychological, and social factors.


Fast-Growing Meningioma in a Woman Undergoing Fertility Treatments.
Meningiomas have long been known to be associated with sexual hormones. We discuss here the case of a woman with a huge meningioma that rapidly grew over the course of a couple years while the patient was simultaneously taking fertility treatments. There is substantial evidence suggesting that fertility treatments can fuel the growth of meningiomas. The potential risks should be considered in women with a previous or family history of meningiomas who plan to undergo fertility treatment. These patients need to be evaluated and a screening imaging of brain MRI (Magnetic Resonant Imaging) should be offered in the middle or toward the end of such a treatment to control and prevent complications of these meningiomas.


Differential effects of in vitro zinc treatment on gene expression in peripheral blood mononuclear cells derived from young and elderly individuals.
Mild zinc deficiency, which is prevalent in vegetarians, diseased individuals, and the general aging population, depresses immunity and increases risk of disease in later life. However, human zinc intervention trials have produced conflicting results, perhaps because many of these trials included young or zinc-sufficient subjects. Since heterogeneity of the adult population may impact on response to dietary zinc, nutrigenomic approaches aimed at understanding the impact of zinc on modulation of gene and protein activities may aid in identifying subsets of the population-in particular the aging population-with increased risk of zinc deficiency who might receive benefit from a dietary zinc intervention and in this way may influence the success of the intervention. In the current study we used nutrigenomic approaches to investigate the impact of age on zinc-regulated gene expression in peripheral blood mononuclear cells. Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, CA) identified several genetic networks and functional canonical pathways which appeared responsive to zinc that were differentially regulated in young and elderly individuals. These include tryptophan metabolism, eicosanoid signaling, p38 mitogen-activated protein kinase (MAPK) signaling, integrin signaling, purine metabolism, G-protein-coupled receptor signaling, and most significantly, peroxisome proliferator-activated receptor (PPAR) signaling. These data suggest that age impacts strongly on the transcriptional effects of zinc and provides evidence to support the hypothesis that young and elderly individuals may respond differentially to zinc intervention.


Exploring Relationships Between Autism Spectrum Disorder Symptoms and Eating Disorder Symptoms in Adults With Anorexia Nervosa: A Network Approach.
Over the past few decades, research has accumulated to suggest a relationship between anorexia nervosa (AN) and autism spectrum disorder (ASD). Elevated ASD traits are present in around one third of those with AN, and there is some evidence to suggest that ASD traits are associated with more severe eating disorder (ED) psychopathology. The current study aimed to examine relationships between ED and ASD symptoms in individuals with a lifetime history of AN using network analysis. One hundred and one participants completed the ED Examination Questionnaire (EDE-Q) and the Social Responsiveness Scale (SRS-2). A regularized partial correlation network was estimated using a graphical least absolute shrinkage and selection operator. Expected influence (EI) and bridge EI values were calculated to identify central and bridge symptoms respectively. Isolation, difficulties with relating to others, and feelings of tension during social situations were most central to the network, while poor self-confidence, concerns over eating around others, and concerns over others seeing one's body were the strongest bridge symptoms. Our findings confirm that interpersonal problems are central to ED psychopathology. They also suggest poor self-confidence and social anxiety-type worries may mediate the relationship between ED and ASD symptoms in those with a lifetime diagnosis of AN. Longitudinal studies examining fluctuations in symptoms over time may be helpful in understanding direction of causality.


Exploring the cortical and subcortical functional magnetic resonance imaging changes associated with freezing in Parkinson's disease.
Freezing of gait is a devastating symptom of advanced Parkinson's disease yet the neural correlates of this phenomenon remain poorly understood. In this study, severity of freezing of gait was assessed in 18 patients with Parkinson's disease on a series of timed 'up and go' tasks, in which all patients suffered from episodes of clinical freezing of gait. The same patients also underwent functional magnetic resonance imaging with a virtual reality gait paradigm, performance on which has recently been shown to correlate with actual episodes of freezing of gait. Statistical parametric maps were created that compared the blood oxygen level-dependent response associated with paroxysmal motor arrests (freezing) to periods of normal motor output. The results of a random effects analysis revealed that these events were associated with a decreased blood oxygen level-dependent response in sensorimotor regions and an increased response within frontoparietal cortical regions. These signal changes were inversely correlated with the severity of clinical freezing of gait. Motor arrests were also associated with decreased blood oxygen level-dependent signal bilaterally in the head of caudate nucleus, the thalamus and the globus pallidus internus. Utilizing a mixed event-related/block design, we found that the decreased blood oxygen level-dependent response in the globus pallidus and the subthalamic nucleus persisted even after controlling for the effects of cognitive load, a finding which supports the notion that paroxysmal increases in basal ganglia outflow are associated with the freezing phenomenon. This method also revealed a decrease in the blood oxygen level-dependent response within the mesencephalic locomotor region during motor arrests, the magnitude of which was positively correlated with the severity of clinical freezing of gait. These results provide novel insights into the pathophysiology underlying freezing of gait and lend support to models of freezing of gait that implicate dysfunction across coordinated neural networks.


Improvements and impacts of GRCh38 human reference on high throughput sequencing data analysis.
Analyses of high throughput sequencing data starts with alignment against a reference genome, which is the foundation for all re-sequencing data analyses. Each new release of the human reference genome has been augmented with improved accuracy and completeness. It is presumed that the latest release of human reference genome, GRCh38 will contribute more to high throughput sequencing data analysis by providing more accuracy. But the amount of improvement has not yet been quantified. We conducted a study to compare the genomic analysis results between the GRCh38 reference and its predecessor GRCh37. Through analyses of alignment, single nucleotide polymorphisms, small insertion/deletions, copy number and structural variants, we show that GRCh38 offers overall more accurate analysis of human sequencing data. More importantly, GRCh38 produced fewer false positive structural variants. In conclusion, GRCh38 is an improvement over GRCh37 not only from the genome assembly aspect, but also yields more reliable genomic analysis results.


Experimentally induced ovine border disease: extensive hypomyelination with minimal viral antigen in neonatal spinal cord.
Border disease (BD) was experimentally induced in 9 lambs by inoculation of their dams with the BD-31 strain of border disease virus (BDV) at 50 days of gestation. These ewes developed serum-neutralizing antibody titers to BDV. The diagnosis of BD in their lambs was confirmed by hairy birthcoats, intrauterine growth retardation, tremors, and hypomyelination. Three clinically healthy age-matched control lambs, whose dams had been given an inoculum containing only BDV-free cell culture supernatant, were studied in parallel. There were significant differences in birth weights and in the lengths of the right tibiae and radii between the affected and the control lambs. There was a gradient in severity of clinical neurologic signs among the affected lambs, which directly correlated with the severity of hypomyelination in their spinal cords. However, the difference in severity of the neurologic deficits did not correlate with differences either in the precolostral serum-neutralizing antibody titers to BDV in these lambs or in the number of BDV antigen-containing cells in their spinal cords. Only approximately 0.01% to 0.3% of spinal cord cells, both in gray matter and white matter, were BDV antigen positive in the affected lambs. These results indicate that extensive infection of CNS cells with their subsequent destruction or functional alteration may not be a critical part of the pathogenesis of the hypomyelination in BD.


Differential effects of leptin administration on feeding and HPT axis function in early-life overfed adult rats.
Early-life overfeeding (OF) disrupts neuroendocrine systems, energy homeostasis and food intake regulation inducing overeating and overweight in adults. Adult rats raised in small litters during lactation, display hyperphagia and overweight since weaning and exhibit a decrease in thyrotropin-releasing hormone (TRH) mRNA expression in hypothalamic paraventricular nucleus (PVN). This is counterintuitive because TRH expression should increase to activate the hypothalamic-pituitary-thyroid (HPT) axis and promote energy expenditure, thus, HPT axis seems inhibited in OF rats. Leptin, an adipocyte-synthesized hormone that stimulates hypothalamic TRH expression, enhances both TRH anorectic effects and HPT axis-induced metabolic rate. To evaluate hypothalamic resistance to the anorectic and HPT axis stimulatory actions of leptin, we injected leptin i.p. to ad libitum fed and to 48-h fasted adult control (reared in normal litters) and to small-litter reared (OF) male Wistar rats. Findings showed that HPT axis was still responsive to leptin, since PVN TRH mRNA levels, median eminence TRH release and T4 serum concentration increased in both, ad libitum and fasted OF rats after leptin administrations. Leptin was ineffective to reduce feeding of OF animals. By comparing leptin receptor (ObRb) expression changes between arcuate and PVN nuclei, we observed that arcuate ObRb was not modified in response to leptin administrations in OF rats, likely accounting for the differential effects in feeding and HPT axis function. Nevertheless, ObRb expression was modified by leptin in the PVN of OF rats to the same extent as controls; this supports the hormone's role as a therapeutic agent for early onset obesity in adults.


Persistent redistribution of poly-adenylated mRNAs correlates with translation arrest and cell death following global brain ischemia and reperfusion.
Although persistent translation arrest correlates with the selective vulnerability of post-ischemic hippocampal cornu ammonis 1 (Ammon's horn) (CA1) neurons, the mechanism of persistent translation arrest is not fully understood. Using fluorescent in situ hybridization and immunofluorescence histochemistry, we studied colocalization of polyadenylated mRNAs [poly(A)] with the following mRNA binding factors: eukaryotic initiation factor (eIF) 4G (translation initiation factor), HuR (ARE-containing mRNA stabilizing protein), poly-adenylated mRNA binding protein (PABP), S6 (small ribosomal subunit marker), T cell internal antigen (TIA-1) (stress granule marker), and tristetraprolin (TTP) (processing body marker). We compared staining in vulnerable CA1 and resistant CA3 from 1 to 48 h reperfusion, following 10 min global ischemia in the rat. In both CA1 and CA3 neurons, cytoplasmic poly(A) mRNAs redistributed from a homogenous staining pattern seen in controls to granular structures we term mRNA granules. The mRNA granules abated after 16 h reperfusion in CA3, but persisted in CA1 neurons to 48 h reperfusion. Protein synthesis inhibition correlated precisely with the presence of the mRNA granules. In both CA1 and CA3, the mRNA granules colocalized with eIF4G and PABP, but not S6, TIA-1 or TTP, indicating that they were neither stress granules nor processing bodies. Colocalization of HuR in the mRNA granules correlated with translation of 70 kDa inducible heat shock protein, which occurred early in CA3 (8 h) and was delayed in CA1 (36 h). Thus, differential compartmentalization of mRNA away from the 40S subunit correlated with translation arrest in post-ischemic neurons, providing a concise mechanism of persistent translation arrest in post-ischemic CA1.


Hepatic stellate cells preferentially induce Foxp3+ regulatory T cells by production of retinoic acid.
The liver has long been described as immunosuppressive, although the mechanisms underlying this phenomenon are incompletely understood. Hepatic stellate cells (HSCs), a population of liver nonparenchymal cells, are potent producers of the regulatory T cell (Treg)-polarizing molecules TGF-β1 and all-trans retinoic acid, particularly during states of inflammation. HSCs are activated during hepatitis C virus infection and may therefore play a role in the enrichment of Tregs during infection. We hypothesized that Ag presentation in the context of HSC activation will induce naive T cells to differentiate into Foxp3(+) Tregs. To test this hypothesis, we investigated the molecular interactions between murine HSCs, dendritic cells, and naive CD4(+) T cells. We found that HSCs alone do not present Ag to naive CD4(+) T cells, but in the presence of dendritic cells and TGF-β1, preferentially induce functional Tregs. This Treg induction was associated with retinoid metabolism by HSCs and was dependent on all-trans retinoic acid. Thus, we conclude that HSCs preferentially generate Foxp3(+) Tregs and, therefore, may play a role in the tolerogenic nature of the liver.


Importance of incomplete lineage sorting and introgression in the origin of shared genetic variation between two closely related pines with overlapping distributions.
Genetic variation shared between closely related species may be due to retention of ancestral polymorphisms because of incomplete lineage sorting (ILS) and/or introgression following secondary contact. It is challenging to distinguish ILS and introgression because they generate similar patterns of shared genetic diversity, but this is nonetheless essential for inferring accurately the history of species with overlapping distributions. To address this issue, we sequenced 33 independent intron loci across the genome of two closely related pine species (Pinus massoniana Lamb. and Pinus hwangshanensis Hisa) from Southeast China. Population structure analyses revealed that the species showed slightly more admixture in parapatric populations than in allopatric populations. Levels of interspecific differentiation were lower in parapatry than in allopatry. Approximate Bayesian computation suggested that the most likely speciation scenario explaining this pattern was a long period of isolation followed by a secondary contact. Ecological niche modeling suggested that a gradual range expansion of P. hwangshanensis during the Pleistocene climatic oscillations could have been the cause of the overlap. Our study therefore suggests that secondary introgression, rather than ILS, explains most of the shared nuclear genomic variation between these two species and demonstrates the complementarity of population genetics and ecological niche modeling in understanding gene flow history. Finally, we discuss the importance of contrasting results from markers with different dynamics of migration, namely nuclear, chloroplast and mitochondrial DNA.


Do men improve their bone mineral density 1 year after parathyroidectomy for primary hyperparathyroidism? Results of a prospective study.
The impact of parathyroidectomy on bone mineral density in men with primary hyperparathyroidism is poorly known. This study aimed to evaluate the bone mineral density and bone remodeling biomarker changes in men with primary hyperparathyroidism 1 year after parathyroidectomy. Men operated for sporadic primary hyperparathyroidism between 2016 and 2022, enrolled in a monocentric prospective cohort, were analyzed. Patients with follow-up <1 year or missing data were excluded. Bone mineral density (dual X-ray absorptiometry) was measured before and 12 months after parathyroidectomy. Bone mineral density change ≥0.03g/cm2 was deemed significant. Bone remodeling biomarkers were serum cross-linked C-telopeptide, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatases. Forty-five men were included (mean age 58.8 ± 13.1 years). Before surgery, 49% had osteopenia, and 11% had osteoporosis. Mean serum calcium and median serum parathyroid hormone levels decreased significantly after surgery (P < .0001). One year after parathyroidectomy, the mean bone mineral density increased significantly at the lumbar spine (+0.04g/cm2 [0.01;0.70], P = .0054), femoral neck (+0.04g/cm2 [0.03;0.05], P < .0001) and total hip (+0.02g/cm2 [0.01;0.03], P = .0002). Considering significant bone mineral density gain (+1 point) and loss (-1 point) at each site, 29/45 patients (64% [95% CI 49;78]) improved. Bone remodeling biomarker concentrations significantly decreased (P < .001). Parathyroidectomy positively affects bone mineral density in men with primary hyperparathyroidism, supporting osteopenia as a surgical indication in these patients.


The complete in-gap electronic structure of colloidal quantum dot solids and its correlation with electronic transport and photovoltaic performance.
The direct observation of the complete electronic band structure of a family of PbS CQD solids via photoelectron spectroscopy is reported. We investigate how materials processing strategies, such as the latest passivation methods that produce record-performance photovoltaics, achieve their performance advances. Halide passivated films show a drastic reduction in states in the midgap, contributing to a marked improvement in the device performance.


A Novel TBX1 Variant Causing Hypoparathyroidism and Deafness.
The TBX1 gene encodes the T-box 1 protein that is a transcription factor involved in development. Haploinsufficiency of the TBX1 gene is reported to cause features similar to DiGeorge syndrome. The TBX1 gene is located within the DiGeorge syndrome region, and studies support that the TBX1gene is responsible for most of the features of the phenotype of hemizygous deletion of chromosome 22q11.2. In this study, we report a family of 4 (a father with 3 children) who presented with congenital hypoparathyroidism and hypocalcemia, facial asymmetry, deafness, normal intelligence, and no cardiac involvement. We performed whole genome sequencing, computational structural analysis of the mutants, and gene expression studies for all affected family members. Whole genome sequencing revealed a paternal inherited novel heterozygous variant, c.1158_1159delinsT p.(Gly387Alafs*73), in the exon 9 isoform C TBX1 gene, causing a loss of nuclear localization sequence (NLS) and transactivation domain (TAD) with no change in gene expression and resulted in a DiGeorge-like phenotype. A pathogenic variant in the TBX1 gene exon 9 C that predicted to cause a loss in the NLS region and most of TAD leads to variable features of hypoparathyroidism, distinctive facial features, deafness, and no cardiac involvement. In addition, our report and previous reports indicate the presence of a wide phenotypic spectrum of TBX1 genetic variants and the consistent absence of cardiac involvement in the case of pathogenic variants on exon 9 isoform C TBX1 gene.


Robotic-assisted gait rehabilitation following stroke: a systematic review of current guidelines and practical clinical recommendations.
Stroke is the third leading cause of adult disability worldwide, and lower extremity motor impairment is one of the major determinants of long-term disability. Although robotic therapy is becoming more and more utilized in research protocols for lower limb stroke rehabilitation, the gap between research evidence and its use in clinical practice is still significant. The aim of this study was to determine the scope, quality, and consistency of guidelines for robotic lower limb rehabilitation after stroke, in order to provide clinical recommendations. We systematically reviewed stroke rehabilitation guideline recommendations between January 1, 2010 and October 31, 2020. We explored electronic databases (N.=4), guideline repositories and professional rehabilitation networks (N.=12). Two independent reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and brief syntheses were used to evaluate and compare the different recommendations, considering only the most recent version. From the 1219 papers screened, ten eligible guidelines were identified from seven different regions/countries. Four of the included guidelines focused on stroke management, the other six on stroke rehabilitation. Robotic rehabilitation is generally recommended to improve lower limb motor function, including gait and strength. Unfortunately, there is still no consensus about the timing, frequency, training session duration and the exact characteristics of subjects who could benefit from robotics. Our systematic review shows that the introduction of robotic rehabilitation in standard treatment protocols seems to be the future of stroke rehabilitation. However, robot assisted gait training (RAGT) for stroke needs to be improved with new solutions and in clinical practice guidelines, especially in terms of applicability.


The importance of bioavailability to the pharmacist.
In many places in North America both by law and by delegation by physicians, pharmacists are responsible for choosing a specific brand or supplier of a drug. Only in the past few years, the importance of this selection has become recognized. Although the clinical importance of variations in biovailability is limited to only a few classes of drugs, adequate bioavailability information on which to base such a choice is imperative. Government and non-government groups now seem to be moving rapidly in the direction of providing guidance to pharmacists in drug selection. The lack of in-vivo data, particularly in patients with the disease in which the drug is used, is badly needed by such groups and individual practitioners in order that any decision on product selection be an informed one.


An Interscholastic Network To Generate LexA Enhancer Trap Lines in Drosophila.
Binary expression systems like the LexA-LexAop system provide a powerful experimental tool kit to study gene and tissue function in developmental biology, neurobiology, and physiology. However, the number of well-defined LexA enhancer trap insertions remains limited. In this study, we present the molecular characterization and initial tissue expression analysis of nearly 100 novel StanEx LexA enhancer traps, derived from the StanEx1 index line. This includes 76 insertions into novel, distinct gene loci not previously associated with enhancer traps or targeted LexA constructs. Additionally, our studies revealed evidence for selective transposase-dependent replacement of a previously-undetected KP element on chromosome III within the StanEx1 genetic background during hybrid dysgenesis, suggesting a molecular basis for the over-representation of LexA insertions at the NK7.1 locus in our screen. Production and characterization of novel fly lines were performed by students and teachers in experiment-based genetics classes within a geographically diverse network of public and independent high schools. Thus, unique partnerships between secondary schools and university-based programs have produced and characterized novel genetic and molecular resources in Drosophila for open-source distribution, and provide paradigms for development of science education through experience-based pedagogy.


Fluorescence optical imaging in pediatric patients with inflammatory and non-inflammatory joint diseases: a comparative study with ultrasonography.
Valid detection of arthritis is essential in differential diagnosis of joint pain. Indocyanin green (ICG)-enhanced fluorescence optical imaging (FOI) is a new imaging method that visualizes inflammation in wrist and finger joints. Objectives of this study were to compare FOI with ultrasonography (US, by gray-scale (GS) and power Doppler (PD)) and clinical examination (CE) and to estimate the predictive power of FOI for discrimination between inflammatory and non-inflammatory juvenile joint diseases. FOI and GSUS/PDUS were performed in both hands of 76 patients with joint pain (53 with juvenile idiopathic arthritis (JIA), 23 with non-inflammatory joint diseases). Inflammation was graded by a semiquantitative score (grades 0-3) for each imaging method. Joints were defined clinically active if swollen or tender with limited range of motion. Sensitivity and specificity of FOI in three phases dependent on ICG enhancement (P1-P3) were analyzed with CE and GSUS/PDUS as reference. For JIA patients, FOI had an overall sensitivity of 67.3%/72.0% and a specificity of 65.0%/58.8% with GSUS/PDUS as reference; specificity was highest in P3 (GSUS 94.3%/PDUS 91.7%). FOI was more sensitive for detecting clinically active joints than GSUS/PDUS (75.2% vs 57.3%/32.5%). In patients with non-inflammatory joint diseases both FOI and US showed positive (i.e., pathological) findings (25% and 14% of joints). The predictive value for discrimination between inflammatory and non-inflammatory joint diseases was 0.79 for FOI and 0.80/0.85 for GSUS/PDUS. Dependent on the phase evaluated, FOI had moderate to good agreement with CE and US. Both imaging methods revealed limitations and should be interpreted cautiously. FOI may provide an additional diagnostic method in pediatric rheumatology. Deutsches Register Klinischer Studien DRKS00012572 . Registered 31 July 2017.


The burden of environmental tobacco smoke exposure on the respiratory health of children 2 months through 5 years of age in the United States: Third National Health and Nutrition Examination Survey, 1988 to 1994.
To measure the effect of environmental tobacco smoke (ETS) on respiratory health in a national sample of young children. The study evaluated children 2 months through 5 years of age participating in the Third National Health and Nutrition Examination Survey, 1988 to 1994. The group was a representative sample of the US population (N = 7680). A parental report of household smoking or maternal smoking during pregnancy ascertained ETS exposure. Respiratory outcomes were based on parental report of wheezing, cough, upper respiratory infection, or pneumonia in the last 12 months and chronic bronchitis or physician-diagnosed asthma at any time. Logistic regression was used to adjust for age, sex, race/ethnicity, birth weight, day care, family history of allergy, breastfeeding, education level of head of household, and household size. Approximately 38% of children were presently exposed to ETS in the home, whereas 23.8% were exposed by maternal smoking during pregnancy. ETS exposure increased chronic bronchitis and three or more episodes of wheezing among children 2 months to 2 years old and asthma among children 2 months to 5 years old. For household exposure, a consistent effect was seen only at >/=20 cigarettes smoked per day. Adjusted odds ratios for increased risk (95% confidence interval) for household exposures (>/=20 cigarettes smoked per day vs none smoked) and maternal prenatal exposure (prenatal smoking vs no smoking), respectively, for children 2 months to 2 years old were chronic bronchitis, 2.5 (1.6, 4.1); 2.2, (1.6, 3); three or more episodes of wheezing, 2.7 (1.7, 4.2), 2.1 (1. 5, 2.9); and for children 2 months to 5 years old were asthma, 2.1 (1.4, 3.2); 1.8 (1.3, 2.6). Reported use within the past month of prescription medications for asthma (beta-agonists or inhaled steroids) was not different between those with asthma reporting ETS exposure and those reporting no exposure; percent of patients with asthma reporting use of medication by household exposure was 0, 25. 7%; 1 to 19 cigarettes smoked per day, 32.9%; and >/=20 cigarettes smoked per day, 23.1%; percent of patients with asthma reporting use of medication by maternal smoking during pregnancy was no, 28.9%; yes, 22.7%. Among children 2 months to 2 years of age exposed to ETS, 40% to 60% of the cases of asthma, chronic bronchitis, and three or more episodes of wheezing were attributable to ETS exposure. For diagnosed asthma among children 2 months through 5 years old, there were 133 800 to 161 600 excess cases. Among exposed children 2 months through 2 years of age, there were 61 000 to 79 200 excess cases of chronic bronchitis and 126 700 to 172 000 excess cases of three or more episodes of wheezing. ETS exposure is common among children in the United States. The reported prevalence of asthma, wheezing, and chronic bronchitis was increased with ETS exposures. No statistically significant increase in the prevalence of upper respiratory infection, pneumonia, or cough was associated with ETS exposure. ETS exposure has little effect on the respiratory health of children between 3 and 5 years of age, with the exception of asthma. ETS appears to increase the prevalence of asthma rather than the severity as measured by medication use. These findings reinforce the need to reduce the exposure of young children to ETS.


Functional and regulatory interactions between Hox and extradenticle genes.
The homeobox gene extradenticle (exd) acts as a cofactor of Hox function both in Drosophila and vertebrates. It has been shown that the distribution of the Exd protein is developmentally regulated at the post-translational level; in the regions where exd is not functional Exd is present only in the cell cytoplasm, whereas it accumulates in the nuclei of cells requiring exd function. We show that the subcellular localization of Exd is regulated by the BX-C genes and that each BX-C gene can prevent or reduce nuclear translocation of Exd to different extents. In spite of this negative regulation, two BX-C genes, Ultrabithorax and abdominal-A, require exd activity for their maintenance and function. We propose that mutual interactions between Exd and BX-C proteins ensure the correct amounts of interacting molecules. As the Hoxd10 gene has the same properties as Drosophila BX-C genes, we suggest that the control mechanism of subcellular distribution of Exd found in Drosophila probably operates in other organisms as well.


Environmental arsenic exposure and its contribution to human diseases, toxicity mechanism and management.
Arsenic is a well-recognized environmental contaminant that occurs naturally through geogenic processes in the aquifer. More than 200 million people around the world are potentially exposed to the elevated level of arsenic mostly from Asia and Latin America. Many adverse health effects including skin diseases (i.e., arsenicosis, hyperkeratosis, pigmentation changes), carcinogenesis, and neurological diseases have been reported due to arsenic exposure. In addition, arsenic has recently been shown to contribute to the onset of non-communicable diseases, such as diabetes mellitus and cardiovascular diseases. The mechanisms involved in arsenic-induced diabetes are pancreatic β-cell dysfunction and death, impaired insulin secretion, insulin resistance and reduced cellular glucose transport. Whereas, the most proposed mechanisms of arsenic-induced hypertension are oxidative stress, disruption of nitric oxide signaling, altered vascular response to neurotransmitters and impaired vascular muscle calcium (Ca2+) signaling, damage of renal, and interference with the renin-angiotensin system (RAS). However, the contributions of arsenic exposure to non-communicable diseases are complex and multifaceted, and little information is available about the molecular mechanisms involved in arsenic-induced non-communicable diseases and also no suitable therapeutic target identified yet. Therefore, in the future, more basic research is necessary to identify the appropriate therapeutic target for the treatment and management of arsenic-induced non-communicable diseases. Several reports demonstrated that a daily balanced diet with proper nutrient supplements (vitamins, micronutrients, natural antioxidants) has shown effective to reduce the damages caused by arsenic exposure. Arsenic detoxication through natural compounds or nutraceuticals is considered a cost-effective treatment/management and researchers should focus on these alternative options. This review paper explores the scenarios of arsenic contamination in groundwater with an emphasis on public health concerns. It also demonstrated arsenic sources, biogeochemistry, toxicity mechanisms with therapeutic targets, arsenic exposure-related human diseases, and onsets of cardiovascular diseases as well as feasible management options for arsenic toxicity.


Pharmacodynamic assays to facilitate preclinical and clinical development of pre-mRNA splicing modulatory drug candidates.
The spliceosome has recently emerged as a new target for cancer chemotherapy and novel antitumor spliceosome targeted agents are under development. Here, we describe two types of novel pharmacodynamic assays that facilitate drug discovery and development of this intriguing class of innovative therapeutics; the first assay is useful for preclinical optimization of small-molecule agents that target the SF3B1 spliceosomal protein in animals, the second assay is an ex vivo validated, gel-based assay for the measurement of drug exposure in human leukocytes. The first assay utilizes a highly specific bioluminescent splicing reporter, based on the skipping of exons 4-11 of a Luc-MDM2 construct, which specifically yields active luciferase when treated with small-molecule spliceosome modulators. We demonstrate that this reporter can be used to monitor alternative splicing in whole cells in vitro. We describe here that cell lines carrying the reporter can be used in vivo for the efficient pharmacodynamic analysis of agents during drug optimization and development. We also demonstrate dose- and time-dependent on-target activity of sudemycin D6 (SD6), which leads to dramatic tumor regression. The second assay relies on the treatment of freshly drawn human blood with SD6 ex vivo treatment. Changes in alternative splicing are determined by RT-PCR using genes previously identified in in vitro experiments. The Luc-MDM2 alternative splicing bioluminescent reporter and the splicing changes observed in human leukocytes should allow for the more facile translation of novel splicing modulators into clinical application.


WisecondorX: improved copy number detection for routine shallow whole-genome sequencing.
Shallow whole-genome sequencing to infer copy number alterations (CNAs) in the human genome is rapidly becoming the method par excellence for routine diagnostic use. Numerous tools exist to deduce aberrations from massive parallel sequencing data, yet most are optimized for research and often fail to redeem paramount needs in a clinical setting. Optimally, a read depth-based analytical software should be able to deal with single-end and low-coverage data-this to make sequencing costs feasible. Other important factors include runtime, applicability to a variety of analyses and overall performance. We compared the most important aspect, being normalization, across six different CNA tools, selected for their assumed ability to satisfy the latter needs. In conclusion, WISECONDOR, which uses a within-sample normalization technique, undoubtedly produced the best results concerning variance, distributional assumptions and basic ability to detect true variations. Nonetheless, as is the case with every tool, WISECONDOR has limitations, which arise through its exclusiveness for non-invasive prenatal testing. Therefore, this work presents WisecondorX in addition, an improved WISECONDOR that enables its use for varying types of applications. WisecondorX is freely available at https://github.com/CenterForMedicalGeneticsGhent/WisecondorX.


[Intercellular integration in the central nervous system].
A humoral mechanism of the intercellular communication in the CNS based on diffusion of neuroactive compounds within the brain extracellular space, was studied. The leading role of the volume transmission was shown in the early stage of ontogeny. Structural basis of this mechanism was studied in adult mammals, and the data on extrasynaptic receptors and release of classical neurotransmitters into the extracellular space was reviewed.


Failure to detect cell-associated enterotoxin B in Staphylococcus aureus by immunofluorescence.
Enterotoxin B-producing and -nonproducing Staphylococcus aureus strains showed cell fluorescence when tested with fluoresceinisothiocyanate-labeled rabbit anti-enterotoxin B globulin, probably as a result of a protein A-immunoglobulin G (Ig G) interaction. No cell-bound enterotoxin B could be detected by immunofluorescence using F(ab(1))(2)-fragments of anti-enterotoxin B globulin. However, soluble enterotoxin B could be estimated by immunofluorescence. Approximately 1,000-fold more enterotoxin B was detected by immunodiffusion as an extracellular product in the media than could be detected in the cell fraction. The results show that intact Ig G is not suitable for the detection of antigens other than protein A on the cell surface of S. aureus in conventional immunofluorescence. For such purposes, the use of F(ab(1))(2)-fragments of Ig G is recommended.


The alpha and gamma tocopherol levels in serum are influenced by the dietary fat quality.
Alpha tocopherol in serum is thought to be of importance in protecting lipids against oxidation and low serum levels of alpha tocopherol has been suggested to increase the risk for coronary heart disease. However, low levels of gamma, rather than alpha, tocopherol have been found in patients with manifest coronary heart disease and in populations with a high incidence of coronary heart disease. The aim of this study was to determine the tocopherol concentrations in serum after two diets with identical nutrient content but with different fat quality, enriched in butter and rapeseed oil-based fats, respectively. Twenty moderately hyperlipidemic, healthy subjects (six females and 14 males) participated in this double-blind cross-over study, where two isoenergetic diets were given in a randomized order during two 3-week periods, interrupted by a wash-out period of 3-4 weeks. The lipid-corrected serum concentrations of alpha and gamma tocopherol increased during the diet rich in rapeseed oil (by 7 and 23%, respectively) compared with on the baseline diet (P < 0.001), while these concentrations decreased (by 5 and 37%, respectively, P < 0.01) during the diet rich in saturated fat. The ratio between alpha and gamma tocopherol decreased significantly during the rapeseed oil diet (-23%, P < 0.01) and increased (+46%, P < 0.001) during the butter diet. Alpha and gamma tocopherol levels in serum are influenced by the type of fat used in the diet. The most unexpected finding is that the lipid-adjusted gamma tocopherol concentration significantly decreased by 37% during a diet rich in saturated fat with an increased ratio between alpha and gamma tocopherol, similar to the situation found in CHD patients.


Delay of nomifensine-induced seizures by fusaric acid, alpha-methyltyrosine and haloperidol.
An In Vivo model is presented to determine the effects of alpha methyl-para-tyrosine methyl ester (MPT), fusaric acid (FA), and haloperidol on nomifensine-induced seizures. All three drugs were active with haloperidol having the greatest effect on delay of onset to convulsion. The results suggest that both dopamine and norepinephrine are involved in nomifensive-induced convulsions and that administering agents known to lower both dopamine and/or norepinepherine in the rat brain delays onset but that haloperidol, which specifically blocks post-synaptic dopamine receptors, had the greatest activity.


Sex differences in the association between alcohol consumption and cognitive performance. EVA Study Group. Epidemiology of Vascular Aging.
Heavy alcohol drinking is associated with cognitive impairment, but little is known concerning the cognitive effect of moderate alcohol consumption. The Epidemiology of Vascular Aging (EVA) Study is a longitudinal study of cognitive and vascular aging. Between June 1991 and June 1993, 1,389 subjects aged 59-71 years (574 men and 815 women) who had been recruited from the electoral rolls of Nantes, France, were examined. Trained psychologists administered a battery of 10 neuropsychological tests assessing most areas of cognitive functioning. Detailed information on alcohol intake was collected during a structured interview. A multiple linear regression model was used to examine the relations between test scores and alcohol consumption at baseline in men and women separately, controlling for age, education, income, depressive symptoms, and smoking status. Odds ratios for being a high cognitive performer (i.e., being in the top 10% of the distribution of summary scores from the neuropsychological battery) were calculated. Among men, neuropsychological test scores were not associated with alcohol consumption in either univariate or multivariate analysis; nor did the proportion of high cognitive performers vary by alcohol consumption. In contrast, among women, significant positive associations between alcohol consumption and cognitive performance were observed for most tests in multivariate analysis. For example, for the Mini-Mental State Examination, the adjusted mean score for female nondrinkers was 27.5 and that for the heaviest drinkers 28.2 (p < 0.001). The odds ratio for being a high cognitive performer was 2.5 (95% confidence interval 1.1-5.7) for women who usually consumed two or more drinks per day in comparison with nondrinkers. These findings suggest that, among women, moderate alcohol consumption may have a beneficial effect on cognitive function.


Lean rats gained more body weight from a high-fructooligosaccharide diet.
Fructooligosaccharides (FOS) are believed to be beneficial to the host growth and its gut health. This article is intended to investigate the different influences of a high-fructooligosaccharide (FOS) diet on the growth and gut microbiota of lean and obese rats. Diet-induced lean and obese rats were fed a high-FOS diet for 8 weeks. Rats' body weight (BW) and feed intake were recorded weekly, and their gut microbiota was analyzed by 16S rDNA sequencing. The results showed that the lean rats gained more BW than the obese ones from the high-FOS diet. In the meanwhile, the gut microbiota in both lean and obese rats was altered by this diet. The abundance of Bacteroidetes was increased significantly (P < 0.05) in the lean rats, while no significant alteration in Firmicutes was observed in all rats after the consumption of a high-FOS diet. In conclusion, this study first reported that the lean rats gained more body weight from a high-FOS diet than the obese ones, and the increase of Bacteroidetes might help rats harvest more energy from the high-FOS diet.


Obstructive sleep apnea, diagnosed by the Berlin questionnaire and association with coronary artery disease severity.
Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep-related disorder that is associated with increased risk of hypertension (HTN) and coronary heart disease. This study aimed to evaluate the correlation between the OSAS and coronary artery disease (CAD) severity. The cross-sectional study was conducted from September 2012 to December 2013. We enrolled 127 patients with chronic stable angina who were referred for coronary angiographic studies in Shahid Chamran and Nour Hospitals in Isfahan, Iran. The Berlin questionnaire (BQ) was used for estimate the probability of OSAS in patients as a low or high probability. Demographic characteristics and metabolic risk factors including diabetes mellitus, HTN, obesity, and smoking also were recorded. The severity of CAD was assessed and compared based on the Gensini score with Mann-Whitney U statistical test. Independent t-test for continuous variables and chi-square test for categorical variables were used. Totally, 65.4% of subjects were considered as high and 34.6% as low probability for OSAS, which 81.1% of them had CAD. There was a significant difference between body mass index, systolic blood pressure, diastolic blood pressure, and ischemic heart disease drug consumption with OSAS probability (P < 0.0500). CAD was accompanied by OSAS significantly (P = 0.0260). The Gensini score was significantly higher in patients with high OSAS probability (100.4 ± 69.1 vs. 65.3 ± 68.9; P = 0.0030). OSAS also increase odds of CAD based on regression analysis (odds ratio, 95% confidence interval = 2.7). This study indicates that more severe CAD is associated with high OSAS probability identified by BQ.


Gender differences in diagnosis and treatment of coronary artery disease from 1981 to 1997. No evidence for the Yentl syndrome.
The aim of the present clinical study was to evaluate whether gender-related differences existed as regards the extent and localization of coronary artery lesions in patients with angiographically documented coronary artery disease, and whether these angiographic findings would lead to differences in further management. Over a 16-year period (1981-1997) we evaluated 1894 patients (1526 men, 368 women) with angiographically documented coronary artery disease (luminal stenosis >/=60%). For each patient the coronary angiographic results and subsequent revascularization procedures (percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery) were analysed. The study period was divided into the early angioplasty years (1981 to 1989) and the current angioplasty years (1990-1997). No gender differences in extent and localization of coronary angiographic lesions were observed. In men and women the incidence of single-vessel disease was 42% and 40%, two-vessel disease 27% and 27%, three-vessel disease 26% and 24%, and left main disease 5% and 8%, respectively (P=ns). Localization of disease in men and women was 36% and 39% for the left anterior descending coronary artery, 34% and 32% for the right coronary artery, and 27% and 26% for the left circumflex coronary artery, respectively (P=ns). There was a significant shift from multi-vessel disease towards single-vessel disease in both men and women (both P<0.001). As to subsequent management, a significant gender difference in favour of women was observed (P=0.021). Over time, the number of angioplasty procedures increased significantly from 11.6% to 23.2% for men (P<0.001), and for women from 17.6% to 28.0% (P=0.025), whereas the number of coronary artery bypass procedures decreased in men from 34.9% to 29. 5% (P=0.024) and in women from 42.6% to 30.6% (P=0.019). Referral to angioplasty (n=535) and coronary artery bypass surgery (n=616) in relation to the extent of the disease did not show any gender bias in favour of men. Our angiographic findings did not show significant gender differences as regards the extent and localization of coronary artery disease in patients with angiographically documented coronary artery disease. More importantly, no substantial evidence could be found for under-referral of women to subsequent therapeutic management. Therefore our study questions the presence of Yentl syndrome in the current era.


Prevalence of Gall Bladder Stones among Type 2 Diabetic Patients in Benghazi Libya: A Case-control Study.
Diabetes mellitus and gall bladder stones are both common and costly diseases. Increasing age, female gender, overweight, familial history of the disease and type 2 diabetes mellitus is all associated with an increased risk of gallstones. Several studies from around the world reported an increased prevalence of gall bladder stones in patients with diabetes mellitus. The aim of this study was to define the frequency of gall bladder stones among Libyan diabetics and to evaluate the possible associated risk factors in these patients. A case-control study was performed during 2007 at Benghazi Diabetes and endocrinology Center. The study involved 161 randomly selected type-2 diabetic patients under regular follow up at the center, and 166 age and sex matched non-diabetic outpatients at the 7th of October teaching hospital. Real-time abdominal ultrasound was performed by two radiologists to examine the abdomen after an overnight fast. About 40% of the diabetic cohort had gall bladder stones as compared to 17.5% of non-diabetic patients. Females were significantly more affected than males. Patients with gall bladder stones were significantly older and had a significantly higher body mass index than those without stones. The prevalence of gallstones in Libyan diabetic patients is higher than the rates reported in other parts of the world. Libyan diabetic patients with gallstones tend to be older and more obese than those without gallstones. Duration of diabetes mellitus and type of treatment does not seem to influence the frequency of gall bladder stones among Libyan diabetics.