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Phosphate is a key component of mineralized tissues and is also part of many organic compounds. Phosphorus homeostasis depends especially upon intestinal absorption, and renal excretion, which are regulated by various hormones, such as PTH, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23. In this review we provide an update of several genetic disorders that affect phosphate transporters through cell membranes or the phosphate-regulating hormones, and, consequently, result in hypophosphatemia.

In recent decades, there has been a significant rise in the utilization of medical cannabis. Understanding the various facets surrounding its usage and regulation is paramount for patients, health professionals, and policymakers. This cross-sectional study conducted at the CANNAVITAL clinic in Lima, Peru aimed to assess the basic knowledge, attitudes towards use, and beliefs regarding regulation and safety of Cannabis sativa L. Among 86 patients (mean age: 41 ± 7.8 years; 53.4% women) actively receiving medical cannabis treatment for at least one year, we utilized the 22-item KUC-22 questionnaire to evaluate their understanding of cannabis, risk factors, legislation, medical and recreational use. The average duration of medical cannabis use was 3 ± 1.2 years. Results showed that 60.2% of patients were familiar with different forms of cannabis consumption, while 77.3% recognized the importance of product quality. Chronic pain, nausea and vomiting (each 23.9%) were the primary conditions treated with cannabis, followed by cancer and epilepsy (both 21.6%). A significant correlation was found between knowledge and cannabis use (p < 0.001). Furthermore, 92% of patients believed that a medical prescription was necessary, while 84.1% engaged in self-medication practices. Concerning perceptions, 69.3% of participants perceived psychological dependence from long-term cannabis use, and 65.9% believed it could cause health damage. Significant correlations were observed between the perception of risk factors, knowledge of legislation, and cannabis use (p < 0.001). In conclusion, Peruvian patients exhibited a high level of knowledge regarding the risks, uses, and regulatory framework surrounding Cannabis sativa L. These findings provide valuable insights into patients' perspectives on medical cannabis, offering important information for medical providers and researchers aiming to enhance cannabinoid-based therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Phasic dopamine activity is believed to both encode reward-prediction errors (RPEs) and to cause the adaptations that these errors engender. If so, a rat working for optogenetic stimulation of dopamine neurons will repeatedly update its policy and/or action values, thus iteratively increasing its work rate. Here, we challenge this view by demonstrating stable, non-maximal work rates in the face of repeated optogenetic stimulation of midbrain dopamine neurons. Furthermore, we show that rats learn to discriminate between world states distinguished only by their history of dopamine activation. Comparison of these results to reinforcement learning simulations suggests that the induced dopamine transients acted more as rewards than RPEs. However, pursuit of dopaminergic stimulation drifted upwards over a time scale of days and weeks, despite its stability within trials. To reconcile the results with prior findings, we consider multiple roles for dopamine signalling., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Colorectal cancer is a widespread neoplasia with high ratios of chemoresistance. Phytochemicals in plant-based extracts could be useful to treat colorectal cancer, and/or reduce chemoresistance. Methanolic extract of avocado mesocarp (MEAM) has demonstrated antitumoral properties, depending on the fruit ripening stage (RS). The aim of this study was to analyze the effects of methanolic extracts of "Hass" avocado fruit at different RS on cytotoxicity, antioxidative, anti-inflammatory, anti-invasive, cell cycle, and epithelial-mesenchymal transition inhibition in colorectal adenocarcinoma cell line HT29. The MEAM showed an increasing concentration of total phenolic compounds as the RS progressed, which was correlated with antioxidant capacity measured by the Ferric Reducing Antioxidant Power assay but not with the 2.2-diphenyl-1-picrylhydrazyl assay. The specific phenolic compounds of MEAM were determined by high-performance liquid chromatography, and it was found that concentrations of epicatechin decreased while concentrations of chlorogenic acid increased as the RS progressed. The HT29 cell line was treated with MEAM for 48 h, and all MEAM had a cytotoxic effect, reported by MTT assay, nevertheless, the strongest effect was associated with the presence of chlorogenic acid. MEAM induced apoptosis and cell cycle arrest in phase G0/G1, reported by flow cytometry. Moreover, MEAM inhibited cell migration evidenced by the wound healing assay. On the other hand, MEAM significantly reduced expression of mRNA of tumor necrosis factor-alpha and cyclooxygenase 2. These effects comprise important inhibition of some hallmarks of cancer. This, in turn, may provide interesting guidelines for developing antitumoral intervention agents.

Introduction: Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities., Methods: We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population., Results: We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio  = 2.93 [2.37-3.63], P = 2.6 × 10 -23 ). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose., Discussion: We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations., Highlights: This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: To establish the possible relation between total caries (TC) and caries severity (CS) with the AMY1 gene copy number (AMY1GCN)., Materials and Methods: This was an observational, cross-sectional, population-based, and association study with 303 participants. Each participant underwent a complete anamnesis and stomatological check-up, and peripheral blood was obtained to extract gDNA. TC and CS were determined as the number of caries at the dental exploration and the number of dental surfaces affected by caries, respectively, and AMY1GCN was determined by qPCR., Results: We found an elevated caries prevalence (92.7%); TC and CS were 8 ± 10 and 10 ± 13 (median ± IR). There were higher TC and CS in those participants with AMY1GCN above the mean value (0.02 and 0.01 p values, respectively). A positive correlation between TC and CS with AMY1GCN (0.11 and 0.125 r values, 0.03 and 0.01 p values, respectively) was found, in addition to an association between TC and CS with AMY1GCN (1.5 and 1.6 OR values, 0.48 and 0.26 p values, respectively)., Conclusion: TC and CS were positively related to the AMY1GCN., Clinical Relevance: Dental caries has a high prevalence and a multifactorial etiology and has been related to a genetic component. Indeed, the salivary enzyme alpha-amylase could play a significant role in caries susceptibility, considering that its codifying gene (AMY1) can show variation in its gene copy number. This can be considered an important factor for the development of caries at a genetic level., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

COVID-19 dashboards with geospatial data visualization have become ubiquitous. There is a growing sense of responsibility to report public health data pushing governments and community organizations to develop and share web-based dashboards. While a substantial body of literature exists on how these GIS technologies and urban analytics approaches support COVID-19 monitoring, their level of social embeddedness, quality and accessibility of user interface, and overall decision-making capabilities has not been rigorously assessed. In this paper, we survey 68 public web-based COVID-19 dashboards using a nominal group technique to find that most dashboards report a wealth of epidemiologic data at the state and county levels. However, these dashboards have limited emphasis on providing granular data (city and neighborhood level) broken down by population sub-groups. We found severe inadequacy in reporting social, behavioral, and economic indicators that shape the trajectory of the pandemic and vice versa. Our survey reveals that most COVID-19 dashboards ignore the provision of metadata, data download options, and narratives around visualizations explaining the data's background, source, and purpose. Based on these lessons, we illustrate an empirical experiment of building a dashboard prototype-the COVID-19 Economic Resilience Dashboard in Arizona. Our dashboard project demonstrates a model that can inform decision-making (beyond plain information sharing) while being accessible by design. To achieve this, we provide localized data, drill-down options by geography and sub-population, visualization narratives, open access to the data source, and accessible features on the interface. We exhibited the value of linking pandemic-related information with socioeconomic data. Our findings suggest a pathway forward for researchers and governments to incorporate more action-oriented data and easy-to-use interfaces as they refine existing and develop new information systems and data analytics dashboards., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Pannexin-1 (Panx1) hemichannel is a non-selective transmembrane channel that may play important roles in intercellular signaling by allowing the permeation of ions and metabolites, such as ATP. Although recent evidence shows that the Panx1 hemichannel is involved in controlling excitatory synaptic transmission, the role of Panx1 in inhibitory transmission remains unknown. Here, we studied the contribution of Panx1 to the GABAergic synaptic efficacy onto CA1 pyramidal neurons (PyNs) by using patch-clamp recordings and pharmacological approaches in wild-type and Panx1 knock-out (Panx1-KO) mice. We reported that blockage of the Panx1 hemichannel with the mimetic peptide 10 Panx1 increases the synaptic level of endocannabinoids (eCB) and the activation of cannabinoid receptors type 1 (CB1Rs), which results in a decrease in hippocampal GABAergic efficacy, shifting excitation/inhibition (E/I) balance toward excitation and facilitating the induction of long-term potentiation. Our finding provides important insight unveiling that Panx1 can strongly influence the overall neuronal excitability and play a key role in shaping synaptic changes affecting the amplitude and direction of plasticity, as well as learning and memory processes.

Bisphenol A (BPA) promotes colon cancer by altering the physiological functions of hormones. Quercetin (Q) can regulate signaling pathways through hormone receptors, inhibiting cancer cells. The antiproliferative effects of Q and its fermented extract (FEQ, obtained by Q gastrointestinal digestion and in vitro colonic fermentation) were analyzed in HT-29 cells exposed to BPA. Polyphenols were quantified in FEQ by HPLC and their antioxidant capacity by DPPH and ORAC. Q and 3,4-dihydroxyphenylacetic acid (DOPAC) were quantified in FEQ. Q and FEQ exhibited antioxidant capacity. Cell viability with Q+BPA and FEQ+BPA was 60% and 50%, respectively; less than 20% of dead cells were associated with the necrosis process (LDH). Treatments with Q and Q+BPA induced cell cycle arrest in the G0/G1 phase, and FEQ and FEQ+BPA in the S phase. Compared with other treatments, Q positively modulated ESR2 and GPR30 genes. Using a gene microarray of the p53 pathway, Q, Q+BPA, FEQ and FEQ+BPA positively modulated genes involved in apoptosis and cell cycle arrest; bisphenol inhibited the expression of pro-apoptotic and cell cycle repressor genes. In silico analyses demonstrated the binding affinity of Q > BPA > DOPAC molecules for ERα and ERβ. Further studies are needed to understand the role of disruptors in colon cancer.

Alcohol consumption has been strongly associated with circadian clock gene expression in mammals. Analysis of clock genes revealed a potential role of Bmal1 in the control of alcohol drinking behavior. However, a causal role of Bmal1 and neural pathways through which it may influence alcohol intake have not yet been established. Here we show that selective ablation of Bmal1 (Cre/loxP system) from medium spiny neurons of the striatum induces sexual dimorphic alterations in alcohol consumption in mice, resulting in augmentation of voluntary alcohol intake in males and repression of intake in females. Per2mRNA expression, quantified by qPCR, decreases in the striatum after the deletion of Bmal1. To address the possibility that the effect of striatal Bmal1 deletion on alcohol intake and preference involves changes in the local expression of Per2, voluntary alcohol intake (two-bottle, free-choice paradigm) was studied in mice with a selective ablation of Per2 from medium spiny neurons of the striatum. Striatal ablation of Per2 increases voluntary alcohol intake in males but has no effect in females. Striatal Bmal1 and Per2 expression thus may contribute to the propensity to consume alcohol in a sex -specific manner in mice., (© 2021. The Author(s).)

Normal aging involves changes in the ability to acquire, consolidate and recall new information. It has been recently proposed that the reconsolidation process is also affected in older adults. Reconsolidation is triggered after reminder presentation, allowing memories to be modified: they can be impaired, strengthened or changed in their content. In young adults it was previously shown that the presentation of repetitive reminders induces memory strengthening one day after reactivation and the presentation of at least one reminder increases memory persistence several days after reactivation. However, until now this process has remained elusive in older adults. We hypothesize that older adults need a stronger reminder to induce memory strengthening through the reconsolidation process than young adults. To test this, we perform a three-day experiment. On day 1, participants learned 15 sound-word associations, on day 2 they received no reminders (NR group), one reminder (R group) or two rounds of reactivations (Rx2 group). Finally, they were tested on day 7. We found that, contrary to our hypothesis, older adults show a memory improvement triggered by repeated labilization/reconsolidation processes to an equal extent than young adults. These results open new perspectives into the use of reconsolidation to improve daily acquired information and the development of therapeutic home used tools to produce memory enhancement in healthy older adults or those with cognitive decline., Competing Interests: The authors have declared that no competing interests exist.

The neurobiological study of reward was launched by the discovery of intracranial self-stimulation (ICSS). Subsequent investigation of this phenomenon provided the initial link between reward-seeking behavior and dopaminergic neurotransmission. We re-evaluated this relationship by psychophysical, pharmacological, optogenetic, and computational means. In rats working for direct, optical activation of midbrain dopamine neurons, we varied the strength and opportunity cost of the stimulation and measured time allocation, the proportion of trial time devoted to reward pursuit. We found that the dependence of time allocation on the strength and cost of stimulation was similar formally to that observed when electrical stimulation of the medial forebrain bundle served as the reward. When the stimulation is strong and cheap, the rats devote almost all their time to reward pursuit; time allocation falls off as stimulation strength is decreased and/or its opportunity cost is increased. A 3D plot of time allocation versus stimulation strength and cost produces a surface resembling the corner of a plateau (the "reward mountain"). We show that dopamine-transporter blockade shifts the mountain along both the strength and cost axes in rats working for optical activation of midbrain dopamine neurons. In contrast, the same drug shifted the mountain uniquely along the opportunity-cost axis when rats worked for electrical MFB stimulation in a prior study. Dopamine neurons are an obligatory stage in the dominant model of ICSS, which positions them at a key nexus in the final common path for reward seeking. This model fails to provide a cogent account for the differential effect of dopamine transporter blockade on the reward mountain. Instead, we propose that midbrain dopamine neurons and neurons with non-dopaminergic, MFB axons constitute parallel limbs of brain-reward circuitry that ultimately converge on the final-common path for the evaluation and pursuit of rewards., Competing Interests: The authors have declared that no competing interests exist.

Context: Hypoglycemia in the outpatient setting has a significant financial impact on the health care system and negative impact on a person's quality of life. Primary care physicians must address a multitude of issues in a visit with a person with type 2 diabetes mellitus (T2DM), often leaving little time to ask about hypoglycemia., Objective: To develop quality measures that focus on outpatient hypoglycemia episodes for patients 65 and older with T2DM, which facilitate a clinician's ability to identify opportunities to improve the quality of care and reduce hypoglycemic episodes., Participants and Process: A technical expert panel established by the Endocrine Society in March 2019, which includes endocrinologists, primary care physicians, a diabetes care and education specialist/pharmacist, and a patient, developed 3 outpatient hypoglycemia quality measures. The measure set is intended to improve quality of care for patients with T2DM who are at greatest risk for hypoglycemia. The measures were available for public comment in July 2019. A fourth measure on shared decision-making was removed from the final measure set based on public feedback., Conclusion: A lack of outpatient hypoglycemia measures focusing on older adults with T2DM is a barrier to improving care of people with diabetes and reducing hypoglycemic episodes. This paper provides measure specifications for 3 measures that may be used to focus quality improvement efforts on patients at greatest risk for hypoglycemia., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer's disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.

The anticancer use of genistein (Gen) has been severely limited due to its low water solubility, low bioavailability, and instability under experimental conditions. To overcome these limitations, we propose a formulation of a hybrid nanomaterial (HNM) based upon the incorporation of Gen into PEGylated silica nanoparticles (PEG-SiNPs) (Gen-PEG-SiHNM), where their physicochemical and biological effects on HT29 cells were evaluated. Genistein-loaded PEGylated silica hybrid nanomaterials were obtained by a simple end effective aqueous dispersion method. Physicochemical properties were determined by its mean particle size, surface charge, amount of cargo, spectroscopic properties, release profiles and aqueous solubility. In vitro biological performance was carried out by evaluating its antioxidant capacity and elucidating its antiproliferative mechanistic. Results showed that small (ca. 33 nm) and spherical particles were obtained with positive surface charge (+9.54 mV). Infrared analyses determined that encapsulation of genistein was successfully achieved with an efficiency of 51%; it was observed that encapsulation process enhanced the aqueous dispersibility of genistein and cumulative release of genistein was pH-dependent. More important, after encapsulation data showed that Gen potentiated its antioxidant and antiproliferative effects on HT29 human colon cancer cells by the modulation of endogenous antioxidant enzymes and H 2 O 2 production, which simultaneously activated two different processes of cell death (apoptosis and autophagy), unlike free genistein that only activated one (apoptosis) in a lower proportion. Overall, our data support that Gen-PEG-SiHNM could be potentially used as alternative treatment for colorectal cancer in a near future., Competing Interests: None.

Food entrainment is the internal mechanism whereby the phase and period of circadian clock genes comes under the control of daily scheduled food availability. Food entrainment allows the body to efficiently realign the internal timing of behavioral and physiological functions such that they anticipate food intake. Food entrainment can occur with or without caloric restriction, as seen with daily schedules of restricted feeding (RF) or restricted treat (RT) that restrict food or treat intake to a single feeding time. However, the extent of clock gene control is more pronounced with caloric restriction, highlighting the role of energy balance in regulating clock genes. Recent studies have implicated dopamine (DA) to be involved in food entrainment and caloric restriction is known to affect dopaminergic pathways to enhance locomotor activity. Since food entrainment results in the development of a distinct behavioral component, called food anticipatory activity (FAA), we examined the role of locomotor sensitization (LS) in food entrainment by 1) observing whether amphetamine (AMPH) sensitization results in enhanced locomotor output of FAA and 2) measuring LS of circadian and non-circadian feeding paradigms to an acute injection of AMPH (AMPH cross-sensitization). Unexpectedly, AMPH sensitization did not show enhancement of FAA. On the contrary, LS did develop with sufficient exposure to RF. LS was present after 2 weeks of RF, but not after 1, 3 or 7 days into RF. When food was returned and rats regain their original body weight at 10-15 days post-RF, LS remained present. LS did not develop to RT, nor to feedings of a non-circadian schedule, e.g. variable restricted feeding (VRF) or variable RT (VRT). Further, when RF was timed to the dark period, LS was observed only when tested at night; RF timed to the light period resulted in LS that was present during day and night. Taken together our results show that LS develops with food entrainment to RF, an effect that is dependent on the chronicity and circadian phase of RF but independent of body weight. Given that LS involves reorganization of DA-regulated motor circuitry, our work provides indirect support for the role of DA in the food entrainment pathway of RF. The findings also suggest differences in neuronal pathways involved in LS from AMPH sensitization and LS from RF.

Aim: To assess if the included vascular endothelial growth factor (VEGF) polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus (T2DM)., Methods: A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study (ETDRS) standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts., Results: In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher's exact test was performed for rs3025021 [OR (95% CI)=0.44(0.08-2.2); P =0.25] and rs2010963 [OR (95% CI)=0.63(0.25-1.6); P =0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows: rs3025021 vs rs3025035: D'=1.0, r 2 =0.1043, P ≤0.0001; rs3025021 vs rs2010963: D'=0.442, r 2 =0.0446, P =0.149; rs3025035 vs rs2010963: D'=0.505, r 2 =0.0214, P =0.142., Conclusion: This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that different populations have different associations for the same polymorphisms.

Because stroke is among the leading causes of death, disability, hospitalizations, and healthcare expenditures in the United States, there is interest in reporting outcomes for patients hospitalized with acute ischemic stroke. The American Heart Association/American Stroke Association, as part of its commitment to promote high-quality, evidence-based care for cardiovascular and stroke patients, fully supports the development of properly risk-adjusted outcome measures for stroke. To accurately assess and report hospital-level outcomes, adequate risk adjustment for case mix is essential. During the development of the Centers for Medicare & Medicaid Services 30-day stroke mortality and 30-day stroke readmission measures, concerns were expressed that these measures were not adequately designed because they do not include a valid initial stroke severity measure, such as the National Institutes of Health Stroke Scale. These outcome measures, as currently constructed, may be prone to mischaracterizing the quality of stroke care being delivered by hospitals and may ultimately harm acute ischemic stroke patients. This article details (1) why the Centers for Medicare & Medicaid Services acute ischemic stroke outcome measures in their present form may not provide adequate risk adjustment, (2) why the measures as currently designed may lead to inaccurate representation of hospital performance and have the potential for serious unintended consequences, (3) what activities the American Heart Association/American Stroke Association has engaged in to highlight these concerns to the Centers for Medicare & Medicaid Services and other interested parties, and (4) alternative approaches and opportunities that should be considered for more accurately risk-adjusting 30-day outcomes measures in patients with ischemic stroke.

Background: Elastofibroma dorsi (ED) is a benign soft tissue tumor that classically presents as an ill-defined mass at the inferior pole of the scapula. Several studies have indicated the benefits of using magnetic resonance imaging (MRI) to identify ED. In this study, we calculate the sensitivity and positive predictive value (PPV) of MRI in the diagnosis of ED using histopathology as the gold standard diagnostic method. Clinical characteristics of ED and radiologic features of MRI as well as treatment options are discussed., Materials and Methods: A systematic retrospective review was performed of all ED patients treated in our center between 1999 and 2009. MRI and histopathology samples were performed in all cases. The MRI sensitivity and PPV in the diagnosis of ED were calculated., Results: A total of 15 patients who were treated within the study period were reviewed; of these, were 14 (3 men, 11 women) true ED cases. MRI scan results matched the histopathology in 14 of 15 patients; 1 false-positive patient was observed, and no false-negative patients (negative MRI and positive histopathology) were noted. The PPV and sensitivity of MRI scan in the diagnosis of ED were 93.3% (95% confidence interval, 68.0%-100.0%) and 100% (95% confidence interval, 75.2%-100.0%) respectively., Conclusions: MRI is a useful tool for assessment of ED and can potentially help avoid the need for unnecessary biopsy and surgery, especially in the asymptomatic patient., (Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.)

The occurrence of crossed aphasia as a complication after temporal lobe epilepsy surgery is extremely rare. We report the case of a 47-year-old right-handed patient with drug-resistant mesial temporal lobe epilepsy (MTLE) who developed a transitory aphasic syndrome after a right temporal anterior lobectomy. This syndrome was characterized by anomia, poor verbal fluency, verbal perseveration, and verbal comprehension difficulties. He also showed writing difficulties, reading substitutions, and calculation task errors. The patient was regularly assessed with language tasks, and showed a spontaneous and progressive recovery of his symptoms, with remaining naming difficulties. We discuss the role that epileptogenic zone could play in cortical reorganization of the language systems., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Different iodinated mouse obestatin peptides have been characterized toward their in vitro stability in the main metabolic compartments plasma, liver and kidney. Using HPLC-UV for quantification, significant differences in the degradation kinetics of the iodinated peptides, arising from both enzymatic proteolysis and dehalogenation, were found when compared to the native, unmodified peptide. HPLC-MS/MS analysis demonstrated that the cleavage sites were dependent upon the biological matrix and the location of the amino acid residue incorporating the iodine atom(s). The degrading proteases were found to target peptide bonds further away from the iodine incorporation, while proteolytic cleavages of nearby peptide bonds were more limited. Diiodinated amino acid residue containing peptides were found to be more susceptible to deiodination than the mono-iodinated derivative. In plasma, the percentage of peptide degradation solely attributed to deiodinase activity after 20 min incubation reached up to 25% for 2,5-diiodo-H(19)-obestatin compared to 20% and only 3% for (3,5-diiodo-Y(16))- and (3-iodo-Y(16)) obestatin, respectively. Hence, our results demonstrate that the different iodinated peptides pose significantly different metabolization properties and thus, also different biological activities are expected for peptides upon iodination., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The aim of the present study is to compare pre- and postsurgical neuropsychological outcome in individuals suffering from mesial temporal lobe epilepsy (mTLE), in order to evaluate prognosis. The selected thirty-five patients had medically mTLE and had undergone an anterior temporal lobectomy (ATL). Neuropsychological evaluation was performed in three different stages: before ATL, 6 months after resection, and a year afterwards. Neuropsychological protocol evaluated attention, verbal memory, visual memory, executive function, language, intelligence, and handedness. There was a significant improvement (P = 0.030) in the group with visual memory deficit after surgery, whereas no changes were observed across patients with verbal memory deficit. No changes were observed in language after surgery. Executive function showed significant improvement 6 months after surgery (P = 0.035). Postoperative outcome of cognitive impairments depends on baseline neuropsychological status of the patients with TLE. In our case series, deficits found in patients with mTLE after ATL did not result in a subjective complaint.

It is well established that naming deficits can be found in temporal lobe epilepsy (TLE). The aim of this study was to determine in Spanish speakers with pharmacoresistant TLE the characteristics of subjective naming difficulties and to examine performance in a definition task and a picture task in left TLE and right TLE. We observed that almost one-third of patients report frequent and severe word finding problems during spontaneous speech. In naming tests, our patients exhibited delayed times for finding words. Even if the target word was identified and semantically activated, there was difficulty with lexical access, which improved when a phonetic cue was given. Left TLE patients derived a lower benefit from phonetic cues in accessing words, even when the word is known and recognized semantically. These findings were not related to any demographic or clinical characteristics analyzed. The fact that the only weakly lateralized variable has been a lexical access facilitation measurement could support a lexical access hypothesis for naming deficits in TLE., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Iodide is a trace element and a key component of thyroid hormones (TH). The availability of this halogen is the rate-limiting step for TH synthesis; therefore, thyroidal iodide uptake and recycling during TH synthesis are of major importance in maintaining an adequate supply. In the rat, the thyroid gland co-expresses a distinctive pair of intrathyroidal deiodinating enzymes: the thyroid iodotyrosine dehalogenase (tDh) and the iodothyronine deiodinase type 1 (ID1). In the present work, we studied the activity of these two dehalogenases in conditions of hypo- and hyperthyroidism as well as during acute and chronic iodide administration in both intact and hypophysectomized (HPX) rats. In order to confirm our observations, we also measured the mRNA levels for both dehalogenases and for the sodium/iodide symporter, the protein responsible for thyroidal iodide uptake. Our results show that triiodothyronine differentially regulates tDh and ID1 enzymatic activities, and that both acute and chronic iodide administration significantly decreases rat tDh and ID1 activities and mRNA levels. Conversely, both enzymatic activities increase when intrathyroidal iodide is pharmacologically depleted in TSH-replaced HPX rats. These results show a regulatory effect by iodide on the intrathyroidal dehalogenating enzymes and suggest that they contribute to the iodide-induced autoregulatory processes involved in the Wolff-Chaikoff effect.

This study used an in vivo mouse model to analyze the response of dendritic cells (DCs) in Peyer's patches (PPs) within the first 48 h of infection with the wild-type murine rotavirus EDIM (EDIM(wt)). After the infection, the absolute number of DCs was increased by 2-fold in the PPs without a modification of their relative percentage of the total cell number. Also, the DCs from PPs of infected mice showed a time-dependent migration to the subepithelial dome (SED) and an increase of the surface activation markers CD40, CD80, and CD86. This response was more evident at 48 h postinfection (p.i.) and depended on viral replication, since DCs from PPs of mice inoculated with UV-treated virus did not show this phenotype. As a result of the activation, the DCs showed an increase in the expression of mRNA for the proinflammatory cytokines interleukin-12/23p40 (IL-12/23p40), tumor necrosis factor alpha (TNF-alpha), and beta interferon (IFN-beta), as well as for the regulatory cytokine IL-10. These results suggest that, a short time after rotavirus infection, the DCs from PPs play a critical role in controlling the infection and, at the same time, avoiding an excessive inflammatory immune response.

The American Heart Association's (AHA's) mission is "to build healthier lives, free of cardiovascular diseases and stroke." This first article in a 2-part series will serve to present an overview of the work the AHA has undertaken to translate evidence into practice for healthcare professionals. It describes the extensive work of the AHA to support and further the delivery of evidence-based medicine, which includes the following: (1) supporting scientific discovery and the next generation of healthcare professionals and researchers; (2) disseminating scientific information; (3) developing evidence-based guidelines and statements; (4) creating and advocating for the implementation of performance indicators/measures; (5) developing clinical decision support and quality improvement tools; and (6) developing directed-cause campaigns, all of which can lead to improved patient care. This article also discusses the need for novel approaches and some of the AHA's evolving strategies to help address gaps in care. The second article, which will be published shortly after this one, will examine the AHA's efforts to engage and empower healthcare consumers to become more involved with their own health and health care.

Little information exists about a causal association between PFO and migraine. Some patients identify Valsalva-provoking activities (VPA) as migraine triggers. Therefore, we speculate about a pathogenic connection. The object of the study is to investigate the prevalence of right-to-left shunt (RLS) in a cohort of patients suffering migraine with aura (MA) and its possible association with migraine attacks triggered by VPA. We investigated the circumstances triggering the migraine attacks, in a consecutive series of 72 MA patients and in a series of migraine without aura age and gender-matched. The presence and extent of RLS was assessed by transcranial Doppler. Massive RLS appeared in 38.9% of MA and in 6.5% of migraine without aura (p<0.001). MA patients identified at least one VPA as headache trigger in 45.8%. A trend was found between these triggering activities and massive RLS, both in MA group OR 2.7 [1.02-7.17] and in all migraine patients OR 2.5 [1.01-6.11]. According to our results, patients with migraine who have larger RLS tend to recognize activities that increase the extent of the shunt as a trigger of their migraine attacks.

This study was designed to determine the effect of Mangifera indica flowers decoction, on the acute and subacute models of induced ulcer in mice and rats. A single oral administration of the aqueous decoction (AD) from M. indica up to a dose of 5 g/kg, p.o. did not produce any signs or symptom of toxicity in the treated animals. The oral pre-treatment with AD (250, 500 and 1000 mg/kg) in rats with gastric lesions induced by ethanol, decreased the gastric lesions from 89.0+/-6.71 (control group) to 9.25+/-2.75, 4.50+/-3.30 and 0, respectively. Pretreatment with AD (250, 500 and 1000 mg/kg) to mice with HCl/ethanol- or stress-induced gastric lesions resulted in a dose-dependent significant decrease of lesion index. In the piroxicam-induced gastric lesions, the gastroprotective effect of AD was reducing with the increase of the AD dose. In the pylorus-ligature, AD (p.o.) significantly decreased the acid output indicating the antisecretory property involved in the gastroprotective effect of M. indica. Treatment with AD during 14 consecutive days significantly accelerated the healing process in subacute gastric ulcer induced by acetic acid in rats. Pretreatment with N-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO-synthase, did not abolish the gastroprotective effects (99% with saline versus 80% with l-NAME) of AD against ethanol-induced gastric lesions. Pretreatment with N-ethylmaleimide (NEM), a blocker of endogenous sulphydryl group, significantly abolished the protective effects of AD against ethanol-induced gastric ulcers (95% with saline versus 47% with NEM). Phytochemical screening showed the presence of steroids, triterpenes, phenolic compounds and flavonoids. Estimation of the global polyphenol content in the AD was performed by Folin-Ciocalteu method and showed approximately 53% of total phenolic on this extract. These findings indicate the potential gastroprotective and ulcer-healing properties of aqueous decoction of M. indica flowers and further support its popular use in gastrointestinal disorders in Caribbean.

Three new 4-hydroxy-benzoic acid derivatives, 4-methoxy-3,5-bis-(3-hydroxy-3-methyl-1-butenyl)benzoate, 3-hydroxy-2-(1-hydroxy-1-methylethyl)-2,3-dihydrobenzofuran-5-carboxylic acid, and 3-hydroxy-2-(1-hydroxy-1-methylethyl)-2,3-dihydrobenzofuran-5-carboxylic acid methyl ester together with eight known compounds, have been isolated from the stems of Piper hispidum. Their structures were elucidated by a detailed spectroscopic analysis. In addition, the cytotoxicity of seven isolated compounds has been evaluated, revealing a moderate activity for three derivatives of dillapiole.

Methanolic and aqueous extracts derived from 43 plant species, selected either from ethnobotanical or chemotaxonomical data, were screened for their antiprotozoal activity against Leishmania donovani and Trypanosoma brucei brucei. The cytotoxic activity against KB cells was also determined. Eight extracts had IC50 values of less than 10 microg/ml against Leishmania donovani. The most active was Triclisia patens with an IC50 value of 1.5 microg/ml against Leishmania donovani. Annona purpurea and Alstonia macrophylla had IC50 values below 10 microg/ml against Trypanosoma brucei brucei. Annona purpurea was the most cytotoxic against KB cells.

Objective: The purpose of this study is to identify specific clinical-electroencephalogram (EEG) patterns at seizure onset in patients with hippocampal sclerosis (HS)., Methods: Sixty-six ictal video-EEG recordings corresponding to 26 patients with HS have been reviewed, focusing on the EEG features found during the first 30 ictal s. The EEG activity has been classified into the following groups: (A) according to spatial distribution: type 1: temporal electrodes on one side; type 2: temporal and adjacent frontal electrodes on one side; and type 3: non-lateralizing electrographic activity; and (B) according to morphology; subtype (a): regular 5-9 Hz rhythmic activity (RA); subtype (b): low-voltage rapid activity, followed by a 5-9 Hz RA; and subtype (c): irregular EEG sharp waves. We analyzed the clinical symptoms sequence and established the relationship with the ictal EEG patterns., Results: Considering spatial distribution and morphology, the most frequent ictal EEG patterns were type 1 (57%), type 2 (37%), and subtype (a): 62%; subtype (b): 27%; and subtype (c): 11%. The sequence of clinical symptoms observed was: aura-->behavioral arrest-->oro-alimentary automatisms-->unilateral hand automatisms. All seizures with aura and including two or more symptoms of the clinical sequence (65%) were associated with a 1a, 1b, 2a or 2b EEG pattern., Conclusions: The identification of a specific clinical-EEG pattern provides a useful tool for the epileptogenic zone localization in non-invasive pre-surgical assessment of patients with hippocampal sclerosis., Significance: The identification of a specific clinical-EEG pattern associated to neuroimaging findings and neuropsychological testing allows indicating surgery for the treatment of epilepsy in patients with hippocampal sclerosis, without performing any further complementary studies.

Objective: To investigate the prevalence of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS., Methods: Mutational screening was performed in affected members of 18 families in which multiple members had symptoms compatible with TRAPS and in 176 consecutive subjects with sporadic (nonfamilial) "TRAPS-like" symptoms. Plasma concentrations of soluble tumor necrosis factor receptor superfamily 1A (sTNFRSF1A) were measured, and fluorescence-activated cell sorter analysis was used to measure TNFRSF1A shedding from monocytes., Results: Eight novel and 3 previously reported TNFRSF1A missense mutations were identified, including an amino acid deletion (Delta D42) in a Northern Irish family and a C70S mutation in a Japanese family, both reported for the first time. Only 3 TNFRSF1A variants were found in patients with sporadic TRAPS (4 of 176 patients). Evidence for nonallelic heterogeneity in TRAPS-like conditions was found: 3 members of the "prototype familial Hibernian fever" family did not possess C33Y, present in 9 other affected members. Plasma sTNFRSF1A levels were low in TRAPS patients in whom renal amyloidosis had not developed, but also in mutation-negative symptomatic subjects in 4 families, and in 14 patients (8%) with sporadic TRAPS. Reduced shedding of TNFRSF1A from monocytes was demonstrated in vitro in patients with the T50M and T50K variants, but not in those with other variants., Conclusion: The presence of TNFRSF1A shedding defects and low sTNFRSF1A levels in 3 families without a TNFRSF1A mutation indicates that the genetic basis among patients with "TRAPS-like" features is heterogeneous. TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology.

Chicken embryonic adipofibroblasts (CEA) accumulate intracytoplasmic lipids when cultured in medium containing chicken serum (CS), but not in medium with fetal bovine serum (FBS). To characterize this process of lipid accumulation, we evaluated the expression of the enzyme glycerol-3-phosphate dehydrogenase (E.C.1.1.1.8) (GPDH), first in chicken tissues and then in CEA cultured under diverse conditions. GPDH activity in adipose depots from 4-wk-old broiler chickens was similar or higher than that shown by liver, the main organ for fatty acid synthesis in chickens, while skeletal muscle had the lowest levels of GPDH. In vitro, GPDH activity increased in CEA cultured in the presence of CS but not in medium with FBS, paralleling the lipid accumulation by these cells. Both lipid accumulation and GPDH activity were further increased in CEA cultured in the presence of embryonic CS. Our results show that GPDH is highly expressed in avian tissues related to lipid metabolism and therefore can be a reliable marker for avian adipogenesis, and suggest that ECS is an optimum source for the purification of avian adipogenic factors.

Bioassay-guided fractionation of the leaves from Andira inermis was undertaken as part of a screening program to verify the traditional use of herbal remedies against malaria. Among the isolated phenolic compounds three novel 2-arylbenzofuran-3-carbaldehydes, andinermal A-C, were obtained together with a new flavanonol glycoside, taxifolin-3-O-(3"-O-trans-cinnamoyl)-alpha-L-rhamnopyranoside.

Four new terpenes including, two sandaracopimaradiene diterpenoids, ent-8(14),15-sandaracopimaradiene-2alpha,18-diol, and ent8(14),15-sandaracopimaradiene-2beta,18-diol, and two lanostane triterpenoids, 23-hydroxy-5alpha-lanosta 7,9(11),24-triene-3-one, and 5alpha-lanosta-7,9(11),24-triene-3alpha,23-diol, were isolated from the methanolic extract prepared from the leaves of G. rhopalocarpa together with the known steroid stigmasterol and the coumarin, scopoletin. The isolates showed weak antiprotozoal activity against Leishmania donovani promastigotes, and Trypanosoma brucei brucei blood stream trypomastigotes, and were devoid of interesting activity towards Plasmodium falciparum. The isolates did not show significant cytotoxic activity against KB cells.

Nineteen plants from the Republic of Panama were selected by their traditional uses in the treatment of hypertension, cardiovascular, mental and feeding disorders and 149 extracts were screened using radioligand-receptor-binding assays. The methanol:dicloromethane extracts of the bark and leaves of Anacardium occidentale L., the leaves of Begonia urophylla Hook., the roots of Bocconia frutescens L., the stems and leaves of Cecropia cf.obtusifolia Bertol., the branches of Clusia coclensis Standl., the bark of Cochlospermum vitifolium (Willd.)Spreng., the roots of Dimerocostus strobilaceus Kuntze, the bark of Guazuma ulmifolia Lam., the leaves of Persea americana Mill. and the branches of Witheringia solanaceae L'Her. inhibited the [3H]-AT II binding (angiotensin II AT1 receptor) more than 50%. Only extracts of the roots of Dimerocostus strobilaceus Kuntze and the stems of Psychotria elata (Sw.) Hammel were potent inhibitors of the [3H] NPY binding (neuropeptide Y Y1 receptor) more than 50% and the ethanolic extracts of the leaves of Cecropia cf. obtusifolia Bertol., the leaves of Hedyosmum bonplandianum H.B.K., the roots of Bocconia frutescens L., the stem of Cecropia cf. obtusifolia Bertol. and the branches of Psychotria elata (Sw.) Hammel showed high inhibition of the [3H] BQ-123 binding (endothelin-1 ET(A) receptor) in a preliminary screening. These results promote the further investigation of these plants using the same assays.

The fertility of the male alpaca under different frequencies of daily consecutive matings was evaluated. Fifteen adult male Huacaya alpacas were divided randomly into three groups of five each to breed lactating female alpacas. The schedule of daily matings was two, four and six consecutive breeding per group and for nine consecutive days. Ovulation was determined by progesterone at seven days after breeding. Pregnancy was determined by ultrasonography at 15 and 30 days after breeding. Two hundred and eighty females were bred with some males not fulfilling their schedule of breeding. There were differences (P < 0.05) in the fertility rate of males breeding two and four times daily (76%) in contrast to 59% for males breeding six times. There were also differences (P < 0.05) in the fertility of individual males. Length of copulation was affected (P < 0.05) by schedule of matings, day of breeding and male. Ovulation was independent of length of copulation. Overall, it seems the fertility of the male alpaca is affected significantly when consecutive matings are over four times a day and for nine consecutive days.