Swimming exercise and diphenyl diselenide-supplemented diet modulate cerebral cortical and striatal GABA uptake in aged rats.

Aging is characterized by several neurochemical modifications involving structural proteins and neurotransmitters. Exercise has been recognized as an enhancer of overall health; whereas, diphenyl diselenide (PhSe)2 has been reported to have antioxidant, anti-inflammatory, and neuroprotective effects in rodents. A combination of pharmacological and non-pharmacological interventions has been proposed to prevent the aging effects. This study aimed to determine the swimming exercise and (PhSe)2 dietary supplementation synergic effects on the [3H] γ-aminobutyric acid (GABA) uptake in aged rats. Male Wistar rats (24 months) received 1 ppm of (PhSe)2 supplemented in the standard chow for 4 weeks. Rats were subjected to swimming training (20 min per day for 4 weeks). After 4 weeks, the [3H]GABA uptake was determined in samples of cerebral cortex and striatum of rats. The results of the present study demonstrate that the association of (PhSe)2-supplemented diet and swimming exercise was effective against the decrease of cerebral cortical and striatal [3H]GABA uptake in aged rats. The association of (PhSe)2 dietary supplementation with swimming exercise modulated the GABA uptake in cerebral structures of aged rats.

FoxO1 is required for physiological cardiac hypertrophy induced by exercise but not by constitutively active PI3K.

The insulin-like growth factor 1 receptor (IGF1R) and phosphoinositide 3-kinase p110α (PI3K) are critical regulators of exercise-induced physiological cardiac hypertrophy and provide protection in experimental models of pathological remodeling and heart failure. Forkhead box class O1 (FoxO1) is a transcription factor that regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K activation in vitro, but its role in physiological hypertrophy in vivo was unknown. We generated cardiomyocyte-specific FoxO1 knockout (cKO) mice and assessed the phenotype under basal conditions and settings of physiological hypertrophy induced by 1) swim training or 2) cardiac-specific transgenic expression of constitutively active PI3K (caPI3KTg+). Under basal conditions, male and female cKO mice displayed mild interstitial fibrosis compared with control (CON) littermates, but no other signs of cardiac pathology were present. In response to exercise training, female CON mice displayed an increase (∼21%) in heart weight normalized to tibia length vs. untrained mice. Exercise-induced hypertrophy was blunted in cKO mice. Exercise increased cardiac Akt phosphorylation and IGF1R expression but was comparable between genotypes. However, differences in Foxo3a, Hsp70, and autophagy markers were identified in hearts of exercised cKO mice. Deletion of FoxO1 did not reduce cardiac hypertrophy in male or female caPI3KTg+ mice. Cardiac Akt and FoxO1 protein expressions were significantly reduced in hearts of caPI3KTg+ mice, which may represent a negative feedback mechanism from chronic caPI3K, and negate any further effect of reducing FoxO1 in the cKO. In summary, FoxO1 contributes to exercise-induced hypertrophy. This has important implications when one is considering FoxO1 as a target for treating the diseased heart.NEW & NOTEWORTHY Regulators of exercise-induced physiological cardiac hypertrophy and protection are considered promising targets for the treatment of heart failure. Unlike pathological hypertrophy, the transcriptional regulation of physiological hypertrophy has remained largely elusive. To our knowledge, this is the first study to show that the transcription factor FoxO1 is a critical mediator of exercise-induced cardiac hypertrophy. Given that exercise-induced hypertrophy is protective, this finding has important implications when one is considering FoxO1 as a target for treating the diseased heart.

CF3-substituted diselenide modulatory effects on oxidative stress, induced by single and repeated morphine administrations, in susceptible tissues of mice.

Studies reveal that oxidative stress is associated with adverse effects of long-term morphine treatment. The m-trifluoromethyl-diphenyl diselenide (CF3) is a multi-target organoselenium compound that has antioxidant properties in different experimental models. This study aimed to investigate the CF3 effects against redox imbalance in peripheral and central tissues of mice, after single or multiple morphine doses. Swiss male mice received a single dose of morphine (5 mg/kg, s.c.) and CF3 (10 mg/kg, i.g.), or morphine was repeatedly injected (5 mg/kg, s.c.) and CF3 (10 mg/kg, i.g.) administered twice daily for 7 days. Oxidative stress was determined in the hippocampus, liver, and kidney. CF3 reversed the increase in reactive species caused by single and multiple morphine doses in the peripheral tissues. CF3 increased hepatic non-protein thiol levels and the superoxide dismutase (SOD) activity decreased by a single morphine dose. CF3 reversed the reduction in SOD activity in the kidney of mice repeatedly exposed to morphine. The study demonstrates that peripheral tissues were more susceptible than the hippocampus to oxidative stress induced by morphine in mice. The results show that CF3 modulated parameters of oxidative stress modified by single and multiple morphine administrations in peripheral and central tissues of mice.

Heat stress on oocyte or zygote compromises embryo development, impairs interferon tau production and increases reactive oxygen species and oxidative stress in bovine embryos produced in vitro.

Interferon tau (IFNT) is the cytokine responsible for the maternal recognition of pregnancy in ruminants and plays a role modulating embryo-maternal communication in the oviduct inducing a local response from immune cells. We aimed to investigate IFNT production, reactive oxygen species, and oxidative stress under the influence of heat stress (HS) during different stages of bovine in vitro embryo production. HS was established when the temperature was gradually raised from 38.5°C to 40.5°C in laboratory incubator, sustained for 6 hr, and decreased back to 38.5°C. To address the HS effects on IFNT production, reactive oxygen species, and oxidative stress, ovaries from a slaughterhouse were used according to treatments: control group (38.5°C); oocytes matured under HS; oocytes fertilized under HS; zygotes cultured in the first day under HS; and cells submitted to HS at oocyte maturation, fertilization, and the first day of zygote culture. The HS negatively affected cleavage and blastocyst rates, in all HS groups. On Day 7, all HS-treated embryos showed decrease IFNT gene and protein expressions, whereas reactive oxygen species were increased in comparison to the control. In conclusion, the compromised early embryo development due to higher temperatures during in vitro oocyte maturation, fertilization, and/or zygote stage have diminished IFNT expression and increased reactive oxygen species in bovine.

Exposure Variability and Target Attainment of Vancomycin: A Systematic Review Comparing Intermittent and Continuous Infusion.

BACKGROUND: Studies comparing the clinical outcomes between vancomycin intermittent infusion (InI) and continuous infusion (CoI) treated patients are generally underpowered. Moreover, due to large differences in the design and efficacy end points in these studies, a meta-analysis of the currently available data is not feasible. Therefore, this systematic review aimed to compare the exposure variability and target attainment with vancomycin during InI and CoI. PATIENTS AND METHODS: A literature search was performed, and clinical studies reporting on vancomycin-treated populations were selected. After exclusion of reviews, case reports, and articles not published in the English language, 505 articles were screened for reported data on vancomycin serum concentrations. A total of 34 studies were included in the review. Relative standard deviations reported in the included studies were assessed, and vancomycin serum concentration variability and target attainment were compared between vancomycin InI and CoI. RESULTS: The variability in serum concentrations was significantly larger for InI than for CoI (relative standard deviations 46.5% and 32.1%, respectively; P = 0.001). Notably, variability appeared to be independent of the study population or design. Studies directly comparing target attainment between both modes of administration denoted higher and faster target attainment with CoI in all instances. CONCLUSIONS: In conclusion, CoI was associated with lower variabilities in the serum concentration and favorable target attainment rates compared with InI. These findings are important because vancomycin exposure is considered a major predictor of the patients' clinical outcomes. However, the role of lower serum concentration variability and higher target attainment rates in achieving better clinical outcomes needs to be evaluated in patients treated with vancomycin CoI compared with InI.

Exploring the early phase of implementation of a vaccine-based clinical decision support system in the community pharmacy.

OBJECTIVE: To explore the implementation strategy of a recombinant zoster vaccine (RZV) clinical decision support (CDS) intervention in community pharmacy workflow to increase second-dose vaccination rates. SETTING: The level of analysis was the unit (e.g., pharmacy). The participants were selected from across approximately 2200 pharmacies in 37 states on the basis of criteria believed to affect implementation success (e.g., size, location) using a sampling matrix. PRACTICE DESCRIPTION: Large supermarket pharmacy chain. PRACTICE INNOVATION: Vaccine-based CDS intervention in community pharmacy workflow. EVALUATION: A mixed-methods contextual inquiry approach explored the implementation of a new RZV CDS workflow intervention. Data collection involved key informant, semistructured interviews and an electronic, Web-based survey. The survey was based on a validated instrument and was made available to all pharmacists nationwide within the study organization to assess views of the implementation's appropriateness, acceptability, and feasibility during early implementation. Afterward, a series of semistructured, in-depth interviews were conducted until a point of saturation was reached. The interview guide was based on selected constructs of the Consolidated Framework for Implementation Research. RESULTS: A total of 1128 survey responses were collected. Survey respondents agreed or strongly agreed that the implementation was acceptable (78.34%), appropriate (79.92%), and feasible (80.53%). Twelve pharmacist participants were interviewed via telephone. Five themes emerged from the interviews, revealing facilitators and barriers that affected implementation of the intervention: intervention characteristics, outer setting, inner setting, characteristics of individuals, and process. CONCLUSION: The implementation of the RZV CDS "nudge" intervention was welcomed, suitable, and operable in the community pharmacy setting to meet the needs of the organization, employees, and patients. The contextual factors identified during the implementation process of this CDS intervention in a community pharmacy setting may be used in scaling this and future CDS interventions for public health initiatives aimed at pharmacists in this setting.

Viral metacommunities associated to bats and rodents at different spatial scales.

One of the main goals of community ecology is to measure the relative importance of environmental filters to understand patterns of species distribution at different temporal and spatial scales. Likewise, the identification of factors that shape symbiont metacommunity structures is important in disease ecology because resulting structures drive disease transmission. We tested the hypothesis that distributions of virus species and viral families from rodents and bats are defined by shared responses to host phylogeny and host functional characteristics, shaping the viral metacommunity structures at four spatial scales (Continental, Biogeographical, Zoogeographical, and Regional). The contribution of host phylogeny and host traits to the metacommunity of viruses at each spatial scale was calculated using a redundant analysis of canonical ordering (RDA). For rodents, at American Continental scale the coherence of viral species metacommunity increased while the spatial scale decreased and Quasi-Clementsian structures were observed. This pattern suggests a restricted distribution of viruses through their hosts, while in the Big Mass (Europe, Africa, and Asia), the coherence decreased as spatial scale decreased. Viral species metacommunities associated with bats was dominated by random structures along all spatial scales. We suggest that this random pattern is a result of the presence of viruses with high occupancy range such as rabies (73%) and coronavirus (27%), that disrupt such structures. At viral family scale, viral metacommunities associated with bats showed coherent structures, with the emergence of Quasi- Clementsian and Checkerboard structures. RDA analysis indicates that the assemblage of viral diversity associated with rodents and bats responds to phylogenetic and functional characteristics, which alternate between spatial scales. Several of these variations could be subject to the spatial scale, in spite of this, we could identify patterns at macro ecological scale. The application of metacommunity theory at symbiont scales is particularly useful for large-scale ecological analysis. Understanding the rules of host-virus association can be useful to take better decisions in epidemiological surveillance, control and even predictions of viral distribution and dissemination. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1556/168.2018.19.2.9 and is accessible for authorized users.

Modeling Flowsheet Data to Support Secondary Use.

The purpose of this study was to create information models from flowsheet data using a data-driven consensus-based method. Electronic health records contain a large volume of data about patient assessments and interventions captured in flowsheets that measure the same "thing," but the names of these observations often differ, according to who performs documentation or the location of the service (eg, pulse rate in an intensive care, the emergency department, or a surgical unit documented by a nurse or therapist or captured by automated monitoring). Flowsheet data are challenging for secondary use because of the existence of multiple semantically equivalent measures representing the same concepts. Ten information models were created in this study: five related to quality measures (falls, pressure ulcers, venous thromboembolism, genitourinary system including catheter-associated urinary tract infection, and pain management) and five high-volume physiological systems: cardiac, gastrointestinal, musculoskeletal, respiratory, and expanded vital signs/anthropometrics. The value of the information models is that flowsheet data can be extracted and mapped for semantically comparable flowsheet measures from a clinical data repository regardless of the time frame, discipline, or setting in which documentation occurred. The 10 information models simplify the representation of the content in flowsheet data, reducing 1552 source measures to 557 concepts. The amount of representational reduction ranges from 3% for falls to 78% for the respiratory system. The information models provide a foundation for including nursing and interprofessional assessments and interventions in common data models, to support research within and across health systems.

Homeostatic effect of p-chloro-diphenyl diselenide on glucose metabolism and mitochondrial function alterations induced by monosodium glutamate administration to rats.

The metabolic syndrome is a group of metabolic alterations considered a worldwide public health problem. Organic selenium compounds have been reported to have many different pharmacological actions, such as anti-hypercholesterolemic and anti-hyperglycemic. The aim of this study was to evaluate the effect of p-chloro-diphenyl diselenide (p-ClPhSe)2, an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats. The rats were treated during the first ten postnatal days with MSG and received (p-ClPhSe)2 (10 mg/kg, intragastrically) from 45th to 51 th postnatal day. Glucose, lipid and lactate levels were determined in plasma of rats. Glycogen levels and activities of tyrosine aminotransferase, hexokinase, citrate synthase and glucose-6-phosphatase (G-6-Pase) were determined in livers of rats. Renal G-6-Pase activity was also determined. The purine content [Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate] and mitochondrial functionality in the liver were also investigated. p-(ClPhSe)2 did not alter the reduction in growth performance and in the body weight caused by MSG but reduced epididymal fat deposition of rats. p-(ClPhSe)2 restored glycemia, triglycerides, cholesterol and lactate levels as well as the glucose metabolism altered in rats treated with MSG. p-(ClPhSe)2 restored hepatic mitochondrial dysfunction and the decrease in citrate synthase activity and ATP and ADP levels caused by MSG in rats. In summary, (p-ClPhSe)2 had homeostatic effects on glucose metabolism and mitochondrial function alterations induced by MSG administration to rats.

The diversity-disease relationship: evidence for and criticisms of the dilution effect.

The dilution effect, that high host species diversity can reduce disease risk, has attracted much attention in the context of global biodiversity decline and increasing disease emergence. Recent studies have criticized the generality of the dilution effect and argued that it only occurs under certain circumstances. Nevertheless, evidence for the existence of a dilution effect was reported in about 80% of the studies that addressed the diversity-disease relationship, and a recent meta-analysis found that the dilution effect is widespread. We here review supporting and critical studies, point out the causes underlying the current disputes. The dilution is expected to be strong when the competent host species tend to remain when species diversity declines, characterized as a negative relationship between species' reservoir competence and local extinction risk. We here conclude that most studies support a negative competence-extinction relationship. We then synthesize the current knowledge on how the diversity-disease relationship can be modified by particular species in community, by the scales of analyses, and by the disease risk measures. We also highlight the complex role of habitat fragmentation in the diversity-disease relationship from epidemiological, evolutionary and ecological perspectives, and construct a synthetic framework integrating these three perspectives. We suggest that future studies should test the diversity-disease relationship across different scales and consider the multiple effects of landscape fragmentation.

Seasonal mosquito (Diptera: Culicidae) dynamics and the influence of environmental variables in a land use gradient from Yucatan, Mexico.

Mosquito-borne diseases constitute a significant global impact on public and animal health. Climatic variables are recognized as major drivers in the mosquitoes' life history, principally rainfall and temperature, which directly influence mosquito abundance. Likewise, urbanization changes environmental conditions, and understanding how environmental variables and urbanization influence mosquito dynamics is crucial for the integrated management of mosquito-borne diseases, especially in the context of climate change. In this study, our aim was to observe the effect of temperature, rainfall, and the percentage of impervious surface on the abundance of mosquito species over a temporal scale of one complete year of fortnightly samplings, spanning from June 2021 to June 2022 in Yucatan, Mexico. We selected nine localities along an urbanization gradient (three natural, three rural, and three urban) from Mérida City to Reserva de la Biosfera Ría Celestún. Using BG-traps, mosquitoes were collected biweekly at each locality. Additionally, we estimated the percentage of impervious surface. Daily data of the maximum, mean and minimum temperatures, diurnal temperature range and rainfall were accumulated weekly. We calculated the accumulated quantities of temperatures and rainfall and lagged from one to four weeks before sampling for each locality. Generalized linear mixed models were then performed to study the influence of environmental variables and percentage of impervious surfaces on each of the 15 most abundant species. A total of 131,525 mosquitoes belonging to 11 genera and 49 species were sampled with BG-Sentinel traps baited with BG-lure and dry ice. The most frequently significative variable is the accumulated precipitation four weeks before the sampling. We observed a positive relationship between Cx. quinquefasciatus and Cx. thriambus with the diurnal temperature range. For Ae. aegypti, we observed a positive relationship with minimum temperature. Conversely, the percentage of impervious surface serves as a proxy of anthropogenic influence and helped us to distinguishing species exhibiting habitat preference for urban and rural environments, versus those preferring natural habitats. Our results characterize the species-specific effects of environmental variables (temperature, rainfall and impervious surface) on mosquito abundance.

Developing practical recommendations for drug-disease interactions in patients with hypertension.

Background: Hypertension, a significant risk factor for cardiovascular diseases, demands proactive management as cardiovascular diseases remain the leading cause of death worldwide. Reducing systolic and diastolic blood pressure levels below recommended reference values of <140/90 mmHg can lead to a significant reduction of the risk of CVD and all-cause mortality. However, treatment of hypertension can be difficult and the presence of comorbidities could further complicate this treatment. Drugs used to manage these comorbidities may inadvertently have an impact on blood pressure, resulting in a phenomenon known as drug-disease interaction. This study aims to assess the safety of medication that can affect blood pressure in patients with hypertension and provide practical recommendations for healthcare professionals. Methods: For the development of recommendations for the drug-disease interaction (DDSI) hypertension, a six-step plan that combined literature selection and multidisciplinary expert opinion was used. The process involved (1) defining the scope of the DDSI and selecting relevant drugs, (2) collecting evidence, (3) data-extraction, (4) reaching of expert consensus, (5) publication and implementation of the recommendations in healthcare systems and (6) updating the information. Results: An increase of 10 mmHg in systolic blood pressure and 5 mmHg in diastolic blood pressure was defined as clinically relevant. Corticosteroids, danazol, and yohimbine caused a clinically relevant DDSI with hypertension. Several other drugs with warnings for hypertension in the official product information were assessed to have no clinically relevant DDSI due to minor influence or lack of data on blood pressure. Drugs with evidence for a relevant change in blood pressure which are prescribed under close monitoring of blood pressure according to clinical guidelines, were deemed to be not clinically relevant for signalling. Conclusion: This study provides specific recommendations that can be implemented directly in clinical practice, for example, in clinical decision support systems, potentially resulting in safer drug use in patients with hypertension and better healthcare by reducing alert fatigue. Future research should focus on evaluating the effectiveness of implementation strategies and their impact on reducing unsafe use of medication in patients with hypertension.

Coronaviruses in bats from Mexico.

Bats are reservoirs for a wide range of human pathogens including Nipah, Hendra, rabies, Ebola, Marburg and severe acute respiratory syndrome coronavirus (CoV). The recent implication of a novel beta (ß)-CoV as the cause of fatal respiratory disease in the Middle East emphasizes the importance of surveillance for CoVs that have potential to move from bats into the human population. In a screen of 606 bats from 42 different species in Campeche, Chiapas and Mexico City we identified 13 distinct CoVs. Nine were alpha (α)-CoVs; four were ß-CoVs. Twelve were novel. Analyses of these viruses in the context of their hosts and ecological habitat indicated that host species is a strong selective driver in CoV evolution, even in allopatric populations separated by significant geographical distance; and that a single species/genus of bat can contain multiple CoVs. A ß-CoV with 96.5 % amino acid identity to the ß-CoV associated with human disease in the Middle East was found in a Nyctinomops laticaudatus bat, suggesting that efforts to identify the viral reservoir should include surveillance of the bat families Molossidae/Vespertilionidae, or the closely related Nycteridae/Emballonuridae. While it is important to investigate unknown viral diversity in bats, it is also important to remember that the majority of viruses they carry will not pose any clinical risk, and bats should not be stigmatized ubiquitously as significant threats to public health.

Contribution of Opioid and Nitrergic Systems to m-Trifluoromethyl diphenyl Diselenide Attenuates Morphine-Induced Tolerance in Mice.

m-Trifluoromethyl diphenyl diselenide (TFDD) has antinociceptive and antidepressant-like properties and attenuates morphine withdrawal signs in mice. This study investigated if TFDD affects the development of morphine tolerance to its antinociceptive and antidepressant-like effects in mice. We also investigated whether TFDD modulates signaling pathways related to morphine tolerance, including the opioid receptors and some parameters of the nitrergic system. Male adult Swiss mice received morphine alone (5 mg/kg, subcutaneous) and in combination with TFDD (10 mg/kg, intragastric) for 7 days. Mice were subjected to hot plate and forced swim tests on days 1, 3, 5, and 7 of the experimental protocol. Repeated TFDD administrations avoided tolerance development mediated by morphine, including its antinociceptive and antidepressant-like effects. A single morphine dose increased MOR and NOx but decreased iNOS contents in the mouse cerebral cortex. In turn, single morphine and TFDD co-administration restored the MOR and iNOS protein levels. On the other hand, morphine repeated doses enhanced DOR and reduced MOR and NOx contents, whereas the morphine and TFDD association reestablished DOR and NOx levels in the mouse cerebral cortex. In conclusion, some opioid and nitrergic system parameters might contribute to TFDD attenuation of antinociceptive and antidepressant-like tolerance induced by morphine in mice.

Antihyperglycemic and hepatoprotective properties of miracle fruit (Synsepalum dulcificum) compared to aspartame in alloxan-induced diabetic mice.

OBJECTIVE: This study was undertaken to investigate the antihyperglycemic potential of miracle fruit (MF) as well as its hepatic safety as compared to aspartame in alloxan-induced diabetic mice. METHODS: MF extracts were prepared and screened for their phytochemical composition using high-performance liquid chromatography (HPLC). Total phenolic, flavonoid and tannin contents and antioxidant potential were also determined. Additionally, MF was evaluated for its sensory attributes. For in vivo work, MF ethanol extract at high (MFH: 500 mg/kg body weight [BW]) and low (MFL: 250 mg/kg BW) doses as well as aspartame were injected intraperitoneally into alloxan-induced diabetic mice. Blood glucose levels were determined following acute and subchronic treatment. At the end of the study, animals were sacrificed, serum was collected for biochemical analysis and liver tissues were obtained for histopathological examination. RESULTS: MF ethanol extract contained more flavonoids and tannins, and had higher 1,1-diphenyl-1-picrylhydrazyl radical-scavenging activity (79.61%) compared to MF aqueous extract (P < 0.05). HPLC analysis of MF ethanol extract also revealed the presence of 10 antioxidants with quercetin comprising the major polyphenol. Additionally, sensory analysis of MF showed that its intake is effective in masking undesirable sourness. Subchronic administration of MFH proved amelioration of hyperglycemia in mice as compared to aspartame. Moreover, aspartame treatment significantly elevated (P < 0.05) the level of alanine aminotransferase and had destructive effects on the liver histopathology; however, hepatic architecture was restored by low and high doses of MF. CONCLUSION: MF is an effective antihyperglycemic with hepatoprotective properties that can be used as a healthier alternative sweetening agent in place of aspartame for sour beverages.

Contribution of cholinergic system and Nrf2/HO-1 signaling to the anti-amnesic action of 7-fluoro-1,3-diphenylisoquinoline-1-amine in mice.

The isoquinoline 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) has been studied due to its multitarget properties, such as modulation of GABAergic and glutamatergic systems, antioxidant, and anti-inflammatory. This study investigated the contribution of oxidative stress, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase (HO-1) signaling, and the cholinergic system to the anti-amnesic action of FDPI in mice. Adult male Swiss mice received FDPI for 5 days (5-25 mg/kg, i.g.); the animals received scopolamine (1 mg/kg, i.p) from day 3-5. The vehicle-control group was carried out. Afterward, mice performed object recognition tests (ORTs). Scopolamine induced amnesia and cholinergic dysfunction by increasing the acetylcholinesterase (AChE) activity and content, decreasing the muscarinic M1 receptor levels in the prefrontal cortex and hippocampus of mice. This study reveals that scopolamine altered oxidative stress parameters differently in the prefrontal cortex and hippocampus of mice. Whereas the prefrontal cortex was susceptible to oxidative stress, none of the parameters evaluated was altered in the hippocampus of scopolamine-treated mice. FDPI at doses of 10 and 25 mg/kg had an anti-amnesic effect in the ORT tests. FDPI 10 mg/kg reversed the increase in the AChE activity and content, oxidative stress parameters, and modulated Nrf2/HO-1 signaling in the prefrontal cortex of scopolamine-exposed mice. Pearson's correlation analyses reinforced the contribution of the prefrontal cortical cholinergic system, oxidative stress as well as Nrf2/HO-1 signaling in the anti-amnesic effect of FDPI. Considering FDPI effects on the hippocampus, it was effective against the cholinergic dysfunction, AChE activity and content, and M1 receptor levels, which collectively could contribute to its anti-amnesic effect.

Chiggers (Acariformes: Trombiculoidea) do not increase rates of infection by Batrachochytrium dendrobatidis fungus in the endemic Dwarf Mexican Treefrog Tlalocohyla smithii (Anura: Hylidae).

Amphibian populations are globally declining at an alarming rate, and infectious diseases are among the main causes of their decline. Two micro-parasites, the fungus Batrachochytrium dendrobatidis (Bd) and the virus Ranavirus (RV) have caused mass mortality of amphibians and population declines. Other, less understood epizootics are caused by macro-parasites, such as Trombiculoidea chiggers. Infection with chiggers can affect frog behavior and survival. Furthermore, synergistic effects of co-infection with both macro and micro-parasites may lead to higher morbidity. To better understand these potential synergies, we investigated the presence and co-infection by chiggers, Bd and RV in the endemic frog Tlalocohyla smithii (T. smithii). Co-infection of Bd, RV, and/or chiggers is expected in habitats that are suitable for their co-occurrence; and if infection with one parasite facilitates infection with the others. On the other hand, co-infection could decrease if these parasites were to differ in their micro-environmental requirements (i.e. niche apportionment). A total of 116 frogs of T. smithii were studied during 2014 and 2016 in three streams within the Chamela-Cuixmala Biosphere Reserve in Jalisco, Mexico. Our results show that 31% of the frogs were infected with Trombiculoidea chiggers (Hannemania sp. and Eutrombicula alfreddugesi); Hannemania prevalence increased with air temperature and decreased in sites with high canopies and with water pH values above 8.5 and below 6.7. Bd prevalence was 2.6%, RV prevalence was 0%, and none of the frogs infected with chiggers were co-infected with Bd. Together, this study suggests that chiggers do not facilitate infection with Bd, as these are apportioned in different micro-habitats. Nevertheless, the statistical power to assure this is low. We recommend further epidemiological monitoring of multiple parasites in different geographical locations in order to provide insight on the true hazards, risks and conservation options for amphibian populations.

m-Trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 modulates the hippocampal neurotoxic adaptations and abolishes a depressive-like phenotype in a short-term morphine withdrawal in mice.

The opioid withdrawal syndrome is defined as a complex phenomenon involving multiple cellular adaptations, which leads to the emergence of aversive physical and affective signs. The m-trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 elicits an antidepressant-like effect by modulating the opioid system in different animal models of mood disorders. Notably, repeated exposure to (m-CF3-PhSe)2 developed neither tolerance nor withdrawal signs in mice. The aim of the present study was to investigate whether (m-CF3-PhSe)2 attenuates the physical signs and the depressive-like phenotype during morphine withdrawal through its neuroprotective effects on oxidative stress, the NMDA receptor and the proBDNF/mBDNF signaling in the hippocampus of mice. Adult Swiss mice received saline solution or escalating doses (20-100 mg/kg, sc) of morphine for six days. For the next three days, the animals were treated with canola oil, (m-CF3-PhSe)2 (5 and 10 mg/kg, ig) or methadone (5 mg/kg, sc) whereas morphine injections were discontinued. On day 9, physical withdrawal signs and depressive-like behavior were assessed 30 min after the last administration of (m-CF3-PhSe)2. Although short-term treatment with (m-CF3-PhSe)2 at both doses suppressed the aversive physical and affective signs in morphine withdrawn-mice, the highest dose of (m-CF3-PhSe)2 per se increased the teeth chattering manifestation. The intrinsic antioxidant property of (m-CF3-PhSe)2 modulated oxidative stress, it also restored the NMDA receptor levels in the hippocampus of morphine withdrawn-mice. Besides, (m-CF3-PhSe)2 downregulated the proBDNF/p-75NTR/JNK pro-apoptotic pathway without affecting the mBDNF/TrkB/ERK/CREB pro-survival signaling in the hippocampus of morphine withdrawn-mice. The results show that (m-CF3-PhSe)2 treatment modulated the hippocampal neurotoxic adaptations and abolished the depressive-like phenotype following morphine withdrawal in mice.

The Development and Proof of Principle Test of TRIAGE: A Practical Question Set to Identify and Discuss Medication-Related Problems in Community Pharmacy.

The pharmacy counter is a good place to identify and discuss medication-related problems. However, there is a lack of practical communication tools to support pharmacy technicians (PTs) in initiating a conversation with patients. This study aimed to develop and test a practical set of questions for PTs, called TRIAGE, to identify problems during encounters. TRIAGE was developed based on insight from the literature, focus groups with PTs and pharmacists, and input from patients and experts. In 10 community pharmacies, 17 PTs used TRIAGE during encounters with patients who collected their cardiovascular medication. For each encounter, PTs registered the identified problems and suggested solutions. A total of 105 TRIAGE conversations were held, 66 for first refill and 39 for follow-up refill prescriptions. In 15 (23%) first refill prescription encounters, a problem was identified. These problems concerned forgetting to take the medication, a complex medication regime or (fear of) side effects. In three (8%) follow-up refill prescription encounters, a problem was identified. Most of the problems were solved on the spot. Pharmacy technicians indicated that they identified medication-related problems with TRIAGE that otherwise would be left unnoticed. They appreciated TRIAGE as a useful instrument for starting the conversation with patients about medication use.

Seasonal changes of faecal cortisol metabolite levels in Gracilinanus agilis (Didelphimorphia: Didelphidae) and its association to life histories variables and parasite loads.

The aim of this study was to evaluate the role of environmental (dry versus wet season) and individual (sex, body mass and reproductive status) factors in the levels of faecal cortisol metabolites (FGCs) in Gracilinanus agilis faecal samples as an index of stress levels in this species; as well as its association with abundance of Eimeria spp, as an indicator of immunocompetence against parasites. Our study found that FGCFGCs are a reliable indicator of adrenal activity in G. agilis. We found that FGCFGCs increase considerably by environmental stressors like the dry season. Moreover, the observed positive association between FGCs and body mass is the result of the effect of season and reproduction in both variables. We also demonstrated that an increase in FGC levels among G. agilis during the dry season is associated with a rise in the probability of being infected by Eimeria spp. Hence, our finding supports the corticosteroid-fitness hypothesis, which predicts that increased glucocorticoids as a response to stressors usually results in decreased fitness of individuals, translated into low future survival and reproductive success, and higher parasite infection. To our knowledge, this is the first study that integrates environmental changes, hormone responses and parasite loads in a US marsupial in both empirical and experimental approaches.