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Menopause has been linked to changes in memory. Oestrogen-containing hormone therapy is prescribed to treat menopause-related symptoms and can ameliorate memory changes, although the parameters impacting oestrogen-related memory efficacy are unclear. Cognitive experience and practice have been shown to be neuroprotective and to improve learning and memory during ageing, with the type of task playing a role in subsequent cognitive outcomes. Whether task complexity matters, and whether these outcomes interact with menopause and oestrogen status, remains unknown. To investigate this, we used a rat model of surgical menopause to systematically assess whether maze task complexity, as well as order of task presentation, impacts spatial learning and memory during middle age when rats received vehicle, low-17β-oestradiol (E(2)) or high-E(2) treatment. The direction, and even presence, of the effects of prior maze experience differed depending on the E(2) dose. Surgical menopause without E(2) treatment yielded the least benefit, as prior maze experience did not have a substantial effect on subsequent task performance for vehicle treated rats regardless of task demand level during the first exposure to maze experience or final testing. High-dose E(2) yielded a variable benefit, and low-dose E(2) produced the greatest benefit. Specifically, low-dose E(2) broadly enhanced learning and memory in surgically menopausal rats that had prior experience on another task, regardless of the complexity level of this prior experience. These results demonstrate that E(2) dose influences the impact of prior cognitive experience on learning and memory during ageing, and highlights the importance of prior cognitive experience in subsequent learning and memory outcomes.

Coronavirus disease 2019 (COVID-19) has underscored longstanding societal differences in the drivers of health and demonstrated the value of applying a health equity lens to engage at-risk communities, communicate with them effectively, share data, and partner with them for program implementation, dissemination, and evaluation. Examples of engagement - across diverse communities and with community organizations; tribes; state and local health departments; hospitals; and universities - highlight the opportunity to apply lessons from COVID-19 for sustained changes in how public health and its partners work collectively to prevent disease and promote health, especially with our most vulnerable communities.

To date, therapies to prevent or treat Alzheimer’s disease (AD) have largely focused on removing excess aggregation-prone amyloid peptide Aβ from the brain, an approach that has produced disappointing clinical outcomes. An alternative hypothesis proposes that Aβ production and aggregation is a symptom of a larger, systemic disease affecting the regulation of lipids, including cholesterol. In this scenario, lipid dysregulation would likely occur early in the disease process, making it an ideal target for predicting risk of mild cognitive impairment (MCI) to AD conversion. Here, we report that levels of filipin, a fluorescent polyene macrolide widely used as a diagnostic tool for diseases of lipid dysregulation, correlate with cellular damage caused by 27-hydroxycholesterol and with dementia status in human peripheral blood cells. These results provide strong preliminary data suggesting that filipin could be of use in the development of a quick and inexpensive method to measure the risk of AD conversion in patients with MCI, supplementing existing testing strategies that focus on the consequences of Aβ accumulation.

MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that function as negative regulators of gene expression by either inhibiting translation or inducing deadenylation-dependent degradation of target transcripts. Notably, deregulation of miRNAs expression is associated with the initiation and progression of human cancers where they act as oncogenes or tumor suppressors contributing to tumorigenesis. Abnormal miRNA expression may provide potential diagnostic and prognostic tumor biomarkers and new therapeutic targets in cancer. Recently, several miRNAs have been shown to initiate invasion and metastasis by targeting multiple proteins that are major players in these cellular events, thus they have been denominated as metastamiRs. Here, we present a review of the current knowledge of miRNAs in cancer with a special focus on metastamiRs. In addition we discuss their potential use as novel specific markers for cancer progression.

The medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) are 2 structures within a larger corticolimbic network mediating goal-directed actions, especially when the procurement of different goals is sensitive to impulsive tendencies. The present study investigated the role of these structures in goal-directed action for differential reward by training rats to respond for sucrose reward at a nosepoke operandum such that longer duration nosepokes (up to 2 s) resulted in correspondingly larger volumes of reward. After 16 weeks of training, neurotoxic lesions of either the mPFC or the NAc-core were performed, followed by reassessment of sustained response behavior. Lesions of mPFC increased choice impulsivity by shifting responding away from large rewards toward rewards of smaller sizes. The total volume of reward earned remained unchanged, thereby dissociating the lesion effects on response parameters from overall motivation for reward. In contrast, NAc-core lesions decreased the total amount of responding and total volume of reward earned without altering choice impulsivity across differing nosepoke durations and reward sizes. These results suggest that the mPFC mediates the ability to maintain behavioral responding over longer durations for larger magnitude rewards, while the NAc-core mediates the initiation of responding, perhaps by affecting motivational drive, independent of reward magnitude.

Oral therapy has become first line treatment for patients with mild to moderate erectile dysfunction (ED). Studies have shown that sildenafil may not be effective in all patients, and has been associated with a variety of adverse effects and an adverse interaction with nitrates and inhibitors of cytochrome P450 enzymes. The objective was to compare the efficacy and safety of three different oral combinations with the highest dose of sildenafil in men with moderate to severe ED. Randomized, double blind, unblinded active-controlled, Phase II study was carried out at three sites in Mexico. After a 4-week placebo run-in period, patients received all four of the following treatments using a 4-way cross-over design: 40 mg phentolamine (PM) +6 mg apomorphine (Apo); 40 mg PM +150 mg papaverine (Pap); 40 mg PM +6 mg Apo +150 mg Pap (Tricombo); 100 mg sildenafil (SC). With the exception of sildenafil tablets, all study medication was blinded. Moderate to severe ED was defined as a less than 50% vaginal penetration success rate during the placebo run-in period. A total of 44 patients were enrolled, of whom 36 completed all four treatment periods. All treatments produced a significant effect in primary efficacy variable (Sexual Encounter Profile) compared to baseline, however, no statistically significant differences were found between treatments. A significant period effect was observed. Also, the four treatments were found not to differ significantly in five out of six secondary efficacy variables. The lowest incidence of treatment-related adverse events (AE) occurred in the 40 mg PM +6 mg Apo group (9.8%), followed by 100 mg SC (15%), and the other two combinations (16.7 and 17.5%, respectively). Nasocongestion and headache were the most frequently reported AE. An oral combination of vasoactive agents may provide an alternative approach to sildenafil. Based on these results a combination of phentolamine and apomorphine warrants further clinical investigation.

Fundamento El perfil farmacologico del propofol ha facilitado su uso en la sedacion prolongada de pacientes con enfermedad pulmonar en cuidados intensivos. Los efectos del propofol sobre el corazon y la circulacion sistemica han sido estudiados con detalle. Sin embargo, sus efectos sobre la circulacion pulmonar son menos conocidos. En este estudio analizamos los efectos del propofol sobre la vasoconstriccion pulmonar hipoxica (VPH). Metodos Se midieron los cambios de la vasoconstriccion pulmonar por hipoxia y angiotensina II antes y tras administrar propofol e intralipid en 42 preparaciones de pulmones aislados de ratas. Propofol e intralipid se aportaron entre dos pares de respuestas a hipoxia (grupos B, C, D y E) y angiotensina (F). Resultados El grupo A fue el control. El grupo B fue tratado con 2 μg/ml de propofol; las respuestas a la hipoxia fueron de 10,41 (5,70) mmHg antes de propofol y 11,17 (5,17) mmHg tras propofol (p = 0,096). En el grupo C la concentracion de propofol fue de 8 μg/ml y las respuestas fueron de 7,39 (2,37) y 8,75 (2,60) (p = 0,063). En el grupo D, la preparacion fue pretratada con azul de metileno (140 μμol/l) y propofol 8 μg/ml, siendo las respuestas de 15,20 (2,28) y 15,60 (3,50) (p = 0,739). En el grupo E, se aportaron 20 μl de intralipid al 20% entre la segunda y tercera respuestas a la hipoxia. La respuesta previa a intralipid fue de 9,82 (3,96) mmHg y de 10,84 (3,68) mmHg las posteriores (p = 0,163). En el grupo F, se estudiaron 2 respuestas a angiotensina II antes y tras propofol 8 μg/ml. Las respuestas fueron de 7,55 (1,87) y 7,94 (2,40) mmHg (p = 0,41), respectivamente. Conclusiones El propofol a las concentraciones estudiadas no modifica la VPH en el pulmon aislado de rata.

The projected need for critical care nurses can be met through the collaborative efforts of nursing education and nursing service. An approach as implemented at our institution with the support of community agencies can be mutually beneficial. It is generally recognized that new graduates tend to seek employment where they had positive student experiences. Although few students may choose critical care as a career, the majority will have a positive memory, which is supportive of the unique contribution of critical care nursing within the scope of the health and care of patients and their families.

Photorefractive keratectomy (PRK) using the Summit emphasis erodible mask was performed on 229 eyes with myopic astigmatism. To analyze the efficacy and safety of the method, we evaluated the following: spectacle corrected visual acuity and refractive error as parameters of efficacy; corneal clarity, decentration of the ablation zone and complications as parameters of safety. Despite the short follow up (the longest was 12 months) our results show that the emphasis erodible mask appears to be an effective surgical method for correcting myopic astigmatism. However, we found a great number of complications and subjective symptoms that worsened the visual outcome. We conclude that the emphasis erodible mask has satisfactory efficacy but unsatisfactory safety. [J Refract Surg. 1995; 11(suppl.):S343-S348.]

El clorhidrato de Ketamina (1×10−3M y 1×10−4M) incrementa el consumo de oxigeno de cortes de cerebro de rata incubados en Krebs-Ringer fosfato conteniendo 5 mM o 100 mM de potasio. La droga no modifica el consumo de oxigeno de homogeneizado de cerebro total.