Critique [of The Effects of Reading Ethnic Literature on the Attitudes of Adolescents by Joan Wynne Sullivan]

The intent of Joan Sullivan\u27s project as described in this article is one that can only be applauded -- working toward minimizing ethnocentrism and xenophobia must be seen as a sine quo non for a nation or a school community which aspires to realize a democratic ideology. Furthermore, there is no more important an age group on which to focus this project than that of the adolescent who is on the threshhold [threshold] of adult freedom and responsibility. Finally, educating the imagination toward a more just society for all through literature is a most meaningful use of the secondary school curriculum

Non-Vitamin K antagonist oral anticoagulants for mechanical heart valves is the door still open?

The estimated prevalence of mitral or aortic valvular heart disease is ≈2.5% in the general population of Western countries, and is expected to rise with population aging. A substantial proportion of patients with valvular heart disease undergoes surgical valve replacement. Mechanical heart valves are much more durable than bioprostheses, and are thus preferentially implanted in patients with a longer life expectancy, but have the major drawback of requiring lifelong anticoagulation to prevent valve thrombosis because of their higher thrombogenicity. The non-vitamin K antagonist oral anticoagulants (NOACs) are replacing vitamin K antagonists in many settings, including bioprostheses, because of their favorable safety and efficacy profiles. However, mechanical heart valves currently pose an absolute contraindication to NOACs based on the results of a single phase II study comparing dabigatran and warfarin (RE-ALIGN [Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement]). That trial was stopped prematurely because of an excess of both stroke and bleeding with the dabigatran doses tested. Because of such negative findings, research in this area has been halted. We believe that several aspects of both the preclinical studies and the RE-ALIGN trial should be critically reevaluated. In our opinion, 1 single trial with a single NOAC does not represent sufficient evidence for dismissing a therapeutic strategy, anticoagulation with NOACs, that has shown better safety and at least similar efficacy as warfarin in the setting of atrial fibrillation and venous thromboembolism,. Herein, we reevaluate this topic to identify the patient profile that has the greatest likelihood of benefit from some of the NOACs, with a focus on factor Xa inhibitors, thus providing some perspectives for basic and translational research

Metabolic syndrome and risk of cancer:a sistematic review and meta-analysis.

OBJECTIVE - Available evidence supports the emerging hypothesis that metabolic syndrome may be associated with the risk of some common cancers. We did a systematic review and meta-analysis to assess the association between metabolic syndrome and risk of cancer at different sites. RESEARCH DESIGN AND METHODS - We conducted an electronic search for articles published through October 2011 without restrictions and by reviewing reference lists from retrieved articles. Every included study was to report risk estimates with 95% CIs for the association between metabolic syndrome and cancer. RESULTS - We analyzed 116 datasets from 43 articles, including 38,940 cases of cancer. In cohort studies in men, the presence of metabolic syndrome was associated with liver (relative risk 1.43, P < 0.0001), colorectal (1.25, P < 0.001), and bladder cancer (1.10, P = 0.013). In cohort studies in women, the presence of metabolic syndrome was associated with endometrial (1.61, P = 0.001), pancreatic (1.58, P < 0.0001), breast postmenopausal (1.56, P = 0.017), rectal (1.52, P = 0.005), and colorectal (1.34, P = 0.006) cancers. Associations with metabolic syndrome were stronger in women than in men for pancreatic (P = 0.01) and rectal (P = 0.01) cancers. Associations were different between ethnic groups: we recorded stronger associations in Asia populations for liver cancer (P = 0.002), in European populations for colorectal cancer in women (P = 0.004), and in U.S. populations (whites) for prostate cancer (P = 0.001). CONCLUSIONS - Metabolic syndrome is associated with increased risk of common cancers; for some cancers, the risk differs betweens sexes, populations, and de finitions of metabolic syndrome

Multidimensional Functional Profiling of Human Neuropathogenic FOXG1 Alleles in Primary Cultures of Murine Pallial Precursors

FOXG1 is an ancient transcription factor gene mastering telencephalic development. A number of distinct structural FOXG1 mutations lead to the “FOXG1 syndrome”, a complex and heterogeneous neuropathological entity, for which no cure is presently available. Reconstruction of primary neurodevelopmental/physiological anomalies evoked by these mutations is an obvious pre-requisite for future, precision therapy of such syndrome. Here, as a proof-of-principle, we functionally scored three FOXG1 neuropathogenic alleles, FOXG1G224S, FOXG1W308X, and FOXG1N232S, against their healthy counterpart. Specifically, we delivered transgenes encoding for them to dedicated preparations of murine pallial precursors and quantified their impact on selected neurodevelopmental and physiological processes mastered by Foxg1: pallial stem cell fate choice, proliferation of neural com-mitted progenitors, neuronal architecture, neuronal activity, and their molecular correlates. Briefly, we found that FOXG1G224S and FOXG1W308X generally performed as a gain-and a loss-of-function-allele, respectively, while FOXG1N232S acted as a mild loss-of-function-allele or phenocopied FOXG1WT . These results provide valuable hints about processes misregulated in patients heterozygous for these mutations, to be re-addressed more stringently in patient iPSC-derivative neuro-organoids. Moreover, they suggest that murine pallial cultures may be employed for fast multidimensional profiling of novel, human neuropathogenic FOXG1 alleles, namely a step propedeutic to timely delivery of therapeutic precision treatments

Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory bulbectomized rats: evaluation of possible serotonergic and dopaminergic underlying mechanisms

Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX) model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed altered voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 μg/kg/infusion). To this aim, olfactory-bulbectomized (OBX) and sham-operated (SHAM) Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous [fixed ratio 1 (FR-1)] schedule of reinforcement in 2 h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behavior after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5-10 mg/kg), did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg) did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2) reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive-like state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats

Neural Networks, Logistic Regression, and Calibration: A Reply

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68566/2/10.1177_0272989X9801800414.pd

Non-monotonic current-to-rate response function in a novel integrate-and-fire model neuron

A novel integrate-and-fire model neuron is proposed to account for a non-monotonic f-I response function, as experimentally observed. As opposed to classical forms of adaptation, the present integrate- and-fire model the spike-emission process incorporates a state - dependent inactivation that makes the probability of emitting a spike decreasing as a function of the mean depolarization level instead of the mean firing rate. \ua9 Springer-Verlag Berlin Heidelberg 2002

Ruptured Brain Arteriovenous Malformations: Surgical Timing and Outcomes-A Retrospective Study of 25 Cases

Background One important problem in treatment of ruptured brain arteriovenous malformations (bAVMs) is surgical timing. The aim of the study was to understand which parameters affect surgical timing and outcomes the most. Materials and Methods Between January 2010 and December 2018, 25patients underwent surgery for a ruptured bAVM at our institute. Intracerebral hemorrhage (ICH) score was used to evaluate hemorrhage severity, while Spetzler-Martin scale for AVM architecture. We divided patients in two groups: early surgery and delayed surgery. The modified Rankin Scale (mRS) evaluated the outcomes. Results Eleven patients were in the early surgery group: age 38 ± 18 years, Glasgow Coma Scale (GCS) 7.64 ± 2.86, ICH score 2.82 ± 0.71, hematoma volume 45.55 ± 23.21 mL. Infratentorial origin of hemorrhage was found in 27.3% cases; AVM grades were I to II in 82%, III in 9%, and IV in 9% cases. Outcome at 3 months was favorable in 36.4% cases and in 54.5% after 1 year. Fourteen patients were in the delayed surgery group: age 41 ± 16 years, GCS 13.21 ± 2.39, ICH score 1.14 ± 0.81, hematoma volume 29.89 ± 21.33 mL. Infratentorial origin of hemorrhage was found in 14.2% cases; AVM grades were I to II in 50% and III in 50%. Outcome at 3 months was favorable in 78.6% cases and in 92.8% after 1 year. Conclusions The early outcome is influenced more by the ICH score, while the delayed outcome by Spetzler-Martin grading. These results suggest that it is better to perform surgery after a rest period, away from the hemorrhage when possible. Moreover, this study suggests how in young patient with a high ICH score and a low AVM grade, early surgery seems to be a valid and feasible therapeutic strategy

Modulation of coordinated activity across cortical layers by plasticity of inhibitory synapses

Louren\ue7o et al. demonstrate that burst firing of layer 5 pyramidal neurons (PNs) induces long-term potentiation of inhibition (LTPi). LTPi strongly affects PN input/output spikes, prevents transfer of information across cortical layers, and affects phase locking of PN firing to cognition-relevant rhythmic activity