Decreased Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 Activity in a Rat Model of Absence Epilepsy and the Effect of ZD7288, an Ih Inhibitor, on the Spike-and-Wave Discharges

<b><i>Introduction:</i></b> Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents of <i>Ih</i> and absence epilepsy seizures are associated, but studies reveal differential results. <b><i>Objective:</i></b> In our study, we aimed to investigate the role of the HCN channels on the expression of spike-and-wave discharges (SWDs) using the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model. <b><i>Methods:</i></b> HCN isoform levels from isolated brains of both naïve nonepileptic Wistar and GAERS groups were evaluated by enzyme-linked immunosorbent assay. ZD7288, an <i>Ih</i> inhibitor as well as an HCN channel antagonist, was administered intracerebroventricularly to the adult GAERS groups, and to evaluate their SWD activities, electroencephalography was recorded. The effect of ZD7288 on the cumulative total duration and number of SWDs and the mean duration of each SWD complex was evaluated. <b><i>Results:</i></b> The HCN2 levels in the cortex and hippocampus of the GAERS group were lower compared to the naïve nonepileptic Wistar group (<i>p</i> &#x3c; 0.05). ZD7288 increased the number of SWDs at the 20th and 120th min with the highest administered dose of 7 μg (<i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> The <i>Ih</i> inhibitor ZD7288 increased the number of SWDs in a genetic absence epilepsy rat model, although this increase may not be significant due to the inconsistent time-dependent effects. In GAERS, the cortical and hippocampal HCN2 channel levels were significantly lower compared to the control group. Further studies are needed with higher doses of ZD7288 to determine if the effects will increase drastically.

Awake prone positioning in nonintubated spontaneous breathing ICU patients with acute hypoxemic respiratory failure (PRONELIFE)—protocol for a randomized clinical trial

Background It is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation-related complications. Design and methods The PRONELIFE study is an investigator-initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all-cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning. Discussion The PRONELIFE study is among the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation—patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible—however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study have the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Trial registration ISRCTN ISRCTN11536318. Registered on 17 September 2021. The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).

INTERACTION OF TOBACCO ABUSE WITH OTHER CONVENTIONAL RISK FACTORS OF CARDIOVASCULAR RISK - SYNERGISTIC IMPACT OR AN INDEPENDENT MENACE?

Objectives: To determine the prevalence, patterns and behavioural attributes of tobacco abuse in patients of acute coronary syndrome (ACS). Furthermore, to assess the interaction of tobacco abuse with other conventional risk factors of cardiovascular disease (CVD). Methodology: This observational study included 230 consecutive patients with ACS. Data was collected regarding total duration and extent of tobacco consumption, “tobacco addiction” and various behavioural patterns related to it. Risk factors profile was acquired for hypertension, diabetes, obesity, family history of premature CVD and dyslipidemia. Odds ratios (OR) with 95% confidence intervals (CI) for these risk factors were calculated for tobacco abusers compared to non-abusers. Results: Among the study population, 63(27.4%) were active tobacco users. Urban residents had lesser odds of being tobacco abusers compared to non-urban residents (0.49, [0.27 – 0.89]). Tobacco abusers had a lower prevalence of hypertension compared to non-abusers (0.44 [0.24 – 0.81]). A similar trend was observed for diabetes, obesity and dyslipidemia, however, the differences could not reach significance thresholds. Cigarette smoking was the commonest mode of tobacco consumption (90.5%). “Tobacco addiction” could be attributed to 84.1% of abusers. Most (82.5%) were willing to give up tobacco abuse and 63.3% had already made attempts at quitting. Conclusion: About one-third of ACS patients were tobacco abusers with the majority being tobacco addicts. Tobacco abuse was observed to be independently implicated as a risk factor in ACS patients. Furthermore, tobacco abuse was inversely related to hypertension translating into a sub-multiplicative / additive impact of hypertension as a risk factor.

The Source Characteristics of the Mw6.4, 2016 Meinong Taiwan Earthquake from Teleseismic Data Using the Hybrid Homomorphic Deconvolution Method

The kinematic source rupture process of the 2016 Meinong earthquake (Mw = 6.4) in Taiwan was derived from apparent source time functions retrieved from teleseismic S-waves by using a refined homomorphic deconvolution method. The total duration of the rupture process was approximately 15 s, and one slip-concentrated area can be represented as the source model based on images representing static slip distribution. The rupture process began in a down-dip direction from the fault toward Tainan City, strongly suggesting that the rupture had a unilateral northwestern direction. The asperity with an area of approximately 15 × 15 km2 and the maximum slip of approximately 2 m were centered 12.8 km northwest of the hypocenter. Coseismic vertical deformation was calculated based on the source model. Compared with the results derived from InSAR (Interferometric Synthetic Aperture Radar) data, our results demonstrated that the location with maximum uplift was accurately well detected, but our maximum value was just approximately 0.4 times of the InSAR-derived value. It reveals that there are the other mechanisms to affect the vertical deformation, rather than only depending on the source model. At different depths, areas west, east, and north of the hypocenter maintained high values of Coulomb stress changes. This explains the mechanism behind aftershocks being triggered and provides a reference for predicting aftershock locations after a large earthquake. The estimated seismic spectral intensities, including spectral acceleration and velocity intensity (SIa and SIv), were derived. Source directivity effects caused damage to buildings, and we concluded that all damaged buildings were located within a SIa value of 400 gal. Destroyed buildings taller than seven floors were located in an area with a SIv value of 30 cm/s. These observations agree with those on damages caused by the 2010 Jiasian earthquake (ML 6.4) in Tainan, Taiwan.

Development of a bowel sound detector adapted to demonstrate the effect of food intake

Objective Bowel sounds (BS) carry useful information about gastrointestinal condition and feeding status. Interest in computerized bowel sound-based analysis has grown recently and techniques have evolved rapidly. An important first step for these analyses is to extract BS segments, whilst neglecting silent periods. The purpose of this study was to develop a convolutional neural network-based BS detector able to detect all types of BS with accurate time stamps, and to investigate the effect of food consumption on some acoustic features of BS with the proposed detector. Results Audio recordings from 40 volunteers were collected and a BS dataset consisting of 6700 manually labelled segments was generated for training and testing the proposed BS detector. The detector attained 91.06% and 90.78% accuracy for the validation dataset and across-subject test dataset, respectively, with a well-balanced sensitivity and specificity. The detection rates evaluated on different BS types were also satisfactory. Four acoustic features were evaluated to investigate the food effect. The total duration and spectral bandwidth of BS showed significant differences before and after food consumption, while no significant difference was observed in mean-crossing rate values. Conclusion We demonstrated that the proposed BS detector is effective in detecting all types of BS, and providing an accurate time stamp for each BS. The characteristics of BS types and the effect on detection accuracy is discussed. The proposed detector could have clinical application for post-operative ileus prognosis, and monitoring of food intake.

Do Games Reduce Math Anxiety? A meta-analysis.

In this paper, we meta-analyse the empirical evidence about the effectiveness of game-based interventions to reduce students' level of math anxiety. After performing a search for randomised controlled studies relevant to game-based intervention for math anxiety, 16 experimental studies with a total of 686 participants described in 11 peer-review articles met the selection criteria.A random-effects meta-analysis indicated a small and non-significant reduction of math anxiety (mean effect size ES=-0.32, CI=[-0.64,0.01]). The results were moderated by several factors: non-digital games were more effective, while digital games had a negligible mean effect size of $ES=-0.13$, $CI=[-0.33,0.08]$. The effect size was moderated also by the total duration of the intervention, to the advantage of longer interventions, and by the type of gameplay: games had a greater effect on math anxiety reduction when they promoted collaborative and social interactions. Such features were only present in non-digital games, while all the digital games analysed were single-player. In the final section of the paper, we discuss future possible research directions. The weak results obtained indicated the need to develop and test games explicitly designed for math anxious students. This will require the investigation of the relationship between game features and math anxiety through the analysis of the behaviour of anxious and non-anxious students at play. Among the features that an anxiety-aware game could employ, we suggest collaborative gameplay, social interactions, adaptability, features promoting intrinsic motivation and real-time measurements of math anxiety.

ARTE PANFLET�RIA: PORTO ALEGRE / Pamphlet art: Porto Alegre

?Arte Panflet�ria: Porto Alegre? � um relato que registra e desdobra uma das performances da s�rie hom�nima que realizo desde 2018. Vestindo roupas sem estampas e portando uma sacola repleta de alfinetes de seguran�a, caminho � procura das panfleteiras e dos panfleteiros.�Aceito todos os an�ncios e discursos distribu�dos nas ruas, oferecendo um ou dois alfinetes de seguran�a para que cada trabalhador(a) decida em que ponto de meu corpo seu panfleto deve ser anexado. Volto para casa somente quando meu corpo est� integralmente panfletado. A performance j� foi realizada seis vezes, entre 2018 e 2019, nas ruas do Rio de Janeiro, Porto Alegre, S�o Paulo, Recife e Buenos Aires, com dura��es que variaram de cinco a oito horas. Aqui, apresento o texto referente � a��o em Porto Alegre, em setembro de 2018, �s v�speras das elei��es, com dura��o total de sete horas.Palavras-chave:Escritos de artista. Performance. Mobilidade urbana. Cr�nica. Pr�tica ambulante.�Abstract?Pamplhet art: Porto Alegre? is a narrative that records and unfolds one of the performances of the homonymous serie that I?ve been conducting since 2018. Wearing clothes without prints and carrying a bag full of safety pins, I walk in search of the pamphleteers. I accept all the advertisements distributed in the streets, offering one or two safety pins so that each worker decides where on my body their flyer should be attached. I only return home when my body is fully pamphleted. The performance has already been performed six times, between 2018 and 2019, in the streets of Rio de Janeiro, Porto Alegre, S�o Paulo, Recife and Buenos Aires, with durations ranging between five and eight hours. Here, I present the text referring to the action in Porto Alegre, in September 2018, on the eve of the elections, with a total duration of seven hours.Keywords:Artist?s writings. Performance. Urban mobility. Chronic. Ambulant practice.

he Relationship between External and Internal Load during Elite Pre-season Friendly Basketball Games.

The aim of this study was to analyse the relationship between External Load (EL) and internal load (IL). Thirteen male basketball players competing at professional level in First Spanish Division (ACB) during six friendly games throughout the 2020/2021 preseason were monitored. The EL variables collected were movement load (ML), movement intensity (MI), box score time (BST), and total duration (TD)] while IL variables monitored were heart rate (HR), respiratory rate (RR), training impulse (TRIMP) and time invested in five HR zones. Very large to almost perfect correlation (r= 0.77-0.91) exists between EL variables except TD. In addition, HR, TRIMP and RR present large to very large correlation (r= 0.55-0.79) with all EL variables except TD. Monitoring HR-based variables would present general information and an estimated prediction of players EL which could allow basketball practitioners to prioritize time invested players internal/external load.

Diabetic Foot Osteomyelitis Caused by Francisella Tularensis

Purpose: A rare patient case of a diabetic foot osteomyelitis caused by Francisella tularensis is presented. Summary: A 69-year-old Caucasian female was admitted for the treatment of diabetic foot osteomyelitis. Her past medical history included type II diabetes mellitus, hypertension, chronic kidney disease, coronary artery disease, hypothyroidism, hyperuricemia and thyroidectomy. Empiric antimicrobial therapy consisting of clindamycin 600mg i.v. every 8hrs and impanel/cilastatin 200 mg i.v. every 6hrs hours was initiated immediately after admission. During her hospitalization, a pus sample from the infection site was taken for culture which showed a gram negative microorganism: Francisella tularensis. The strain was resistant to all the antibiotics tested with the exception of ciprofloxacin, ofloxacin, gentamicin, ceftazidime, cefepime, piperacillin/tazobactam and colistin. After culture results, the treatment regimen was changed to piperacillin/tazobactam 4.5g i.v. every 12hrs and ciprofloxacin 400mg i.v. every 12hrs. The patient continued to receive both antibiotics during hospitalization for 9 days with noted clinical improvement. The patient was discharged on piperacillin/tazobactam 4.5g i.v. every 12hrs and oral ciprofloxacin 500mg every 12hrs to complete a total duration of 6 weeks. Conclusion: This is the first reported case of a diabetic foot osteomyelitis caused by Francisella tularensis.

Pulse Methylprednisolone with Oral Prednisolone versus Adrenocorticotropic Hormone in Children with West Syndrome: a Randomized Controlled Trial

Background and Purpose: West syndrome is an epileptic encephalopathy of infancy. According to guidelines, adrenocorticotrophic hormone (ACTH) is probably effective for the short-term management of infantile spasm, but there is little uniformity in treatment due to variable response. This study has been done to evaluate the efficacy of pulse methylprednisolone as compared to ACTH in children with West syndrome.Methods: Children between 3 months to 24 months with the diagnosis of West syndrome were included and ACTH and pulse methyl prednisolone followed by oral prednisolone were given after randomization. Total duration of treatment was 6 weeks in both groups.Results: Total 87 children were enrolled; 12 patients lost in follow up. Finally, 43 received ACTH and 32 received pulse methylprednisolone. In pulse methylprednisolone group, 28.13% showed 50-80% response, 28.13% showed 80-99% response and 21.87% patients showed 100% response. In ACTH group, 41.86% showed 50-80% response, 25.58% showed 80-99% response and only 3 (6.97%) patients showed 100% response. Methylprednisolone treatment regimen did not cause significant or persistent adverse effects.Conclusions: Pulse methylprednisolone followed by oral prednisolone for 6 weeks is as effective as ACTH. Thus, methylprednisolone therapy can be an important alternative to ACTH.