Characterization of Comments About bioRxiv and medRxiv Preprints.

Importance: Preprints have been increasingly used in biomedical science, and a key feature of many platforms is public commenting. The content of these comments, however, has not been well studied, and it is unclear whether they resemble those found in journal peer review. Objective: To describe the content of comments on the bioRxiv and medRxiv preprint platforms. Design, Setting, and Participants: In this cross-sectional study, preprints posted on the bioRxiv and medRxiv platforms in 2020 were accessed through each platform's application programming interface on March 29, 2021, and a random sample of preprints containing between 1 and 20 comments was evaluated independently by 3 evaluators using an instrument to assess their features and general content. Main Outcome and Measures: The numbers and percentages of comments from authors or nonauthors were assessed, and the comments from nonauthors were assessed for content. These nonauthor comments were assessed to determine whether they included compliments, criticisms, corrections, suggestions, or questions, as well as their topics (eg, relevance, interpretation, and methods). Nonauthor comments were also analyzed to determine whether they included references, provided a summary of the findings, or questioned the preprint's conclusions. Results: Of 52 736 preprints, 3850 (7.3%) received at least 1 comment (mean [SD] follow-up, 7.5 [3.6] months), and the 1921 assessed comments (from 1037 preprints) had a median length of 43 words (range, 1-3172 words). The criticisms, corrections, or suggestions present in 694 of 1125 comments (61.7%) were the most prevalent content, followed by compliments (n = 428 [38.0%]) and questions (n = 393 [35.0%]). Criticisms usually regarded interpretation (n = 286), methodological design (n = 267), and data collection (n = 238), while compliments were mainly about relevance (n = 111) and implications (n = 72). Conclusions and Relevance: In this cross-sectional study of preprint comments, topics commonly associated with journal peer review were frequent. However, only a small percentage of preprints posted on the bioRxiv and medRxiv platforms in 2020 received comments on these platforms. A clearer taxonomy of peer review roles would help to describe whether postpublication peer review fulfills them.

Behavioral manifestations in rodent models of autism spectrum disorder: protocol for a systematic review and network meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with severe social communication, interaction, and sensory processing impairments. Efforts to understand its etiology and pathophysiology are crucial for improving treatment and prevention measures. Preclinical models of ASD are essential for investigating the biological mechanisms and should present translatability potential. We aim to evaluate the consistency of the most commonly used rodent models of ASD in displaying autistic-like behavior through a systematic review and meta-analysis. METHODS: This review will focus on the most frequently used autism models, surveying studies of six genetic (Ube3a, Pten, Nlgn3, Shank3, Mecp2, and Fmr1), three chemically induced (valproic acid (VPA), lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly(I:C))), and one inbred model (BTBR T+ Itpr3tf/J mouse strain). Two independent reviewers will screen the records. Data extraction of behavioral outcomes and risk of bias evaluation will be performed. We will conduct a meta-analysis whenever at least five studies investigate the same model and behavioral outcome. We will also explore the heterogeneity and publication bias. Network meta-analyses are planned to compare different models. DISCUSSION: By shortening the gap between animal behavior and human endophenotypes or specific clinical symptoms, we expect to help researchers on which rodent models are adequate for research of specific behavioral manifestations of autism, which potentially require a combination of them depending on the research interest. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021226299 .

Acute cylindrospermopsin exposure: Pulmonary and liver harm and mitigation by dexamethasone.

Cylindrospermopsin (CYN) is a cyanotoxin of increasing worldwide environmental importance as it can harm human beings. Dexamethasone is a steroidal anti-inflammatory agent. Thus, we aimed at evaluating the pulmonary outcomes of acute CYN intoxication and their putative mitigation by dexamethasone. Male BALB/c mice received intratracheally a single dose of saline or CYN (140 µg/kg). Eighteen hours after exposure, mice instilled with either saline solution (Ctrl) or CYN were intramuscularly treated with saline (Tox) or 2 mg/kg dexamethasone (Tox + dexa) every 6 h for 48 h. Pulmonary mechanics was evaluated 66 h after instillation using the forced oscillation technique (flexiVent) to determine airway resistance (RN), tissue viscance (G) and elastance (H). After euthanasia, the lungs were removed and separated for quantification of CYN, myeloperoxidase activity and IL-6 and IL-17 levels plus histological analysis. CYN was also measured in the liver. CYN increased G and H, alveolar collapse, PMN cells infiltration, elastic and collagen fibers, activated macrophages, peroxidase activity in lung and hepatic tissues, as well as IL-6 and IL-17 levels in the lung. Tox + Dexa mice presented total or partial reversion of the aforementioned alterations. Briefly, CYN impaired pulmonary and hepatic characteristics that were mitigated by dexamethasone.

Variable Ventilation Associated With Recruitment Maneuver Minimizes Tissue Damage and Pulmonary Inflammation in Anesthetized Lung-Healthy Rats.

BACKGROUND: Recruitment maneuver and positive end-expiratory pressure (PEEP) can be used to counteract intraoperative anesthesia-induced atelectasis. Variable ventilation can stabilize lung mechanics by avoiding the monotonic tidal volume and protect lung parenchyma as tidal recruitment is encompassed within the tidal volume variability. METHODS: Forty-nine (7 per group) male Wistar rats were anesthetized, paralyzed, and mechanically ventilated. A recruitment maneuver followed by stepwise decremental PEEP titration was performed while continuously estimating respiratory system mechanics using recursive least squares. After a new recruitment, animals were ventilated for 2 hours in volume-control with monotonic (VCV) or variable (VV) tidal volumes. PEEP was adjusted at a level corresponding to the minimum elastance or 2 cm H2O above or below this level. Lungs were harvested for histologic analysis (left lung) and cytokines measurement (right lung). Seven animals were euthanized before the first recruitment as controls. RESULTS: A time-dependent increase in respiratory system elastance was observed and significantly minimized by PEEP (P < .001). Variable ventilation attenuated the amount of concentrations of proinflammatory mediators in lung homogenate: neutrophil cytokine-induced neutrophil chemoattractant 1 (VV = 40 ± 5 and VCV = 57 ± 8 pg/mg; P < .0001) and interleukin-1ß (VV = 59 ± 25 and VCV = 261 ± 113 pg/mg; P < .0001). Variable ventilation was also associated with lower structural lung parenchyma damage. Significant reductions in air fraction at dorsal and caudal lung regions were observed in all ventilated animals (P < .001). CONCLUSIONS: Variable ventilation was more protective than conventional ventilation within the applied PEEP levels.

Electrocardiographic evaluation of healthy dogs treated with ophthalmic solution of timolol maleate 0.5%: preliminary study / Avaliação eletrocardiográfica de cães clinicamente hígidos sob tratamento com solução oftálmica de maleato de timolol 0.5%: estudo preliminar

Timolol maleate 0.5% is a drug recommended for glaucoma treatment in dogs. After administration, it is absorbed to systemic circulation and being an antagonist of beta adrenergic receptors it has important systemic side effects on cardiac electrical conduction. The present study evaluated the modification caused by ophthalmic timolol 0.5% in the electrocardiogram. Six clinically normal dogs were selected to participate in two different ophthalmic treatments: in the first one, a placebo (hypromellose 0.5%) was used and in the second one, timolol 0.5% was administered. Each solution was applied twice a day, for 14 days. The electrocardiographic parameters were measured in times: zero, 10, 60, 120, 240, 360 and 720 min after ocular solution instillation in first, seventh and 14th days of each treatment. The differences found in electrocardiogram were more evident between 120 and 240 min after instillation of timolol 0.5% when compared with placebo treatment. The rhythm was irregular, with sinus arrhythmia and sinus bradycardia moments. The RR and PR intervals lengthen notoriously (p 0.05) from the first day of timolol administration, and are more expressive in the 14th day of treatment. The QT interval demonstrated a few changes, just lengthening noticeably (p 0.05) in the 14th day of timolol application. The QTc interval did not show expressive change. Despite the changes in the electrocardiogram, no clinical manifestation related to beta-adrenoceptor antagonists were observed. One must consider, however, that the animals studied were healthy and thus, clinical signs could result from the changes implied by the use of timolol in animals with pre-existing heart disease. Therefore, cardiac assessment of patients prior to prescription of ophthalmic timolol is recommended.

O maleato de timolol 0,5% é um fármaco recomendado para tratamento de glaucoma em cães. Após instilação, e absorvido para a circulação sistêmica e por ser um antagonista beta-adrenérgico pode promover efeitos colaterais sistêmicos importantes sobre a condução elétrica cardíaca. No presente estudo, foi avaliada a alteração causada pelo timolol 0,5% oftálmico no eletrocardiograma. Foram selecionados seis cães hígidos para participar de dois tratamentos oftálmicos diferentes: no primeiro foi instilado placebo (hipromelose 0,5%) e no segundo utilizou-se timolol 0,5%. O colírio foi instilado a cada 12 horas por 14 dias. Os parâmetros eletrocardiográficos foram mensurados nos tempos: zero, 10, 60, 120, 240, 360 e 720 minutos após instilação da solução ocular nos dias primeiro, sétimo e décimo quarto de cada tratamento. As alterações eletrocardiográficas foram mais evidentes entre 120 e 240 minutos pós-instilação de timolol 0,5% quando comparado com o tratamento placebo. O ritmo foi irregular, com momentos de arritmia sinusal e bradicardia sinusal. Os intervalos RR e PR prolongaram significativamente (p 0,05) desde o primeiro dia de instilação de timolol, sendo o prolongamento mais expressivo no décimo quarto dia de tratamento. O intervalo QT demonstrou pouca variação, apenas prolongando significativamente (p 0,05) no décimo quarto dia de aplicação de timolol. O intervalo QTc não demonstrou alteração significativa (p > 0,05). Apesar das alterações encontradas, não foram observadas manifestações clínicas relacionadas ao timolol nos animais estudados. Deve-se considerar, porém, que os animais em questão eram hígidos e, portanto, as alterações decorrentes do uso do timolol em animais com cardiopatias preexistentes poderiam promover sinais clínicos, sendo recomendada a avaliação cardíaca de pacientes previamente à prescrição do timolol oftálmico.