Notes

Smokers' answers to be able to being addressed while smoking cigarettes in a out of doors voluntary smoke-free sector: A great observational review.
Epithelial polyploidization after injury is a conserved phenomenon recently shown to improve barrier restoration during wound healing. Whether lung injury can induce alveolar epithelial polyploidy is not known. We show that bleomycin injury induces alveolar type 2 cell (AT2) hypertrophy and polyploidy. AT2 polyploidization is also seen in short term ex vivo cultures, where AT2-to-AT1 transdifferentiation is associated with substantial binucleation due to failed cytokinesis. Both hypertrophic and polyploid features of AT2 cells can be attenuated by inhibiting the integrated stress response using the small molecule ISRIB. These data suggest that AT2 hypertrophic growth and polyploidization may be a feature of alveolar epithelial injury. Because AT2 cells serve as facultative progenitors for the distal lung epithelium, a propensity for injury-induced binucleation has implications for AT2 self-renewal and regenerative potential upon reinjury, which may benefit from targeting the integrated stress response.Over the past decades, a growing interest has emerged toward understanding the impact that the exposure to human suffering produces in mental health professionals, leading to the identification of three constructs vicarious traumatization (VT), compassion fatigue (CF), and secondary trauma (ST). However, little is known about how these conditions affect psychologists. A systematic review and a meta-analysis were conducted to examine the evidence about the effects of occupational exposure to trauma and suffering in studies that included psychologists among their samples. Fifty-two studies were included comprising 10,233 participants. JNK-IN-8 in vivo Overall, the results showed that most professionals did not experience relevant distress due to their work, yet some of them developed clinically significant symptoms (i.e., PTSD). However, solid conclusions could not be drawn due to the numerous methodological difficulties found in this research field (i.e., group heterogeneity, lack of comparison groups, and conceptual overlap). Thus, it is necessary to further investigate this topic with scientific rigor to understand these stressors and develop evidence-based interventions.
Autism spectrum disorders (ASDs) are neurodevelopmental diseases characterized by communication inabilities, social interaction impairment, repetitive behavior, as well as learning problems. Although the exact mechanism underlying this disease is still obscure, researchers believe that several factors play a significant role in its development and pathogenesis. Some authors have reported an association between adipokines family and autism. C1q/TNF-related protein-1 (CTRP1) is a member of the adipokines family, and we hypothesized that this adipokine might have an influential role in the pathogenesis of ASDs. Since there is no specific marker for screening the disease, we evaluated CTRP1 as a potential marker for achieving this purpose.

Blood samples were collected from 82 (41 ASDs boys, 41 healthy boys as controls) children aged 5-7 years old. CTRP1 gene expression and CTRP1 serum level were measured by quantitative realtime-PCR and enzyme-linked immunosorbent assay methods, respectively.

It was found that CTRP1 is significantly elevated in autistic children in comparison to healthy controls, both at the gene expression level, as well as at the serum level; demonstrating a good diagnostic value with a good range of sensitivity and specificity for detecting ASDs.

CTRP1 expression is elevated in ASDs boys aged 5-7years old, suggesting a role for this adipokine in ASDs pathophysiology. Also, receiver operating characteristic curve analyses revealed that this adipokine could be utilized as a diagnostic biomarker for differentiating ASDs patients from healthy individuals along with other recently proposed biomarkers.
CTRP1 expression is elevated in ASDs boys aged 5-7 years old, suggesting a role for this adipokine in ASDs pathophysiology. Also, receiver operating characteristic curve analyses revealed that this adipokine could be utilized as a diagnostic biomarker for differentiating ASDs patients from healthy individuals along with other recently proposed biomarkers.Rationale Current therapies for obstructive sleep apnea (OSA) are limited by insufficient efficacy, compliance, or tolerability. An effective pharmacological treatment for OSA is warranted. Carbonic anhydrase inhibition has been shown to ameliorate OSA. Objectives To explore safety and tolerability of the carbonic anhydrase inhibitor sulthiame (STM) in OSA. Methods A 4-week double-blind, randomized, placebo-controlled dose-guiding trial was conducted in patients with moderate and/or severe OSA not tolerating positive airway pressure treatment. Measurements and Main Results Intermittent paresthesia was reported by 79%, 67%, and 18% of patients receiving 400 mg STM (n = 34), 200 mg STM (n = 12), and placebo (n = 22), respectively. Dyspnea was reported after 400 mg STM (18%). Six patients in the higher dose group withdrew because of adverse events. There were no serious adverse events. STM reduced the apnea-hypopnea index from 55.2 to 33.0 events/h (-41.0%) in the 400-mg group and from 61.1 to 40.6 events/h (-32.1%) after 200 mg (P  less then  0.001 for both). Corresponding placebo values were 53.9 and 50.9 events/h (-5.4%). The apnea-hypopnea index reduction threshold of ⩾50% was reached in 40% of patients after 400 mg, 25% after 200 mg, and 5% after placebo. Mean overnight oxygen saturation improved by 1.1% after 400 and 200 mg (P  less then  0.001 and P = 0.034, respectively). Patient-related outcomes were unchanged. Conclusions STM showed a satisfactory safety profile in moderate and/or severe OSA. STM reduced OSA, on average, by more than 20 events/h, one of the strongest reductions reported in a drug trial in OSA. Larger scale clinical studies of STM in OSA are justified. Clinical trial registered with www.clinicaltrialsregister.eu (2017-004767-13).Rationale There is growing evidence that chronic obstructive pulmonary disease (COPD) can be caused and exacerbated by air pollution exposure. Objectives To document the impact of short-term air pollution exposure on inflammation markers, proteases, and antiproteases in the lower airways of older adults with and without COPD. Methods Thirty participants (10 ex-smokers with mild to moderate COPD and 20 healthy participants [9 ex-smokers and 11 never-smokers]), with an average age of 60 years, completed this double-blinded, controlled, human crossover exposure study. Each participant was exposed to filtered air (control) and diesel exhaust (DE), in washout-separated 2-hour periods, in a randomly assigned order. Bronchoscopy was performed 24 hours after exposure to collect lavage. Cell counts were performed on blood and airway samples. ELISAs were performed to measure acute inflammatory proteins, matrix proteinases, and antiproteases in the airway and blood samples. Measurements and Main Results In former smokers with COPD, but not in the other participants, exposure to DE increased serum amyloid A (effect estimate, 1.67; 95% confidence interval [CI], 1.21-2.30; P = 0.04) and matrix metalloproteinase 10 (effect estimate, 2.61; 95% CI, 1.38-4.91; P = 0.04) in BAL. Circulating lymphocytes were increased after DE exposure (0.14 [95% CI, 0.05-0.24] cells × 109/L; P = 0.03), irrespective of COPD status. Conclusions A controlled human crossover study of DE exposure reveals that former smokers with COPD may be susceptible to an inflammatory response compared with ex-smokers without COPD or never-smoking healthy control participants. Clinical trial registered with www.clinicaltrials.gov (NCT02236039).
In the field of drug delivery, controlling the release of therapeutic substances at localized targets has become a primary focus of medical research, especially in the field of cancer treatment. Magnetic nanoparticles are one of the most promising drug carriers thanks to their biocompatibility and (super)paramagnetic properties. These properties allow for the combination between imaging modalities and specific release of drugs at target sites using either local stimulus (
. pH, conjugation of biomarkers, …) or external stimulus (
. external magnetic field).

This review provides an update on recent advances with the development of targeted drug delivery systems based on magnetic nanoparticles (MNPs). This overview focuses on active targeting strategies and systems combining both imaging and therapeutic modalities (
. theranostics). If most of the examples concern the particular case of cancer therapy, the possibility of using MNPs for other medical applications is also discussed.

The development of cle of drug at targeted locations mediated by various stimuli. Advances in the field should lead to the implementation of such systems into clinical trials, especially systems enabling drug tracking in the body.
Chromosomal translocations involving the mixed-lineage leukemia (MLL, KMT2A, MLL1) genes result in the production of MLL fusion proteins, which cause abnormal transcriptional regulation leading to acute leukemia (AL). Menin (MEN1) protein is essential for MLL to regulate the expression of related target genes. High-affinity interactions between the amino terminus of MLL proteins and Menin proteins are required to mediate the oncogenic transformation of MLL fusion proteins. Therefore, inhibition of Menin and MLL interaction is a potential therapeutic strategy for MLL rearrangement (MLL-r) leukemia and can provide a new choice for treatment of other diseases. Therefore, researchers have made great efforts to explore small-molecule Menin-MLL interaction inhibitors.

This review is to provide an overview of the patented Menin-MLL protein-protein interaction inhibitors from 2014 to 2021.

Menin-MLL interaction inhibitors have therapeutic potential in the treatment of acute leukemia, such as AML and ALL. SNDX-5613 and KO-539 have been granted orphan drug designation by the FDA for treatment of refractory/relapsed leukemia and AML, respectively. In addition, they are undergoing clinical evaluation for other indications. It is clear that Menin-MLL interaction inhibitors have promising benefits in the clinical treatment of leukemia and other diseases.
Menin-MLL interaction inhibitors have therapeutic potential in the treatment of acute leukemia, such as AML and ALL. SNDX-5613 and KO-539 have been granted orphan drug designation by the FDA for treatment of refractory/relapsed leukemia and AML, respectively. In addition, they are undergoing clinical evaluation for other indications. It is clear that Menin-MLL interaction inhibitors have promising benefits in the clinical treatment of leukemia and other diseases.
We examine individuals' ability to detect social bots among Twitter personas, along with participant and persona features associated with that ability.

Social media users need to distinguish bots from human users. We develop and demonstrate a methodology for assessing those abilities, with a simulated social media task.

We analyze performance from a signal detection theory perspective, using a task that asked lay participants whether each of 50 Twitter personas was a human or social bot. We used the agreement of two machine learning models to estimate the probability of each persona being a bot. We estimated the probability of participants indicating that a persona was a bot with a generalized linear mixed-effects model using participant characteristics (social media experience, analytical reasoning, and political views) and stimulus characteristics (bot indicator score and political tone) as regressors.

On average, participants had modest sensitivity (d') and a criterion that favored responding "human.
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