Clusters of a Few Bound Cofilins Sever Actin Filaments.

Cofilin is an essential actin filament severing protein that accelerates the assembly dynamics and turnover of actin networks by increasing the number of filament ends where subunits add and dissociate. It binds filament subunits stoichiometrically and cooperatively, forming clusters of contiguously-bound cofilin at sub-saturating occupancies. Filaments partially occupied with cofilin sever at boundaries between bare and cofilin-decorated segments.

Effects of Scale on Multimodal Deixis: Evidence From Quiahije Chatino.

As humans interact in the world, they often orient one another's attention to objects through the use of spoken demonstrative expressions and head and/or hand movements to point to the objects. Although indicating behaviors have frequently been studied in lab settings, we know surprisingly little about how demonstratives and pointing are used to coordinate attention in large-scale space and in natural contexts. This study investigates how speakers of Quiahije Chatino, an indigenous language of Mexico, use demonstratives and pointing to give directions to named places in large-scale space across multiple scales (local activity, district, state).

Structural basis of fast- and slow-severing actin-cofilactin boundaries.

Members of the ADF/cofilin family of regulatory proteins bind actin filaments cooperatively, locally change actin subunit conformation and orientation, and sever filaments at "boundaries" between bare and cofilin-occupied segments. A cluster of bound cofilin introduces two distinct classes of boundaries due to the intrinsic polarity of actin filaments, one at the "pointed" end side and the other at the "barbed" end-side of the cluster; severing occurs more readily at the pointed end side of the cluster ("fast-severing" boundary) than the barbed end side ("slow-severing" boundary). A recent electron-cryomicroscopy (cryo-EM) model of the slow-severing boundary revealed structural "defects" at the interface that potentially contribute to severing.

17β-estradiol reduces SARS-CoV-2 infection in vitro.

The COVID-19 has originated from Wuhan, China, in December 2019 and has been affecting the public health system, society, and economy in an unheard-of manner. There is no specific treatment or vaccine available for COVID-19. Previous data showed that men are more affected than women by COVID-19, then we hypothesized whether sex hormones could be protecting the female organism against the infection.

Pterostilbene influences glycemia and lipidemia and enhances antioxidant status in the liver of rats that consumed sucrose solution.

Aims: The present study investigated the potential effects of pterostilbene (PT) on glycemic and lipid profiles, fat storage, cardiovascular indices, and hepatic parameters of rats fed with sucrose solution.

Main Methods: 24 male Wistar rats received either drinking water or a 40% sucrose solution over a period of 140 days. After this period, animals were randomly allocated into four groups (n = 6): Control (C), C + Pterostilbene (PT), Sucrose (S), and S + PT.

Periodic changes in chemical composition and in vitro digestibility of locally available Gramineae feed resources in the Philippines.

Efficient utilization of locally available feed resources is needed for further development of livestock productions in the tropics. However, an inadequate supply of nourish grass is common, and limited information exists regarding the chemical composition and digestibility of locally available feed resources in the different season. There were few reliable information concerning nutritive value of Gramineae resources in dry and rainy seasons in the Philippines.

Chemometrics Applied in the Development of a Water Quality Indicator System for the Brazilian Amazon.

The objective of this work was to develop a method to calculate the water quality index (WQI) using chemometric methods. The study was carried out at the Curuá-Una hydroelectric power plant in the state of Pará in the Brazilian Amazon. Eight collection stations in four periods (winter, intermediate I, summer, and intermediate II) and 29 parameters were selected.

Self-Reported Variables as Determinants of Upper Limb Musculoskeletal Symptoms in Assembly Line Workers.

Background: Assembly lines work is frequently associated to work-related upper limb musculoskeletal disorders. The related disability and absenteeism make it important to implement efficient health surveillance systems. The main objective of this study was to identify self-reported variables that can determine work-related upper limb musculoskeletal symptoms-discomfort/pain-during a 6-month follow-up.

Lymphoangiocrine signals promote cardiac growth and repair.

Recent studies have suggested that lymphatics help to restore heart function after cardiac injury. Here we report that lymphatics promote cardiac growth, repair and cardioprotection in mice. We show that a lymphoangiocrine signal produced by lymphatic endothelial cells (LECs) controls the proliferation and survival of cardiomyocytes during heart development, improves neonatal cardiac regeneration and is cardioprotective after myocardial infarction.

αIIbβ3 variants in ten families with autosomal dominant macrothrombocytopenia: Expanding the mutational and clinical spectrum.

Background: Rare pathogenic variants in either the ITGA2B or ITGB3 genes have been linked to autosomal dominant macrothrombocytopenia associated with abnormal platelet production and function, deserving the designation of Glanzmann Thrombasthenia-Like Syndrome (GTLS) or ITGA2B/ITGB3-related thrombocytopenia.

Objectives: To describe a series of patients with familial macrothrombocytopenia and decreased expression of αIIbβ3 integrin due to defects in the ITGA2B or ITGB3 genes.

Methods: We reviewed the clinical and laboratory records of 10 Portuguese families with GTLS (33 patients and 11 unaffected relatives), including the functional and genetic defects.

Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells.

Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers (PSs) with different charges through different linking strategies; "Click" conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and "Lysine" conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.

Working time and upper limb musculoskeletal symptoms: a longitudinal study among assembly line workers.

This study followed assembly line workers during 7 months, comprising a 4-wk season holidays. The main purposes were to determine the potential effect of working time on the presence and intensity of upper limb musculoskeletal symptoms, as to verify the effect of 4 wk of job interruption in the upper limb musculoskeletal symptoms presence and intensity. Data was collected during 6 moments.

Minimum important change values for pain and disability: which is the best to identify a meaningful response in patients with chronic nonspecific low back pain?

Purpose: To examine the association between different minimum important change (MIC) values for pain and disability and a successful response in global perception of improvement in patients with chronic nonspecific low back pain (CNLBP).

Methods: A prospective cohort study was conducted. At baseline, all participants completed a sociodemographic and clinical questionnaire, the Numeric Pain Rating Scale and the Quebec Back Pain Disability Scale (QBPDS).

PODO447: a novel antibody to a tumor-restricted epitope on the cancer antigen podocalyxin.

Background: The success of new targeted cancer therapies has been dependent on the identification of tumor-specific antigens. Podocalyxin (Podxl) is upregulated on tumors with high metastatic index and its presence is associated with poor outcome, thus emerging as an important prognostic and theragnostic marker in several human cancers. Moreover, in human tumor xenograft models, Podxl expression promotes tumor growth and metastasis.

Antifungal activity of β-lapachone against azole-resistant spp. and its aspects upon biofilm formation.

The purpose of this study was to assess the antifungal effect of β-lapachone (β-lap) on azole-resistant strains of spp. in both planktonic and biofilm form. The antifungal activity of β-lap was evaluated by broth microdilution, flow cytometry and the comet assay.

Risk of pressure injury among users of emergency care units.

Objective: To identify the risk of pressure injury in patients of emergency care units.

Method: Descriptive, cross-sectional, and quantitative by applying the Braden scale to 377 patients from eight units in Paraná, between April and September 2016. Descriptive statistics and Spearman's correlation were used, with a significance of 0.

Multimodal strategy for hand hygiene in field hospitals of COVID-19.

Objective: Reflect and propose adaptations to the Multimodal Hand Hygiene Strategy for field hospitals, in the context of the COVID-19 pandemic.

Method: Reflective study, carried out in April 2020, based on the recommendations of the World Health Organization and the guide for the implementation of the five components of the Multimodal Strategy: system change related to infrastructure; training/education; evaluation and feedback; reminders in the workplace; and institutional security climate.

Results: The Multimodal Strategy, proposed for hospitals in general, can be adapted for field hospitals in order to reduce the transmission of the SARS-CoV-2 virus.

CIM6P/IGF-2 Receptor Ligands Reverse Deficits in Angelman Syndrome Model Mice.

Angelman syndrome (AS), a genetic disorder that primarily affects the nervous system, is characterized by delayed development, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy). No existing therapies are capable of comprehensively treating the deficits in AS; hence, there is an urgent need to identify new treatments.

Recommendations for hemodynamic monitoring for critically ill children-expert consensus statement issued by the cardiovascular dynamics section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC).

Background: Cardiovascular instability is common in critically ill children. There is a scarcity of published high-quality studies to develop meaningful evidence-based hemodynamic monitoring guidelines and hence, with the exception of management of shock, currently there are no published guidelines for hemodynamic monitoring in children. The European Society of Paediatric and Neonatal Intensive Care (ESPNIC) Cardiovascular Dynamics section aimed to provide expert consensus recommendations on hemodynamic monitoring in critically ill children.

Association between nursing work conditions and adverse events in neonatal and pediatric Intensive Care Units.

Objective: To investigate the association between intensive nursing staff's work conditions and the occurrence of adverse events in patients.

Method: Evaluative documentary study conducted in six public neonatal and pediatric Intensive Care Units from hospitals in Paraná state, from April 2017 to January 2018. The predictive variables concerning staff sizing and work environment were measured through the instruments Nursing Activities Score and Brazilian Nursing Work Index-Revised.

Improving the Pharmacodynamics and In Vivo Activity of ENPP1-Fc Through Protein and Glycosylation Engineering.

Enzyme replacement with ectonucleotide pyrophosphatase phospodiesterase-1 (ENPP1) eliminates mortality in a murine model of the lethal calcification disorder generalized arterial calcification of infancy. We used protein engineering, glycan optimization, and a novel biomanufacturing platform to enhance potency by using a three-prong strategy. First, we added new N-glycans to ENPP1; second, we optimized pH-dependent cellular recycling by protein engineering of the Fc neonatal receptor; finally, we used a two-step process to improve sialylation by first producing ENPP1-Fc in cells stably transfected with human α-2,6-sialyltransferase (ST6) and further enhanced terminal sialylation by supplementing production with 1,3,4-O-Bu ManNAc.

Incidental Finding of Tuberculosis During Evaluation for Delayed Wound Healing.

Cutaneous tuberculosis (TB) is an uncommon form of extrapulmonary TB that can be difficult to diagnose. The following case is about a 14-year-old female who was experiencing delayed wound healing after an incision and drainage of a chest wall abscess. A computed tomography scan of her chest obtained 2 months after the procedure revealed pulmonary findings consistent with TB.

Renally Excretable and Size-Tunable Silver Sulfide Nanoparticles for Dual-Energy Mammography or Computed Tomography.

Significant effort has been focused on developing renally-clearable nanoparticle agents since efficient renal clearance is important for eventual clinical translation. Silver sulfide nanoparticles (AgS-NP) have recently been identified as contrast agents for dual energy mammography, computed tomography (CT) and fluorescence imaging and probes for drug delivery and photothermal therapy with good biocompatibility. However, most AgS-NP reported to date are not renally excretable and are observed to accumulate and remain in the reticuloendothelial system (RES) organs, liver and spleen, for a long time, which could negatively impact their likelihood for translation.