Case report: First report of and coinfection in an immunocompromised patient.

Legionnaires' disease (LD) is a serious type of pneumonia, typically contracted by susceptible people through the inhalation of aerosols contaminated with . In this report, the first case of coinfection with - is described. A possible source of the Lp infection may be the hotel in Paris (France) where the patient had stayed before developing the symptoms.

p140Cap modulates the mevalonate pathway decreasing cell migration and enhancing drug sensitivity in breast cancer cells.

p140Cap is an adaptor protein involved in assembling multi-protein complexes regulating several cellular processes. p140Cap acts as a tumor suppressor in breast cancer (BC) and neuroblastoma patients, where its expression correlates with a better prognosis. The role of p140Cap in tumor metabolism remains largely unknown.

The role of tumor microenvironment in drug resistance: emerging technologies to unravel breast cancer heterogeneity.

Breast cancer is a highly heterogeneous disease, at both inter- and intra-tumor levels, and this heterogeneity is a crucial determinant of malignant progression and response to treatments. In addition to genetic diversity and plasticity of cancer cells, the tumor microenvironment contributes to tumor heterogeneity shaping the physical and biological surroundings of the tumor. The activity of certain types of immune, endothelial or mesenchymal cells in the microenvironment can change the effectiveness of cancer therapies via a plethora of different mechanisms.

p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response.

The p140Cap adaptor protein is a tumor suppressor in breast cancer associated with a favorable prognosis. Here we highlight a function of p140Cap in orchestrating local and systemic tumor-extrinsic events that eventually result in inhibition of the polymorphonuclear myeloid-derived suppressor cell function in creating an immunosuppressive tumor-promoting environment in the primary tumor, and premetastatic niches at distant sites. Integrative transcriptomic and preclinical studies unravel that p140Cap controls an epistatic axis where, through the upstream inhibition of β-Catenin, it restricts tumorigenicity and self-renewal of tumor-initiating cells limiting the release of the inflammatory cytokine G-CSF, required for polymorphonuclear myeloid-derived suppressor cells to exert their local and systemic tumor conducive function.

Advantages and drawbacks of helmet noninvasive support in acute respiratory failure.

Introduction: Non-invasive ventilation (NIV) represents an effective strategy for managing acute respiratory failure. Facemask NIV is strongly recommended in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with hypercapnia and acute cardiogenic pulmonary edema (ACPE). Its role in managing acute hypoxemic respiratory failure (AHRF) remains a debated issue.

SARS-CoV-2-The Role of Natural Immunity: A Narrative Review.

Background: Both natural immunity and vaccine-induced immunity to COVID-19 may be useful to reduce the mortality/morbidity of this disease, but still a lot of controversy exists.

Aims: This narrative review analyzes the literature regarding these two immunitary processes and more specifically: (a) the duration of natural immunity; (b) cellular immunity; (c) cross-reactivity; (d) the duration of post-vaccination immune protection; (e) the probability of reinfection and its clinical manifestations in the recovered patients; (f) the comparisons between vaccinated and unvaccinated as to the possible reinfections; (g) the role of hybrid immunity; (h) the effectiveness of natural and vaccine-induced immunity against Omicron variant; (i) the comparative incidence of adverse effects after vaccination in recovered individuals vs. COVID-19-naïve subjects.

Helmet noninvasive support for acute hypoxemic respiratory failure: rationale, mechanism of action and bedside application.

Introduction: Helmet noninvasive support may provide advantages over other noninvasive oxygenation strategies in the management of acute hypoxemic respiratory failure. In this narrative review based on a systematic search of the literature, we summarize the rationale, mechanism of action and technicalities for helmet support in hypoxemic patients.

Main Results: In hypoxemic patients, helmet can facilitate noninvasive application of continuous positive-airway pressure or pressure-support ventilation via a hood interface that seals at the neck and is secured by straps under the arms.

Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression.

Cholesterol is an essential lipid primarily synthesized in the liver through the mevalonate pathway. Besides being a precursor of steroid hormones, bile acid, and vitamin D, it is an essential structural component of cell membranes, is enriched in membrane lipid rafts, and plays a key role in intracellular signal transduction. The lipid homeostasis is finely regulated end appears to be impaired in several types of tumors, including breast cancer.

miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression.

MicroRNAs (miRNAs) are small, non-coding RNAs about 22 nucleotides in length that regulate the expression of target genes post-transcriptionally, and are highly involved in cancer progression. They are able to impact a variety of cell processes such as proliferation, apoptosis and differentiation and can consequently control tumor initiation, tumor progression and metastasis formation. miRNAs can regulate, at the same time, metabolic gene expression which, in turn, influences relevant traits of malignancy such as cell adhesion, migration and invasion.

Hemodynamic response to positive end-expiratory pressure and prone position in COVID-19 ARDS.

Background: Use of high positive end-expiratory pressure (PEEP) and prone positioning is common in patients with COVID-19-induced acute respiratory failure. Few data clarify the hemodynamic effects of these interventions in this specific condition. We performed a physiologic study to assess the hemodynamic effects of PEEP and prone position during COVID-19 respiratory failure.

Docking Protein p130Cas Regulates Acinar to Ductal Metaplasia During Pancreatic Adenocarcinoma Development and Pancreatitis.

Background & Aims: Acinar to ductal metaplasia is the prerequisite for the initiation of Kras-driven pancreatic ductal adenocarcinoma (PDAC), and candidate genes regulating this process are emerging from genome-wide association studies. The adaptor protein p130Cas emerged as a potential PDAC susceptibility gene and a Kras-synthetic lethal interactor in pancreatic cell lines; however, its role in PDAC development has remained largely unknown.

Methods: Human PDAC samples and murine Kras-dependent pancreatic cancer models of increasing aggressiveness were used.

p130Cas/ and p140Cap/ Adaptors: The Yin Yang in Breast Cancer?

p130Cas/ is an adaptor protein devoid of any enzymatic or transcriptional activity, whose modular structure with various binding motifs, allows the formation of multi-protein signaling complexes. This results in the induction and/or maintenance of signaling pathways with pleiotropic effects on cell motility, cell adhesion, cytoskeleton remodeling, invasion, survival, and proliferation. Deregulation of p130Cas/ adaptor protein has been extensively demonstrated in a variety of human cancers in which overexpression of p130Cas/BCAR1 correlates with increased malignancy.

Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial.

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19.

Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone.

Design, Setting, And Participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200).

The N-terminal domain of the adaptor protein p140Cap interacts with Tiam1 and controls Tiam1/Rac1 axis.

The p140Cap adaptor protein, encoded by the gene, negatively controls tumor progression, as demonstrated in the subgroup of -amplified breast cancers and in neuroblastoma patients, where high p140Cap expression predicts a decreased probability of developing metastasis, with a significantly prolonged survival. In NeuT mice, a preclinical model or Her2-positive breast cancer, we previously reported that p140Cap counteracts Her2-dependent breast cancer progression, associating with the specific Rac1 Guanine Nucleotide Exchange Factor, Tiam1, and limiting the activation of both Tiam1 and Rac1. Here, we show that in TUBO breast cancer cells derived from the NeuT tumors, p140Cap expression causes Tiam1 redistribution along the apicobasal junctional axis.

Thromboelastography clot strength profiles and effect of systemic anticoagulation in COVID-19 acute respiratory distress syndrome: a prospective, observational study.

Objective: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated.

The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness.

The p140Cap adaptor protein is a scaffold molecule encoded by the SRCIN1 gene, which is physiologically expressed in several epithelial tissues and in the neurons. However, p140Cap is also strongly expressed in a significant subset of cancers including breast cancer and neuroblastoma. Notably, cancer patients with high p140Cap expression in their primary tumors have a lower probability of developing a distant event and ERBB2-positive breast cancer sufferers show better survival.

Tidal Volume Lowering by Instrumental Dead Space Reduction in Brain-Injured ARDS Patients: Effects on Respiratory Mechanics, Gas Exchange, and Cerebral Hemodynamics.

Background: Limiting tidal volume (V), plateau pressure, and driving pressure is essential during the acute respiratory distress syndrome (ARDS), but may be challenging when brain injury coexists due to the risk of hypercapnia. Because lowering dead space enhances CO clearance, we conducted a study to determine whether and to what extent replacing heat and moisture exchangers (HME) with heated humidifiers (HH) facilitate safe V lowering in brain-injured patients with ARDS.

Methods: Brain-injured patients (head trauma or spontaneous cerebral hemorrhage with Glasgow Coma Scale at admission < 9) with mild and moderate ARDS received three ventilatory strategies in a sequential order during continuous paralysis: (1) HME with V to obtain a PaCO within 30-35 mmHg (HME1); (2) HH with V titrated to obtain the same PaCO (HH); and (3) HME1 settings resumed (HME2).

Comparison of the Asleep-Awake-Asleep Technique and Monitored Anesthesia Care During Awake Craniotomy: A Systematic Review and Meta-analysis.

Awake craniotomy (AC) is the preferred surgical option for intractable epilepsy and resection of tumors adjacent to or within eloquent cortical areas. Monitored anesthesia care (MAC) or an asleep-awake-asleep (SAS) technique is most widely used during AC. We used a random-effects modeled meta-analysis to synthesize the most recent evidence to determine whether MAC or SAS is safer and more effective for AC.

Author Correction: Modeling ErbB2-p130Cas interaction to design new potential anticancer agents.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.