. Conflicts in instrument invention at the Medici court: the pendulum clock, and the Accademia del Cimento.

This essay proposes that the only publication of the Accademia del Cimento, referred to as ,1 Accademia del Cimento, (Firenze: Per Giuseppe Cocchini, 1667). had as one of its main goals the celebration of the House of Medici's paternity of cutting-edge experiments and instruments during the reign of Grand Duke Ferdinando II. These included Ferdinando II's thermometers and hygrometers, Torricelli's experiment and barometer, and Galileo's pendulum as a clock-regulator.

Differential inflammatory conditioning of the bone marrow by acute myeloid leukemia and its impact on progression.

Inflammation promotes solid tumor progression, but how regulatory mechanisms of inflammation may affect leukemia is less well studied. Using annexin A5 (ANXA5), a calcium-binding protein known for apoptosis, which we discovered to be differentially expressed in the bone marrow microenvironment (BMM) of mice with acute myeloid (AML) vs chronic myeloid leukemia, as a model system, we unravel here a circuit in which AML-derived tumor necrosis factor α (TNF-α) dose-dependently reduces ANXA5 in the BMM. This creates an inflammatory BMM via elevated levels of prostaglandin E2 (PGE2).

Susceptibility of the Different Oxygen-Sensing Probes to Interferences in Respirometric Bacterial Assays with Complex Media.

Respirometric microbial assays are gaining popularity, but their uptake is limited by the availability of optimal O sensing materials and the challenge of validating assays with complex real samples. We conducted a comparative evaluation of four different O-sensing probes based on Pt-porphyrin phosphors in respirometric bacterial assays performed on standard time-resolved fluorescence reader. The macromolecular MitoXpress, nanoparticle NanO2 and small molecule PtGlc and PtPEG probes were assessed with cells in five growth media: nutrient broth (NB), McConkey (MC), Rapid Coliform ChromoSelect (RCC), M-Lauryl lauryl sulfate (MLS), and Minerals-Modified Glutamate (MMG) media.

Stem Cell Responsiveness to Imatinib in Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR-ABL fusion gene, which results from the Philadelphia chromosome. Since the introduction of tyrosine kinase inhibitors (TKI) such as imatinib mesylate (IM), the clinical outcomes for patients with CML have improved significantly. However, IM resistance remains the major clinical challenge for many patients, underlining the need to develop new drugs for the treatment of CML.

How Lung Volume Recruitment Maneuvers Enhance Respiratory Function in Multiple Sclerosis Patients: A Quasi-Randomized Pilot Study.

: In patients with multiple sclerosis (MS), a decrease in muscle strength can lead to limitations in pulmonary functions, potentially causing respiratory complications. To address these challenges, the lung volume recruitment (LVR) maneuver has emerged as a potential intervention. This study sought to evaluate the impact of a four-week LVR protocol on respiratory function in secondary progressive MS patients.

Development of a potency assay for CD34 cell-based therapy.

We have previously shown that intracardiac delivery of autologous CD34 cells after acute myocardial infarction (AMI) is safe and leads to long term improvement. We are now conducting a multicenter, randomized, controlled Phase I/IIb study in post-AMI to investigate the safety and efficacy of intramyocardial injection of expanded autologous CD34 cells (ProtheraCytes) (NCT02669810). Here, we conducted a series of in vitro studies characterizing the growth factor secretion, exosome secretion, gene expression, cell surface markers, differentiation potential, and angiogenic potential of ProtheraCytes clinical batches to develop a potency assay.

Distinct and targetable role of calcium-sensing receptor in leukaemia.

Haematopoietic stem cells (HSC) reside in the bone marrow microenvironment (BMM), where they respond to extracellular calcium [eCa] via the G-protein coupled calcium-sensing receptor (CaSR). Here we show that a calcium gradient exists in this BMM, and that [eCa] and response to [eCa] differ between leukaemias. CaSR influences the location of MLL-AF9 acute myeloid leukaemia (AML) cells within this niche and differentially impacts MLL-AF9 AML versus BCR-ABL1 leukaemias.

High frequency of gastrointestinal complaints, but insignificant prevalence of gluten-sensitive enteropathies in Brazilian fibromyalgia patients.

Introduction/objectives: Coeliac disease (CD) and non-coeliac gluten sensitivity (NCGS) cause symptoms like those seen in patients with fibromyalgia (FM) and functional gastrointestinal disorders. There is no consistent data on frequency of these symptoms and no study performed duodenal biopsies to investigate CD/NCGS in Brazilian FM patients. Therefore, we sought to verify the prevalence of CD/NCGS in FM patients and the association between gastrointestinal manifestations and FM symptoms.

Phosphoproteome Profiling of Klebsiella pneumoniae under Zinc-Limited and Zinc-Replete Conditions.

The bacterial pathogen Klebsiella pneumoniae causes nosocomial infections with the acquisition of multidrug resistance, impeding treatment options. This study investigated the effect of zinc limitation on the phosphoproteome of K. pneumoniae using quantitative mass spectrometry.

A telescopic paradox: the artisans of the Accademia del Cimento, their instruments and their (in)visibility.

The brief life of the Accademia del Cimento (1657-1667), the first known society with a purely experimental programme, is entangled with the most surprising advancements in the history of scientific instruments of that century, from the telescope to the microscope, the thermometer to the barometer, the hygrometer to the pendulum as a time-regulator, and more. The making of instruments at the Florentine court shows the interaction of princely, scholarly and artisanal actors. This paper explores this collaboration and shows how the supposed "invisibility' of artisans depended on their proximity to the academicians and princes, who mainly communicated verbally with them, directly or through middlemen.

Deciphering the Cardiovascular Potential of Human CD34 Stem Cells.

Ex vivo monitored human CD34 stem cells (SCs) injected into myocardium scar tissue have shown real benefits for the recovery of patients with myocardial infarctions. They have been used previously in clinical trials with hopeful results and are expected to be promising for cardiac regenerative medicine following severe acute myocardial infarctions. However, some debates on their potential efficacy in cardiac regenerative therapies remain to be clarified.

The molecular landscape of breast mucoepidermoid carcinoma.

Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare salivary gland-type tumor characterized by epidermoid, basaloid, intermediate, and/or mucinous cells arranged in solid and cystic patterns. Despite their triple-negative phenotype, breast MECs are generally considered low-risk malignancies but their biology is largely unexplored; therefore, guidelines for clinical management are lacking. Here, we sought to characterize the molecular landscape of breast MECs.

Heterosubstituted Derivatives of PtPFPP for O Sensing and Cell Analysis: Structure-Activity Relationships.

Biological applications of phosphorescent probes for sensing molecular oxygen (O) and bioimaging have gained popularity, but their choice is rather limited. We describe a family of new heterosubstituted phosphorescent bioprobes based on the Pt(II)-tetrakis(pentafluorophenyl)porphyrin (PtPFPP) dye. The probes are produced by simple click modification of its -fluorine atoms with thiols, such as 1/2-thio-glucose, thio-poly(ethylene glycol) (PEG), or cysteamine.

Impact of mesenchymal stromal cell-derived vesicular cargo on B-cell acute lymphoblastic leukemia progression.

Leukemia cells reciprocally interact with their surrounding bone marrow microenvironment (BMM), rendering it hospitable to leukemia cell survival, for instance through the release of small extracellular vesicles (sEVs). In contrast, we show here that BMM deficiency of pleckstrin homology domain family M member 1 (PLEKHM1), which serves as a hub between fusion and secretion of intracellular vesicles and is important for vesicular secretion in osteoclasts, accelerates murine BCR-ABL1+ B-cell acute lymphoblastic leukemia (B-ALL) via regulation of the cargo of sEVs released by BMM-derived mesenchymal stromal cells (MSCs). PLEKHM1-deficient MSCs and their sEVs carry increased amounts of syntenin and syndecan-1, resulting in a more immature B-cell phenotype and an increased number/function of leukemia-initiating cells (LICs) via focal adhesion kinase and AKT signaling in B-ALL cells.

A molecular reappraisal of matrix-producing breast metaplastic carcinoma highlighted by PLAG1 and MYC rearrangements.

Background: Very little is currently known about molecular alteration of matrix-producing carcinoma of the breast. However, the morphological similarity with other neoplasm with a myxo-chondroid component is remarkable. In this pilot study we evaluated the molecular alterations involving and genes in 12 cases of matrix producing carcinoma.

The differential role of the lipid raft-associated protein flotillin 2 for progression of myeloid leukemia.

Lipid raft-associated proteins play a vital role in membrane-mediated processes. The lipid microdomain-associated protein flotillin 2 (FLOT2), which has a scaffolding function, is involved in polarization, as well as in actin cytoskeletal organization of primitive and mature hematopoietic cells and has been associated with different malignancies. However, its involvement in myeloid leukemias is not well studied.

Correlation between Pre- and Post-Surgical Findings for Long-Term Neurocognitive and Behaviour Development Due to Posterior Fossa Pilocytic Astrocytomas: The Trend after 10 Years.

Objective: The objective of the present study was to selectively evaluate the long-term impact of posterior fossa pilocytic astrocytomas, which are known to be among the most benign forms of paediatric brain tumours on neurocognitive and behavioural functions.

Methods: Children that were operated on for a posterior fossa pilocytic astrocytoma in the Pediatric Neurosurgery Department of the Catholic University Medical School were selected according to the following criteria: (a) age > 5 years (in order to have a complete set of neurocognitive evaluations data), (b) ability to perform a complete set of tests before and after surgery, and (c) children that had a regular follow-up up to 10 years from the surgical treatment.

Results: Forty-three percent of the children selected for the present study showed a borderline IQ before surgery, which is a result corresponding to those previously reported in the literature for children affected by posterior fossa pilocytic astrocytomas; praxis and visual perception were the selective functions that were more frequently affected.

The age of the bone marrow microenvironment influences B-cell acute lymphoblastic leukemia progression via CXCR5-CXCL13.

B-cell acute lymphoblastic leukemia (B-ALL) occurs most commonly in children, whereas chronic myeloid leukemia is more frequent in adults. The myeloid bias of hematopoiesis in elderly individuals has been considered causative, but the age of the bone marrow microenvironment (BMM) may be contributory. Using various murine models of B-ALL in young vs old mice, we recapitulated B-ALL preponderance in children vs adults.