Microtissue Culture Provides Clarity on the Relative Chondrogenic and Hypertrophic Response of Bone-Marrow-Derived Stromal Cells to TGF-β1, BMP-2, and GDF-5.

Chondrogenic induction of bone-marrow-derived stromal cells (BMSCs) is typically accomplished with medium supplemented with growth factors (GF) from the transforming growth factor-beta (TGF-β)/bone morphogenetic factor (BMP) superfamily. In a previous study, we demonstrated that brief (1-3 days) stimulation with TGF-β1 was sufficient to drive chondrogenesis and hypertrophy using small-diameter microtissues generated from 5000 BMSC each. This biology is obfuscated in typical large-diameter pellet cultures, which suffer radial heterogeneity.

A tumour-spheroid manufacturing and cryopreservation process that yields a highly reproducible product ready for direct use in drug screening assays.

If it were possible to purchase tumour-spheroids as a standardised product, ready for direct use in assays, this may contribute to greater research reproducibility, potentially reducing costs and accelerating outcomes. Herein, we describe a workflow where uniformly sized cancer tumour-spheroids are mass-produced using microwell culture, cryopreserved with high viability, and then cultured in neutral buoyancy media for drug testing. C4-2B prostate cancer or MCF-7 breast cancer cells amalgamated into uniform tumour-spheroids after 48 h of culture.

Cystic fibrosis-related mortality in the United States from 1999 to 2020: an observational analysis of time trends and disparities.

Cystic fibrosis transmembrane conductance regulator modulators have revolutionized cystic fibrosis (CF) care in the past decade. This study explores the CF-related mortality trends in the US from 1999 to 2020. We extracted CF-related mortality data from the CDC WONDER database.

Method for manufacture and cryopreservation of cartilage microtissues.

The financial viability of a cell and tissue-engineered therapy may depend on the compatibility of the therapy with mass production and cryopreservation. Herein, we developed a method for the mass production and cryopreservation of 3D cartilage microtissues. Cartilage microtissues were assembled from either 5000 human bone marrow-derived stromal cells (BMSC) or 5000 human articular chondrocytes (ACh) each using a customized microwell platform (the Microwell-mesh).

gene silencing dampens bone marrow stromal cell hypertrophy, but it also dampens chondrogenesis.

For bone marrow stromal cells (BMSC) to be useful in cartilage repair their propensity for hypertrophic differentiation must be overcome. A single day of TGF-β1 stimulation activates intrinsic signaling cascades in BMSCs which subsequently drives both chondrogenic and hypertrophic differentiation. TGF-β1 stimulation upregulates , a transcription factor known to contribute to hypertrophic differentiation, and remains upregulated even if TGF-β1 is subsequently withdrawn from the chondrogenic induction medium.

A wolf in sheep's clothing: Dogs confer an unrecognized risk for their immunocompromised master.

Bordetella bronchiseptica is a pleomorphic gram-negative coccobacillus that commonly causes respiratory tract infections in canines, felines, and swine. Human infections are rare. We report a case of Bordetella bronchiseptica pneumonia in a 67-year-old immunocompromised host.

Inhibition of BMP signaling with LDN 193189 can influence bone marrow stromal cell fate but does not prevent hypertrophy during chondrogenesis.

Bone morphogenetic protein (BMP) cascades are upregulated during bone marrow-derived stromal cell (BMSC) chondrogenesis, contributing to hypertrophy and preventing effective BMSC-mediated cartilage repair. Previous work demonstrated that a proprietary BMP inhibitor prevented BMSC hypertrophy, yielding stable cartilage tissue. Because of the significant therapeutic potential of a molecule capable of hypertrophy blockade, we evaluated the capacity of a commercially available BMP type I receptor inhibitor with similar properties, LDN 193189, to prevent BMSC hypertrophy.

Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial.

Background: Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints?

Methods And Findings: Multicentre double-blind randomized clinical trial.

Impact of Fellows-as-Teachers Workshops on Teaching Rounds: An Observational Study in an ICU.

Unlabelled: During training, fellows serve as teachers and role models for junior colleagues. Fellows-as-teachers curricula may support these roles, but little is known about their effectiveness and durability. We sought to measure the long-term effects on ICU rounds after administering fellows-as-teachers workshops.

Draft Genome Sequence of Bacillus lehensis M136, Isolated from the Manleluag Hyperalkaline Spring in Pangasinan, Philippines.

Here, we report the draft whole-genome sequence of M136, isolated from a hyperalkaline spring located in Pangasinan, Philippines. From 24 scaffolds, the total genome assembly length is 3,985,437 bp. Industrially important genes like cyclodextrin glycosyltransferase (CGTase) and proteases were detected in this draft genome.

Tumour necrosis factor (TNF) inhibitor-induced isolated pleural granulomas: a rare adverse effect.

A 53-year-old man with a history of Crohn's disease on infliximab, presented with several weeks of cough and dyspnoea. He had a right-sided pleural effusion, found to be exudative with lymphocytic predominance. He underwent right-sided video-assisted thoracic surgery (VATS) with biopsies and pleurodesis.

Complex sleep apnea syndrome.

Complex sleep apnea is the term used to describe a form of sleep disordered breathing in which repeated central apneas (>5/hour) persist or emerge when obstructive events are extinguished with positive airway pressure (PAP) and for which there is not a clear cause for the central apneas such as narcotics or systolic heart failure. The driving forces in the pathophysiology are felt to be ventilator instability associated oscillation in PaCO2 arterial partial pressure of Carbon Dioxide, continuous cositive airway pressure (CPAP) related increased CO2 carbon dioxide elimination, and activation of airway and pulmonary stretch receptors triggering these central apneas. The prevalence ranges from 0.

Fabrication of porous hydroxyapatite scaffolds as artificial bone preform and its biocompatibility evaluation.

In this study, a novel porous hydroxyapatite scaffold was designed and fabricated to imitate natural bone through a multipass extrusion process. The conceptual design manifested unidirectional microchannels at the exterior part of the scaffold to facilitate rapid biomineralization and a central canal that houses the bone marrow. External and internal fissures were minimized during microwave sintering at 1,100 °C.

Biphasic calcium phosphate loading on polycaprolactone/poly(lacto-co-glycolic acid) membranes for improved tensile strength, in vitro biocompatibility, and in vivo tissue regeneration.

Electrospun polycaprolactone and poly(lacto-co-glycolide) membranes were loaded with biphasic calcium phosphate powder to facilitate osteoconductivity. Different concentrations of biphasic calcium phosphate powder were added to the polymer solution, and successful loading was confirmed by X-ray diffraction analysis, transmission electron microscope, and scanning electron microscope with energy-dispersive spectroscopy visualization. The effect of the added biphasic calcium phosphate on the polymer membrane was investigated in terms of the material's tensile strength and strain, in vitro cytocompatibility, and in vivo tissue regeneration.

Bioactive glass incorporation in calcium phosphate cement-based injectable bone substitute for improved in vitro biocompatibility and in vivo bone regeneration.

In this work, we fabricated injectable bone substitutes modified with the addition of bioactive glass powders synthesized via ultrasonic energy-assisted hydrothermal method to the calcium phosphate-based bone cement to improve its biocompatibility. The injectable bone substitutes was initially composed of a powder component (tetracalcium phosphate, dicalcium phosphate dihydrate and calcium sulfate dehydrate) and a liquid component (citric acid, chitosan and hydroxyl-propyl-methyl-cellulose) upon which various concentrations of bioactive glass were added: 0%, 10%, 20% and 30%. Setting time and compressive strength of the injectable bone substitutes were evaluated and observed to improve with the increase of bioactive glass content.

Assessing learning outcomes and cost effectiveness of an online sleep curriculum for medical students.

Objective: Sleep disorders are highly prevalent across all age groups but often remain undiagnosed and untreated, resulting in significant health consequences. To overcome an inadequacy of available curricula and learner and instructor time constraints, this study sought to determine if an online sleep medicine curriculum would achieve equivalent learner outcomes when compared with traditional, classroom-based, face-to-face instruction at equivalent costs.

Method: Medical students rotating on a required clinical clerkship received instruction in 4 core clinical sleep-medicine competency domains in 1 of 2 delivery formats: a single 2.

Fabrication and biocompatibility of novel bilayer scaffold for skin tissue engineering applications.

In this study, a novel bilayer scaffold composed of electrospun polycaprolactone and poly(lacto-co-glycolic acid) (PCL/PLGA) membrane and glutaraldehyde (3.5% v/v) cross-linked chitosan/gelatin hydrogel was fabricated using two methods: electrospinning of the membrane onto the lyophilized hydrogel (BS-1) and membrane underlaying and casting method (BS-2). The morphology of the fabricated scaffolds was examined by scanning electron microscope (SEM).

Preparation and characterization of electrospun PCL/PLGA membranes and chitosan/gelatin hydrogels for skin bioengineering applications.

In this study, two distinct systems of biomaterials were fabricated and their potential use as a bilayer scaffold (BS) for skin bioengineering applications was assessed. The initial biomaterial was a polycaprolactone/poly(lacto-co-glycolic acid) (PCL/PLGA) membrane fabricated using the electrospinning method. The PCL/PLGA membrane M-12 (12% PCL/10% PLGA, 80:20) displayed strong mechanical properties (stress/strain values of 3.

Upper esophageal sphincter and gastroesophageal junction pressure changes act to prevent gastroesophageal and esophagopharyngeal reflux during apneic episodes in patients with obstructive sleep apnea.

Background: Gastroesophageal reflux (GER) is thought to be induced by decreasing intraesophageal pressure during obstructive sleep apnea (OSA). However, pressure changes in the upper esophageal sphincter (UES) and gastroesophageal junction (GEJ) pressure during OSA events have not been measured. The aim of this study was to determine UES and GEJ pressure change during OSA and characterize the GER and esophagopharyngeal reflux (EPR) events during sleep.

Terminating motor events for TLESR are influenced by the presence and distribution of refluxate.

Transient lower esophageal sphincter relaxation (TLESR) is frequently associated with reflux events and terminates with a primary or secondary peristaltic wave. However, it is unclear whether the presence and properties of the refluxate affect TLESR-termination events. The aims of this study were to determine the pattern of terminating esophageal motor activity after TLESR in healthy subjects and factors affecting the type of terminating motor event.

The high prevalence of restless legs syndrome symptoms in liver disease in an academic-based hepatology practice.

Study Objectives: Survey-based epidemiologic studies suggest that restless legs syndrome (RLS) affects approximately 10% of the general population and can cause significantly reduced quality of life due to sleep disturbance. This condition is more prevalent in certain disease states, such as iron deficiency anemia, neuropathy, and renal insufficiency. No such prevalence data exists for RLS in liver disease.

Obstructive sleep apnea caused by carotid body tumor: case report.

Obstructive sleep apnea (OSA) results from a structural compromise of the upper airway combined with decrease in muscle tone during sleep. Overt upper airway pathology is rare, however a variety of pharyngeal tumors have been well described as a cause of OSA. We describe a case of a mass originating in the carotid body resulting in severe OSA with hypersomnia resistant to positive pressure ventilation.