Nanomedicines blocking adaptive signals in cancer cells overcome tumor TKI resistance.

Tumor resistance to tyrosine kinase inhibitors (TKIs) is an inexorable clinical event. The manipulation of adaptive changes in cancer cells while inhibiting the signaling pathways could be an effective strategy for overcoming TKI resistance toward reducing tumor relapse and prolonging survival. Here, we tested this approach by using polymeric nanomedicines delivering the pan-kinase inhibitor staurosporine (STS) to treat renal cell carcinoma (RCC) resistant to the multi-targeted TKI sunitinib.

Depressed, hypertense and sore: Long-term effects of fluoxetine, propranolol and diclofenac exposure in a top predator fish.

Pharmaceutical compounds are continuously released into the aquatic environment, resulting in their ubiquitous presence in many estuarine and coastal systems. As pharmaceuticals are designed to produce effects at very low concentrations and target specific evolutionary conserved pathways, there are growing concerns over their potential deleterious effects to the environment and specifically to aquatic organisms, namely in early life-stages. In this context, the long-term effects of exposure of juvenile meagre Argyrosomus regius to three different pharmaceuticals were investigated.

Effects of medium chain triglycerides supplementation on insulin sensitivity and beta cell function: A feasibility study.

Objective: Medium chain triglycerides (MCT) have unique metabolic properties which may improve insulin sensitivity (Si) and beta cell function but data in humans are limited. We conducted a 6-week clinical trial of MCT oil supplementation.

Methods: 22 subjects without diabetes (8 males, 14 females, mean ± standard error age 39±2.

Associations Between Maternal Thyroid Function in Pregnancy and Obstetric and Perinatal Outcomes.

Context: The effects of maternal subclinical hypothyroidism on pregnancy outcomes are not clear.

Objective: We aimed to assess potential associations between maternal thyrotropin (thyroid-stimulating hormone [TSH]) levels in pregnancy and obstetric and perinatal outcomes.

Design: Retrospective cohort study.

Designing and Evaluating a Digital Family Health History Tool for Spanish Speakers.

Digital family health history tools have been developed but few have been tested with non-English speakers and evaluated for acceptability and usability. This study describes the cultural and linguistic adaptation and evaluation of a family health history tool (VICKY: VIrtual Counselor for Knowing Your Family History) for Spanish speakers. In-depth interviews were conducted with 56 Spanish-speaking participants; a subset of 30 also participated in a qualitative component to evaluate the acceptability and usability of Spanish VICKY.

Does do not resuscitate (DNR) always mean DNR? Exploring DNR orders in small animal veterinary medicine.

This study investigated the use of and adherence to do not resuscitate (DNR) orders in small animal veterinary medicine. A link to a survey of respondent characteristics and clinical scenarios in which interpretation of the DNR order was questionable was distributed by e-mail to veterinarians in specialty and general practice, veterinary technicians, and veterinary students on veterinary e-mail lists in North America and Europe. Complete responses were obtained from 648 individuals, including 493 veterinarians, 58 veterinary technicians, and 97 veterinary students.

One-Pot Synthesis of PEG-Poly(amino acid) Block Copolymers Assembling Polymeric Micelles with PEG-Detachable Functionality.

Block copolymers composed of poly(ethylene glycol) (PEG) and poly(amino acids) (PAA) segments have shown exceptional features for developing biocompatible nanostructures. While the conventional methods for synthesizing PEG-PAA provide excellent control of the degree of polymerization and polydispersity, these protocols involve several steps, which increase the time and costs, and reduce the number of possible block copolymer designs. In this study, we developed a one-pot synthetic method for PEG-PAA block copolymers by doing sequential ring-opening polymerizations (ROP) of ethylene oxide (EO) and the -carboxyanhydrides (NCAs) of amino acids promoted by the organic base 1,1,3,3-tetramethylguanidine (TMG) as the catalyst.

Apoptotic Cell-Inspired Polymeric Particles for Controlling Microglial Inflammation toward Neurodegenerative Disease Treatment.

Apoptotic cells are known to suppress microglial inflammation in the brain by presenting phosphatidylserine. In this study, we newly designed polymeric particles that expose the anti-inflammatory site of phosphatidylserine to serve as an apoptotic cell-mimetic anti-inflammatory platform. The prepared anti-inflammatory particles showed no cytotoxicity and significantly inhibited the production of the inflammatory cytokine interleukin-6 against lipopolysaccharide stimulation in the microglia cell line MG6.

Unrestricted Direct Access to Physical Therapist Services Is Associated With Lower Health Care Utilization and Costs in Patients With New-Onset Low Back Pain.

Background: Low back pain (LBP) is one of the most prevalent conditions for which patients seek physical therapy in the United States. The American Physical Therapy Association categorizes direct access to physical therapist services into 3 levels: limited, provisional, and unrestricted.

Objective: The objective of this study was to evaluate the association of level of access to physical therapist services with LBP-related health care utilization and costs.

Evaluation of the milk clotting properties of an aspartic peptidase secreted by .

Traditionally, chymosin has been used for milk-clotting, but this naturally occurring enzyme is in short supply and its use has raised religious and ethical concerns. Because milk-clotting peptidases are a promising substitute for chymosin in cheese preparation, there is a need to find and test the specificity of these enzymes. Here, we evaluated the milk-clotting properties of an aspartic peptidase secreted by .

Single-Stranded DNA-Packaged Polyplex Micelle as Adeno-Associated-Virus-Inspired Compact Vector to Systemically Target Stroma-Rich Pancreatic Cancer.

Despite the rigidity of double-stranded DNA (dsDNA), its packaging is used to construct nonviral gene carriers due to its availability and the importance of its double-helix to elicit transcription. However, there is an increasing demand for more compact-sized carriers to facilitate tissue penetration, which may be easily fulfilled by using the more flexible single-stranded DNA (ssDNA) as an alternative template. Inspired by the adeno-associated virus (AAV) as a prime example of a transcriptionally active ssDNA system, we considered a methodology that can capture unpaired ssDNA within the polyplex micelle system (PM), an assembly of DNA and poly(ethylene glycol)--poly(l-lysine) (PEG-PLys).

Patient Possession of Excess Medication Supply in the VA: A Retrospective Database Study.

Background: Medication overlap leading to medication excess is a form of therapeutic duplication, itself a type of potentially inappropriate prescribing.

Objective: To determine the prevalence of potential medication excess in the Veterans Health Administration (VHA) and identify associated medication-level, patient-level, and system-level factors.

Research Design: A retrospective database study.

Observational retrospective study of the association of initial healthcare provider for new-onset low back pain with early and long-term opioid use.

Objective: This study examined the association of initial provider treatment with early and long-term opioid use in a national sample of patients with new-onset low back pain (LBP).

Design: A retrospective cohort study of patients with new-onset LBP from 2008 to 2013.

Setting: The study evaluated outpatient and inpatient claims from patient visits, pharmacy claims and inpatient and outpatient procedures with initial providers seen for new-onset LBP.

Health outcomes for Massachusetts infants after fresh versus frozen embryo transfer.

Objective: To compare neonatal health outcomes after fresh versus frozen ET (FET).

Design: Retrospective analysis of a population-based database of linked clinically assisted reproductive technology (ART) data with state vital records. Multivariable logistic regression was used to model the association between deliveries from fresh versus FET and adverse health outcomes, controlling for maternal characteristics.

Chemosensitizing Effect of Cernumidine Extracted from Solanum cernuum on Bladder Cancer Cells in Vitro.

Cernumidine (CER) is a guanidinic alkaloid isolated from Solanum cernuum leaves. In this work, we investigated the cytotoxicity, chemosensitizing effect of cernumidine to cisplatin (cDDP) and the possible mechanism of action of the combination on bladder cancer cells. Cernumidine showed cytotoxicity and could sensitize bladder cancer cells to cisplatin.

Hospitalization before and after delivery in fertile, subfertile, and ART-treated women.

Purpose: Pre-pregnancy and post-delivery hospitalizations were compared as markers for health among women who conceived using assisted reproductive technology (ART), non-ART medically assisted reproduction (MAR), no treatment (unassisted subfertile), and who were fertile.

Methods: We analyzed hospital discharge data linked to Massachusetts birth certificates from 2004 to 2013 within 5 years prior to pregnancy and 8-365 days post-delivery. ART deliveries were linked from a national ART database; MAR deliveries had fertility treatment but not ART; unassisted subfertile women had subfertility but no ART or MAR; and fertile women had none of these.

Frailty and Function in Heart Failure: Predictors of 30-Day Hospital Readmission?

Background And Purpose: Although there have been decreases noted in 30-day readmission rates for persons with heart failure since enactment of the Hospital Readmissions Reduction Program, costs related to heart failure readmissions remain high. Consequently, there is a need to better identify persons with heart failure who are at risk for 30-day hospital readmission. Therefore, this study aimed to compare the ability of measures of function and frailty to predict 30-day hospital readmissions for adults 65 years and older with heart failure.

Synergistic Effects of Climate Change and Marine Pollution: An Overlooked Interaction in Coastal and Estuarine Areas.

Coastal areas have been increasingly affected by human activities, marine pollution and climate change are among the most important pressures affecting these environments. Human-induced pressures occur in a cumulative way and generate additive, antagonistic or synergistic effects. Knowledge on synergistic effects is crucial to coastal zone management, since they may imply a change in human uses of these systems, as well as dedicated action plans in order to reduce hazards and environmental risks.

Ligand-Installed Nanocarriers toward Precision Therapy.

Development of drug-delivery systems that selectively target neoplastic cells has been a major goal of nanomedicine. One major strategy for achieving this milestone is to install ligands on the surface of nanocarriers to enhance delivery to target tissues, as well as to enhance internalization of nanocarriers by target cells, which improves accuracy, efficacy, and ultimately enhances patient outcomes. Herein, recent advances regarding the development of ligand-installed nanocarriers are introduced and the effect of their design on biological performance is discussed.

A scale to measure nurses' and providers' patient centered care in primary care settings.

Objectives: 1) Refine pilot scale measuring patients' experiences of outpatient nurses' and providers' care; 2) Determine variance explained by (a) pilot scale items and (b) "Survey of Health Experiences of Patients" (SHEP)/"Consumer Assessment of Health Care Providers and Systems" (CAHPS) scale items.

Methods: Randomly selected Veteran patients with recent visits with primary care outpatient nurses and providers (n = 1192) completed scales: pilot "PCC in Primary Care: Nurses and Providers Scale" and SHEP/CAHPS scale items. Factor analyses conducted using structural equation modeling (SEM), variance measurement using regression strategies.

Polymeric Micelles Loading Proteins through Concurrent Ion Complexation and pH-Cleavable Covalent Bonding for In Vivo Delivery.

Protein drugs have great potential as targeted therapies, yet their application suffers from several drawbacks, such as instability, short half-life, and adverse immune responses. Thus, protein delivery approaches based on stimuli-responsive nanocarriers can provide effective strategies for selectively enhancing the availability and activation of proteins in targeted tissues. Herein, polymeric micelles with the ability of encapsulating proteins are developed via concurrent ion complexation and pH-cleavable covalent bonding between proteins and block copolymers directed to pH-triggered release of the protein payload.

Pregnant women in treatment for opioid use disorder: Material hardships and psychosocial factors.

Background: While pregnant women in treatment for opioid use disorder (OUD) face considerable challenges, common material hardships- food insecurity and housing instability, known to negatively impact maternal-child health, have been inadequately researched within this population. This study describes food/housing hardships and evaluates associations with key psychosocial factors.

Methods: A single-site prospective study, 100 3rd trimester women receiving prenatal care and medication-assisted treatment for OUD were interviewed, including screening for food/housing hardships, depressive symptoms, intimate partner vulnerability; and self-reported post-traumatic stress disorder (PTSD) history.

Long-term exposure to increasing temperatures on scleractinian coral fragments reveals oxidative stress.

Global warming is leading to increases in tropical storms' frequency and intensity, allowing fragmentation of reef-forming coral species, but also to coral bleaching and mortality. The first level of organism's response to an environmental perturbation occurs at the cellular level. This study investigated the long-term oxidative stress on fragments of nine Indo-Pacific reef-forming coral species exposed for 60 days to increasing temperatures (30 °C and 32 °C) and compared results with control temperature (26 °C).

Health Literacy and Income Mediate Racial/Ethnic Asthma Disparities.

Background: Health literacy and socioeconomic status (SES) are associated with both race/ethnicity and asthma outcomes. The extent to which health literacy and SES mediate racial/ethnic asthma disparities is less clear.

Objective: To determine if health literacy and SES mediate racial/ethnic asthma disparities using advanced mediation analyses.