Improved depressive symptoms, and emotional regulation and reactivity, in individuals with obstructive sleep apnea after short- and long-term CPAP therapy use.

Obstructive Sleep Apnoea (OSA) is associated with high rates of depression; however, if and how treatment of OSA improves depressive symptoms is unclear. To further understand this link we considered the role of emotional regulation - the ability to control and express our emotional responses - thought to be a central component of depression. This study aimed to assess changes in depressive symptoms and emotional responses in individuals with OSA after 4- and 12-months of continuous positive airway pressure (CPAP) treatment. One-hundred and twenty-one OSA participants (50 female, Mage = 51.93; mean AHI = 36.27) were recruited from a tertiary clinical sleep service prior to CPAP initiation, and randomised to either a CPAP group or a 4 month wait-list group. Participants completed the Center for Epidemiological Studies Depression Scale, the Emotional Reactivity Scale and the Difficulties in Emotion Regulation Scale at baseline, and 1-, 2-, and 4-months follow-up. The CPAP group also completed the questionnaires 12-months after CPAP initiation. CPAP use at 1 month and 12 months was 5.1h/night and 4.9h/night, respectively. Significant improvements in depressive symptoms, emotional regulation and reactivity, and subjective sleepiness were observed after 4 months in both groups, however, the within group changes were only significant for those using CPAP. After 12-months of CPAP treatment, these improvements were maintained. There was no association between CPAP treatment adherence and improvements in any outcome. CPAP treatment for 12 months may reduce symptoms of depression and improve emotional regulation in individuals with OSA.

Tailoring cognitive behavioural therapy for insomnia across contexts, conditions, and individuals: What do we know, where do we go?

Cognitive behavioural therapy for insomnia (CBT-I) is considered the front-line treatment for insomnia. Despite the demonstrated effectiveness of CBT-I, it is necessary to consider how CBT-I may be tailored to different individuals. The purpose of the present review is to provide a summary of literature on tailoring CBT-I to different individuals and provide directions for future research. This review focused on the following domains of adaptation: (i) tailoring CBT-I components to individuals with comorbid mental or physical health conditions such as comorbid depression and pain; (ii) adapting CBT-I delivery for different contexts in which individuals exist, such as inpatient, educational, and different social/cultural settings, (iii) adapting CBT-I to specific individuals via case-formulation in clinical settings. We highlight current gaps in the exploration of tailored CBT-I, including a lack of research methodology to evaluate tailored interventions, a need for the integration of ongoing individualised assessment to inform treatment, and the necessary involvement of consumers and stakeholders throughout the research and treatment development process. Together, this review showed abundant adaptations in CBT-I already exist in the literature. Future research is needed in understanding when and how to apply adaptations in CBT-I and evaluate the benefits of these adaptations.

Strange themes in pandemic dreams: Insomnia was associated with more negative, anxious and death-related dreams during the COVID-19 pandemic.

Dreaming and insomnia are important markers of distress in times of crisis. Here, we present a longitudinal, mixed-methods study examining changes in dreaming between individuals with and without insomnia symptoms and their relationship to mental health during the COVID-19 pandemic. A global survey examining insomnia symptoms, dreams and mental health was launched in April 2020 and followed participants over 12 months. Of 2240 participants, 1009 (45%) reported dream changes at baseline. A higher proportion of participants with new-onset insomnia reported dream changes (55%) than those with pre-existing insomnia (45%) or good sleepers (36%). Overall, thematic analysis identified key dream change themes of increased dream activity, with participants dreaming vividly, in high-definition, and with a strong negative charge. Themes around survival, adjusting to pandemic life, meaning-making and poor sleep quality were also noted. Linguistic Inquiry Word Count showed that individuals with insomnia used more negative words to describe their dream changes than good sleepers. Specifically, the new-onset insomnia group used more anxious and death-related words than those who slept well. Notably, all groups experienced a significant reduction in dream activity by 3-month follow-up. Lastly, dream changes were associated with worse mental health symptoms over time, and this effect was more pronounced in individuals with insomnia. Our results highlight that insomnia symptoms, especially new-onset insomnia, are associated with more negative dream changes during collective stressful events, potentially compounding daytime distress and mental health symptoms over time. During times of crisis, dreaming and insomnia may reveal an important target for mental health interventions.

Insomnia is a key risk factor for persistent anxiety and depressive symptoms: A 12-month longitudinal cohort study during the COVID-19 pandemic.

BACKGROUND: Insomnia is a risk factor for affective disorders. This study examined whether individuals with insomnia symptoms early in the pandemic, either pre-existing or new-onset, were more vulnerable to anxiety and depressive symptoms over time than those who maintained normal sleep. Additionally, sleep-related factors such as pre-sleep arousal were assessed for their influence on clinically significant anxiety and depression risk. METHODS: Using a global online survey with 3-, 6-, and 12-month follow-ups between April 2020 and May 2021, data from 2069 participants (M = 46.16 ± 13.42 years; 75.3 % female) with pre-existing, new-onset, or no insomnia symptoms was examined using mixed-effects and logistic regression models. RESULTS: New-onset and pre-existing insomnia predicted persistent anxiety and depressive symptoms longitudinally (p's < 0.001), over other known risk factors, including age, sex, and previous psychiatric diagnoses. Anxiety and depressive symptoms in both insomnia groups remained above clinically significant thresholds at most time points, whereas normal sleepers remained subclinical. Pre-sleep arousal was found to increase the risk of clinically significant anxiety (OR = 1.05) and depressive symptoms (OR = 1.09) at 12-months. Sleep effort contributed to anxiety (OR = 1.06), whereas dysfunctional sleep-related beliefs and attitudes predicted clinically significant depression (OR = 1.22). LIMITATIONS: Insomnia group categorization was based on self-report at baseline supported by a validated measure. High participant attrition was observed at 3-months (53 %; n = 971), but retention remained steady till 12-months (63 %, n = 779). CONCLUSIONS: Insomnia is a modifiable risk factor for persistent anxiety and depressive symptoms that needs to be addressed in mental healthcare. Additionally, pre-sleep arousal may be an important transdiagnostic process linking insomnia with affective disorders.

Mindfulness-Based Strategies for Improving Sleep in People with Psychiatric Disorders.

PURPOSE OF THE REVIEW: To review the recent literature on mindfulness-based strategies for improving self-report and objective measures of sleep, in individuals with psychiatric disorders. RECENT FINDINGS: Currently, research provides some support for the use of mindfulness-based interventions to improve sleep amongst individuals with psychiatric comorbidities. The strongest evidence was for the use of standardized programs, particularly for improving sleep in anxiety and depressive disorders. There is a paucity of well-controlled studies using validated subjective or objective measures of sleep. As these interventions were not specifically designed to target sleep, observed improvements may be an indirect consequence of reduced psychiatric symptoms. There is insufficient research into the application of mindfulness-based strategies to improve sleep or treat sleep disorders in people with psychiatric disorders. Well-controlled studies using standardized, mindfulness-based interventions developed to target sleep, such as mindfulness-based therapy for insomnia, may optimize the potential benefits of mindfulness for sleep in psychiatric populations.

Overscreening and Underscreening in Solid-Electrolyte Grain Boundary Space-Charge Layers.

Polycrystalline solids can exhibit material properties that differ significantly from those of equivalent single-crystal samples, in part, because of a spontaneous redistribution of mobile point defects into so-called space-charge regions adjacent to grain boundaries. The general analytical form of these space-charge regions is known only in the dilute limit, where defect-defect correlations can be neglected. Using kinetic Monte Carlo simulations of a three-dimensional Coulomb lattice gas, we show that grain boundary space-charge regions in nondilute solid electrolytes exhibit overscreening-damped oscillatory space-charge profiles-and underscreening-decay lengths that are longer than the corresponding Debye length and that increase with increasing defect-defect interaction strength. Overscreening and underscreening are known phenomena in concentrated liquid electrolytes, and the observation of functionally analogous behavior in solid electrolyte space-charge regions suggests that the same underlying physics drives behavior in both classes of systems. We therefore expect theoretical approaches developed to study nondilute liquid electrolytes to be equally applicable to future studies of solid electrolytes.

Optimizing In Vitro Osteogenesis in Canine Autologous and Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells with Dexamethasone and BMP-2.

A growing body of work suggests that canine mesenchymal stromal cells (cMSCs) require additional agonists such as bone morphogenic protein-2 (BMP-2) for consistent in vitro osteogenic differentiation. BMP-2 is costly and may challenge the translational relevance of the canine model. Dexamethasone enhances osteogenic differentiation of human MSCs (hMSCs) and is widely utilized in osteogenic protocols. The aim of this study was to determine the effect of BMP-2 and dexamethasone on early- and late-stage osteogenesis of autologous and induced pluripotent stem cell (iPS)-derived cMSCs. Two preparations of marrow-derived cMSCs were selected to represent exceptionally or marginally osteogenic autologous cMSCs. iPS-derived cMSCs were generated from canine fibroblasts. All preparations were evaluated using alkaline phosphatase (ALP) activity, Alizarin Red staining of osteogenic monolayers, and quantitative polymerase chain reaction. Data were reported as mean ± standard deviation and compared using one- or two-way analysis of variance and Tukey or Sidak post hoc tests. Significance was established at P < 0.05. In early-stage assays, dexamethasone decreased ALP activity for all cMSCs in the presence of BMP-2. In late-stage assays, inclusion of dexamethasone and BMP-2 at Day 1 of culture produced robust monolayer mineralization for autologous cMSCs. Delivering 100 nM dexamethasone at Day 1 improved mineralization and reduced the BMP-2 concentrations required to achieve mineralization of the marginal cMSCs. For iPS-cMSCs, dexamethasone was inhibitory to both ALP activity and monolayer mineralization. There was increased expression of osteocalcin and osterix with BMP-2 in autologous cMSCs but a more modest expression occurred in iPS cMSCs. While autologous and iPS-derived cMSCs respond similarly in early-stage osteogenic assays, they exhibit unique responses to dexamethasone and BMP-2 in late-stage mineralization assays. This study demonstrates that dexamethasone and BMP-2 can be titrated in a time- and concentration-dependent manner to enhance osteogenesis of autologous cMSC preparations. These results will prove useful for investigators performing translational studies with cMSCs while providing insight into iPS-derived cMSC osteogenesis.

A new method for dentine matrix metalloproteinase extraction.

In addition to their involvement in tissue remodelling, matrix metalloproteinases (MMPs), in the oral environment, are linked to leakage in the resin-dentine interface through their involvement in the proteolytic degradation of the resin-dentine hybrid layer. Numerous studies have evaluated dentine MMP activity and the vast majority of those studies have used an MMP extraction protocol to semi-purify the MMPs from dentine, first described around 20 years ago. This is a protocol that requires 32 days for completion. The technique is based on the three-step sequential use of NaCl solution for pulverised dentine washing, then guanidine HCl and EDTA to demineralise the pulverised dentine to extract the MMPs. In this study, a new one-step dentine MMP extraction protocol was adapted to extract dentine MMPs in only four days. This was achieved by eliminating the NaCl washing step and combining the guanidine HCl and EDTA into one extraction solution that also contained proteinase inhibitors. Fifty-two dentine MMP extracts were obtained utilising the two different extraction methods. The amount of total and endogenously active MMP-2 in the specimens was assayed utilising a human MMP-2 activity enzyme-linked immunosorbent assay (ELISA). The study results showed that the new extraction method is as effective as the traditional three-step extraction method in semi-purifying dentine MMP-2.

Market basket analysis of safety at active highway-railroad grade crossings.

INTRODUCTION: Data from the Federal Railroad Administration show high numbers of incidents at the approximately 210,446 highway-railroad grade crossings across the United States. One cause for this unsettling trend is the problem of drivers stopping within the dynamic envelope zone (DEZ) of the train while in queue. This research seeks to study DEZ stopping behavior at highway-railroad grade crossings by evaluating regulatory signage and further analyze variables that may affect this behavior. METHOD: A comparative safety analysis is undertaken to evaluate the effectiveness of the standard "Do Not Stop on Tracks" (R8-8) sign by using percentage change calculations and chi-squared tests. The study then conducts a market basket analysis (MBA) to extrapolate on these results and to identify underlying factors associated with observed driver behavior using variables influenced by visibility, perception, and maneuverability. RESULTS: Rather low reductions in safety violations resulted from the R8-8 installation, including a 2.2% reduction in DEZ stopping behavior and only a slight 3.7% increase in compliance. The results of the MBA identified associations that affirmed assumptions about driver behavior, while other associations were not as direct but altogether helped broaden the understanding of interactions at grade crossings. CONCLUSIONS: This study concluded that the R8-8 had a positive but minimal effect on driver behavior at the grade crossings. The MBA successfully demonstrated its value by providing further insight on the safety analysis and by increasing the number of variables that can be analyzed simultaneously. The methodology offers the scientific community an innovative approach to analyzing driver behavior. Practical Applications: The results identified important variables for developing preventive measures, which will ultimately help reduce safety violations at grade crossings. The MBA can provide practical insight for railroad safety professionals and transportation engineers when determining problematic intersections and can be used to improve the education on grade crossing interactions.

Characterizing the Cellular Response to Nitrogen-Doped Carbon Nanocups.

Carbon nanomaterials, specifically, carbon nanotubes (CNTs) have many potential applications in biology and medicine. Currently, this material has not reached its full potential for application due to the potential toxicity to mammalian cells, and the incomplete understanding of how CNTs interface with cells. The chemical composition and structural features of CNTs have been shown to directly affect their biological compatibility. The incorporation of nitrogen dopants to the graphitic lattice of CNTs results in a unique cup shaped morphology and minimal cytotoxicity in comparison to its undoped counterpart. In this study, we investigate how uniquely shaped nitrogen-doped carbon nanocups (NCNCs) interface with HeLa cells, a cervical cancer epithelial cultured cell line, and RPE-1 cells, an immortalized cultured epithelial cell line. We determined that NCNCs do not elicit a cytotoxic response in cells, and that they are uptaken via endocytosis. We have conjugated fluorescently tagged antibodies to NCNCs and shown that the protein-conjugated material is also capable of entering cells. This primes NCNCs to be a good candidate for subsequent protein modifications and applications in biological systems.

What are the Conditions of Riparian Ecosystems? Identifying Impaired Floodplain Ecosystems across the Western U.S. Using the Riparian Condition Assessment (RCA) Tool.

Environmental stressors associated with human land and water-use activities have degraded many riparian ecosystems across the western United States. These stressors include (i) the widespread expansion of invasive plant species that displace native vegetation and exacerbate streamflow and sediment regime alteration; (ii) agricultural and urban development in valley bottoms that decouple streams and rivers from their floodplains and reduce instream wood recruitment and retention; and (iii) flow modification that reduces water quantity and quality, degrading aquatic habitats. Here we apply a novel drainage network model to assess the impacts of multiple stressors on reach-scale riparian condition across two large U.S. regions. In this application, we performed a riparian condition assessment evaluating three dominant stressors: (1) riparian vegetation departure from historical condition; (2) land-use intensity within valley bottoms; and (3) floodplain fragmentation caused by infrastructure within valley bottoms, combining these stressors in a fuzzy inference system. We used freely available, geospatial data to estimate reach-scale (500 m) riparian condition for 52,800 km of perennial streams and rivers, 25,600 km in Utah, and 27,200 km in 12 watersheds of the interior Columbia River Basin (CRB). Model outputs showed that riparian condition has been at least moderately impaired across ≈70% of the streams and rivers in Utah and ≈49% in the CRB. We found 84% agreement (Cohen's ĸ = 0.79) between modeled reaches and field plots, indicating that modeled riparian condition reasonably approximates on-the-ground conditions. Our approach to assessing riparian condition can be used to prioritize watershed-scale floodplain conservation and restoration by providing network-scale data on the extent and severity of riparian degradation. The approach that we applied here is flexible and can be expanded to run with additional riparian stressor data and/or finer resolution input data.

Validation of a Screening Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose in a US Commercial Health Plan Claims Database.

Objective: To validate a risk index that estimates the likelihood of overdose or serious opioid-induced respiratory depression (OIRD) among medical users of prescription opioids. Subjects and Methods: A case-control analysis of 18,365,497 patients with an opioid prescription from 2009 to 2013 in the IMS PharMetrics Plus commercially insured health plan claims database (CIP). An OIRD event occurred in 7,234 cases. Four controls were selected per case. Validity of the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), developed previously using Veterans Health Administration (VHA) patient data, was assessed. Multivariable logistic regression was used within the CIP study population to develop a slightly refined RIOSORD. The composition and performance of the CIP-based RIOSORD was evaluated and compared with VHA-based RIOSORD. Results: VHA-RIOSORD performed well in discriminating OIRD events in CIP (C-statistic = 0.85). Additionally, re-estimation of logistic model coefficients in CIP yielded a 0.90 C-statistic. The resulting comorbidity and pharmacotherapy variables most highly associated with OIRD and retained in the CIP-RIOSORD were largely concordant with VHA-RIOSORD. These variables included neuropsychiatric and cardiopulmonary disorders, impaired drug excretion, opioid characteristics, and concurrent psychoactive medications. The average predicted probability of OIRD ranged from 2% to 83%, with excellent agreement between predicted and observed incidence across risk classes. Conclusions: RIOSORD had excellent predictive accuracy in a large population of US medical users of prescription opioids, similar to its performance in VHA. This practical risk index is designed to support clinical decision-making for safer opioid prescribing, and its clinical utility should be evaluated prospectively.

Efficient farnesylation of an extended C-terminal C(x)3X sequence motif expands the scope of the prenylated proteome.

Protein prenylation is a post-translational modification that has been most commonly associated with enabling protein trafficking to and interaction with cellular membranes. In this process, an isoprenoid group is attached to a cysteine near the C terminus of a substrate protein by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase type I or II (GGTase-I and GGTase-II). FTase and GGTase-I have long been proposed to specifically recognize a four-amino acid CAAX C-terminal sequence within their substrates. Surprisingly, genetic screening reveals that yeast FTase can modify sequences longer than the canonical CAAX sequence, specifically C(x)3X sequences with four amino acids downstream of the cysteine. Biochemical and cell-based studies using both peptide and protein substrates reveal that mammalian FTase orthologs can also prenylate C(x)3X sequences. As the search to identify physiologically relevant C(x)3X proteins begins, this new prenylation motif nearly doubles the number of proteins within the yeast and human proteomes that can be explored as potential FTase substrates. This work expands our understanding of prenylation's impact within the proteome, establishes the biologically relevant reactivity possible with this new motif, and opens new frontiers in determining the impact of non-canonically prenylated proteins on cell function.

In-vitro characterization of canine multipotent stromal cells isolated from synovium, bone marrow, and adipose tissue: a donor-matched comparative study.

BACKGROUND: The dog represents an excellent large animal model for translational cell-based studies. Importantly, the properties of canine multipotent stromal cells (cMSCs) and the ideal tissue source for specific translational studies have yet to be established. The aim of this study was to characterize cMSCs derived from synovium, bone marrow, and adipose tissue using a donor-matched study design and a comprehensive series of in-vitro characterization, differentiation, and immunomodulation assays. METHODS: Canine MSCs were isolated from five dogs with cranial cruciate ligament rupture. All 15 cMSC preparations were evaluated using colony forming unit (CFU) assays, flow cytometry analysis, RT-PCR for pluripotency-associated genes, proliferation assays, trilineage differentiation assays, and immunomodulation assays. Data were reported as mean ± standard deviation and compared using repeated-measures analysis of variance and Tukey post-hoc test. Significance was established at p < 0.05. RESULTS: All tissue samples produced plastic adherent, spindle-shaped preparations of cMSCs. Cells were negative for CD34, CD45, and STRO-1 and positive for CD9, CD44, and CD90, whereas the degree to which cells were positive for CD105 was variable depending on tissue of origin. Cells were positive for the pluripotency-associated genes NANOG, OCT4, and SOX2. Accounting for donor and tissue sources, there were significant differences in CFU potential, rate of proliferation, trilineage differentiation, and immunomodulatory response. Synovium and marrow cMSCs exhibited superior early osteogenic activity, but when assessing late-stage osteogenesis no significant differences were detected. Interestingly, bone morphogenic protein-2 (BMP-2) supplementation was necessary for early-stage and late-stage osteogenic differentiation, a finding consistent with other canine studies. Additionally, synovium and adipose cMSCs proliferated more rapidly, displayed higher CFU potential, and formed larger aggregates in chondrogenic assays, although proteoglycan and collagen type II staining were subjectively decreased in adipose pellets as compared to synovial and marrow pellets. Lastly, cMSCs derived from all three tissue sources modulated murine macrophage TNF-α and IL-6 levels in a lipopolysaccharide-stimulated coculture assay. CONCLUSIONS: While cMSCs from synovium, marrow, and adipose tissue share a number of similarities, important differences in proliferation and trilineage differentiation exist and should be considered when selecting cMSCs for translational studies. These results and associated methods will prove useful for future translational studies involving the canine model.

Combined tibial plateau levelling osteotomy and tibial tuberosity transposition for treatment of cranial cruciate ligament insufficiency with concomitant medial patellar luxation.

OBJECTIVES: To describe the surgical technique and report short-term outcome for combined tibial plateau levelling osteotomy and tibial tuberosity transposition (TPLO-TTT) as an option in the treatment of cranial cruciate ligament insufficiency with concomitant medial patellar luxation. METHODS: Medical records were reviewed (2011-2013) of dogs that underwent a standard tibial plateau levelling osteotomy followed by a tibial tuberosity transposition in the frontal plane and stabilized with pin and tension-band wire fixation as a component of surgical treatment for combined cranial cruciate ligament insufficiency and medial patellar luxation. Signalment, fixation method together with any ancillary procedures, function at the in-hospital follow-up examinations, and any complications were recorded. Healing was assessed retrospectively based on the grading criteria of the International Society Of Limb Salvage. RESULTS: Fifteen stifle joints in 11 dogs were identified; 13 stifles were available for in-hospital follow-up. All 13 achieved union (3 with grade III/IV and 10 with grade IV/IV radiographic healing scores); mean time to healing was 10.6 (± 2.9) weeks. Patellar ligament thickening was also identified radiographically in seven of the 13 of stifle joints. All dogs were reported to have mild or no lameness at their last follow-up examination. No catastrophic or major postoperative complications occurred that required additional surgery. Patellar re-luxation did not occur in any of the 13 stifles available for in-hospital follow-up. CLINICAL SIGNIFICANCE: The TPLO-TTT was found to be a reliable and effective technique when used as a part of the treatment of combined cranial cruciate ligament insufficiency with concomitant medial patellar luxation in this series of dogs.

Real-world glycemic outcomes in patients with type 2 diabetes initiating exenatide once weekly and liraglutide once daily: a retrospective cohort study.

AIM: The glucagon-like peptide-1 receptor agonists exenatide once weekly (QW) and liraglutide once daily (QD) have demonstrated improvements in glycemic outcomes in patients with type 2 diabetes mellitus in randomized clinical trials. However, little is known about their real-world comparative effectiveness. This retrospective cohort study used the Quintiles Electronic Medical Record database to evaluate the 6-month change in glycated hemoglobin (A1C) for patients initiating exenatide QW or liraglutide QD. METHODS: Patients with type 2 diabetes mellitus prescribed exenatide QW (n=664) or liraglutide QD (n=3,283) between February 1, 2012 and May 31, 2013 were identified. Baseline A1C measures were from 75 days before to 15 days after initiating exenatide QW or liraglutide QD, with follow-up measures documented at 6 months (±45 days). Adjusted linear regression models compared the difference in mean A1C change. A priori defined sensitivity analysis was performed in the subgroup of patients with baseline A1C ≥7.0% and no prescription for insulin during the 12-month pre-index period. RESULTS: For exenatide QW and liraglutide QD, respectively, mean (SD) age of the main study cohort was 58.01 (10.97) and 58.12 (11.05) years, mean (SD) baseline A1C was 8.4% (1.6) and 8.4% (1.6), and 48.2% and 54.2% of patients were women. In adjusted models, change in A1C did not differ between exenatide QW and liraglutide QD during 6 months of follow-up. Results were consistent in the subgroup analyses. CONCLUSION: In a real-world setting, A1C similarly improves in patients initiating exenatide QW or liraglutide QD.

Hispanics' Satisfaction with Free Clinic Providers: An Analysis of Patient-Centered Medical Home Characteristics.

Hispanic Americans are less likely to be insured and they experience cultural and linguistic barriers that may prevent them from obtaining necessary and preventive healthcare. Adoption of Patient Centered Medical Home (PCMH) concepts in healthcare settings utilized by Hispanics could improve Hispanic patients' satisfaction with their healthcare providers. This study examined the association between Spanish-speaking and non-Spanish-speaking patients' perceptions of PCMH characteristics and satisfaction with the provider. Data were collected using a self-administered survey from two unaffiliated free clinics. Logistic regression modeled the associations between patients' perceptions of PCMH and their satisfaction with their provider, and their desire to see the same provider in the future. The sample consisted of 367 adults; 44 % were Spanish-speaking. Spanish-speaking patients were younger, less educated, and had fewer chronic conditions than non-Spanish-speaking patients. In adjusted analyses for each population, better ratings of the provider's communication skills were associated with increased satisfaction with the provider (Spanish-speaking: OR = 8.33, 95 % CI = 2.19-31.76; non-Spanish-speaking: OR = 31.39, 95 % CI = 6.91-142.62), and willingness to see the provider again (Spanish-speaking: OR = 12.54, 95 % CI = 2.80-56.24; non-Spanish-speaking: OR = 8.77, 95 % CI = 2.40-31.96). Among Spanish-speakers, lower perceived discrimination was associated with 137 % increased odds and higher perceived staff helpfulness had 212 % increased odds of seeing the provider again. Relative to other PCMH components, interpersonal skills were the most important factors in patient satisfaction with free clinics. Increased training for clinicians on cultural competence and clinician-patient communication may lead to improved patient satisfaction for both Spanish and non-Spanish speakers seen at free clinics, particularly clinics in states without Medicaid expansion.

Cell division patterns and chromosomal segregation defects in oral cancer stem cells.

Oral squamous cell carcinoma (OSCC) is a serious public health problem caused primarily by smoking and alcohol consumption or human papillomavirus. The cancer stem cell (CSC) theory posits that CSCs show unique characteristics, including self-renewal and therapeutic resistance. Examining biomarkers and other features of CSCs is critical to better understanding their biology. To this end, the results show that cellular SOX2 immunostaining correlates with other CSC biomarkers in OSCC cell lines and marks the rare CSC population. To assess whether CSC division patterns are symmetrical, resulting in two CSC, or asymmetrical, leading to one CSC and one cancer cell, cell size and fluorescence intensity of mitotic cells stained with SOX2 were analyzed. Asymmetrical SOX2 distribution in ≈25% of the mitoses analyzed was detected. Chromosomal instability, some of which is caused by chromosome segregation defects (CSDs), is a feature of cancer cells that leads to altered gene copy numbers. We compare chromosomal instability (as measured by CSDs) between CSCs (SOX2+) and non-CSCs (SOX2-) from the same OSCC cell lines. CSDs were more common in non-CSCs (SOX2-) than CSCs (SOX2+) and in symmetrical CSC (SOX2+) mitotic pairs than asymmetrical CSC (SOX2+/SOX2-) mitotic pairs. CSCs showed fewer and different types of CSDs after ionizing radiation treatment than non-CSCs. Overall, these data are the first to demonstrate both symmetrical and asymmetrical cell divisions with CSDs in OSCC CSC. Further, the results suggest that CSCs may undergo altered behavior, including therapeutic resistance as a result of chromosomal instability due to chromosome segregation defects. © 2016 Wiley Periodicals, Inc.

Patient Perceptions of Patient-Centered Medical Home Characteristics and Satisfaction with Free Clinic Services.

The patient-centered medical home (PCMH) is a model of health care delivery designed to improve patient health outcomes by increasing the effectiveness of primary care. The effectiveness of PCMH on vulnerable populations is still largely unknown. The purpose of this study was to examine the relationship between patient perceptions of PCMH characteristics and patient satisfaction among Spanish-speaking and non-Spanish-speaking patients receiving health care at free clinics. A self-administered survey was used to collect data in 2 free clinics in the United States in 2013. Patients were primarily young and female; 44% were Spanish speaking. Patient perceptions of PCMH characteristics were assessed using multi-item Consumer Assessment of Healthcare Providers and Systems scales developed by the Agency for Healthcare Research and Quality. Patient satisfaction was assessed as satisfaction with care received at the clinic and willingness to recommend the provider. Multivariate logistic regression modeled the association between PCMH components and these 2 patient satisfaction measures. In adjusted analyses among Spanish speakers, satisfaction with clinic care was associated with staff helpfulness (OR = 6.03, 95% CI = 1.87-19.46) and no perceived discrimination (OR = 2.55, 95% CI = 1.22-5.33). For non-Spanish speakers, provider communication and politeness significantly increased odds of satisfaction with clinic services. Provider communication was strongly associated with patients' intention to recommend the provider to others for both Spanish speakers and non-Spanish speakers (OR = 4.83, 95% CI = 1.35-17.24; OR = 5.42, 95% CI = 1.54-19.09, respectively). Findings suggest that interpersonal characteristics of providers and clinic staff are critical to patient satisfaction among vulnerable populations served by free clinics. Future studies should examine PCMH components and clinical outcomes among this population.

The Competition between Elimination Pathways in the Reactions of a Wide Variety of Bases with 2-Fluoro- and 2-Chlorobutane in the Gas Phase.

Ab initio methods are used to examine the regio- and stereoselectivities of the elimination reactions of 2-fluorobutane and 2-chlorobutane with a series of nucleophiles (F(-), HO(-), CH3O(-), (CH3)3CO(-), NH2(-), CH3(-), H(-), Cl(-), HS(-), and PH2(-)). The data suggest that regiochemistry is most closely related to the nature of the transition state on the E2 spectrum with E1cb-like reactions favoring the least-substituted alkene product and E1-like reactions favoring the most-substituted alkene product. There appears to be no correlation between the extent of π-bond formation (as measured by the Cα-Cß distance) and the preference for forming the more highly substituted alkene. The stereochemistry (E vs Z) is less sensitive to the nucleophile and is relatively constant with the exception of a few systems that appear to have long-range interactions that reduce the bias against the Z product. Comparisons with experimental results in solution show, with a few exceptions, similar reactivity trends in solution and the gas phase.