Differences in the regulatory strategies of marine oligotrophs and copiotrophs reflect differences in motility.

Aquatic bacteria frequently are divided into lifestyle categories oligotroph or copiotroph. Oligotrophs have proportionately fewer transcriptional regulatory genes than copiotrophs and are generally non-motile/chemotactic. We hypothesized that the absence of chemotaxis/motility in oligotrophs prevents them from occupying nutrient patches long enough to benefit from transcriptional regulation. We first confirmed that marine oligotrophs are generally reduced in genes for transcriptional regulation and motility/chemotaxis. Next, using a non-motile oligotroph (Ca. Pelagibacter st. HTCC7211), a motile copiotroph (Alteromonas macleodii st. HOT1A3), and [14 C]l-alanine, we confirmed that l-alanine catabolism is not transcriptionally regulated in HTCC7211 but is in HOT1A3. We then found that HOT1A3 took 2.5-4 min to initiate l-alanine oxidation at patch l-alanine concentrations, compared to <30 s for HTCC7211. By modelling cell trajectories, we predicted that, in most scenarios, non-motile cells spend <2 min in patches, compared to >4 min for chemotactic/motile cells. Thus, the time necessary for transcriptional regulation to initiate prevents transcriptional regulation from being beneficial for non-motile oligotrophs. This is supported by a mechanistic model we developed, which predicted that HTCC7211 cells with transcriptional regulation of l-alanine metabolism would produce 12% of their standing ATP stock upon encountering an l-alanine patch, compared to 880% in HTCC7211 cells without transcriptional regulation.

Does Adjunction of Autologous Osteoblastic Cells Improve the Results of Core Decompression in Early-stage Femoral Head Osteonecrosis? A Double-blind, Randomized Trial.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a disabling disease that can ultimately progress to collapse of the femoral head, often resulting in THA. Core decompression of the femoral head combined with cell therapies have shown beneficial effects in previous clinical studies in patients with early-stage (Association Research Circulation Osseous [ARCO] Stage I and II) ONFH. However, high-quality evidence confirming the efficacy of this treatment modality is still lacking. QUESTIONS/PURPOSES: (1) Is core decompression combined with autologous osteoblastic cell transplantation superior to core decompression with placebo implantation in relieving disease-associated pain and preventing radiologic ONFH progression in patients with nontraumatic early-stage ONFH? (2) What adverse events occurred in the treatment and control groups? METHODS: This study was a Phase III, multicenter, randomized, double-blind, controlled study conducted from 2011 to 2019 (ClinicalTrails.gov registry number: NCT01529008). Adult patients with ARCO Stage I and II ONFH were randomized (1:1) to receive either core decompression with osteoblastic cell transplantation (5 mL with 20 x 10 6 cells/mL in the study group) or core decompression with placebo (5 mL of solution without cells in the control group) implantation. Thirty percent (68 of 230) of the screened patients were eligible for inclusion in the study; of these, 94% (64 of 68) underwent a bone marrow harvest or sham procedure (extended safety set) and 79% (54 of 68) were treated (study group: 25 patients; control group: 29). Forty-nine patients were included in the efficacy analyses. Similar proportions of patients in each group completed the study at 24 months of follow-up (study group: 44% [11 of 25]; control: 41% [12 of 29]). The study and control groups were comparable in important ways; for example, in the study and control groups, most patients were men (79% [27 of 34] and 87% [26 of 30], respectively) and had ARCO Stage II ONFH (76% [19 of 25] and 83% [24 of 29], respectively); the mean age was 46 and 45 years in the study and control groups, respectively. The follow-up period was 24 months post-treatment. The primary efficacy endpoint was the composite treatment response at 24 months, comprising the clinical response (clinically important improvement in pain from baseline using the WOMAC VA3.1 pain subscale, defined as 10 mm on a 100-mm scale) and radiologic response (the absence of progression to fracture stage [≥ ARCO Stage III], as assessed by conventional radiography and MRI of the hips). Secondary efficacy endpoints included the percentages of patients achieving a composite treatment response, clinical response, and radiologic response at 12 months, and the percentage of patients undergoing THA at 24 months. We maintained a continuous reporting system for adverse events and serious adverse events related to the study treatment, bone marrow aspiration and sham procedure, or other study procedures throughout the study. A planned, unblinded interim analysis of efficacy and adverse events was completed at 12 months. The study was discontinued because our data safety monitoring board recommended terminating the study for futility based on preselected futility stopping rules: conditional power below 0.20 and p = 0.01 to detect an effect size of 10 mm on the 100-mm WOMAC VA3.1 pain subscale (improvement in pain) and the absence of progression to fracture (≥ ARCO Stage III) observed on radiologic assessment, reflecting the unlikelihood that statistically beneficial results would be reached at 24 months after the treatment. RESULTS: There was no difference between the study and control groups in the proportion of patients who achieved a composite treatment response at 24 months (61% [14 of 23] versus 69% [18 of 26]; p = 0.54). There was no difference in the proportion of patients with a treatment response at 12 months between the study and control groups (14 of 21 versus 15 of 23; p = 0.92), clinical response (17 of 21 versus 16 of 23; p = 0.38), and radiologic response (16 of 21 versus 18 of 23; p = 0.87). With the numbers available, at 24 months, there was no difference in the proportion of patients who underwent THA between the study and control groups (24% [six of 25] versus 14% [four of 29]). There were no serious adverse events related to the study treatment, and only one serious adverse event (procedural pain in the study group) was related to bone marrow aspiration. Nonserious adverse events related to the treatment were rare in the study and control groups (4% [one of 25] versus 14% [four of 29]). Nonserious adverse events related to bone marrow or sham aspiration were reported by 15% (five of 34) of patients in the study group and 7% (two of 30) of patients in the control group. CONCLUSION: Our study did not show any advantage of autologous osteoblastic cells to improve the results of core decompression in early-stage (precollapse) ONFH. Adverse events related to treatment were rare and generally mild in both groups, although there might have been a potential risk associated with cell expansion. Based on our findings, we do not recommend the combination of osteoblastic cells and core decompression in patients with early-stage ONFH. Further, well-designed studies should be conducted to explore whether other treatment modalities involving a biological approach could improve the overall results of core decompression. LEVEL OF EVIDENCE: Level II, therapeutic study.

Development and Initial Validation of the Persevering Hope Scale: Measuring Wait-Power in Four Independent Samples.

Hope has been conceptualized as agency and pathways to achieve goals. However, this goal-directed conceptualization does not encapsulate all situations in which hope may be beneficial. To address the dispositional motivation to endure when a desired goal seems unattainable, unlikely, or even impossible (i.e., goal-transcendent hope), we provide initial psychometric evidence for the new Persevering Hope Scale (PHS). We developed and refined the PHS with undergraduates at a public college (Study 1) and replicated our findings in a community adult sample (Study 2). We replicated and extended these findings using longitudinal data with undergraduates at a faith-based college (Study 3) and a community sample of chronically ill adults (Study 4), and examined measurement invariance (Study 5). Scores on the PHS demonstrated robust evidence of estimated internal consistency and of criterion-related, convergent/discriminant, and incremental validity. Estimated temporal stability was modest. Partial scalar invariance was evidenced across samples, and full scalar invariance was evidenced across gender, race/ethnicity, and time. These preliminary findings suggest that the PHS is a psychometrically sound measure of persevering hope. Its use can broaden the current body of literature on trait hope to include goal-transcendent hope and advance research on the nature and benefits of this important construct.

What's important for recovery after a total knee replacement? A systematic review of mixed methods studies.

BACKGROUND: Understanding how patients perceive and prioritise various aspects of recovery following total knee replacement, including pain, function and return to activity, will help clinicians in pre-operative consultations by ensuring they effectively address patient concerns and managing their expectations. AIMS: The aim of this study is to identify aspects of recovery that are important to people after a total knee replacement. METHODS: Studies were identified from Medline, Embase, PsycInfo, Cochrane Library and Web of Science. This mixed methods review included all original study types (quantitative, qualitative, discrete choice experiments and mixed methods design). Reviews and non-peer-reviewed publications were excluded. Studies with participants (age ≥ 18 years) who had a primary TKR for osteoarthritis were included. Studies of people with unicompartmental knee, patella-femoral or revision knee replacement were excluded. Recovery attributes were extracted from individual papers and grouped into recovery themes. RESULTS: A total of 23 studies with 8404 participants and 18 recovery themes were developed. The most frequently identified overarching theme was pain, followed by activities of daily living, mobility (walking), recreational activities, specific functional movements of the knee, use of walking aids, sexual activity and range of motion of the knee. Medical complications were an infrequently reported theme, however, was deemed to be high importance. CONCLUSIONS: Reducing pain, returning of activities and daily living and mobility are the three most frequently reported recovery domains for people after TKR. Clinicians should be aware of recovery themes, to ensure they are explored sufficiently when consenting for a TKR. Future research should aim to determine the relative importance of these attributes compared to each other. Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253699.

Metabolism of key atmospheric volatile organic compounds by the marine heterotrophic bacterium Pelagibacter HTCC1062 (SAR11).

Plants and phytoplankton are natural sources of the volatile organic compounds (VOCs) acetone and isoprene, which are reactive and can alter atmospheric chemistry. In earlier research we reported that, when co-cultured with a diatom, the marine bacterium Pelagibacter (strain HTCC1062; 'SAR11 clade') reduced the concentration of compounds tentatively identified as acetone and isoprene. In this study, experiments with Pelagibacter monocultures confirmed that these cells are capable of metabolizing acetone and isoprene at rates similar to bacterial communities in seawater and high enough to consume substantial fractions of the total marine acetone and isoprene budgets if extrapolated to global SAR11 populations. Homologues of an acetone/cyclohexanone monooxygenase were identified in the HTCC1062 genome and in the genomes of a wide variety of other abundant marine taxa, and were expressed at substantial levels (c. 10-4 of transcripts) across TARA oceans metatranscriptomes from ocean surface samples. The HTCC1062 genome lacks the canonical isoprene degradation pathway, suggesting an unknown alternative biochemical pathway is used by these cells for isoprene uptake. Fosmidomycin, an inhibitor of bacterial isoprenoid biosynthesis, blocked HTCC1062 growth, but the cells were rescued when isoprene was added to the culture, indicating SAR11 cells may be capable of synthesizing isoprenoid compounds from exogenous isoprene.

Ancient co-option of an amino acid ABC transporter locus in Pseudomonas syringae for host signal-dependent virulence gene regulation.

Pathogenic bacteria frequently acquire virulence traits via horizontal gene transfer, yet additional evolutionary innovations may be necessary to integrate newly acquired genes into existing regulatory pathways. The plant bacterial pathogen Pseudomonas syringae relies on a horizontally acquired type III secretion system (T3SS) to cause disease. T3SS-encoding genes are induced by plant-derived metabolites, yet how this regulation occurs, and how it evolved, is poorly understood. Here we report that the two-component system AauS-AauR and substrate-binding protein AatJ, proteins encoded by an acidic amino acid-transport (aat) and -utilization (aau) locus in P. syringae, directly regulate T3SS-encoding genes in response to host aspartate and glutamate signals. Mutants of P. syringae strain DC3000 lacking aauS, aauR or aatJ expressed lower levels of T3SS genes in response to aspartate and glutamate, and had decreased T3SS deployment and virulence during infection of Arabidopsis. We identified an AauR-binding motif (Rbm) upstream of genes encoding T3SS regulators HrpR and HrpS, and demonstrated that this Rbm is required for maximal T3SS deployment and virulence of DC3000. The Rbm upstream of hrpRS is conserved in all P. syringae strains with a canonical T3SS, suggesting AauR regulation of hrpRS is ancient. Consistent with a model of conserved function, an aauR deletion mutant of P. syringae strain B728a, a bean pathogen, had decreased T3SS expression and growth in host plants. Together, our data suggest that, upon acquisition of T3SS-encoding genes, a strain ancestral to P. syringae co-opted an existing AatJ-AauS-AauR pathway to regulate T3SS deployment in response to specific host metabolite signals.

Multi-Stimuli-Responsive Janus Hollow Polydopamine Nanotubes.

A tubular-shaped Janus nanoparticle based on polydopamine that responds to near-infrared, magnetic, and pH stimuli is reported. The robust tubular polydopamine structure was obtained by optimizing the halloysite template-to-dopamine ratio during synthesis. The inner and outer surfaces of the tube were exposed at different steps of the template-sonication--etching process, enabling the differential surface modification of these surfaces. Poly(ethylene glycol) (PEG) and poly(N-isopropylacrylamide) (PNIPAM) were grafted to the outer and inner surface of the nanotube, respectively. The PEG-coated surface limited aggregation of the nanoparticles at elevated temperatures. The PNIPAM-coated interior enhanced doxorubicin loading and endowed the nanoparticle with temperature-responsive behavior. The deposition of precipitated Fe3O4 nanoparticles further modified the nanoparticles. The resulting magnetic Janus nanoparticles responded to pH, temperature, and magnetic fields. Temperature changes could be induced by near-infrared laser, and all three stimuli were found to influence release rates of adsorbed doxorubicin from the nanoparticles. The interaction of the stimuli on release kinetics was elucidated using a linear mixed model; reduced pH and NIR irradiation enhanced release while applying a static magnetic field retarded release. Furthermore, the mechanism was shifted toward Fickian behavior by applying a static magnetic field and low pH conditions. However, NIR irradiation only shifted the behavior toward Fickian behavior at low pH.

Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses.

Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine-glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine-glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.

Understanding religious attachment among christians seeking spiritually integrated psychotherapies: A mixed methods study.

OBJECTIVE: This mixed methods study aimed to understand ways of viewing and experiencing religious attachment among Christians in spiritually integrated psychotherapies. METHOD: In total, 190 Christian-affiliated clients completed narrative responses about religious and parental attachment along with validated measures of spiritual and psychological functioning toward the start of treatment. RESULTS: An inductive content analysis revealed ten ways in which clients were viewing and experiencing God. Although painful themes were expressed, clients more frequently discussed comforting themes related to religious attachment. Additional analyses demonstrated convergence with parental attachment and quantitative measures of spirituality and mental health. CONCLUSION: Religious attachment appears to primarily provide a sense of strength and comfort for Christians seeking care. Findings also indicate clients view and experience God in similar ways as their parents or caregivers. As such, assessing and affirming clients' faith may facilitate positive changes in how they view and experience themselves and others in treatment.

Religious/spiritual struggles and psychological distress: A test of three models in a longitudinal study of adults with chronic health conditions.

OBJECTIVE: This study tested three conceptual explanatory models that have been theorized to account for the linkages between religious/spiritual (R/S) struggles and psychological distress: the primary model (i.e., R/S struggles lead to psychological distress), the secondary model (i.e., psychological distress leads to R/S struggles), and the complex model (i.e., R/S struggles and psychological distress reciprocally exacerbate each other). METHODS: Using prospective data from a sample of US adults living with chronic health conditions (n = 302), we performed a cross-lagged panel analysis with three timepoints to test for evidence of potential causal relations between R/S struggles and psychological distress. RESULTS: Consistent with the complex conceptual model of R/S struggles, we found evidence of positive reciprocal associations between R/S struggles and psychological distress. CONCLUSION: The findings highlight the importance of attending to the dynamic interplay between R/S struggles and psychological distress when working with adults who have chronic health conditions.

Evaluation of Rotator Cuff Augmentation of Proximal Humerus Fracture Fixation.

Proximal humerus fractures represent one of the most common fractures in the elderly, and are increasingly treated with surgical fixation. Suture augmentation attaching the rotator cuff to the plate has been advocated to combat varus collapse and other associated complications. The objective of this study was to evaluate the contribution of rotator cuff augmentation to stability of proximal humerus fracture fixation. Twelve shoulder specimens from six cadavers underwent simulated two-part and three-part proximal humerus fractures. Matched specimens from the same cadaver were randomized to suture augmentation with locking plate fixation vs. locking plate fixation alone. Greater tuberosity fragment displacement was recorded during cyclic rotational strain of the glenohumeral joint. Greater tuberosity displacement in the two-part fracture model trended towards greater motion without suture augmentation, but did not reach statistical significance (0.032 + 0.012 mm vs. 0.213 + 0.109 mm, p = 0.130). In the three-part fracture model, there was a statistically significant decrease in fracture displacement in the presence of suture augmentation (0.068 + 0.025 mm vs. 2.392 + 0.373 mm, p < 0.001). No specimens demonstrated premature failure during cyclic loading. Suture augmentation of locking plate fixation of three-part proximal humerus fractures results in decreased fracture displacement than locked plating alone, during rotational stresses simulating in vivo rotator cuff deformation forces. (Journal of Surgical Orthopaedic Advances 31(2):119-122, 2022).

Resource loss and mental health during COVID-19: Psychosocial protective factors among U.S. older adults and those with chronic disease.

Across the globe, COVID-19 has disproportionately affected the physical and mental health of several vulnerable groups. In a series of two cross-sectional studies conducted April to July 2020, we examined its acute mental health effects on two vulnerable U.S. community samples-home-bound older adults who were at or below the poverty line (Study 1, N = 293, Mage  = 76.94, SD = 8.64; 75.1% female, 67.9% Black) and adults with chronic disease (Study 2, N = 322, Mage  = 62.20, SD = 12.22; 46.3% female, 28.3% racial/ethnic minorities). Based on the conservation of resources theory, we hypothesised that pandemic-related resource loss would be associated with greater mental distress, but perceived social support and positive psychological characteristics (trait resilience and optimism) would buffer against this adverse effect. Across both samples of vulnerable adults, pandemic-related resource loss was related to mental distress. Perceived social support was related to lower mental distress but did not consistently buffer the effect of resource loss on mental health. However, in Study 2, both trait resilience and optimism buffered this relationship. Findings are discussed in terms of their implications for the conservation of resources theory.

The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex.

A disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein essential for embryonic development, and its dysregulation underlies disorders such as cancer, Alzheimer's disease, and inflammation. ADAM10 is a "molecular scissor" that proteolytically cleaves the extracellular region from >100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors, and chemokines. ADAM10 has been recently proposed to function as six distinct scissors with different substrates, depending on its association with one of six regulatory tetraspanins, termed TspanC8s. However, it remains unclear to what degree ADAM10 function critically depends on a TspanC8 partner, and a lack of monoclonal antibodies specific for most TspanC8s has hindered investigation of this question. To address this knowledge gap, here we designed an immunogen to generate the first monoclonal antibodies targeting Tspan15, a model TspanC8. The immunogen was created in an ADAM10-knockout mouse cell line stably overexpressing human Tspan15, because we hypothesized that expression in this cell line would expose epitopes that are normally blocked by ADAM10. Following immunization of mice, this immunogen strategy generated four Tspan15 antibodies. Using these antibodies, we show that endogenous Tspan15 and ADAM10 co-localize on the cell surface, that ADAM10 is the principal Tspan15-interacting protein, that endogenous Tspan15 expression requires ADAM10 in cell lines and primary cells, and that a synthetic ADAM10/Tspan15 fusion protein is a functional scissor. Furthermore, two of the four antibodies impaired ADAM10/Tspan15 activity. These findings suggest that Tspan15 directly interacts with ADAM10 in a functional scissor complex.

Perceived and actual posttraumatic growth in religiousness and spirituality following disasters.

OBJECTIVE: Religious/spiritual (R/S) growth is a core domain of posttraumatic growth (PTG). However, research on R/S growth following disasters has over-relied on retrospective self-reports of growth. We therefore examined longitudinal change in religiousness/spirituality following two disasters. METHOD: Religious survivors of Hurricanes Harvey (Study 1) and Irma (Study 2) completed measures of perceived R/S PTG, general religiousness/spirituality ("current standing"-R/S PTG), and subfacets of religiousness/spirituality (spiritual fortitude, religious motivations, and benevolent theodicies). In Study 1, 451 participants responded at 1-month and 2-month postdisaster. In Study 2, participants responded within 5-days predisaster and at 1-month (N = 1,144) and 6-months postdisaster (N = 684). RESULTS: In both studies, perceived R/S PTG was weakly related to longitudinal increases in general religiousness/spirituality and in most of its subfacets, but reliable growth in any R/S outcome was rare. Additionally, Study 2 revealed evidence that actual change in psychological well-being is associated with actual (but not perceived) R/S PTG, but disaster survivors tend to exhibit declines in their religiousness/spirituality, spiritual fortitude, and religious motivations. CONCLUSIONS: Results suggest disaster survivors are only modestly accurate in perceiving how much positive R/S change they experience following a disaster. We discuss implications for clinical practice, scientific research, and empirical and conceptual work on PTG more broadly.

Why humility is vital to effective humanitarian aid leadership: a review of the literature.

Organisational scientists are paying increasing attention to humility, following a larger trend in scholarship highlighting the relational and interdependent nature of leadership and business. A growing body of evidence identifies humility as vital to effective organisational leadership, facilitating positive organisational outcomes, such as lower voluntary turnover and greater follower job satisfaction. To date, research on the subject has focused on certain specific organisational contexts, including businesses, hospitals, and schools. This paper reviews the existing literature and explores why humility may be an especially important leader trait in international humanitarian aid organisations and relief work-a context that is not only uniquely challenging, but also one that would seemingly stand to benefit keenly from the quality. It argues that humility is essential for effective leadership because it is normative of good character, it is predictive of positive outcomes, and it corresponds to a genuine representation of the nature of humanitarian aid.

eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation.

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

A practice-based evidence investigation of God representations in spiritually integrated psychotherapies.

OBJECTIVE: This practice-based evidence study examined trajectories of God representations and psychological distress among Christians participating in spiritually integrated psychotherapies (SIPs). METHODS: In total, 17 clinicians practicing SIPs in a mid-sized city on the US Gulf Coast implemented session-to-session assessments of these outcomes with 158 clients over a 4-month period and also reported their use of specific spiritual interventions after each session (e.g., affirmed client's divine worth). RESULTS: Multivariate growth modeling revealed clients' psychological distress decreased over the study period whereas authoritarian God representations increased and benevolent God representations remained stable. In addition, clients who increased in benevolent representations of God had a greater likelihood of experiencing alleviation of psychological distress. CONCLUSION: These findings affirm the potential efficacy of SIPs and cultural importance of belief in a benevolent deity as a source of strength, identity, and potential healing among Christians clients who prefer a spiritually integrated approach in psychotherapy.

Pan-tissue transcriptome analysis of long noncoding RNAs in the American beaver Castor canadensis.

BACKGROUND: Long noncoding RNAs (lncRNAs) have roles in gene regulation, epigenetics, and molecular scaffolding and it is hypothesized that they underlie some mammalian evolutionary adaptations. However, for many mammalian species, the absence of a genome assembly precludes the comprehensive identification of lncRNAs. The genome of the American beaver (Castor canadensis) has recently been sequenced, setting the stage for the systematic identification of beaver lncRNAs and the characterization of their expression in various tissues. The objective of this study was to discover and profile polyadenylated lncRNAs in the beaver using high-throughput short-read sequencing of RNA from sixteen beaver tissues and to annotate the resulting lncRNAs based on their potential for orthology with known lncRNAs in other species. RESULTS: Using de novo transcriptome assembly, we found 9528 potential lncRNA contigs and 187 high-confidence lncRNA contigs. Of the high-confidence lncRNA contigs, 147 have no known orthologs (and thus are putative novel lncRNAs) and 40 have mammalian orthologs. The novel lncRNAs mapped to the Oregon State University (OSU) reference beaver genome with greater than 90% sequence identity. While the novel lncRNAs were on average shorter than their annotated counterparts, they were similar to the annotated lncRNAs in terms of the relationships between contig length and minimum free energy (MFE) and between coverage and contig length. We identified beaver orthologs of known lncRNAs such as XIST, MEG3, TINCR, and NIPBL-DT. We profiled the expression of the 187 high-confidence lncRNAs across 16 beaver tissues (whole blood, brain, lung, liver, heart, stomach, intestine, skeletal muscle, kidney, spleen, ovary, placenta, castor gland, tail, toe-webbing, and tongue) and identified both tissue-specific and ubiquitous lncRNAs. CONCLUSIONS: To our knowledge this is the first report of systematic identification of lncRNAs and their expression atlas in beaver. LncRNAs-both novel and those with known orthologs-are expressed in each of the beaver tissues that we analyzed. For some beaver lncRNAs with known orthologs, the tissue-specific expression patterns were phylogenetically conserved. The lncRNA sequence data files and raw sequence files are available via the web supplement and the NCBI Sequence Read Archive, respectively.

Bowl-Shaped Polydopamine Nanocapsules: Control of Morphology via Template-Free Synthesis.

Synthesis of hollow polydopamine bowl-shaped nanoparticles (nanobowls), as small as 80 nm in diameter, via a one-pot template-free rapid method is reported. Addition of dopamine to a solution of 0.606 mg/mL tris(hydroxymethyl)aminomethane in an ethanol/water mixed solvent resulted in the formation of hollow spherical nanocapsules within 2 h. At longer reaction times, the formation of conventional solid nanospheres dominated the reaction. The wall thickness of the nanocapsules increased with increasing dopamine concentration in the reaction medium. Wall thickness was also influenced by oxygen availability during the reaction. Nanocapsules with thin walls were prone to collapse. When dried, over 90% of the nanocapsules with wall thickness on the order of 11 nm collapsed. Also, the degree of collapse of individual nanoparticles changed from complete to partial to no collapse as the wall thickness was increased. Varying the ethanol content affected the cavity size and overall dimension of the nanocapsules produced but did not result in a significant change to the wall thickness. A mechanism describing the formation of the nanocapsules and their subsequent collapse into nanobowls is presented. The shape-tunable nanobowls prepared through this green, rapid, and affordable method are expected to have applications in the biomedical, electrochemical, and catalytic fields.

Sulforaphane Bioavailability and Chemopreventive Activity in Men Presenting for Biopsy of the Prostate Gland: A Randomized Controlled Trial.

Previous studies suggest compounds such as sulforaphane (SFN) derived from cruciferous vegetables may prevent prostate cancer development and progression. This study evaluated the effect of broccoli sprout extract (BSE) supplementation on blood histone deacetylase (HDAC) activity, prostate RNA gene expression, and tissue biomarkers (histone H3 lysine 18 acetylation (H3K18ac), HDAC3, HDAC6, Ki67, and p21). A total of 98 men scheduled for prostate biopsy were allocated into either BSE (200 µmol daily) or a placebo in our double-blind, randomized controlled trial. We used nonparametric tests to evaluate the differences of blood HDAC activity and prostate tissue immunohistochemistry biomarkers between treatment groups. Further, we performed RNA-Seq analysis on the prostate biopsies and identified 40 differentially expressed genes correlated with BSE treatment, including downregulation of two genes previously implicated in prostate cancer development, AMACR and ARLNC1. Although urine and plasma SFN isothiocyanates and individual SFN metabolites were statistically higher in the treatment group, our results did not show a significant difference in HDAC activity or prostate tissue biomarkers. This study indicates BSE supplementation correlates with changes in gene expression but not with several other prostate cancer biomarkers. More research is required to fully understand the chemopreventive effects of BSE supplementation on prostate cancer.