E2-Loaded Microcapsules and Bone Marrow-Derived Mesenchymal Stem Cells with Injectable Scaffolds for Endometrial Regeneration Application.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been recognized as new candidates for the treatment of serious endometrial injuries. However, owing to the local microenvironment of damaged endometrium, transplantation of BMSCs yielded disappointing results. In this study, Pectin-Pluronic® F-127 hydrogel as scaffolds were fabricated to provide three-dimensional architecture for the attachment, growth, and migration of BMSCs. E2 was encapsulated into the W/O/W microspheres to construct pectin-based E2-loaded microcapsules (E2 MPs), which has the potential to serve as a long-term reliable source of E2 for endometrial regeneration. Then, the BMSCs/E2 MPs/scaffolds system was injected into the uterine cavity of mouse endometrial injury model for treatment. At 4 weeks after transplantation, the system increased proliferative abilities of uterine endometrial cells, facilitated microvasculature regeneration, and restored the ability of endometrium to receive an embryo, suggesting that the BMSCs/E2 MPs/scaffolds system is a promising treatment option for endometrial regeneration. Furthermore, the mechanism of E2 in promoting the repair of endometrial injury was also investigated. Exosomes are critical paracrine mediators that act as biochemical cues to direct stem cell differentiation. In this study, it was found that the expression of endometrial epithelial cell (EEC) markers was upregulated in BMSCs treated by exosomes secreted from endometrial stromal cells (ESCs-Exos). Exosomes derived from E2-stimulated ESCs further promoted the expression level of EECs markers in BMSCs, suggesting exosomes released from ESCs by E2 stimulation could enhance the differentiation efficiency of BMSCs. Therefore, exosomes derived from ESCs play paracrine roles in endometrial regeneration stimulated by E2 and provide optimal estrogenic response.

Mental imagery of suicide and non-suicidal self-injury: A meta-analysis and systematic review.

BACKGROUND: The vast majority of research on, and clinical assessment of, cognitions related to suicide and non-suicidal self-injury (NSSI) has focused on verbal thoughts. And yet, mental imagery is more realistic and emotionally arousing than verbal thoughts. METHODS: We conducted a systematic review and meta-analysis documenting the prevalence of suicidal and NSSI mental imagery and describing the content and characteristics of suicidal and NSSI mental imagery, links between suicidal and NSSI mental imagery and suicidal and NSSI behavior, and how to intervene on suicidal and NSSI mental imagery. Studies published through December 17, 2022 were identified through a systematic search of MEDLINE and PsycINFO. RESULTS: Twenty-three articles were included. Prevalence rates of suicidal (73.56%) and NSSI (84.33%) mental imagery were high among clinical samples. Self-harm mental imagery commonly depicts engagement in self-harm behavior and is experienced as vivid, realistic, and preoccupying. When experimentally induced, self-harm mental imagery reduces physiological and affective arousal. Preliminary evidence suggests that suicidal mental imagery is associated with suicidal behavior. CONCLUSIONS: Suicidal and NSSI mental imagery are highly prevalent and may be associated with heightened risk for self-harm behavior. Assessments and interventions for self-harm should consider incorporating and addressing suicidal and NSSI mental imagery to mitigate risk.

Maternal nutrition and effects on offspring vascular function.

Maternal nutrition during pregnancy may have profound effects on the developing fetus and impact risk for cardiovascular disease later in life. Here, we provide a narrative review on the impact of maternal diet during pregnancy on offspring vascular function. We review studies reporting effects of maternal micronutrient (folic acid, iron) intakes, high-fat diets, dietary energy restriction, and low protein intake on offspring endothelial function. We discuss the differences in study design and outcomes and potential underlying mechanisms contributing to the vascular phenotypes observed in the offspring. We further highlight key gaps in the literature and identify targets for future investigations.

Characterization of root-associated fungi and reduced plant growth in soils from a New Mexico uranium mine.

Characterizing the diverse, root-associated fungi in mine wastes can accelerate the development of bioremediation strategies to stabilize heavy metals. Ascomycota fungi are well known for their mutualistic associations with plant roots and, separately, for roles in the accumulation of toxic compounds from the environment, such as heavy metals. We sampled soils and cultured root-associated fungi from blue grama grass (Bouteloua gracilis) collected from lands with a history of uranium (U) mining and contrasted against communities in nearby, off-mine sites. Plant root-associated fungal communities from mine sites were lower in taxonomic richness and diversity than root fungi from paired, off-mine sites. We assessed potential functional consequences of unique mine-associated soil microbial communities using plant bioassays, which revealed that plants grown in mine soils in the greenhouse had significantly lower germination, survival, and less total biomass than plants grown in off-mine soils but did not alter allocation patterns to roots versus shoots. We identified candidate culturable root-associated Ascomycota taxa for bioremediation and increased understanding of the biological impacts of heavy metals on microbial communities and plant growth.

Efficacy of Transcendental Meditation to Reduce Stress Among Health Care Workers: A Randomized Clinical Trial.

Importance: Health care workers (HCWs) have been experiencing substantial stress and burnout, and evidence-based mitigation strategies are needed. Transcendental Meditation (TM) is a mantra meditation practice with potential efficacy in reducing stress. Objective: To assess the efficacy of TM practice in reducing stress among HCWs over a 3-month period. Design, Setting, and Participants: This single-center open-label randomized clinical trial was conducted among HCWs at an academic medical center from November 19, 2020, to August 31, 2021. Inclusion criteria comprised a score of 6 points or greater on the Subjective Units of Distress Scale and an increase of 5% or greater in baseline heart rate or an increase of 33% or greater in galvanic skin response after exposure to a stressful script. Exclusion criteria included the use of antipsychotic or ß blocker medications, current suicidal ideation, or previous TM training. Of 213 HCWs who participated in prescreening, 95 attended in-person visits, resulting in 80 eligible participants who were randomized to receive a TM intervention (TM group) or usual treatment (control group). Interventions: The TM group practiced TM for 20 minutes twice daily over a 3-month period. The control group received usual treatment, which consisted of access to wellness resources. Main Outcomes and Measures: The primary outcome was change in acute psychological distress measured by the Global Severity Index. Secondary outcomes included changes in burnout (measured by the Maslach Burnout Inventory), insomnia (measured by the Insomnia Severity Index), and anxiety (measured by the Generalized Anxiety Disorder-7 scale). Results: Among 80 participants, 66 (82.5%) were women, with a mean (SD) age of 40 (11) years. One participant (1.3%) was American Indian or Alaska Native, 5 (6.3%) were Asian, 12 (15.0%) were Black, 59 (73.8%) were White, and 3 (3.8%) were of unknown or unreported race; 4 participants (5.0%) were Hispanic, and 76 (95.0%) were non-Hispanic. A total of 41 participants were randomized to the TM group, and 39 were randomized to the control group. Participants in the TM group did not show a statistically significant decrease in psychological distress on the Global Severity Index compared with those in the control group (-5.6 points vs -3.8 points; between-group difference, -1.8 points; 95% CI, -4.2 to 0.6 points; P = .13). Compared with the control group, the TM group had significantly greater reductions in the secondary end points of emotional exhaustion (Maslach Burnout Inventory subscore: -8.0 points vs -2.6 points; between-group difference, -5.4 points; 95% CI, -9.2 to -1.6 points; P = .006), insomnia (Insomnia Severity Scale score: -4.1 points vs -1.9 points; between-group difference, -2.2 points; 95% CI, -4.4 to 0 points; P = .05), and anxiety (Generalized Anxiety Disorder-7 score: -3.1 points vs -0.9 points; between-group difference, -2.2 points; 95% CI, -3.8 to -0.5; P = .01) at 3 months. A total of 38 participants (92.7%) in the TM group adhered to home practice. Conclusions and Relevance: In this randomized clinical trial, TM practice among HCWs over a 3-month period did not result in a statistically significant reduction in the primary outcome of acute psychological distress compared with usual treatment but significantly improved the secondary outcomes of burnout, anxiety, and insomnia. These findings suggest that TM may be a safe and effective strategy to alleviate chronic stress among HCWs. Trial Registration: ClinicalTrials.gov identifier: NCT04632368.

Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial.

BACKGROUND: In mouse models of skin cancer, high-dose oral vitamin D3 (VD3; cholecalciferol) combined with photodynamic therapy (PDT) can improve the clearance of squamous precancers (actinic keratoses [AKs]). OBJECTIVE: To determine whether oral VD3 can improve the clinical efficacy of a painless PDT regimen in humans with AK. METHODS: The baseline lesion counts and serum 25-hydroxyvitamin D3 levels were determined. In group 1, 29 patients underwent gentle debridement and 15-minute aminolevulinic acid preincubation with blue light (30 minutes; 20 J/cm2). In group 2, 29 patients took oral VD3 (10,000 IU daily for 5 or 14 days) prior to debridement and PDT. Lesion clearance was assessed at 3 to 6 months. RESULTS: In group 1, the mean clearance rates of facial AK were lower in patients with VD3 deficiency (25-hydroxyvitamin D3 level < 31 ng/dL; clearance rate, 40.9% ± 42%) than in patients with normal 25-hydroxyvitamin D3 levels (62.6% ± 14.2%). High-dose VD3 supplementation (group 2) significantly improved the overall AK lesion response (72.5% ± 13.6%) compared with that in group 1 (54.4% ± 22.8%). No differences in side effects were noted. LIMITATIONS: Nonrandomized trial design (interventional cohort matched to registry-based controls). CONCLUSIONS: Oral VD3 pretreatment significantly improves AK clinical responses to PDT. The regimen appears promising and well tolerated.

Allergen Immunotherapy Extract Shortages and Their Effects on Clinical Care: A Work Group Report of the AAAAI Immunotherapy, Allergen Standardization, and Allergy Diagnostics Committee.

Allergen immunotherapy (AIT) is the only disease-modifying therapy indicated for treatment of allergic asthma, rhinitis, conjunctivitis, and Hymenoptera hypersensitivity. Manufacturing of the extracts used in AIT involve multistep complex processes as well as regulatory oversight. Furthermore, some source materials are vulnerable to unexpected events of nature. Given these circumstances, allergen extract supply can be disrupted with a potential to adversely impact patient care. A group of members from the American Academy of Allergy, Asthma, and Immunology (AAAAI) Immunotherapy, Allergy Standardization and Allergy Diagnostic Committee formed a workgroup to assess the frequency and effects of allergen extract shortages and associated factors. This workgroup developed a survey that was distributed to a random 20% of the AAAAI membership. In addition, the group also performed a review of the scientific literature on allergen extract supply and shortage. Based on the findings of the survey study and literature review, the workgroup reports frequency and extent of shortages, potential ways to improve communication with suppliers, and need for further guidance in patient care during times of shortage.

Birth elicits a conserved neuroendocrine response with implications for perinatal osmoregulation and neuronal cell death.

Long-standing clinical findings report a dramatic surge of vasopressin in umbilical cord blood of the human neonate, but the neural underpinnings and function(s) of this phenomenon remain obscure. We studied neural activation in perinatal mice and rats, and found that birth triggers activation of the suprachiasmatic, supraoptic, and paraventricular nuclei of the hypothalamus. This was seen whether mice were born vaginally or via Cesarean section (C-section), and when birth timing was experimentally manipulated. Neuronal phenotyping showed that the activated neurons were predominantly vasopressinergic, and vasopressin mRNA increased fivefold in the hypothalamus during the 2-3 days before birth. Copeptin, a surrogate marker of vasopressin, was elevated 30-to 50-fold in plasma of perinatal mice, with higher levels after a vaginal than a C-section birth. We also found an acute decrease in plasma osmolality after a vaginal, but not C-section birth, suggesting that the difference in vasopressin release between birth modes is functionally meaningful. When vasopressin was administered centrally to newborns, we found an ~ 50% reduction in neuronal cell death in specific brain areas. Collectively, our results identify a conserved neuroendocrine response to birth that is sensitive to birth mode, and influences peripheral physiology and neurodevelopment.

Suicidal Mental Imagery in Psychiatrically Hospitalized Adolescents.

Suicide is the second leading cause of death in adolescents and suicide rates in this population have increased in recent years. A critical step in preventing suicide is improving the accuracy of suicide risk assessment. Measurement of suicidal cognitions typically emphasizes assessment of verbal thoughts about suicide. Recent research suggests, however, that suicidal mental imagery, or mentally imagining suicide-related content, may be even more strongly associated with suicidal behavior. No research has evaluated suicidal mental imagery in adolescents, however. The present study evaluated suicidal mental imagery and suicidal verbal thoughts in a sample of adolescents (N = 159) admitted to an adolescent psychiatric inpatient unit. Of those adolescents who reported suicidal cognitions, 63.73% reported suicidal mental imagery. Adolescents who reported suicidal mental imagery had 2.40 greater odds of having made a suicide attempt, after accounting for history of suicidal verbal thoughts and relevant covariates. Findings suggest that suicidal mental imagery should be directly assessed when evaluating suicide risk, and that treatments may be optimized by targeting both suicidal verbal thoughts and suicidal mental imagery.

Object manufacture based on a memorized template: Goffin's cockatoos attend to different model features.

Although several nonhuman animals have the ability to recognize and match templates in computerized tasks, we know little about their ability to recall and then physically manufacture specific features of mental templates. Across three experiments, Goffin cockatoos (Cacatua goffiniana), a species that can use tools in captivity, were exposed to two pre-made template objects, varying in either colour, size (long or short) or shape (I or L-shaped), where only one template was rewarded. Birds were then given the opportunity to manufacture versions of these objects themselves. We found that all birds carved paper strips from the same colour material as the rewarded template, and half were also able to match the size of a template (long and short). This occurred despite the template being absent at test and birds being rewarded at random. However, we found no evidence that cockatoos could carve L-shaped pieces after learning that L-shaped templates were rewarded, though their manufactured strips were wider than in previous tests. Overall, our results show that Goffin cockatoos possess the ability to physically adjust at least the size dimension of manufactured objects relative to a mental template. This ability has previously only been shown in New Caledonian crows, where template matching was suggested as a potential mechanism allowing for the cumulative cultural transmission of tool designs. Our results show that within avian tool users, the ability to recreate a physical template from memory does not seem to be restricted to species that have cumulative tool cultures.

Mechanical stimulation of human dermal fibroblasts regulates pro-inflammatory cytokines: potential insight into soft tissue manual therapies.

OBJECTIVE: Soft tissue manual therapies are commonly utilized by osteopathic physicians, chiropractors, physical therapists and massage therapists. These techniques are predicated on subjecting tissues to biophysical mechanical stimulation but the cellular and molecular mechanism(s) mediating these effects are poorly understood. Previous studies established an in vitro model system for examining mechanical stimulation of dermal fibroblasts and established that cyclical strain, intended to mimic overuse injury, induces secretion of numerous pro-inflammatory cytokines. Moreover, mechanical strain intended to mimic soft tissue manual therapy reduces strain-induced secretion of pro-inflammatory cytokines. Here, we sought to partially confirm and extend these reports and provide independent corroboration of prior results. RESULTS: Using cultures of primary human dermal fibroblasts, we confirm cyclical mechanical strain increases levels of IL-6 and adding long-duration stretch, intended to mimic therapeutic soft tissue stimulation, after cyclical strain results in lower IL-6 levels. We also extend the prior work, reporting that long-duration stretch results in lower levels of IL-8. Although there are important limitations to this experimental model, these findings provide supportive evidence that therapeutic soft tissue stimulation may reduce levels of pro-inflammatory cytokines. Future work is required to address these open questions and advance the mechanistic understanding of therapeutic soft tissue stimulation.

The role of intra-operative cell salvage in patient blood management for revision hip arthroplasty: a prospective cohort study.

Cell salvage is an important component of blood management in patients undergoing revision hip arthroplasty surgery. However concerns regarding efficacy and patient selection remain. The aims of this study were to describe intra-operative blood loss, cell salvage re-infusion volumes and red blood cell transfusion rates for revision hip procedures and to identify factors associated with the ability to salvage sufficient blood intra-operatively to permit processing and re-infusion. Data were collected from a prospective cohort of 664 consecutive patients undergoing revision hip surgery at a single tertiary centre from 31 March 2015 to 1 April 2018. Indications for revision surgery were aseptic (n = 393 (59%)) fracture (n = 160 (24%)) and infection (n = 111 (17%)). Salvaged blood was processed and re-infused when blood loss exceeded 500 ml. Mean (SD) intra-operative blood loss was 1038 (778) ml across all procedures. Salvaged blood was re-infused in 505 of 664 (76%) patients. Mean (SD) re-infusion volume was 253 (169) ml. In total, 246 of 664 (37%) patients received an allogeneic red blood cell transfusion within 72 h of surgery. Patients undergoing femoral component revision only (OR (95%CI) 0.41 (0.23-0.73)) or acetabular component revision only (0.53 (0.32-0.87)) were less likely to generate sufficient blood salvage volume for re-infusion compared with revision of both components. Compared with aseptic indications, patients undergoing revision surgery for infection (1.87 (1.04-3.36)) or fracture (4.43 (2.30-8.55)) were more likely to generate sufficient blood salvage volume for re-infusion. Our data suggest that cell salvage is efficacious in this population. Cases where the indication is infection or fracture and where both femoral and acetabular components are to be revised should be prioritised.

The effects of phytase and xylanase supplementation on performance and egg quality in laying hens.

1. The aim of this study was to evaluate the effects of phytase and xylanase and their interaction on laying hen performance, egg quality, phosphorus (P) digestibility, phytate breakdown, volatile fatty acid (VFA) production and peptide YY concentration. 2. Two hundred and forty hens were allocated to cages at 22 weeks of age based on a 3 × 2 arrangement with phytase (0, 300 or 1500 FTU/kg) and xylanase (0 or 12 000 BXU/kg) as factors. 3. Phytase increased hen-day production (P < 0.05), daily egg mass (P < 0.05) and P digestibility with increasing levels of phytase (P < 0.001). Phytase fed at 1500 FTU/kg reduced IP6 and IP5 and increased myo-inositol concentration in gizzard digesta (P < 0.05). Phytase fed at 300 FTU/kg reduced IP6 in ileal digesta (P < 0.05); however, IP6 and IP5 were further reduced and myo-inositol increased when phytase was added at 1500 FTU/kg (P < 0.05). 4. Xylanase improved feed efficiency when phytase was fed at 300 FTU/kg (P < 0.05). In the absence of phytase, xylanase reduced dry matter and Ca digestibilities (P < 0.05). 5. Neither phytase nor xylanase had an effect on peptide YY or caecal VFA concentrations.

Evaluation of How Integrative Oncology Services Are Valued between Hematology/Oncology Patients and Hematologists/Oncologists at a Tertiary Care Center.

Evidence regarding opinions on integrative modalities by patients and physicians is lacking. Methods. A survey study was conducted assessing how integrative modalities were valued among hematology/oncology patients and hematologists and oncologists at a major tertiary medical center. Results. 1008 patients and 55 physicians were surveyed. With the exception of support groups, patients valued nutrition services, exercise therapy, spiritual/religious counseling, supplement/herbal advice, support groups, music therapy, and other complimentary medicine services significantly more than physicians (P ≤ 0.05). Conclusion. With the exception of support groups, patients value integrative modalities more than physicians. Perhaps with increasing education, awareness, and acceptance by providers and traditional institutions, integrative modalities could be equally valued between patients and providers. It is possible that increased availability and utilization of integrative oncology modalities at tertiary hospital sites could improve patient satisfaction, quality of life, and other clinical endpoints.

The effects of xylanase on grower pig performance, concentrations of volatile fatty acids and peptide YY in portal and peripheral blood.

Non-starch polysaccharides (NSP) present in wheat and barley can act as anti-nutrients leading to an increase in digesta viscosity and a reduction in nutrient digestibility. Xylanase, an NSP-degrading enzyme, has been shown to increase nutrient digestibility in pigs. The objectives of this study were: (1) to identify the optimum inclusion level of xylanase in grower pig diets by measuring the effect of increasing enzyme levels on growth performance, the concentration of volatile fatty acids (VFA) and peptide YY concentration in portal and peripheral blood of grower pigs and (2) to increase our understanding of the interrelationships between xylanase inclusion, VFA production and peptide YY secretion. A total of 512 grower pigs ((Large White×Landrace)×MAXGRO) were allocated to pens creating 32 replicates of four pigs per pen per treatment. Pigs were allocated to trial weighing 14.2±0.31 kg and remained on trial until ~41.5±3.31 kg. The experiment was a dose response design with four inclusion levels (0, 8000, 16 000 or 32 000 BXU/kg) of xylanase (Econase XT). Diets were cereal-based wheat, barley mix formulated to meet or exceed the nutrient requirements of grower pigs. Body weight and feed intake were recorded to calculate growth performance. Pen faecal samples were collected to estimate DM, organic matter (OM) and crude fibre (CF) apparent total-tract digestibility. At the end of the trial 16 pigs per treatment were euthanised by schedule 1 procedures. Peripheral and portal blood samples were collected for peptide YY and VFA analysis. The addition of xylanase to the diet had no effect on growth performance, DM, OM or CF total-tract digestibility; however, xylanase tended to have a quadratic effect on ileum pH with higher pH values recorded for pigs fed a diet supplemented with 8000 and 16 000 BXU/kg xylanase (P<0.1). Xylanase had no effect on peptide YY levels or VFA concentration. Total VFA concentration was higher in portal compared with peripheral blood (P<0.05). In conclusion, the addition of xylanase had no effect on grower pig performance, nutrient digestibility, VFA concentration or peptide YY concentration when fed up to 32 000 BXU/kg over a 35-day period. Pig performance was good for all treatments throughout the trial suggesting that diet quality was sufficient thus there were no beneficial effects of adding xylanase.

NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience.

Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF). Increased NRSF binding to chromatin was accompanied by sequential repressive epigenetic changes which outlasted NRSF binding. chromatin immunoprecipitation-seq analyses of NRSF targets identified gene networks that, in addition to Crh, likely contributed to the augmented care-induced phenotype, including diminished depression-like and anxiety-like behaviors. Together, we believe these findings provide the first causal link between enriched neonatal experience, synaptic refinement and induction of epigenetic processes within specific neurons. They uncover a novel mechanistic pathway from neonatal environment to emotional resilience.

Patient Attitudes Toward Local Anesthesia With or Without Sedation for Minor Hand Procedures.

The purpose of this study was to assess patient preferences in this population with respect to anesthesia for minor hand procedures. This prospective cohort study assessed 183 patients undergoing minor hand surgery to determine their preferences for local-only anesthesia with or without sedation and the reasons for their choices. Fifty-six percent of patients preferred local anesthesia with sedation, 43% preferred local-only anesthesia, and 2% had no preference. Caucasian patients were 2.7 times more likely to choose local-only anesthesia. Other than race, no other demographics showed statistical significance with respect to anesthesia preference. Patients with a prior history of local-only anesthesia were half as likely to choose it again for future surgeries. Use of an IV and awareness of procedure were the most consistent factors affecting patient decisions. Nearly half of the patients preferred local-only anesthesia. Further prospective studies evaluating outcomes and patient satisfaction with these two types of anesthesia are necessary. (Journal of Surgical Orthopaedic Advances 27(4):317-320, 2018).

Use of a highly parallel microfluidic flow cell array to determine therapeutic drug dose response curves.

A high-throughput, microfluidic flow cell array (MFCA) system has been modified to enable drug screening against small-volume cell-, and tissue cultures. The MFCA is composed of a 3D channel network that simultaneously flows fluids through forty-eight 830 µm by 500 µm flow cells, which physically divide and fluidically seal an existing culture into multiple compartments when docked onto the surface of a cell or tissue culture dish. The modified system provides temperature (37 °C) and CO2/pH level controls, while continuously flowing solutions (media or other liquid such as drug suspensions) over the cells/tissues. These assays were enhanced and validated using inverted microscopy and fluorescent staining techniques which also allow real time viability and toxicity assessments. This work presents the results of this new generation in vitro drug testing assay performed using this modified MFCA system. This setup allows the testing of 48 drug combinations on 48 different cell-, tissue specimen at once under flow conditions. All 48 flow cells were utilized to test 5 different concentrations of cisplatin (CDDP). CDDP solutions in various concentrations were continually flowed over cultured human ovarian cancer cells for 48 h. Viability assessments were performed using red-orange calcein and SYTOX ® Green nucleic acid stains. Cells were imaged at the beginning and end of the experiment (48 h). In order to compare and validate MFCAs suitability as drug screening assay, MTT assays were performed on cells. We found that both, MTT and MFCA assays generated dose-response curves with similar profiles. Innovative advantages of the MFCA system include the ability of handling smaller amounts of solutions compared to conventional and current state of the art drug screening and cell viability/toxicity methods. It also provides the ability to continually deliver fresh solution to the cell samples, while eliminating wastes that are produced. Based on our here reported findings MFCA may have a strong potential of providing a more physiological model than current state of the art static MTT assays.

EULAR revised recommendations for the management of fibromyalgia.

OBJECTIVE: The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were 'expert opinion'. METHODS: A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. RESULTS: 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only 'strong for' therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as 'weak for' based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). CONCLUSIONS: These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.