Explore the vast range of titles available.

Fascioliasis (or fasciolosis) is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving 'molecular toolbox' for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation. The exploitation of these resources is undermined by the absence of effective culture/maintenance systems that would support in vitro studies on juvenile fluke development/biology. Here we report markedly improved in vitro maintenance methods for Fasciola hepatica that achieved 65% survival of juvenile fluke after 6 months in standard cell culture medium supplemented with 50% chicken serum. We discovered that this long-term maintenance was dependent upon fluke growth, which was supported by increased proliferation of cells resembling the \"neoblast\" stem cells described in other flatworms. Growth led to dramatic morphological changes in juveniles, including the development of the digestive tract, reproductive organs and the tegument, towards more adult-like forms. The inhibition of DNA synthesis prevented neoblast-like cell proliferation and inhibited growth/development. Supporting our assertion that we have triggered the development of juveniles towards adult-like fluke, mass spectrometric analyses showed that growing fluke have an excretory/secretory protein profile that is distinct from that of newly-excysted juveniles and more closely resembles that of ex vivo immature and adult fluke. Further, in vitro maintained fluke displayed a transition in their movement from the probing behaviour associated with migrating stage worms to a slower wave-like motility seen in adults. Our ability to stimulate neoblast-like cell proliferation and growth in F. hepatica underpins the first simple platform for their long-term in vitro study, complementing the recent expansion in liver fluke resources and facilitating in vitro target validation studies of the developmental biology of liver fluke.

Background The OPTIMIZE trial is a multi-site, comparative effectiveness research (CER) study that uses a Sequential Multiple Assessment Randomized Trial (SMART) designed to examine the effectiveness of complex health interventions (cognitive behavioral therapy, physical therapy, and mindfulness) for adults with chronic low back pain. Modifications are anticipated when implementing complex interventions in CER. Disruptions due to COVID have created unanticipated challenges also requiring modifications. Recent methodologic standards for CER studies emphasize that fully characterizing modifications made is necessary to interpret and implement trial results. The purpose of this paper is to outline the modifications made to the OPTIMIZE trial using the Framework for Reporting Adaptations and Modifications to Evidence-Based Interventions (FRAME) to characterize modifications to the OPTIMIZE trial in response to the COVID pandemic and other challenges encountered. Methods The FRAME outlines a strategy to identify and report modifications to evidence-based interventions or implementation strategies, whether planned or unplanned. We use the FRAME to characterize the process used to modify the aspects of the OPTIMIZE trial. Modifications were made to improve lower-than-anticipated rates of treatment initiation and COVID-related restrictions. Contextual modifications were made to permit telehealth delivery of treatments originally designed for in-person delivery. Training modifications were made with study personnel to provide more detailed information to potential participants, use motivational interviewing communication techniques to clarify potential participants’ motivation and possible barriers to initiating treatment, and provide greater assistance with scheduling of assigned treatments. Results Modifications were developed with input from the trial’s patient and stakeholder advisory panels. The goals of the modifications were to improve trial feasibility without compromising the interventions’ core functions. Modifications were approved by the study funder and the trial steering committee. Conclusions Full and transparent reporting of modifications to clinical trials, whether planned or unplanned, is critical for interpreting the trial’s eventual results and considering future implementation efforts. Trial registration ClinicalTrials.gov NCT03859713. Registered on March 1, 2019

Flow chart depicting the methods, preparing, and characterizing, by histological, and scanning electron microscopy, of wet (PW-HAM) and dry (PD-HAM)of wound healing dressing, and preparation of nanoparticles (HAMP ZnO NP); and application of HAM wound dressing. The preparation of unique wet and dry wound dressing products derived from unprocessed human amniotic membrane (UP-HAM) is described. The UP-HAM was decellularized, and the constituent proteins were cross-linked and stabilized before being trimmed and packed in sterile Nucril-coated laminated aluminium foil pouches with isopropyl alcohol to manufacture processed wet human amniotic membrane (PW-HAM). The dry type of PD-HAM was prepared by decellularizing the membrane, UV irradiating it, lyophilizing/freeze-drying it, sterilizing it, and storing it at room temperature. The UP-HAM consists of a translucent yellowish mass of flexible membranes with an average thickness of 42 μm. PW-HAM wound dressings that had been processed, decellularized, and dehydrated had a thinner average thickness of 30 μm and lacked nuclear-cellular structures. Following successful decellularization, discrete bundle of fibrous components in the stromal spongy layers, microvilli and reticular ridges were still evident on the surface of the processed HAM, possibly representing the location of the cells that had been removed by the decellularization process. Both wet and dry HAM wound dressings are durable, portable, have a shelf life of 3–5 years, and are available all year. A slice of HAM dressing costs 1.0 US$/cm 2 . Automation and large-scale HAM membrane preparation, as well as storage and transportation of the dressings, can all help to establish advanced technologies, improve the efficiency of membrane production, and reduce costs. Successful treatment of wounds to the cornea of the eye was achieved with the application of the HAM wound dressings. The HAM protein analysis revealed 360 μg proteins per gram of tissue, divided into three main fractions with MWs of 100 kDa, 70 kDa, and 14 kDa, as well as seven minor proteins, with the 14 kDa protein displaying antibacterial properties against human pathogenic bacteria. A wide range of antibacterial activity was observed after treatment with 75 μg/ml zinc oxide nanoparticles derived from human amniotic membrane proteins (HAMP-ZnO NP), including dose-dependent biofilm inhibition and inhibition of Gram-positive ( S. aureus, S. mutans, E. faecalis , and L. fusiformis ) and Gram-negative bacteria ( S. sonnei, P. aeruginosa, P. vulgaris, and C. freundii).

Neck pain frequently is managed by physical therapists. The development of classification methods for matching interventions to subgroups of patients may improve clinical outcomes. The purpose of this study was to describe a proposed classification system for patients with neck pain by examining data for consecutive patients receiving physical therapy interventions. Standardized methods for collecting baseline and intervention data were used for all patients receiving physical therapy interventions for neck pain over 1 year. Outcome variables were the Neck Disability Index (NDI), numeric pain rating, and number of visits. Treatment was provided at the discretion of the physical therapist. After the completion of treatment, each patient was classified by use of baseline variables. The interventions received by the patient were categorized as being matched or not matched to the classification. Outcomes for patients who received matched interventions were compared with those for patients who received nonmatched interventions. The interrater reliability of the classification algorithm was examined with a subset of 50 patients. A total of 274 patients were included in this study (74% women; age [X+/-SD]=44.4+/-16.0 years). The most common classification was centralization (34.7%); next were exercise and conditioning (32.8%) and mobility (17.5%). The interrater reliability for classification decisions was high (kappa=.95, 95% confidence interval [CI]=0.87-1.0). A total of 113 patients (41.2%) received interventions matched to the classification. Receiving matched interventions was associated with greater improvements in the NDI (mean difference=5.6 points, 95% CI=2.6-8.6) and in pain ratings (mean difference=0.74 point, 95% CI=0.21-1.3) than receiving nonmatched interventions. The development of classification methods for patients with neck pain may improve the outcomes of physical therapy intervention. This study was done to examine a previously proposed classification system for patients receiving physical therapy interventions for neck pain. Receiving interventions matched to the classification system was associated with better outcomes than receiving nonmatched interventions. Although the design of this study prohibited drawing conclusions about the effectiveness of the system, the results suggest that further research on the system may be warranted.

Psychological distress is common in individuals undergoing total joint arthroplasty (TJA). Understanding psychological phenotypes and their transitions from before to after surgery can inform risk stratification and targeted care. This study aimed to characterize psychological phenotypes, examine transitions, and compare patient outcomes across phenotypes. This retrospective study included 494 patients who underwent primary hip (43%) or knee (57%) arthroplasty at Duke University Health System (2018–2024). Latent transition analysis identified and examined transitions of psychological phenotypes preoperatively and postoperatively using the Optimal Screening for Prediction of Referral and Outcome Yellow Flag tool. Demographic characteristics, phenotype transitions, Patient‐Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI), PROMIS Physical Function (PF), pain intensity, and high‐impact chronic pain (HICP) were compared across phenotypes. The optimal model fit was a constrained model comprising five classes: class 1 (low self‐efficacy with poor pain coping), class 2 (low distress), class 3 (poor pain coping), class 4 (high distress), and class 5 (low self‐efficacy with acceptance). Most patients (n = 271, 55%) transitioned to a different phenotype. The probabilities for remaining in the same class ranged from 0.19 (poor pain coping) to 0.61 (low distress). The incidence of high distress was 6% within 12 months after TJA. High distress was associated with lower PROMIS‐PF and higher PROMIS‐PI scores, pain intensity, and prevalence of HICP (P < 0.001). Transitions were observed across all phenotypes, with some demonstrating greater stability and others showing more state‐like variability. Identifying phenotypes with distinct trajectories and outcomes may support targeted screening and preoperative risk stratification.

Medicare beneficiaries frequently receive physical therapy for musculoskeletal conditions. Little information is available about this care. The purposes of this study were: (1) to describe characteristics, clinical outcomes, and utilization for Medicare beneficiaries receiving physical therapy in outpatient clinics within one integrated health care system; (2) to compare characteristics, outcomes, and utilization based on the body region affected; and (3) to examine factors predictive of outcomes and utilization. This was a prospective, longitudinal study. Medicare beneficiaries aged 65 years or older (n=1,840 episodes of care) participated in the study. Descriptive statistics were calculated for patient characteristics and outcomes. Comparisons were made based on body region. Regression models evaluated factors associated with change in pain, improved outcome, and utilization. The patients' mean age was 74.2 years (SD=6.3), and 65.3% were female. The most common body regions were the lumbar spine, shoulder, and knee, collectively accounting for 71.3% of the episodes of care. Patients attended a mean of 6.8 visits (SD=4.7), and 63.9% experienced an improved outcome. Episodes of care for lumbar spine conditions had less reduction in pain, whereas shoulder conditions and foot/ankle conditions showed the greatest improvement. Care for hip conditions was least likely to result in an improved outcome. Knee conditions were most likely to have an improved outcome. Care for shoulder and knee conditions had the highest number of visits. Factors associated with greater reduction in pain and improved outcomes included greater initial pain or disability and attending more visits. Factors associated with greater utilization included a postsurgical condition and higher initial pain rating. Limitations The study was performed in one geographic region within a single health care delivery system. The results provide information on outcomes of physical therapy for Medicare beneficiaries in one health care system. Further research is needed to examine optimal utilization and care for these patients.

Physical therapists often attend continuing education (CE) courses to improve their overall clinical performance and patient outcomes. However, evidence suggests that CE courses may not improve the outcomes for patients receiving physical therapy for the management of neck pain. The purpose of this study was to investigate the effectiveness of an ongoing educational intervention for improving the outcomes for patients with neck pain. The study participants were 19 physical therapists who attended a 2-day CE course focusing on the management of neck pain. All patients treated by the therapists in this study completed the Neck Disability Index (NDI) and a pain rating scale at the initial examination and at their final visit. Therapists from 11 clinics were invited to attend a 2-day CE course on the management of neck pain. After the CE course, the therapists were randomly assigned to receive either ongoing education consisting of small group sessions and an educational outreach session or no further education. Clinical outcomes achieved by therapists who received ongoing education and therapists who did not were compared for both pretraining and posttraining periods. The effects of receiving ongoing education were examined by use of linear mixed-model analyses with time period and group as fixed factors; improvements in disability and pain as dependent variables; and age, sex, and the patient's initial NDI and pain rating scores as covariates. Patients treated by therapists who received ongoing education experienced significantly greater reductions in disability during the study period (pretraining to posttraining) than those treated by therapists who did not receive ongoing training (mean difference=4.2 points; 95% confidence interval [CI]=0.69, 7.7). Changes in pain did not differ for patients treated by the 2 groups of therapists during the study period (mean difference=0.47 point; 95% CI=-0.11, 1.0). Therapists in the ongoing education group also used fewer visits during the posttraining period (mean difference=1.5 visits; 95% CI=0.81, 2.3). The results of this study demonstrated that ongoing education for the management of neck pain was beneficial in reducing disability for patients with neck pain while reducing the number of physical therapy visits. However, changes in pain did not differ for patients treated by the 2 groups of therapists. Although it appears that a typical CE course does not improve the overall outcomes for patients treated by therapists attending that course, more research is needed to evaluate other educational strategies to determine the most clinically effective and cost-effective interventions.

INTRODUCTION: Chitons (Polyplacophora) are molluscs considered to have a simple nervous system without cephalisation. The position of the class within Mollusca is the topic of extensive debate and neuroanatomical characters can provide new sources of phylogenetic data as well as insights into the fundamental biology of the organisms. We report a new discrete anterior sensory structure in chitons, occurring throughout Lepidopleurida, the order of living chitons that retains plesiomorphic characteristics. RESULTS: The novel “Schwabe organ” is clearly visible on living animals as a pair of streaks of brown or purplish pigment on the roof of the pallial cavity, lateral to or partly covered by the mouth lappets. We describe the histology and ultrastructure of the anterior nervous system, including the Schwabe organ, in two lepidopleuran chitons using light and electron microscopy. The oesophageal nerve ring is greatly enlarged and displays ganglionic structure, with the neuropil surrounded by neural somata. The Schwabe organ is innervated by the lateral nerve cord, and dense bundles of nerve fibres running through the Schwabe organ epithelium are frequently surrounded by the pigment granules which characterise the organ. Basal cells projecting to the epithelial surface and cells bearing a large number of ciliary structures may be indicative of sensory function. The Schwabe organ is present in all genera within Lepidopleurida (and absent throughout Chitonida) and represents a novel anatomical synapomorphy of the clade. CONCLUSIONS: The Schwabe organ is a pigmented sensory organ, found on the ventral surface of deep-sea and shallow water chitons; although its anatomy is well understood, its function remains unknown. The anterior commissure of the chiton oesophagial nerve ring can be considered a brain. Our thorough review of the chiton central nervous system, and particularly the sensory organs of the pallial cavity, provides a context to interpret neuroanatomical homology and assess this new sense organ.

Acute low back pain (LBP) is highly prevalent, with a presumed favorable prognosis; however, once chronic, LBP becomes a disabling and expensive condition. Acute to chronic LBP transition rates vary widely owing to absence of standardized operational definitions, and it is unknown whether a standardized prognostic tool (ie, Subgroups for Targeted Treatment Back tool [SBT]) can estimate this transition or whether early non-guideline concordant treatment is associated with the transition to chronic LBP. To assess the associations between the transition from acute to chronic LBP with SBT risk strata; demographic, clinical, and practice characteristics; and guideline nonconcordant processes of care. This inception cohort study was conducted alongside a multisite, pragmatic cluster randomized trial. Adult patients with acute LBP stratified by SBT risk were enrolled in 77 primary care practices in 4 regions across the United States between May 2016 and June 2018 and followed up for 6 months, with final follow-up completed by March 2019. Data analysis was conducted from January to March 2020. SBT risk strata and early LBP guideline nonconcordant processes of care (eg, receipt of opioids, imaging, and subspecialty referral). Transition from acute to chronic LBP at 6 months using the National Institutes of Health Task Force on Research Standards consensus definition of chronic LBP. Patient demographic characteristics, clinical factors, and LBP process of care were obtained via electronic medical records. Overall, 5233 patients with acute LBP (3029 [58%] women; 4353 [83%] White individuals; mean [SD] age 50.6 [16.9] years; 1788 [34%] low risk; 2152 [41%] medium risk; and 1293 [25%] high risk) were included. Overall transition rate to chronic LBP at six months was 32% (1666 patients). In a multivariable model, SBT risk stratum was positively associated with transition to chronic LBP (eg, high-risk vs low-risk groups: adjusted odds ratio [aOR], 2.45; 95% CI, 2.00-2.98; P < .001). Patient and clinical characteristics associated with transition to chronic LBP included obesity (aOR, 1.52; 95% CI, 1.28-1.80; P < .001); smoking (aOR, 1.56; 95% CI, 1.29-1.89; P < .001); severe and very severe baseline disability (aOR, 1.82; 95% CI, 1.48-2.24; P < .001 and aOR, 2.08; 95% CI, 1.60-2.68; P < .001, respectively) and diagnosed depression/anxiety (aOR, 1.66; 95% CI, 1.28-2.15; P < .001). After controlling for all other variables, patients exposed to 1, 2, or 3 nonconcordant processes of care within the first 21 days were 1.39 (95% CI, 1.21-2.32), 1.88 (95% CI, 1.53-2.32), and 2.16 (95% CI, 1.10-4.25) times more likely to develop chronic LBP compared with those with no exposure (P < .001). In this cohort study, the transition rate to chronic LBP was substantial and increased correspondingly with SBT stratum and early exposure to guideline nonconcordant care.

Summary Klebsiella pneumoniae is an important cause of community‐acquired and nosocomial pneumonia. Evidence indicates that Klebsiella might be able to persist intracellularly within a vacuolar compartment. This study was designed to investigate the interaction between Klebsiella and macrophages. Engulfment of K. pneumoniae was dependent on host cytoskeleton, cell plasma membrane lipid rafts and the activation of phosphoinositide 3‐kinase (PI3K). Microscopy studies revealed that K. pneumoniae resides within a vacuolar compartment, the Klebsiella‐containing vacuole (KCV), which traffics within vacuoles associated with the endocytic pathway. In contrast to UV‐killed bacteria, the majority of live bacteria did not co‐localize with markers of the lysosomal compartment. Our data suggest that K. pneumoniae triggers a programmed cell death in macrophages displaying features of apoptosis. Our efforts to identify the mechanism(s) whereby K. pneumoniae prevents the fusion of the lysosomes to the KCV uncovered the central role of the PI3K–Akt–Rab14 axis to control the phagosome maturation. Our data revealed that the capsule is dispensable for Klebsiella intracellular survival if bacteria were not opsonized. Furthermore, the environment found by Klebsiella within the KCV triggered the down‐regulation of the expression of cps. Altogether, this study proves evidence that K. pneumoniae survives killing by macrophages by manipulating phagosome maturation that may contribute to Klebsiella pathogenesis. Prevailing belief states that the human pathogens Klebsiella pneumoniae is an extracellular pathogen. However, in this work, we demonstrate that K. pneumoniae co‐opts the maturation of the phagosome manipulating a PI3K‐AKT‐RAB14 signalling cascade. Here, we also demonstrate that by preventing the activation of this cascade, the macrophages eliminate intracellular Klebsiella.