In vitro effects of nonesterified fatty acids on bovine neutrophils oxidative burst and viability

An in vitro study was conducted to examine the influence of nonesterified fatty acids (NEFA) on bovine polymorphonuclear leukocytes (PMN). Eight healthy, midlactating Holstein cows were used as blood donors. Blood PMN were isolated and incubated with a mixture of NEFA, reflecting composition of bovine plasma NEFA at concentrations that were intended to mimic those found in blood of cows undergoing high, moderate, or low lipomobilization intensity (2, 1, 0.5, 0.25, 0.125, and 0.0625 mM). Control samples were incubated in absence of NEFA. Phagocytosis and oxidative burst activities were assessed by a 2-color flow cytometric method, which was based on oxidation of intracellular dihydrorhodamine 123 to green fluorescent rhodamine 123. Oxidative burst products were generated by incubating PMN with Staphylococcus aureus labeled with propidium iodide. A flow cytometric technique was used to detect PMN viability, necrosis, and apoptosis using fluorescein isothiocyanate-labeled annexin-V and propidium iodide. Phagocytic activity was not affected by NEFA. The highest concentration of NEFA (2 mM) was associated with a dramatic increase of phagocytosis-associated oxidative burst activities with a reduction in cell viability (48.0 vs. 97.5% in control samples) and with a marked increase of necrosis (49.4 vs. 0.5% in control samples). Conversely, the mixture of NEFA did not affect the occurrence of apoptosis. Enhancement of the oxidative burst associated with the highest concentration of NEFA might explain the reduced viability and higher percentage of necrosis observed under the same conditions. This study demonstrated a substantial resistance of bovine PMN to an overload of fatty acids. However, observation that the highest concentration of NEFA regulated some PMN functions encourages the possibility of in vivo studies to assess the relationships between intensity of lipomobilization, plasma NEFA, and bovine PMN functions

Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent

Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1

Scrotal cancer: Incidence, survival and second primary tumours in the Netherlands since 1989

Background: Since the 1970s there have been few epidemiological studies of scrotal cancer. We report on the descriptive epidemiology of scrotal cancer in the Netherlands. Methods: Data on all scrotal cancer patients were obtained from the Netherlands Cancer Registry (NCR) in the period 1989-2006 and age-standardised incidence rates were calculated also according to histology and stage. Relative survival was calculated and multiple primary tumours were studied. Results: The overall incidence rate varied around 1.5 per 1 000 000 person-years, most frequently being squamous cell carcinoma (27%), basal cell carcinoma (19%) and Bowen's disease (15%). Overall 5-year relative survival was 82%, being 77% and 95% for patients with squamous and basal cell carcinoma, respectively. In all, 18% of the patients were diagnosed with a second primary tumour. Conclusion: The incidence rate of scrotal cancer did not decrease, although this was expected; affected patients might benefit from regular checkups for possible new cancers

Hypertrophic abductor hallucis muscle with nerve compression syndrome

A 13-year-old girl presented with a soft tissue swelling at the posteromedial side of the foot. This swelling had been present since birth but recently started to cause discomfort and radiating pain to the plantar aspect of the first and second toes. A magnetic resonance imaging (MRI) showed a soft tissue mass (2,6 x 3,7 x 13 centimetres) at the posteromedial side of the foot with signal-intensity similar to the intensity of muscle tissue on all the different sequences. There was no pathological contrast enhancement. Anatomically this mass was located at the abductor hallucis muscle (AH), representing a prominence or hypertrophy of the abductor hallucis muscle (Fig A). The diagnosis was made of a hypertrofic abductor hallucis muscle with narrowing the space for the medial plantar branches of the tibial nerve (circle) at the crossover between the flexor hallucis longus and flexor digitorum longus tendons (arrow), the quadratus plantae muscle (QP) and flexor digitorum brevis muscle (FDB) (Fig B). Example of a normal fibromuscular tunnel (Fig. C). Our patient was treated conservatively first and referred to a foot surgeon

Improving sleep and learning in rehabilitation after stroke, part 2 (INSPIRES2): study protocol for a home-based randomised control trial of digital cognitive behavioural therapy (dCBT) for insomnia

Introduction Consolidation of motor skill learning, a key component of rehabilitation post-stroke, is known to be sleep dependent. However, disrupted sleep is highly prevalent after stroke and is often associated with poor motor recovery and quality of life. Previous research has shown that digital cognitive behavioural therapy (dCBT) for insomnia can be effective at improving sleep quality after stroke. Therefore, the aim of this trial is to evaluate the potential for sleep improvement using a dCBT programme, to improve rehabilitation outcomes after stroke. Methods and analysis We will conduct a parallel-arm randomised controlled trial of dCBT (Sleepio) versus treatment as usual among individuals following stroke affecting the upper limb. Up to 100 participants will be randomly allocated (2:1) into either the intervention (6–8 week dCBT) or control (continued treatment as usual) group. The primary outcome of the study will be change in insomnia symptoms pre to post intervention compared with treatment as usual. Secondary outcomes include improvement in overnight motor memory consolidation and sleep measures between intervention groups, correlations between changes in sleep behaviour and overnight motor memory consolidation in the dCBT group and changes in symptoms of depression and fatigue between the dCBT and control groups. Analysis of covariance models and correlations will be used to analyse data from the primary and secondary outcomes. Ethics and dissemination The study has received approval from the National Research Ethics Service (22/EM/0080), Health Research Authority (HRA) and Health and Care Research Wales (HCRW), IRAS ID: 306 291. The results of this trial will be disseminated via presentations at scientific conferences, peer-reviewed publication, public engagement events, stakeholder organisations and other forms of media where appropriate. Trial registration number NCT05511285

Improving sleep and learning in rehabilitation after stroke, part 2 (INSPIRES2): study protocol for a home-based randomised control trial of digital cognitive behavioural therapy (dCBT) for insomnia

INTRODUCTION: Consolidation of motor skill learning, a key component of rehabilitation post-stroke, is known to be sleep dependent. However, disrupted sleep is highly prevalent after stroke and is often associated with poor motor recovery and quality of life. Previous research has shown that digital cognitive behavioural therapy (dCBT) for insomnia can be effective at improving sleep quality after stroke. Therefore, the aim of this trial is to evaluate the potential for sleep improvement using a dCBT programme, to improve rehabilitation outcomes after stroke. METHODS AND ANALYSIS: We will conduct a parallel-arm randomised controlled trial of dCBT (Sleepio) versus treatment as usual among individuals following stroke affecting the upper limb. Up to 100 participants will be randomly allocated (2:1) into either the intervention (6–8 week dCBT) or control (continued treatment as usual) group. The primary outcome of the study will be change in insomnia symptoms pre to post intervention compared with treatment as usual. Secondary outcomes include improvement in overnight motor memory consolidation and sleep measures between intervention groups, correlations between changes in sleep behaviour and overnight motor memory consolidation in the dCBT group and changes in symptoms of depression and fatigue between the dCBT and control groups. Analysis of covariance models and correlations will be used to analyse data from the primary and secondary outcomes. ETHICS AND DISSEMINATION: The study has received approval from the National Research Ethics Service (22/EM/0080), Health Research Authority (HRA) and Health and Care Research Wales (HCRW), IRAS ID: 306 291. The results of this trial will be disseminated via presentations at scientific conferences, peer-reviewed publication, public engagement events, stakeholder organisations and other forms of media where appropriate. TRIAL REGISTRATION NUMBER: NCT05511285

Domain-specific versus generalized cognitive screening in acute stroke

Cognitive assessments after stroke are typically short form tests developed for dementia that generates pass/fail classifications (e.g. the MoCA). The Oxford Cognitive Screen (OCS) provides a domain-specific cognitive profile designed for stroke survivors. This study compared the use of the MoCA and the OCS in acute stroke with respect to symptom specificity and aspects of clinical utility. A cross-sectional study with a consecutive sample of 200 stroke patients within 3 weeks of stroke completing MoCA and OCS. Demographic data, lesion side and Barthel scores were recorded. Inclusivity was assessed in terms of completion rates and reasons for non-completion were evaluated. The incidence of cognitive impairments on both the MoCA and OCS sub-domains was calculated and differences in stroke specificity, cognitive profiles and independence of the measures were addressed. The incidence of acute cognitive impairment was high: 76 % of patients were impaired on MoCA, and 86 % demonstrated at least one impairment on the cognitive domains assessed in the OCS. OCS was more sensitive than MoCA overall (87 vs 78 % sensitivity) and OCS alone provided domain-specific information on prevalent post-stroke cognitive impairments (neglect, apraxia and reading/writing ability). Unlike the MOCA, the OCS was not dominated by left hemisphere impairments but gave differentiated profiles across the contrasting domains. The OCS detects important cognitive deficits after stroke not assessed in the MoCA, it is inclusive for patients with aphasia and neglect and it is less confounded by co-occurring difficulties in these domains

Practical Routes to Preregistration: A Guide to Enhanced Transparency and Rigour in Neuropsychological Research

Preregistration is the act of formally documenting a research plan before collecting (or at least before analysing) the data. It allows those reading a final research report to know which aspects of a study were decided before sight of the data, and which were added later. This enables informed evaluation of the severity with which scientific claims have been tested. We, as the British Neuropsychological Society Open Research Group, conducted a survey to explore awareness and adoption of open research practices within our field. Neuropsychology involves the study of relatively rare or hard-to-access participants, creating practical challenges that, according to our survey, are perceived as barriers to preregistration. We survey the available routes to preregistration, and suggest that the barriers are all surmountable in one way or another. However, there is a tension, in that higher levels of bias control require greater restriction over the flexibility of preregistered studies, but such flexibility is often essential for neuropsychological research. Researchers must therefore consider which route provides the right balance of rigour and pragmatic flexibility to render a preregistered project viable for them. By mapping out the issues and potential solutions, and by signposting relevant resources and publication routes, we hope to facilitate well-reasoned decision-making and empower neuropsychologists to enhance the transparency and rigour of their research. Although we focus neuropsychology, our guidance is applicable to any field that studies hard-to-access human samples, or involves arduous or expensive means of data collection

Optimising Psychoeducation for Transient Ischaemic Attack and Minor Stroke Management (OPTIMISM): Protocol for a feasibility randomised controlled trial

Background: A transient ischaemic attack (TIA) and minor stroke are medical emergencies and often a warning sign of future strokes if remain untreated. Few studies have investigated the long-term psychosocial effects of TIA and minor stroke. Secondary prevention and medical management are often the primary focus with limited access offered for further psychosocial support. Psychoeducational interventions can provide education and advice to people with physical health conditions and, with suitable tailoring, could be appropriate for people after TIA and minor stroke. This study aims to develop a group psychoeducational intervention for people after TIA and minor stroke and to test whether it is acceptable and feasible. Methods: This mixed-methodology study involves two phases: Phase 1) A qualitative study to determine the content of a suitable intervention; Phase 2) A single-centre feasibility randomised controlled trial to evaluate the acceptability of this intervention. The overall study has ethical approval. Stroke survivors have been involved in designing and monitoring the trial. The aim is to recruit 30-40 participants from a Stroke/TIA Service, within 6 months following their diagnosis. Participants will be randomly allocated to either the usual care control group or the intervention group (psychoeducational programme). The programme will consist of six group sessions based on providing education, psychological and social support. The primary outcomes will relate to the feasibility aims of the study. Outcomes will be collected at 3 and 6 months to assess mood, quality of life, knowledge and satisfaction, and resource use. Discussion: There is a need to develop and evaluate effective interventions that enhance the education provided to people after TIA and minor stroke and to promote their psychosocial wellbeing. Findings will indicate the acceptability of the intervention and parameters needed to conduct a definitive trial