A scoping review of 'Pacing' for management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): lessons learned for the long COVID pandemic.

BACKGROUND: Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people with ME/CFS. Whilst a definitive definition of pacing is not unanimous within the literature or healthcare providers, it typically comprises regulating activity to avoid post exertional malaise (PEM), the worsening of symptoms after an activity. Until now, characteristics of pacing, and the effects on patients' symptoms had not been systematically reviewed. This is problematic as the most common approach to pacing, pacing prescription, and the pooled efficacy of pacing was unknown. Collating evidence may help advise those suffering with similar symptoms, including long COVID, as practitioners would be better informed on methodological approaches to adopt, pacing implementation, and expected outcomes. OBJECTIVES: In this scoping review of the literature, we aggregated type of, and outcomes of, pacing in people with ME/CFS. ELIGIBILITY CRITERIA: Original investigations concerning pacing were considered in participants with ME/CFS. SOURCES OF EVIDENCE: Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature, to fully capture patient surveys not published in academic journals. METHODS: A scoping review was conducted. Review selection and characterisation was performed by two independent reviewers using pretested forms. RESULTS: Authors reviewed 177 titles and abstracts, resulting in 17 included studies: three randomised control trials (RCTs); one uncontrolled trial; one interventional case series; one retrospective observational study; two prospective observational studies; four cross-sectional observational studies; and five cross-sectional analytical studies. Studies included variable designs, durations, and outcome measures. In terms of pacing administration, studies used educational sessions and diaries for activity monitoring. Eleven studies reported benefits of pacing, four studies reported no effect, and two studies reported a detrimental effect in comparison to the control group. CONCLUSIONS: Highly variable study designs and outcome measures, allied to poor to fair methodological quality resulted in heterogenous findings and highlights the requirement for more research examining pacing. Looking to the long COVID pandemic, our results suggest future studies should be RCTs utilising objectively quantified digitised pacing, over a longer duration of examination (i.e. longitudinal studies), using the core outcome set for patient reported outcome measures. Until these are completed, the literature base is insufficient to inform treatment practises for people with ME/CFS and long COVID.

Dual-task decrements in mono-, bi- and multilingual participants: Evidence for multilingual advantage.

Evidence suggests that language processing in bilinguals is less left-lateralized than in monolinguals. We explored dual-task decrement (DTD) for mono-, bi- and multilinguals in a verbal-motor dual-task paradigm. We expected monolinguals to show greater DTD than bilingual participants, who would show greater DTD than multilingual participants. Fifty right-handed participants (18 monolingual, 16 bilingual, 16 multilingual) completed verbal fluency and manual motor tasks in isolation and concurrently. Tasks were completed twice in isolation (left-handed, right-handed) and twice as dual-tasks (left-handed, right-handed); participants' motor-executing hands served proxy for hemispheric activation. Results supported the hypotheses. Completing dual-tasks incurred greater cost for manual motor tasks than for verbal fluency tasks. Negative cost of performing dual-tasks diminished as number of languages spoken increased; in fact, multilingual individuals demonstrated a dual-task advantage in both tasks when using the right hand, strongest in the verbal task. Dual-tasking had the greatest negative impact on verbal fluency of monolingual participants when the motor task was completed with the right hand; for bi- and multi-lingual participants, the greatest negative impact on verbal fluency was seen when the motor task was completed with the left hand. Results provide support for the bi-lateralization of language function in bi- and multilingual individuals.

Irony as a Test of the Presupposition-Denial Account: An ERP Study.

According to the Presupposition-Denial Account, complement set reference arises when focus is on the shortfall between the amount conveyed by a natural language quantifier and a larger, expected amount. Negative quantifiers imply a shortfall, through the denial of a presupposition, whereas positive quantifiers do not. An exception may be provided by irony. One function of irony is to highlight, through indirect negation, the shortfall between what is expected/desired, and what is observed. Thus, a positive quantifier used ironically should also lead to a shortfall and license complement set reference. Using ERPs, we examined whether reference to the complement set is more felicitous following a positive quantifier used ironically than one used non-ironically. ERPs during reading showed a smaller N400 for complement set reference following an ironic compared to a non-ironic context. The shortfall generated thorough irony is sufficient to allow focus on the complement set, supporting the Presupposition-Denial Account.

Initial tweet valence, abuse volume, and observer Dark Tetrad characteristics influence perceptions of female celebrity abuse on Twitter.

Research into relationships between victim-generated content, abuse received, and observer characteristics when considering Twitter abuse has been limited to male victims. We evaluated participant perceptions of female celebrity victims and abuse received on Twitter. We used a 3 (Initial Tweet Valence; negative, neutral, positive) × 2 (Abuse Volume; low, high) repeated measures design and online survey method. Participants were shown tweets generated by six female celebrities, counterbalanced such that each participant saw each celebrity in one Valence-Volume condition. Stimuli were presented across six 'lists' such that celebrity 'victims' could be rotated across Valence-Volume pairings. Participants rated-per target stimulus-the level of blame attributable to the victim and the perceived severity of the incident. Furthermore, participants were asked to complete a Dark Tetrad scale-measuring their Machiavellianism, Narcissism, Psychopathy, and Sadism. Analyses determined that victim-blaming was influenced by victim Initial Tweet Valence (greater victim-blaming associated with more-negative content) and observer Machiavellianism. Perceived severity was influenced by victim Initial Tweet Valence, Volume of Abuse received, and observer Machiavellianism. Results were consistent with previous research involving male celebrity victims. Further research is needed to understand the contributions of participants' hostile and benevolent sexism, as well as the role of victim attractiveness.

A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long-COVID in Scotland: Part I.

BACKGROUND: Commonly reported symptoms of long COVID may have different patterns of prevalence and presentation across different countries. While some limited data have been reported for the United Kingdom, national specificity for Scotland is less clear. We present a cross-sectional survey to examine the symptom prevalence, frequency, and severity of long COVID for people living with the condition in Scotland. METHODS: An online survey was created in the English language and was available between April 21, 2022 and August 5, 2022. Participants were included if they were ≥18 years old, living in Scotland, and had self-diagnosed or confirmed long COVID; and excluded if they were hospitalized during their initial infection. Within this article we quantify symptom prevalence, frequency, severity, and duration. RESULTS: Participants (n = 253) reported the most prevalent long-COVID symptoms to be post-exertional malaise (95%), fatigue/tiredness (85%), and cognitive impairment (68%). Fatigue/tiredness, problems with activities of daily living (ADL), and general pain were most frequently occurring, while sleep difficulties, problems with ADL, and nausea were the most severe. Scottish Index of Multiple Deprivation associated with symptom number, severity, and frequency, whereas vaccine status, age, sex, and smoking status had limited or no association. CONCLUSIONS: These findings outline the challenges faced for those living with long COVID and highlight the need for longitudinal research to ascertain a better understanding of the condition and its longer-term societal impact.

A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long COVID in Scotland: Part II.

BACKGROUND: There has been some effort to map the prevalence, frequency, and severity of symptoms of long COVID at local and national levels. However, what is frequently absent from such accounts is details of the impact the disease and its symptoms have had on those living with the condition. In this article, we present details of the impact on work, caring, and mental health gathered using a cross-sectional survey. METHODS: Data were collected using an online survey that was available from April 21, 2022, to August 5, 2022. Included participants had either self-diagnosed or confirmed long COVID, were living in Scotland, and were aged ≥18 years. Hospitalization during initial COVID-19 infection was an exclusion criterion. Participants were asked to report on the impact of their illness on everyday activities such as working, studying, or caring. They also completed an assessment of their current mood. RESULTS: People with long COVID were often severely impacted in their ability to work and study. Severe impact on work and study were predicted by more severe and more frequent fatigue, more severe pain, and more severe cognitive impairment. Respondents' ability to care for child dependents was also associated with more severe and more frequent fatigue, and more severe cognitive impairments. More severe pain associated with greater impact on adult care. Negative mood correlated most strongly with frequency and severity of neurological symptoms, including lack of attention, loss of smell, impaired sense of smell, loss of taste, impaired sense of taste, and loss of appetite. CONCLUSIONS: Long COVID has a significant impact on ability to work, study, and care for dependents. The severity of this impact is associated with specific symptom burden, including fatigue, pain, and cognitive impairment.

Exploring the effects of COVID-19 restrictions on wellbeing across different styles of lockdown.

Countries have instigated different restrictions in response to the COVID-19 pandemic. For instance, nationwide, strict "lockdown" in Scotland was enacted with breaches punishable by law, whereas restrictions in Japan allowed for travel and interaction, with citizens requested rather than required to conform. We explored the impact of these differential strategies on health behaviours and wellbeing. In February 2021, 138 Scottish and 139 Japanese participants reported their demographic information, pandemic-induced health behaviour-change (alcohol consumption, diet, perceived sleep quality, physical activity), negative mood, and perceived social isolation. Scottish participants' health behaviours were characterised by greater change (typically negative), most likely due to greater lifestyle disruption, whereas Japanese participants' behaviours were more-stable. Negative changes to health behaviours were typically associated with poorer mental wellbeing and isolation. Interestingly though, Japanese participants reported greater negative mood but not isolation despite the less-restrictive lockdown. Taken together, different lockdown styles led to different changes in health behaviours.

More Than 100 Persistent Symptoms of SARS-CoV-2 (Long COVID): A Scoping Review.

Background: Persistent coronavirus disease 2019 (COVID-19) symptoms are increasingly well-reported in cohort studies and case series. Given the spread of the pandemic, number of individuals suffering from persistent symptoms, termed 'long COVID', are significant. However, type and prevalence of symptoms are not well reported using systematic literature reviews. Objectives: In this scoping review of the literature, we aggregated type and prevalence of symptoms in people with long COVID. Eligibility Criteria: Original investigations concerning the name and prevalence of symptoms were considered in participants ≥4-weeks post-infection. Sources of Evidence: Four electronic databases [Medline, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL)] were searched. Methods: A scoping review was conducted using the Arksey and O'Malley framework. Review selection and characterisation was performed by three independent reviewers using pretested forms. Results: Authors reviewed 2,711 titles and abstracts for inclusion with 152 selected for full-text review. 102 articles were subsequently removed as this did not meet inclusion criteria. Thus, fifty studies were analysed, 34 of which were described as cohort studies or prospective cohort studies, 14 were described as cross-sectional studies, one was described as a case control study, and one was described as a retrospective observational study. In total, >100 symptoms were identified and there was considerable heterogeneity in symptom prevalence and setting of study. Ten studies reported cardiovascular symptoms, four examined pulmonary symptoms, 25 reported respiratory symptoms, 24 reported pain-related symptoms, 21 reported fatigue, 16 reported general infection symptoms, 10 reported symptoms of psychological disorders, nine reported cognitive impairment, 31 reported a sensory impairment, seven reported a dermatological complaint, 11 reported a functional impairment, and 18 reported a symptom which did not fit into any of the above categories. Conclusion: Most studies report symptoms analogous to those apparent in acute COVID-19 infection (i.e., sensory impairment and respiratory symptoms). Yet, our data suggest a larger spectrum of symptoms, evidenced by >100 reported symptoms. Symptom prevalence varied significantly and was not explained by data collection approaches, study design or other methodological approaches, and may be related to unknown cohort-specific factors.

Social isolation during COVID-19 lockdown impairs cognitive function.

Studies examining the effect of social isolation on cognitive function typically involve older adults and/or specialist groups (e.g., expeditions). We considered the effects of COVID-19-induced social isolation on cognitive function within a representative sample of the general population. We additionally considered how participants 'shielding' due to underlying health complications, or living alone, performed. We predicted that performance would be poorest under strictest, most-isolating conditions. At five timepoints over 13 weeks, participants (N = 342; aged 18-72 years) completed online tasks measuring attention, memory, decision-making, time-estimation, and learning. Participants indicated their mood as 'lockdown' was eased. Performance typically improved as opportunities for social contact increased. Interactions between participant sub-groups and timepoint demonstrated that performance was shaped by individuals' social isolation levels. Social isolation is linked to cognitive decline in the absence of ageing covariates. The impact of social isolation on cognitive function should be considered when implementing prolonged pandemic-related restrictive conditions.

Words from the wizarding world: Fictional words, context, and domain knowledge.

The influence of domain knowledge on reading behavior has received limited investigation compared to the influence of, for example, context and/or word frequency. The current study tested participants with and without domain knowledge of the Harry Potter (HP) universe. Fans and non-fans read sentences containing HP, high-frequency (HF), or low-frequency target-words. Targets were presented in contexts that were supportive or unsupportive within a 2 (group: fans, non-fans) × 3 (context: HP, HF, LF) × 3 (word type: HP, HF, LF) mixed design. Thirty-two fans and 22 non-fans read 72 two-sentence experimental items while eye-movement behavior was recorded: Initial sentences established context; second sentences contained target-words. Fans processed HP words faster than non-fans. No group difference was observed on HF or LF processing durations, suggesting equivalent reading capabilities. In HP contexts, HP and LF targets were processed equivalently. Processing of HF and LF words was facilitated by their supportive context as expected. Non-fans made more regressions into the target region in HP contexts and regressed more into HP targets than other targets; fans regressed into target word regions equivalently across all context and word types. Results suggest that domain knowledge influences early but not immediate lexical access, while the processing effect of novelty was seen in regressive eye movements. These results are more supportive of modular accounts of linguistic processing and serial models of eye movement control. Words without grounding in reality, or true embodiment, were integrated into fans' mental lexicons. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Changes in Diet, Sleep, and Physical Activity Are Associated With Differences in Negative Mood During COVID-19 Lockdown.

The United Kingdom and Scottish governments instigated a societal lockdown in response to the COVID-19 pandemic. Subsequently, many experienced substantial lifestyle changes alongside the stresses of potentially catching the virus or experiencing bereavement. Stressful situations and poorer health behaviors (e.g., higher alcohol consumption, unhealthy diet, poorer sleep quality, physical inactivity) are frequently linked to poor mental health. Our objective was to examine changes in health behaviors and their relationship with negative mood during COVID-19 lockdown. We also considered associations between health behaviors and socio-demographic differences and COVID-19-induced changes. 399 participants completed a questionnaire asking about their personal situation and health behaviors during lockdown as well as a negative mood scale. The significance threshold for all analyses was α = 0.05. Poorer diet was linked to more-negative mood, and to changes to working status. Poorer sleep quality was linked with more-negative mood, and with 'shielding' from the virus. Being less physically active was related to more-negative mood and student status, whereas being more physically active was linked to having or suspecting COVID-19 infection within the household. Increased alcohol consumption was linked to living with children, but not to negative mood. Changes to diet, sleep quality, and physical activity related to differences in negative mood during COVID-19 lockdown. This study adds to reports on poor mental health during lockdown and identifies lifestyle restrictions and changes to health behaviors which may, to some extent, be responsible for higher negative mood. Our data suggests that it is advisable to maintain or improve health behaviors during pandemic-associated restrictions.

Corrigendum: Changes in Diet, Sleep, and Physical Activity Are Associated With Differences in Negative Mood During COVID-19 Lockdown.

[This corrects the article DOI: 10.3389/fpsyg.2020.588604.].

The use of ultrasonication to aid recellularization of acellular natural tissue scaffolds for use in anterior cruciate ligament reconstruction.

Tissue engineering offers a promising solution to the replacement of anterior cruciate ligament. A decellularized porcine patella tendon scaffold was produced by immersing whole tissues sequentially in hypotonic buffer, 0.1% (w/v) sodium dodecyl sulfate (SDS) in hypotonic buffer, and nuclease solution prior to sterilization with 0.1% (w/v) peracetic acid. Initial studies revealed that primary human tenocytes would attach to, but failed to penetrate into, the decellularized scaffold. A novel use of ultrasonication was therefore developed to allow extrinsic cells to migrate into the acellular scaffold. Various intensities of ultrasonication were tested in order to produce a microscopically more open porous matrix without damaging the overall architecture of the scaffold. Ultrasonication treatment with the intensity of 360 W and a pulse time of 1 s for a total of 1 min was found to be the optimal treatment. This process did not have a significant effect upon the biochemical constituents (collagen, glycosaminoglycans), nor did it denature the collagen. Moreover, the acellular sonicated scaffold retained the essential biomechanical characteristics of the native tissue. Primary human tenocytes penetrated into the center of whole acellular sonicated scaffolds over a 3-week period in static culture. The viability of the cells in the center of the scaffold (depth of circa 2.5 mm) was, however, compromised. To circumvent the problem of nutrient limitation, acellular sonicated scaffolds were split into fascicular scaffolds (500 mum thick). Cells seeded onto the fascicular scaffolds penetrated throughout the scaffold and remained viable after 3 weeks of culture. This study has shown that an acellular biocompatible tendon scaffold can be produced using 0.1% (w/v) SDS and that ultrasonication can provide a novel method to enhance the recellularization of decellularized natural tissues.

Exploring the Measurement of Markedness and Its Relationship with Other Linguistic Variables.

Antonym pair members can be differentiated by each word's markedness-that distinction attributable to the presence or absence of features at morphological or semantic levels. Morphologically marked words incorporate their unmarked counterpart with additional morphs (e.g., "unlucky" vs. "lucky"); properties used to determine semantically marked words (e.g., "short" vs. "long") are less clearly defined. Despite extensive theoretical scrutiny, the lexical properties of markedness have received scant empirical study. The current paper employs an antonym sequencing approach to measure markedness: establishing markedness probabilities for individual words and evaluating their relationship with other lexical properties (e.g., length, frequency, valence). Regression analyses reveal that markedness probability is, as predicted, related to affixation and also strongly related to valence. Our results support the suggestion that antonym sequence is reflected in discourse, and further analysis demonstrates that markedness probabilities, derived from the antonym sequencing task, reflect the ordering of antonyms within natural language. In line with the Pollyanna Hypothesis, we argue that markedness is closely related to valence; language users demonstrate a tendency to present words evaluated positively ahead of those evaluated negatively if given the choice. Future research should consider the relationship of markedness and valence, and the influence of contextual information in determining which member of an antonym pair is marked or unmarked within discourse.

The osteolytic response of macrophages to challenge with particles of Simplex P, Endurance, Palacos R, and Vertebroplastic bone cement particles in vitro.

The capacity of clinically relevant wear particles from Simplex P, Endurance, Vertebroplastic and Palacos R bone cements to activate macrophages to produce cytokines and bone resorbing activity in vitro was compared. Cement particles were generated aseptically by using a pin on plate rig. The particles were irregular in shape, and there were no significant differences in the particle characteristics of the different bone cement types (mean equivalent circle diameter range 0.225--0.36 mum, mean area range 0.048--0.063 microm(2), mean aspect ratio range 1.481--1.593, and mean length 0.412--0.523 microm). The volumetric concentration of particles in the 0.1- to 1.0-microm size range was 85% Palacos R, 82% Endurance, 80% Simplex P, and 77% Vertebroplastic. Particles were cultured with C3H macrophages at 100 microm(3) per cell for 24 h. Cytokines were determined by enzyme-linked immunosorbent assay and bone resorption (BR) measured by Ca(45) release from murine calvarias. Particles of Palacos R and Endurance stimulated enhanced production of TNF-alpha, IL-1-beta, and IL-6 (p<0.05; ANOVA). Simplex P particles only stimulated IL-1-beta (p<0.05; ANOVA). Vertebroplastic particles did not stimulate production of any of the cytokines. Particles of Palacos R generated the highest BR (1.38), but this did not reach statistical significance. The BRs for the other bone cements were no greater than the control. Hence, compared with the same volumetric concentrations, particles of Palacos R and Endurance were the most, and particles of Vertebroplastic were the least biologically reactive.

The influence of molecular weight, crosslinking and counterface roughness on TNF-alpha production by macrophages in response to ultra high molecular weight polyethylene particles.

The response of murine macrophages to clinically relevant polyethylene wear particles generated from different polyethylenes at various time points and volumetric doses in vitro was evaluated. Clinically relevant ultra high molecular weight polyethylene (UHMWPE) wear debris was generated in vitro in a lubricant of RPMI 1640 supplemented with 25% (v/v) foetal calf serum using a multi-directional pin-on-plate wear rig under sterile conditions. Wear debris was cultured with C3H murine peritoneal macrophages at various particle volume (microm(3)): cell number ratios. The secretion of TNF-alpha was determined by ELISA. Initially the effect of molecular weight of UHMWPE was considered. Higher molecular weight GUR415HP was shown to have a lower wear rate than the lower molecular weight GUR1120, however a greater volume of the wear debris produced by the high molecular weight GUR415HP was in the 0.1-1.0 microm size range. Wear debris from GUR415HP produced significant levels of TNF-alpha at a concentration of 1 microm(3)/cell while at least 10 microm(3)/cell of GUR1120 wear debris per cell was needed to produce significant levels of TNF-alpha. Secondly the effects of crosslinking GUR1050 was examined when worn against a scratched counterface. The wear rate of the material was shown to decrease as the level of crosslinking increased. However the materials crosslinked with 5 and 10 Mrad of gamma irradiation produced higher percentages of 0.1-1.0 microm size wear particles than the non-crosslinked material. While the crosslinked material was able to stimulate cells to produce significantly elevated TNF-alpha levels at a particle concentration of just 0.1 microm(3)/cell only concentrations of 10 microm(3)/cell and above of the non-crosslinked wear debris were stimulatory. When the counterface was changed from scratched to smooth the wear rate for all three GUR1050 materials was further reduced. For the first time nanometre size wear particles were observed from polyethylene which reduced the percentage mass of debris in the 0.1-1.0 microm size range. For all three materials on the smooth counterface only concentrations of 50 microm(3)/cell and above were stimulatory. This study has demonstrated that molecular weight, crosslinking and counterface roughness are important factors in determining the biological activity of polyethylene.

Comparison of the biological activity of grade GUR 1120 and GUR 415HP UHMWPE wear debris.

This study evaluated the in vitro response of murine macrophages to clinically relevant polyethylene particles from two grades of UHMWPE at varying volume doses. Clinically relevant UHMWPE wear debris was generated in vitro using a tri-pin-on-disc tribometer. The debris was observed using a scanning electron microscope and analysed by image analysis. There was no significant difference in the wear rates of the two grades of UHMWPE. Analysis of the wear debris showed that GUR 415HP produced a higher percentage of mass of debris in the submeter size range compared to GUR 1120. The wear debris was co-cultured with C3H murine peritoneal macrophages at particle volume (microm(3)): cell number ratios of 100 :1, 50 :1, 10 :1 and 1 :1 for both grades of UHMWPE and additionally at 0.5 :1 and 0.1 :1 for grade GUR 415HP. The secretion of TNF-alpha was determined by ELISA. Significantly elevated levels of TNF-alpha were secreted at 100 :1 ratio when macrophages were challenged with wear debris from GUR 1120 and at 10 :1 and 1 :1 for debris from GUR 415HP. The results suggested that the greater percentage mass of debris in the submicrometer size range from GUR 415HP lead to a substantial increase in biological activity for this grade of UHMWPE on a volume for volume basis when compared with GUR 1120.

Investigation of the regenerative capacity of an acellular porcine medial meniscus for tissue engineering applications.

Previously, we have described the development of an acellular porcine meniscal scaffold. The aims of this study were to determine the immunocompatibility of the scaffold and capacity for cellular attachment and infiltration to gain insight into its potential for meniscal repair and replacement. Porcine menisci were decellularized by exposing the tissue to freeze-thaw cycles, incubation in hypotonic tris buffer, 0.1% (w/v) sodium dodecyl sulfate in hypotonic buffer plus protease inhibitors, nucleases, hypertonic buffer followed by disinfection using 0.1% (v/v) peracetic, and final washing in phosphate-buffered saline. In vivo immunocompatibility was assessed after implantation of the acellular meniscal scaffold subcutaneously into galactosyltransferase knockout mice for 3 months in comparison to fresh and acellular tissue treated with α-galactosidase (negative control). The cellular infiltrates in the explants were assessed by histology and characterized using monoclonal antibodies against: CD3, CD4, CD34, F4/80, and C3c. Static culture was used to assess the potential of acellular porcine meniscal scaffold to support the attachment and infiltration of primary human dermal fibroblasts and primary porcine meniscal cells in vitro. The explants were surrounded by capsules that were more pronounced for the fresh meniscal tissue compared to the acellular tissues. Cellular infiltrates compromised mononuclear phagocytes, CD34-positive cells, and nonlabeled fibroblastic cells. T-lymphocytes were sparse in all explanted tissue types and there was no evidence of C3c deposition. The analysis revealed an absence of a specific immune response to all of the implanted tissues. Acellular porcine meniscus was shown to be capable of supporting the attachment and infiltration of primary human fibroblasts and primary porcine meniscal cells. In conclusion, acellular porcine meniscal tissue exhibits excellent immunocompatibility and potential for cellular regeneration in the longer term.