PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome: A case report and review of the literature.

PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a rare autoinflammatory disorder often arising in pediatric patients. We present a case of an 18-year-old female with a past medical history of growth failure, immunoglobulin A nephropathy, and inflammatory arthritis who presented to a pediatric dermatology clinic with findings of acne, psoriasiform dermatitis, and hidradenitis suppurativa, whose clinical, genetic, and laboratory findings were most consistent with PAMI syndrome. We conducted a literature review to better characterize this rare condition in the context of dermatologic findings. Recognition of the distinctive skin findings seen in PAMI syndrome can help distinguish it from other inflammatory disorders, enabling expedited diagnosis and treatment.

Psoriatic arthritis of the temporomandibular joint: A systematic review.

OBJECTIVES: Psoriasis is an inflammatory condition brought on by the immune system. This study aimed to perform a systematic review related to psoriatic arthritis (PsA) of the temporomandibular joint (TMJ). METHODS: The search strategy was developed by a radiologist expert with more than 20 years of experience. The search was performed without time restrictions in five electronic databases: PubMed, Web of Science, Embase, Scopus and Ovid. The search strategy was based on MeSH and Emtree terms. The methodological quality of the studies was rated using the quality assessment tools from the National Heart Lung and Blood Institute (NHLBI). RESULTS: Twenty-three publications were included, 10 being case reports. One hundred-fifty-one patients with TMJ PsA were reported. Psoriasis evolution ranged from 1.5 years to 24 years. Clinical symptoms of TMJ involvement included: TMJ pain and sounds, limited range of jaw movements, preauricular swelling, malocclusion, headache, tinnitus, neck stiffness and altered dietary function. TMJ was evaluated by magnetic resonance imaging (six studies), computed tomography (eight articles) and by ultrasonography findings (two articles). For TMJ treatment, topical and systemic medication was reported in 11 studies. Five studies included patients needing surgical procedures for TMJ ankylosis. CONCLUSIONS: A relationship between TMD and psoriasis has been revealed. TMJ PsA has been investigated and debated, although the radiographic findings or clinical symptoms of PsA are not noticeably different from other forms of TMJ arthritis. Conservative therapy can lead to significant improvement of TMJ function.

A nuclear factor kappa B reporter cell line used to evaluate ex vivo the net inflammatory effect of plasma samples from patients with rheumatoid arthritis, psoriasis, or COVID-19.

BACKGROUND: The overall clinical outcome of inflammatory conditions is the result of the balance between pro-inflammatory and anti-inflammatory mediators. Because nuclear factor kappa B (NF-ĸB) is at the bottom of many inflammatory conditions, methods to evaluate the net effect of inflammation modulators on this master regulator have been conceptualized for years. METHODS: Using an ex vivo NF-ĸB reporter cell line-based assay, plasma samples of patients with rheumatoid arthritis (n = 27), psoriasis (n = 15), or severe coronavirus disease-19 (COVID-19) (n = 21) were investigated for NF-ĸB activation compared to plasma samples from 9 healthy volunteers. RESULTS: When separated by C-reactive protein (CRP) threshold levels, samples of patients exhibiting increased CRP levels (≥5 mg/l) activated NF-ĸB more efficiently than samples from patients with levels below 5 mg/l (P = 0.0001) or healthy controls (P = 0.04). Overall, there was a moderate association of CRP levels with NF-ĸB activation (Spearman r = 0.66; p < 0.0001). Plasma from COVID-19 patients activated NF-ĸB more efficiently (mean 2.4-fold compared to untreated reporter cells) than samples from any other condition (healthy controls, 1.8-fold, P = 0.0025; rheumatoid arthritis, 1.7-fold, P < 0.0001; psoriasis, 1.7-fold, P < 0.0001). In contrast, effects of rheumatoid arthritis, psoriasis, or healthy volunteer samples did not differ. CONCLUSION: This study shows that a NF-ĸB reporter cell line can be used to evaluate the net inflammatory effect of clinical plasma samples. Patients with chronic but stable rheumatoid arthritis or psoriasis do not exhibit increased plasma levels of NF-ĸB-activating compounds as opposed to COVID-19 patients with high inflammatory burden.

14-3-3 modulation of the inflammatory response.

Regulation of inflammation is a central part of the maintenance of homeostasis by the immune system. One important class of regulatory protein that has been shown to have effects on the inflammatory process are the 14-3-3 proteins. Herein we describe the roles that have been identified for 14-3-3 in regulation of the inflammatory response. These roles encompass regulation of the response that affect inflammation at the genetic, molecular and cellular levels. At a genetic level 14-3-3 is involved in the regulation of multiple transcription factors and affects the transcription of key effectors of the immune response. At a molecular level many of the constituent parts of the inflammatory process, such as pattern recognition receptors, protease activated receptors and cytokines are regulated through phosphorylation and recognition by 14-3-3 whilst disruption of the recognition processes has been observed to result in clinical syndromes. 14-3-3 is also involved in the regulation of cell proliferation and differentiation, this has been shown to affect the immune system, particularly T- and B-cells. Finally, we discuss how abnormal levels of 14-3-3 contribute to undesirable immune responses and chronic inflammatory conditions.

The effect of celecoxib in traumatic heterotopic ossification around temporomandibular joint in mice.

OBJECTIVE: In this study, the role of inflammation in traumatic heterotopic ossification around temporomandibular joint (THO-TMJ), as well as the preventive and treatment effect of celecoxib in THO-TMJ both in vivo and in vitro were explored. DESIGN: A surgically-induced THO-TMJ mouse model and a co-culture model of ATDC-5 or MC3T3-E1 and RAW-264.7 cells were used in this study for in vivo and in vitro research. RESULTS: A series of inflammatory factors, such as CD3, CD68, CD20, IL-10, IL-6 and TNF-α, were activated 48 h after trauma in a THO-TMJ model. Local trauma initiated systemic inflammatory responses as well as T cell- and macrophage-mediated local inflammatory responses around TMJ. In addition, expression of COX-2 was significantly elevated. The findings also showed that local injection of celecoxib could effectively alleviate the inflammatory response around TMJ at the early stage of trauma and inhibit the formation of THO-TMJ in vivo. Meanwhile, celecoxib could inhibit chondrogenic differentiation of ATDC-5 and osteogenic differentiation of MC3T3-E1 under inflammatory condition in vitro. Furthermore, celecoxib could inhibit the expression of Bmpr1b in the injured condylar cartilage at the initiation stage of THO-TMJ, which implied that Bmpr1b expressed by the residual condylar cartilage might be related to the pathogenesis of THO-TMJ. CONCLUSIONS: Inflammation played a crucial role in the pathogenesis of THO-TMJ, and anti-inflammation might be a possible choice to inhibit THO-TMJ, which provided scientific clues for the mechanisms, pharmacotherapy and molecular intervention of THO-TMJ.

Isozymes inhibited by active site blocking: versatility of calcium indifferent hesperidin binding to phospholipase A2 and its significance.

sPLA2 is released under inflammatory conditions from neutrophils, basophils and T-cells. They cleave the cellular phospholipids leading to the release of arachidonic acid and there by provide intermediates for biosynthesis of inflammatory mediators. The focus of this study is on the interaction of hesperidin, a natural flavonoid with Group IB, IIA, and V and X isozymes of sPLA2. Affinity of hesperidin towards PLA2 isozymes was analyzed through enzymatic studies and molecular modeling. The experiments showed that hesperidin competitively inhibited PLA2 with IC50 of 5.1 µM. Molecular modeling studies revealed the association of hesperidin with the docking scores -6.90, -9.53, -5.63 and -8.29 kcal for isozymes Group IB, IIA, V and X of PLA2 respectively. Their binding energy values were calculated as -20.25, -21.63, -21.66 and -33.43 kcal for the Group IB, IIA, V and X respectively. Structural model for Group V was made by homology modeling since no structural coordinates were available. Molecular dynamics studies were carried out to evaluate the structural stability of protein ligand complex. The analyses showed that hesperidin blocked the entry of the substrate to the active site of PLA2 and it was indifferent to the differences of the isozymes. Hence, hesperidin might serve as lead for designing highly specific anti-inflammatory drugs directed to the PLA2 isozyme specific to various diseases, with IC50 value of therapeutic significance.

Childhood Transverse Myelitis with Atypical Fever Presentation: A Case Report.

Transverse myelitis (TM) is a rare inflammatory spinal cord disorder, particularly uncommon in children. It is characterized by symptoms such as motor weakness, sensory disturbances, and autonomic dysfunction. This report describes a 10-year-old male presenting with bilateral lower limb weakness, urinary and fecal incontinence, and high-grade fever. Initial treatment at a local hospital with corticosteroids and antibiotics did not yield significant improvements, prompting advanced care at a tertiary facility. A magnetic resonance imaging (MRI) confirmed a longitudinally extensive TM lesion. Subsequent management with plasmapheresis led to satisfactory clinical improvement. This case highlights the importance of early consideration of TM in pediatric patients with acute neurological deficits and supports the use of aggressive therapeutic strategies for better outcomes.

Effects and underlying mechanism of micro-nano-structured zirconia surfaces on biological behaviors of human gingival fibroblasts under inflammatory conditions.

Zirconia is one of the most commonly used materials for abutments of dental implants, especially in the anterior region. Soft tissue integration to the zirconia abutment surface remains a challenge. Peri-implant soft tissue integration serves as a physiological barrier, attenuating pathogen penetration and preventing peri­implant disease. The surface microstructure of zirconia has significant effects on the biological behaviors of human gingival fibroblasts (HGFs), but the effects under inflammatory conditions are still unclear. In this study, we established two micro-nano structures on zirconia surfaces using a femtosecond laser, including microgrooves with widths of 30 µm (G3) and 60 µm (G6) and depths of 5 µm, and nanoparticles inside the microgrooves. Polished surfaces were used as controls. HGFs were seeded onto the three groups of zirconia specimens and stimulated with lipopolysaccharide. The HGFs on micro-nano-structured zirconia surfaces exhibited lower inflammatory responses and higher cell adhesion, proliferation, and migration under inflammatory conditions compared with the polished surfaces. Additionally, the G3 group exhibited lower inflammatory responses and higher cell adhesion and migration than the G6 group. The micro-nano-structured zirconia surface exhibited decreased neutrophil infiltration and increased M2-type macrophage polarization in vivo. To explore the molecular mechanism, RNA sequencing and gene silencing were utilized, which revealed two critical target genes regulated by the G3 group. Overall, we proposed an innovative micro-nano-structured zirconia surface that reduced the in vitro and in vivo inflammatory responses and promoted HGF adhesion, migration, and proliferation under inflammatory conditions, in which TRAFD1 and NLRC5 were the underlying key genes. STATEMENT OF SIGNIFICANCE: Zirconia is one of the most commonly used materials for abutments, especially in the anterior region. The surface microstructure of zirconia has significant effects on the biological behaviors of human gingival fibroblasts (HGFs), but few studies have investigated these effects under inflammatory conditions, and the mechanism remains unclear. In this study, we developed an innovative micro-nano-structured zirconia surface using a femtosecond laser, which reduces the in vitro and in vivo pro-inflammatory responses and promotes HGFs adhesion, migration, and proliferation under inflammatory conditions compared with the polished zirconia surface. The potential underlying mechanism was also investigated. This work has provided some theoretical basis for the micro-nano-structured zirconia surface in potentially reducing the inflammation and enhancing peri­implant soft-tissue integration under inflammatory conditions.

Dry Crusty Nose: Not Just Rhinosinusitis! Hidden IgG4-related Disease Without IgG4 Level Rise.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition that can affect various organs. Localized sinonasal IgG4-RD is a rare condition characterized by bone and soft-tissue invasion. In this report, we present a case of a patient initially diagnosed with chronic rhinosinusitis, who underwent endoscopic sinus surgery and was later found to have biopsy proven IgG4-related sinonasal disease despite having normal serum levels of IgG4, resulting in erosion of the right lamina papyracea.

IgG4-related disease-rare but you should not forget it.

Immunoglobulin G4-related disease is a systemic immune-mediated disease with insidious evolution characterized by fibroinflammatory lesions over virtually any organ system. Despite the remarkable progression of knowledge, its etiology remains undefined. Due to its relapse-remitting pattern, it could accumulate irreversible damage, increasing comorbidities and mortality. This paper emphasizes key concepts for diagnosing and treating patients with this condition.

Testing the feasibility and acceptability of an online 'Fatigue and Activity Management Education for Work (FAME-W) programme' for individuals with inflammatory arthritis.

INTRODUCTION: Fatigue and Activity Management Education for Work (FAME-W) is a four-week, occupational therapy led programme focussing on fatigue management strategies. FAME-W was designed to be delivered in person; however, due to COVID-19 pandemic it was modified to be an online group-based self-management intervention. The purpose of this study was to test the feasibility and acceptability of the online delivery format of FAME-W. METHODS: This was a mixed methods study. Participants were randomly allocated to intervention or control group. Participants in the intervention group received a four-week online FAME-W. The control group participants received a FAME-W handbook. Participants were required to complete questionnaires on work presenteeism, fatigue, mood, Health Related Quality of Life and pain at baseline, and 3 months post-intervention. Participants in the intervention group attended a focus group immediately following the completion of the programme and the control group participated in individual interviews. RESULTS: Seven of ten individuals recruited participated in the study. Majority of participants had Rheumatoid Arthritis and were working full-time. The mean age of intervention participants was 53 ± 10.4 and 56.5 ± 3.7 for the controls. All participants in the intervention group had 100% attendance, completed all study measures and activities. Participants had positive comments about the programme format, content, and delivery. Improvements were observed in most measures at follow up. CONCLUSION: Results suggest that an online programme to improve work ability was feasible and acceptable to individuals with inflammatory arthritis. The online delivery format was favoured over attending a centre-based programme. The findings support a definitive intervention trial of online FAME-W.

Adherence with mycophenolate mofetil in patients with autoimmune inflammatory rheumatic diseases in coventry: Signs of progress but challenges remain.

OBJECTIVE: The study investigated adherence with MMF treatment among patients attending rheumatology clinics at University Hospitals Coventry and Warwickshire NHS Trust (UHCW) with Autoimmune inflammatory rheumatic diseases (AIIRDs). METHODS: This retrospective study collated hospital pharmacy data in patients who requested the prescription for MMF between January 2015 and December 2018. Clinical data were obtained from paper and electronic notes. Data were analysed using Microsoft Excel. Ethical approval was obtained through Coventry University. RESULTS: We recruited 144 patients into this study with age range from 18 to 91 years, including 100 females and 44 males. There were 112 White patients, 22 of South Asian origin, 3 East Asian and 4 black patients. SLE (56), scleroderma (18), mixed connective tissue disease (15), myositis (13), vasculitis (13) were the commonest diagnoses. Overall adherence with Mycophenolate mofetil was 62%. The adherence rates were below 80% for all age groups with ∼60% of patients having adherence levels of >60%. Poor adherence with MMF correlated with 3-fold increase in risk of flares compared to good adherence (p = 0.002). We also found a significant difference between Asian patients (mean adherence 47%) and White patients (mean adherence 65%, p < 0.001). CONCLUSION: Adherence with MMF has improved considerably compared to historical studies, although these remain suboptimal. Certain population groups such as young adults, elderly and Asian patients continue to have lower adherence and higher risk of flares. Strategies are needed to improve adherence levels overall and specifically in the high-risk groups to reduce risk of flares and organ damage.

Prevalence of Clostridioides difficile Infection After Ileal Pouch-anal Anastomosis in Patients With Chronic Antibiotic-dependent Pouchitis and Crohn's-like Disease of the Pouch.

BACKGROUND: Recurrent or chronic antibiotic therapy is a therapeutic hallmark of chronic antibiotic-dependent pouchitis (CADP) or Crohn's-like disease of the pouch. Antibiotics alter the gut microbiome, which may increase the risk of Clostridioides difficile infection (CDI). The aim of this study was to determine the prevalence of CDI in patients with CADP and Crohn's-like disease of the pouch. METHODS: We conducted a retrospective cohort study of patients with CADP or Crohn's-like disease of the pouch at a tertiary academic medical center. The primary outcome was prevalence of CDI. Secondary outcomes included antibiotic therapy at the time of CDI diagnosis, treatment regimens for CDI, and subsequent outcomes. RESULTS: Overall, 18 of 198 (9.1%) included patients developed CDI. Treatment with antibiotics at the time of CDI diagnosis occurred in 7 of 18 (39%) patients. Preoperative history of CDI was significantly associated with increased risk of developing CDI following ileal pouch anal anastomosis (IPAA) compared with those with no prior history of CDI (12 of 18 [67%] vs 11 of 180 [6%]; P < .001). In 16 of 18 (89%) patients, CDI treatment was initiated with predominantly oral vancomycin (72%) or metronidazole (17%). CONCLUSION: Although chronic inflammatory conditions of the pouch arise postoperatively, the prevalence of CDI in this population appears to be similar compared with the general population of patients with inflammatory bowel disease prior to and post IPAA. Preoperative CDI appears to be the greatest risk for postoperative CDI and may require extra vigilance in the assessment of CDI after IPAA.

Comparative Clinical Study on Periodontal Health Status and Early Diagnosis of Periodontal Diseases Quantified through Clinical Periodontal Indices on a Group of Children and Adolescents with and without Cardiovascular Diseases.

It is well known that bacterial plaque is the main etiological factor that causes the appearance of periodontal diseases and carious disease. Periodontal diseases can affect children and adolescents and are manifested in the form of gingivitis, but also the early form of chronic periodontitis as well as aggressive marginal periodontitis associated with local or general factors. Early periodontitis is frequently undiagnosed by clinicians due to a lack of knowledge of the specific symptoms. Certain systemic diseases, such as cardiovascular diseases, can create favorable conditions for the appearance and progression of severe manifestations of periodontal disease; also, recent research highlights that individuals with periodontal disease present an increased risk of developing cardiovascular diseases. Children with congenital or acquired cardiovascular diseases are at increased risk for complications resulting from the growth of microorganisms in the oral cavity, presenting a risk of infective endocarditis. The specific aim was to highlight the existing differences between the periodontal health of children with cardiovascular diseases and that of children without these diseases. The analyzed group included 124 patients, represented by children and adolescents, aged between 7 and 17 years, who were divided into four subgroups depending on the presence or absence of cardiovascular diseases and periodontal disease. A specialized clinical examination was performed for each patient, and periodontal clinical parameters were quantified (plaque index, gingival bleeding index, gingival index, community periodontal index of treatment needs) and associated with the diagnosis of general condition. Patients diagnosed with periodontal disease underwent specialized treatment and were called to a control visit 3 months after treatment. Statistical analysis showed significant differences between subgroups with much higher values of clinical parameters for patients with cardiovascular disease. Also, the response to the treatment was better in the case of patients in the control subgroup without cardiovascular diseases. The present study highlighted the interaction of three factors in the progression of periodontal diseases: subgingival microbiota, immune system response and environmental factors.

Fears about COVID-19 and perceived risk among people with rheumatoid arthritis or ankylosing spondylitis following the initial lockdown in Aotearoa New Zealand.

BACKGROUND: The COVID-19 pandemic has disrupted all aspects of life and may raise particular fears for people with rheumatic disease. There is a need for research on fears and perceived risk of SARS-CoV-2 so as to understand the impact on wellbeing and inform service provision. OBJECTIVES: The aim of this study was to examine the correlates of COVID-19 fears and perceived risk of SARS-CoV-2 among people with rheumatoid arthritis or ankylosing spondylitis. DESIGN: A cross-sectional survey design was applied in Aotearoa New Zealand in the period after initial nationwide lockdowns. METHOD: An online survey was completed from July to September 2020 by 126 individuals with rheumatoid arthritis (n = 96) or ankylosing spondylitis (n = 30) who had previously been recruited to the Patient Opinion Real-Time Anonymous Liaison (PORTAL) study in 2015 or 2018. The survey included demographics and health information as well as measures of COVID-19 fears and experiences, functional disability and fatigue-related disability. RESULTS: Fears about COVID-19 were higher among younger participants, those who had been tested for SARS-CoV-2, and those who experienced more flares over the initial lockdown. Perceived risk of SARS-CoV-2 infection was also higher among individual who had been tested for SARS-CoV-2 and those taking biologic medications. CONCLUSION: Fears about COVID-19 and perceived risk of infection are related to age, health and medications among individuals with rheumatoid arthritis or ankylosing spondylitis. These findings inform how health professionals can help address the concerns of particular groups of people with rheumatic disease by providing relevant information about the ongoing effects of the pandemic.

Gold nanoparticles targeting the autophagy-lysosome system to combat the inflammation-compromised osteogenic potential of periodontal ligament stem cells: From mechanism to therapy.

Although substantial data indicate that the osteogenic potential of periodontal ligament stem cells (PDLSCs) is compromised under inflammatory conditions, the underlying mechanism remains largely unexplored. In this study, we found that both the autophagy levels and autophagic flux levels were decreased in PDLSCs incubated under inflammatory conditions (I-PDLSCs). Based on the increased expression of LC3 II (at an autophagy level) and decreased accumulation of LC3 II (at an autophagic flux level) in I-PDLSCs, we speculated that the disruption of I-PDLSC autophagy arose from dysfunction of the cellular autophagy-lysosome system. Subsequently, our hypothesis was demonstrated by inhibited autophagosome-lysosome fusion, damaged lysosomal function, and suppressed activation of transcription factor EB (TFEB, a master regulator of the autophagy-lysosome system) in I-PDLSCs and verified by TFEB overexpression in I-PDLSCs. We found that gold nanoparticle (Au NP) treatment rescued the osteogenic potential of I-PDLSCs by restoring the inflammation-compromised autophagy-lysosome system. In this context, Au NP ceased to be effective when TFEB was knocked down in PDLSCs. Our data demonstrate the crucial role of the autophagy-lysosome system in cellular osteogenesis under inflammatory conditions and suggest a new target for rescuing inflammation-induced cell dysfunction using nanomaterials to aid cell biology and tissue regeneration.

Human Milk Oligosaccharides Differently Modulate Goblet Cells Under Homeostatic, Proinflammatory Conditions and ER Stress.

SCOPE: Human milk oligosaccharides (hMOs) have beneficial effects on intestinal barrier function, but the mechanisms of action are not well understood. Here, the effects of hMOs on goblet cells, which indicate that some hMOs may enhance mucus barrier function through direct modulation of goblet cell function, are studied. METHODS AND RESULTS: The modulatory effects of 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), lacto-N-triaose II (LNT2), and galacto-oligosaccharides (GOS) on the expression of goblet cell secretory related genes MUC2, TFF3, and RETNLB, and the Golgi-sulfotransferase genes CHST5 and GAL3ST2 of LS174T are determined by real-time quantitative RT-PCR. 3-FL, LNT2, and GOS-modulated LS174T gene expression profiles in a dose- and time-dependent manner. In addition, the upregulation of MUC2 is confirmed by immunofluorescence staining. Effects of 2'-FL, 3-FL, LNT2, and GOS on gene transcription of LS174T are also assessed during exposure to TNF-α, IL-13, or tunicamycin. During TNF-α challenge, 3-FL and LNT2 enhance MUC2 and TFF3 gene expression. After IL-13 exposure, 2'-FL, 3-FL, and LNT2 all show upregulating effects on MUC2; 3-FL and LNT2 also enhance TFF3 expression. LNT2 significantly reverses Tm-induced downregulation of TFF3, RETNLB, and CHST5. CONCLUSION: The findings indicate that hMOs may enhance mucus barrier function through direct modulation of intestinal goblet cells. Effects are structure- and stressor-dependent.

Economic and objective burden of caregiving on informal caregivers of patients with systemic vasculitis.

INTRODUCTION: Systemic vasculitis (SV) is associated with substantial economic impact to patients and the healthcare system but little is known about the burden of SV on informal caregivers. We evaluated the objective caregiving burden experienced by informal caregivers of patients with SV. METHODS: We surveyed adult patients and their informal caregivers on the physical, emotional, social and economic impacts of SV. We asked patients about the extent to which they felt they were a burden to their identified caregivers. Caregivers reported the direct and indirect economic impact of SV, including employment disturbance, income loss and relative time investment of caregiving for their care recipient's SV. We used the Inventory of Caregiving Activities Questionnaire to compute the objective caregiving burden. RESULTS: We analysed data from 68 SV patient-caregiver dyads. Patients reported moderate levels of subjective burden to their caregivers. Over one-quarter of caregivers reported ever having lost some income owing to caregiving for SV. Caregivers reported spending a median of 19 weekly hours on various caregiving tasks, including a median 17 weekly hours on household activities. DISCUSSION: Given the extended hours that caregivers spend caring for their care recipient, intervention targets should aim to reduce caregiver burnout in the SV population. Future research should examine the relationship between the objective burden of caregiving for SV and the overall physical health, mental health and quality of life of caregivers.

Non-neuronal, but atropine-sensitive ileal contractile responses to short-chain fatty acids: age-dependent desensitization and restoration under inflammatory conditions in mice.

Intestinal epithelial cells sense short-chain fatty acids (SCFAs) to secrete non-neuronal acetylcholine (ACh). However, the roles of luminalSCFAs and epithelialACh under normal and pathological conditions remain unknown. We examined ileal contractile responses toSCFAs at different ages and their mucosal cholinergic alterations under inflammatory conditions. Ileal contractile responses toSCFAs in 1-day-old pups to 7-week-old mice were compared using an isotonic transducer, and responses to an intraperitoneal injection of lipopolysaccharide (LPS) were analyzed in 7-week-old mice. ThemRNAexpression levels of aSCFAactivate free fatty acid receptor, acetylcholinesterase (AChE), choline acetyltransferase (Chat), and choline transporter-like protein 4 (CTL4) were measured using real-time quantitativeRT-PCRAChE was analyzed by histochemical and optical enzymatic assays. Atropine-sensitive ileal contractile responses toSCFAs occurred in all 1-day-old pups, but were frequently desensitized after the weaning period. These contractile responses were not inhibited by tetrodotoxin and did not appear when the mucosal layer had been scraped off. Contractile desensitization in 7-week-old mice was abolished in the presence of theAChE inhibitor, eserine, which was consistent with increasedAChE activity after weaning. Ileal contractions toSCFAs in adult mice were restored byLPS, which significantly increased the epithelialmRNAexpression of Chat andCTL4. Atropine-sensitive ileal contractile responses toSCFAs constitutively occur in the newborn period, and are desensitized during developmental stages following the up-regulated expression ofAChE in the villous mucosa, but are restored under inflammatory conditions possibly via the release of epithelialACh.