Immunoregulatory role of Jalpha281 T cells in aged mice developing lupus-like nephritis

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Valpha14 Jalpha281 chains paired with some Vbeta domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jalpha281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jalpha281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jalpha281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jalpha281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jalpha281+ cells, probably associated with the activation of marginal zone B cells.     

The prevalence of constipation at admission and after 1 week of palliative care: a multi-center study

Aim: To assess the prevalence and intensity of constipation in advanced-cancer patients referred to palliative care, and to assess changes after 1 week of specialist palliative care.

Methods: This was a prospective multi-center study in advanced patients for a period of 1 year. At admission (T0), age, gender, primary tumor, concomitant diseases, Karnofsky status, Palliative prognostic score (PaP), Edmonton Symptom Assessment scale (ESAS), Memorial Delirium Assessment Scale (MDAS), and bowel function index (BFI) were collected. In BFI, high values represent severe constipation. The use of medication was also recorded, as well as possible causes of constipation. The same parameters were recorded 1 week after admission for palliative care (T7).

Results: A total of 246 patients were screened for constipation. The mean BFI at T0 was 42.4 (SD?=?26.92). One hundred and sixty-three patients (66.3%) had a BFI >28. The mean BFI at T7 was 35.7 (SD?=?28.8), with a significant decrease from T0 to T7 (p?=?.000). A significant decrease of BFI in patients with a BFI >28 was reported (p?=?.000). In patients with a BFI ≤28 there was a significant worsening of constipation (p?=?.000). In patients with a BFI >28 at T0 there was a significant increase in the use of laxatives at T7 in comparison with patients having a BFI ≤28 (p?=?.002). In patients with a BFI ≤28 at T0, who had a significant worsening of BFI (Δ?>?12), the use of laxatives was significantly lower in comparison to patients who had a BFI >28 (p?=?.000). In the multivariate analysis, dehydration and the use of benzodiazepines were independently associated with higher BFI scores.

Conclusion: Constipation is present in approximately two-thirds of patients, and is principally associated with dehydration and the use of benzodiazepines. Patients with normal bowel function at initial assessment may see a worsening in their condition a week later due to lack of prevention or subsequent under-treatment.     

The intriguing role of Rifaximin in gut barrier chronic inflammation and in the treatment of Crohn’s disease

Introduction: The gastrointestinal tract acts as a functional unit organized as a semipermeable multilayer system, in which commensal gut microbiota represents the anatomical barrier. Recently, several studies have highlighted the involvement of gut microbiota in inflammatory bowel diseases (IBD) pathogenesis, in sustaining gut barrier chronic inflammation, and in conditioning disease course and therapeutical response. This evidence provides a rationale for treating patients with gut microbiota modifiers. Among these, Rifaximin represents a non-traditional antibiotic able to act as a ‘eubiotic’ on intestinal barrier.

Area covered: The purpose of this narrative review is to explore the impact of Rifaximin on gut barrier and gut microbiota in IBD, in particular in Crohn’s disease (CD), and to analyze its potential therapeutic applications.

Expert opinion: The possibility of a beneficial activity of Rifaximin in chronic intestinal inflammation and CD has been debated and evaluated with different studies having obtained promising but still preliminary data. Larger trials are therefore needed. This gut-specific antibiotic could represent an alternative to systemic antibiotics thanks to its favorable safety profile and promising efficacy data. Rifaximin could exert, when appropriate, a synergic effect with immunomodulators in IBD, acting on both the microbial and the immunological sides of gut barrier impairment.     

Neuroprotective effect of omega-3 polyunsaturated fatty acids in the 6-OHDA model of Parkinson's disease is mediated by a reduction of inducible nitric oxide synthase

Objective: Parkinson's disease (PD) is characterized by deterioration of the nigrostriatal system and associated with chronic neuroinflammation. Glial activation has been associated with regulating the survival of dopaminergic neurons and is thought to contribute to PD through the release of proinflammatory and neurotoxic factors, such as reactive nitric oxide (NO) that triggers or exacerbates neurodegeneration in PD. Polyunsaturated fatty acids (PUFAs) exert protective effects, including antiinflammatory, antiapoptotic, and antioxidant activity, and may be promising for delaying or preventing PD by attenuating neuroinflammation and preserving dopaminergic neurons. The present study investigated the effects of fish oil supplementation that was rich in PUFAs on dopaminergic neuron loss, the density of inducible nitric oxide synthase (iNOS)-immunoreactive cells, and microglia and astrocyte reactivity in the substantia nigra pars compacta (SNpc) and striatal dopaminergic fibers.

Methods: The animals were supplemented with fish oil for 50 days and subjected to unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-induced lesions as a model of PD.

Results: Fish oil mitigated the loss of SNpc neurons and nerve terminals in the striatum that was caused by 6-OHDA. This protective effect was associated with reductions of the density of iNOS-immunoreactive cells and microglia and astrocyte reactivity.

Discussion: These results suggest that the antioxidant and antiinflammatory properties of fish oil supplementation are closely related to a decrease in dopaminergic damage that is caused by the 6-OHDA model of PD.     

Work,retirement, and muscle strength loss in old age

Reduced muscle strength is an accurate predictor of functional limitations, disability, and mortality. Hence, understanding which socio‐economic factors contribute to preserve muscle strength in old age is central to the design of social policies that help reducing these health risks. Using data on handgrip strength collected by the Survey of Health, Ageing and Retirement in Europe for the population of Europeans aged 50+ and the exogenous variation in pension eligibility age across countries over time, we estimate that the retirement transition has a short‐term positive causal effect on muscle strength. However, this protective effect is not persistent, as retirement speeds up the age‐related trend in muscle strength loss, especially for blue‐collar workers and males. The “holy grail” of early retirement may not be such a good deal for retirees' longevity and physical functioning late in life.     

A Qualitative Assessment of Community Attitudes and Barriers to Family Planning Use in the Trifinio Region of Southwest Guatemala

Introduction Our aim was to identify beliefs about and specific barriers to use of birth spacing methods that married and cohabitating women in the Trifinio Sur-Oeste region of Guatemala report in order to design future family planning educational programs. Methods We conducted key informant interviews with community health workers and focus groups with married or cohabitating women. We used inductive and deductive coding to identify common themes. Using these themes, we created explanatory models for decision-making context and identified barriers to family planning use, community educational needs, and potential interventions. Results Thirty-seven women, aged 20–47 years, with an average of 3.5 children and a 2nd grade education level, were included in focus groups. Women had accurate knowledge about benefits of birth spacing however had poor knowledge of family planning methods. Most common barriers included lack of spousal approval, difficulty accessing contraceptive methods, lack of knowledge, and fear of adverse effects. Women were interested in increased education for men, adolescents, and themselves. Discussion Targeted education for women, men, and adolescents is needed to improve family planning uptake in the Trifinio region. Programming should focus on increasing knowledge and acceptability of birth spacing methods and increasing constructive dialogue among couples.     

Assessing exclusionary power of a paternity test involving a pair of alleged grandparents

BACKGROUND: The power of a genetic test battery to exclude a pair of individuals as grandparents is an important consideration for parentage testing laboratories. However, a reliable method to calculate such a statistic with short-tandem repeat (STR) genetic markers has not been presented. STUDY DESIGN AND METHODS: Two formulae describing the random grandparents not excluded (RGPNE) statistic at a single genetic locus were derived: RGPNE = a(4 - 6a + 4a(2)- a(3)) when the paternal obligate allele (POA) is defined and RGPNE = 2[(a + b)(2 - a - b)][1 - (a + b)(2 - a - b)] + [(a + b)(2 - a - b)] when the POA is ambiguous. A minimum number of genetic markers required to yield cumulative RGPNE values of not greater than 0.01 was calculated with weighted average allele frequencies of the CODIS STR loci. RGPNE data for actual grandparentage cases are also presented to empirically examine the exclusionary power of routine casework. RESULTS: A comparison of RGPNE and random man not excluded (RMNE) values demonstrates the increased difficulty involved in excluding two individuals as grandparents compared to excluding a single alleged parent. A minimum of 12 STR markers is necessary to achieve RGPNE values of not greater than 0.01 when the mother is tested; more than 25 markers are required without the mother. Cumulative RGPNE values for each of 22 nonexclusionary grandparentage cases were not more than 0.01 but were significantly weaker when calculated without data from the mother. CONCLUSION: Calculation of the RGPNE provides a simple means to help minimize the potential of false inclusions in grandparentage analyses. This study also underscores the importance of testing the mother when examining the parents of an unavailable alleged father (AF).     

Effect of post-retained composite restoration of MOD preparations on the fracture resistance of endodontically treated teeth

PURPOSE: The present study aimed to compare the fracture resistance and failure patterns of endodontically treated premolars with MOD preparations restored using different material combinations. The null hypothesis postulated that there was no association between the fracture resistance of endodontically treated premolars and the resin composite materials or the post-and-core system used to build up the restorations. MATERIALS AND METHODS: Eighty single-rooted maxillary premolars were used. After endodontic treatment and preparation of MOD preparations, 8 groups of 10 samples each were created, using the following material combinations: group 1 (control), flowable and microhybrid resin composites; group 2, flowable A; group 3, flowable B; group 4, microhybrid resin A; group 5, microhybrid resin B; group 6, flowable B + microhybrid resin B; group 7, flowable A + microhybrid resin A + post A; group 8, flowable B + microhybrid resin B + post B. Mechanical static fracture tests were performed loading the specimens till fracture. RESULTS: The mean failure loads (N) were 502 (control), 470 (group 7), 445 (group 8), 441 (group 6), 405 (group 5), 364 (group 4), 317 (group 2), and 302 (group 3). Statistically significant differences were found between groups 1 vs 2, 1 vs 3, and 3 vs 7 (p < 0.05). CONCLUSION: The fracture resistance of endodontically treated premolars with MOD preparations was enhanced by the use of the sandwich technique. The samples restored with posts predominantly showed restorable fractures, while teeth restored without posts mostly displayed unrestorable failures.