Autophagy has emerged as a key mechanism in the survival and function of T and B lymphocytes, and its activation was involved in apoptosis resistance in rheumatoid arthritis (RA). To investigate ...whether the relationship between autophagy and apoptosis may impact the response to the therapy, we analyzed ex vivo spontaneous autophagy and apoptosis in patients with RA subjected to treatment with anti-tumor necrosis factor (TNF) drugs and in vitro the effects of TNFα and anti-TNF drugs on cell fate.
Peripheral blood mononuclear cells (PBMCs) from 25 RA patients treated with anti-TNF drugs were analyzed for levels of autophagy marker LC3-II by western blot and for the percentage of annexin V-positive apoptotic cells by flow cytometry. The same techniques were used to assess autophagy and apoptosis after in vitro treatment with TNFα and etanercept in both PBMCs and fibroblast-like synoviocytes (FLS) from patients with RA.
PBMCs from patients with RA responsive to treatment showed a significant reduction in LC3-II levels, associated with an increased apoptotic activation after 4 months of therapy with anti-TNF drugs. Additionally, the expression of LC3-II correlated with DAS28. TNFα was able to induce autophagy in a dose-dependent manner after 24 h of culture in RA PBMCs and FLS. Moreover, etanercept caused a significant reduction of autophagy and of levels of citrullinated proteins.
Our results show how the crosstalk between autophagy and apoptosis can sustain the survival of immune cells, thus influencing RA progression. This suggests that inhibition of autophagy represents a possible therapeutic target in RA.
Background
Patients with joint hypermobility syndrome/Ehlers–Danlos syndrome, hypermobility type (JHS/EDS‐HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain ...remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia.
Methods
In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS‐HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal‐pain perceptive thresholds and the wind‐up ratio and recorded a standard nerve conduction study to assess non‐nociceptive fibres and laser‐evoked potentials, assessing nociceptive fibres.
Results
Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind‐up ratio.
Conclusions
While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS‐HT, the lowered cold and heat pain thresholds and increased wind‐up ratio imply that pain in JHS/EDS‐HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms.
What does this study add?
In patients with JHS/EDS‐HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain.
The use of food supplements containing botanicals is increasing in European markets. Although intended to maintain the health status, several cases of adverse effects to Plant Food Supplements (PFS) ...have been described.
To describe the self-reported adverse effects collected during the European PlantLIBRA PFS Consumer Survey 2011-2012, with a critical evaluation of the plausibility of the symptomatology reported using data from the literature and from the PlantLIBRA Poisons Centers' survey.
From the total sample of 2359 consumers involved in the consumers' survey, 82 subjects reported adverse effects due to a total of 87 PFS.
Cases were self-reported, therefore causality was not classified on the basis of clinical evidence, but by using the frequency/strength of adverse effects described in scientific papers: 52 out of 87 cases were defined as possible (59.8%) and 4 as probable (4.6%). Considering the most frequently cited botanicals, eight cases were due to Valeriana officinalis (garden valerian); seven to Camellia sinensis (tea); six to Ginkgo biloba (Maidenhair tree) and Paullinia cupana (guarana). Most adverse events related to the gastrointestinal tract, nervous and cardiovascular systems.
Comparing the data from this study with those published in scientific papers and obtained by the PlantLIBRA Poisons Centers' survey, some important conclusions can be drawn: severe adverse effects to PFS are quite rare, although mild or moderate adverse symptoms can be present. Data reported in this paper can help health professionals (and in particular family doctors) to become aware of possible new problems associated with the increasing use of food supplements containing botanicals.
Understanding how injuries occur (inciting circumstances) is useful for developing etiological hypotheses and prevention strategies. The aims of this study were 1) to evaluate the feasibility of a ...method combining video and Global Positioning System data to estimate the speed and acceleration of activities leading to injuries and 2) to use this method to analyse the inciting circumstances leading to non-contact injuries.
Retrospective descriptive study.
Injury inciting circumstances from 46 elite players over three seasons were analysed from video recordings and from external load measures collected through Catapult Vector S7 Global Positioning System.
In total 34 non-contact injuries were analysed. Sixteen out of the seventeen hamstring injuries occurred when players were running for (median and interquartile range) 16.75 m (8.42–26.65 m) and achieved a peak speed of 29.28 km·h−1 (26.61–31.13 km·h−1) which corresponded to 87.55 % of players' maximal speed (78.5 %–89.75 %). Of the three adductor injuries, one occurred whilst the player was decelerating without the ball, one occurred whilst the player was accelerating and controlling the ball at knee level, and one occurred whilst the player was performing an instep kick. Two quadriceps injuries occurred whilst the players were kicking either whilst walking or running.
From the preliminary results reported in this study most hamstring injuries occurred when players ran >25 km·h−1 and above 80 % of their maximal speed. This study suggests that this novel approach can allow a detailed and standardised analysis of injury inciting circumstances.
There is no agreement on how to classify, define or diagnose hip-related pain—a common cause of hip and groin pain in young and middle-aged active adults. This complicates the work of clinicians and ...researchers. The International Hip-related Pain Research Network consensus group met in November 2018 in Zurich aiming to make recommendations on how to classify, define and diagnose hip disease in young and middle-aged active adults with hip-related pain as the main symptom. Prior to the meeting we performed a scoping review of electronic databases in June 2018 to determine the definition, epidemiology and diagnosis of hip conditions in young and middle-aged active adults presenting with hip-related pain. We developed and presented evidence-based statements for these to a panel of 37 experts for discussion and consensus agreement. Both non-musculoskeletal and serious hip pathological conditions (eg, tumours, infections, stress fractures, slipped capital femoral epiphysis), as well as competing musculoskeletal conditions (eg, lumbar spine) should be excluded when diagnosing hip-related pain in young and middle-aged active adults. The most common hip conditions in young and middle-aged active adults presenting with hip-related pain are: (1) femoroacetabular impingement (FAI) syndrome, (2) acetabular dysplasia and/or hip instability and (3) other conditions without a distinct osseous morphology (labral, chondral and/or ligamentum teres conditions), and that these terms are used in research and clinical practice. Clinical examination and diagnostic imaging have limited diagnostic utility; a comprehensive approach is therefore essential. A negative flexion–adduction–internal rotation test helps rule out hip-related pain although its clinical utility is limited. Anteroposterior pelvis and lateral femoral head–neck radiographs are the initial diagnostic imaging of choice—advanced imaging should be performed only when requiring additional detail of bony or soft-tissue morphology (eg, for definitive diagnosis, research setting or when planning surgery). We recommend clear, detailed and consistent methodology of bony morphology outcome measures (definition, measurement and statistical reporting) in research. Future research on conditions with hip-related pain as the main symptom should include high-quality prospective studies on aetiology and prognosis. The most common hip conditions in active adults presenting with hip-related pain are: (1) FAI syndrome, (2) acetabular dysplasia and/or hip instability and (3) other conditions without distinct osseous morphology including labral, chondral and/or ligamentum teres conditions. The last category should not be confused with the incidental imaging findings of labral, chondral and/or ligamentum teres pathology in asymptomatic people. Future research should refine our current recommendations by determining the clinical utility of clinical examination and diagnostic imaging in prospective studies.
The essay addresses the political implications of popular disturbances occasioned by the waves of bad harvests and periodic grain shortages in Britain during the XVIIIth century. The debate and the ...documents of the time do not seem to validate the critical hypotheses connected with the Foucaultian idea of governmentality or with the Smithian defence of free trade in grain. More fruitful are the theses of E.P. Thompson and J. Bohstedt, both related to the relationship between subsistence, deference and social stability. Measures relating to "spirituous liquors" and popular reaction to them are also considered.
Thyroid dysfunction in COVID-19 patients Baldelli, R.; Nicastri, E.; Petrosillo, N. ...
Journal of endocrinological investigation,
12/2021, Letnik:
44, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Purpose
“Non thyroidal illness syndrome” (NTIS) or “euthyroid sick syndrome” (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of ...serum T
3
(fT3), sometimes followed by reduction of serum T
4
(fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection.
Methods
We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients.
Results
Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found.
Conclusions
COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.
Summary
Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as ...supported by the high occurrence of periodontitis. In this case–control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real‐time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non‐remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.
‐Significant correlation between P. gingivalis rate in total bacteria genomes and disease activity in terms of DAS28 values and remission status.
‐Oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to a more active disease.
‐Beyond citrullination and antibody production, P. gingivalis could be implicated in triggering a pro‐inflammatory state in rheumatoid arthritis.
Hip-related pain is a well-recognised complaint among active young and middle-aged active adults. People experiencing hip-related disorders commonly report pain and reduced functional capacity, ...including difficulties in executing activities of daily living. Patient-reported outcome measures (PROMs) are essential to accurately examine and compare the effects of different treatments on disability in those with hip pain. In November 2018, 38 researchers and clinicians working in the field of hip-related pain met in Zurich, Switzerland for the first International Hip-related Pain Research Network meeting. Prior to the meeting, evidence summaries were developed relating to four prioritised themes. This paper discusses the available evidence and consensus process from which recommendations were made regarding the appropriate use of PROMs to assess disability in young and middle-aged active adults with hip-related pain. Our process to gain consensus had five steps: (1) systematic review of systematic reviews; (2) preliminary discussion within the working group; (3) update of the more recent high-quality systematic review and examination of the psychometric properties of PROMs according to established guidelines; (4) formulation of the recommendations considering the limitations of the PROMs derived from the examination of their quality; and (5) voting and consensus. Out of 102 articles retrieved, 6 systematic reviews were selected and assessed for quality according to AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews). Two showed moderate quality. We then updated the most recent review. The updated literature search resulted in 10 additional studies that were included in the qualitative synthesis. The recommendations based on evidence summary and PROMs limitations were presented at the consensus meeting. The group makes the following recommendations: (1) the Hip and Groin Outcome Score (HAGOS) and the International Hip Outcome Tool (iHOT) instruments (long and reduced versions) are the most appropriate PROMs to use in young and middle-aged active adults with hip-related pain; (2) more research is needed into the utility of the HAGOS and the iHOT instruments in a non-surgical treatment context; and (3) generic quality of life measures such as the EuroQoL-5 Dimension Questionnaire and the Short Form Health Survey-36 may add value for researchers and clinicians in this field. We conclude that as none of the instruments shows acceptable quality across various psychometric properties, more methods studies are needed to further evaluate the validity of these PROMS—the HAGOS and iHOT—as well as the other (currently not recommended) PROMS.
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