Measuring and increasing rates of self-isolation in the context of COVID-19: a systematic review with narrative synthesis.

OBJECTIVES: This study aimed to investigate (1) definitions of self-isolation used during the COVID-19 pandemic; (2) measures used to quantify adherence and their reliability, validity, and acceptability; (3) rates of self-isolation adherence; and (4) factors associated with adherence. STUDY DESIGN: This was a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Synthesis Without Meta-analysis (PRISMA) guidelines (PROSPERO record CRD42022377820). METHODS: MEDLINE, PsycINFO, Embase, Web of Science, PsyArXiv, medRxiv, and grey literature sources were searched (1 January 2020 to 13 December 2022) using terms related to COVID-19, isolation, and adherence. Studies were included if they contained original, quantitative data of self-isolation adherence during the COVID-19 pandemic. We extracted definitions of self-isolation, measures used to quantify adherence, adherence rates, and factors associated with adherence. RESULTS: We included 45 studies. Self-isolation was inconsistently defined. Four studies did not use self-report measures. Of 41 studies using self-report, one reported reliability; another gave indirect evidence for the lack of validity of the measure. Rates of adherence to self-isolation for studies with only some concerns of bias were 51%-86% for COVID-19 cases, 78%-94% for contacts, and 16% for people with COVID-19-like symptoms. There was little evidence that self-isolation adherence was associated with sociodemographic or psychological factors. CONCLUSIONS: There was no consensus in defining, operationalising, or measuring self-isolation, resulting in significant risk of bias in included studies. Future definitions of self-isolation should state behaviours to be enacted and duration. People recommended to self-isolate should be given support. Public health campaigns should aim to increase perceived effectiveness of self-isolation and promote accurate information about susceptibility to infection.

[Optimization of sentinel lymph node biopsy in breast cancer by intraoperative axillary palpation]. / Optimización de la biopsia selectiva de ganglio centinela en el cáncer de mama mediante palpación axilar intraoperatoria.

INTRODUCTION: Sentinel node biopsy (SNB) by radioisotopes is a widely accepted and reliable surgical method for staging breast cancer in patients with unknown positive axillary lymph nodes involvement. The main limitation of this method is due to the appearance of false negatives that may be caused by tumor lymph node blockage of the sentinel lymph node and uptake in the neighboring lymph nodes. Infiltered sentinel nodes are generally increased in size and firm. Thus, they can be detected by intraoperative palpation, even when there is no uptake by the radiotracer. AIM: To reduce the false negative rates by applying intraoperative axillary palpation after SNB. METHOD: Over a two-year period, we complemented the SNB in 168 patients with careful intraoperative axillary palpation, detecting and removing all the palpable suspicious lymph nodes (SLN) that were analyzed as sentinel nodes RESULTS: In 32 out of 168 patients, 50 palpable SLN were found. In 3 out of 32 patients, 4 infiltrated SLNs were demonstrated with negative SNB and positive axillary lymphadenectomy. Thus, intraoperative palpation avoided false negative results. In one patient, one palpable SLN with tumor involvement was observed and SNB was also positive. In the remaining 28 patients, the histological analysis of 45 SLN was negative for tumor but SNB was positive in 3 patients. CONCLUSION: Intraoperative axillary palpation, once the SNB was done, reduced the false negative rate. Thus, we consider that it should be included as one more part of this procedure.

Flexor Hallucis Longus tendon rupture in RA-patients is associated with MTP 1 damage and pes planus.

BACKGROUND: To assess the prevalence of and relation between rupture or tenosynovitis of the Flexor Hallucis Longus (FHL) tendon and range of motion, deformities and joint damage of the forefoot in RA patients with foot complaints. METHODS: Thirty RA patients with painful feet were analysed, their feet were examined clinically for the presence of pes planus and range of motion (ROM), radiographs were scored looking for the presence of forefoot damage, and ultrasound examination was performed, examining the presence of tenosyovitis or rupture of the FHL at the level of the medial malleolus. The correlation between the presence or absence of the FHL and ROM, forefoot damage and pes planus was calculated. RESULTS: In 11/60(18%) of the feet, a rupture of the FHL was found. This was associated with a limited motion of the MTP1-joint, measured on the JAM (chi2 = 10.4, p = 0.034), a higher prevalence of pes planus (chi2 = 5.77, p = 0.016) and a higher prevalence of erosions proximal at the MTP-1 joint (chi2 = 12.3, p = 0.016), and joint space narrowing of the MTP1 joint (chi2 = 12.7, p = 0.013). CONCLUSION: Rupture of the flexor hallucis longus tendon in RA-patients is associated with limited range of hallux motion, more erosions and joint space narrowing of the MTP-1-joint, as well as with pes planus.

Patient-perceived satisfactory improvement (PPSI): interpreting meaningful change in pain from the patient's perspective.

The assessment of clinically meaningful changes in patient-reported pain has become increasingly important when interpreting results of clinical studies. However, proposed response criteria, such as the minimal clinically important difference, do not correspond with the growing need for information on truly meaningful, individual improvements. The aim of the present study was to investigate satisfactory improvements in pain from the patient's perspective. Data were collected in a 2-week prospective study of 181 arthritis patients treated with a local corticosteroid injection. Baseline and follow-up pain were assessed on 100mm visual analogue scales for pain intensity (VAS-PI). At baseline, patients also marked a hypothetical level on a VAS-PI representing a satisfactory improvement in pain. Patient-perceived satisfactory improvement (PPSI) was constructed using a 5-point categorical rating of change scale at follow-up as the anchor. PPSI was associated with a minimal reduction of 30mm or 55% on the VAS-PI. Since absolute change in pain associated with satisfactory improvement proved highly dependent on baseline pain, percent change scores performed better in classifying improved patients. The 55% threshold for satisfactory improvement was consistent over the course of treatment and reasonably consistent across groups of patients. Our data suggest that PPSI is a clinically relevant and stable concept for interpreting truly meaningful improvements in pain from the individual perspective.

Phosphorylation of troponin I by protein kinase A accelerates relaxation and crossbridge cycle kinetics in mouse ventricular muscle.

Phosphorylation of cardiac myofibrils by cAMP-dependent protein kinase (PKA) can increase the intrinsic rate of myofibrillar relaxation, which may contribute to the shortening of the cardiac twitch during beta-adrenoceptor stimulation. However, it is not known whether the acceleration of myofibrillar relaxation is due to phosphorylation of troponin I (TnI) or of myosin binding protein-C (MyBP-C). To distinguish between these possibilities, we used transgenic mice that overexpress the nonphosphorylatable, slow skeletal isoform of TnI in the myocardium and do not express the normal, phosphorylatable cardiac TNI: The intrinsic rate of relaxation of myofibrils from wild-type and transgenic mice was measured using flash photolysis of diazo-2 to rapidly decrease the [Ca(2+)] within skinned muscles from the mouse ventricles. Incubation with PKA nearly doubled the intrinsic rate of myofibrillar relaxation in muscles from wild-type mice (relaxation half-time fell from approximately 150 to approximately 90 ms at 22 degrees C) but had no effect on the relaxation rate of muscles from the transgenic mice. In parallel studies with intact muscles, we assessed crossbridge kinetics indirectly by determining f(min) (the frequency for minimum dynamic stiffness) during tetanic contractions. Stimulation of beta-adrenoceptors with isoproterenol increased f(min) from 1.9 to 3.1 Hz in muscles from wild-type mice but had no effect on f(min) in muscles from transgenic mice. We conclude that the acceleration of myofibrillar relaxation rate by PKA is due to phosphorylation of TnI, rather than MyBP-C, and that this may be due, at least in part, to faster crossbridge cycle kinetics.

Isomyosin transitions in ventricles of aldosterone-salt hypertensive rats.

The isomyosin composition in left and right ventricles from aldosterone-salt-treated hypertensive rats and from vehicle-infused and aldosterone-infused normotensive control rats was compared. A significant incremental increase (20%) in the percentage of V3 isomyosin and parallel decrease in the percentage of V1 isomyosin occurred in both left and right ventricles from aldosterone-salt-treated animals compared with those in normotensive vehicle-infused controls. No change in the ventricular isomyosin distribution was observed in animals infused with aldosterone without salt, which indicates that aldosterone does not directly affect the ventricular isomyosin composition. The changes in left ventricular isomyosin composition were accompanied by significant left ventricular hypertrophy (38%; p less than 0.05), whereas no hypertrophy was observed in the right ventricle. Plasma thyroxine levels were significantly lower in aldosterone-salt-treated rats (3.7 +/- 0.6 micrograms/dl; p less than 0.05) than in normotensive vehicle-infused (6.0 +/- 0.7 micrograms/dl) or aldosterone-infused (6.7 +/- 0.3 micrograms/dl) controls. These results indicate that factors such as alterations in thyroid status or a volume overload component of this hypertensive model, in addition to increased systolic blood pressure, may contribute to a biventricular shift in isomyosin composition in the aldosterone-salt model of hypertension.

The selective adherence of lymphoblasts to antigenic cell monolayers. A method for determining the specificity of lymphocytes proliferating in response to histocompatibility antigens.

The specificity and intensity of the immune response of rat lymph nodes draining a skin allograft were examined by exploiting a monolayer of donor-type thoracic duct lymphocytes as an immunoabsorbent. Stable monolayers were produced by attaching lymphocytes from different strains of rat to Petri dishes pretreated with poly-L-lysine. The responding lymph node cells were labelled in vitro with [3H]Thymidine, incubated on the monolayer and mechanically separated into non-adherent and adherent fractions. The radioactivity associated with the adherent fraction was 7--8 times greater when the monolayer displayed the immunizing major histocompatibility antigens than when syngeneic or 'third party' monolayers were used. The non-specific adherence to syngeneic monolayers was low and consistent. Immunization to minor histocompatibility antigens may also be studied by this method.

Incremental cost-effectiveness of cyclooxygenase 2-selective versus nonselective nonsteroidal anti-inflammatory drugs in a cohort of coumarin users: a pharmacoeconomic analysis linked to a case-control study.

BACKGROUND: A previous case-control study involving concomitant users of coumarin and nonsteroidal anti-inflammatory drugs (NSAIDs) found that cyclooxygenase 2 (COX-2)-selective NSAIDs were associated with fewer bleeding complications than nonselective NSAIDs. OBJECTIVE: The goal of this study was to determine the incremental cost-effectiveness of COX-2-selective versus nonselective NSAIDs in relation to the occurrence of bleeding complications in a cohort of concomitant coumarin users. METHODS: The pharmacoeconomic evaluation was linked to a case-control analysis (patients with and without bleeding complications) based on data from the earlier study in users of concomitant coumarin and NSAIDs. Medical costs associated with NSAID use and bleeding complications were estimated according to Dutch guidelines for pharmacoeconomic analyses, based on Dutch drug prices and national averages for health care costs. Rofecoxib, meloxicam, and nabumetone were considered COX-2 selective. Total costs were calculated and compared for 2 hypothetical scenarios in which patients used either COX-2-selective or nonselective NSAIDs. Sensitivity analyses were performed in which both the odds ratios (ORs) and the costs of NSAIDs and bleeding episodes were varied. RESULTS: A total of 1,491 bleeding complications occurred in 4400 coumarin users: among the 221 (15%) NSAID users with a bleeding episode, 96% used a nonselective NSAID and 4% used a COX-2-selective NSAID. The adjusted OR of a bleeding episode for nonselective compared with COX-2-selective NSAIDs was 3.07 (95% CI, 1.18-8.03). The estimated mean cost of a bleeding episode was 478 per patient. Factoring in the excess cost of a COX-2-selective NSAID compared with a nonselective NSAID, as well as the cost savings in averted bleeding episodes, it was determined that there would be net medical cost savings of 53,800 and 162 averted bleeding episodes if the entire patient group received COX-2-selective NSAIDs rather than nonselective NSAIDs. The sensitivity analysis showed these results to be robust. CONCLUSION: In this study population of concomitant coumarin and NSAID users, the reduction in bleeding complications with the use of more expensive COX-2-selective inhibitors was associated with net medical cost savings compared with nonselective NSAIDs.

C-terminal isoforms of the myosin heavy chain and smooth muscle function.

Two myosin heavy chain isoforms expressed in smooth muscle, SM1 (204 kDa) and SM2 (200 kDa), are derived from alternate splicing that results in different amino acid sequences at their non-helical C-terminal tail regions. These isoforms are developmentally regulated and differentially expressed in various smooth muscle tissues. The functional role of myosin isoforms differing at the C-terminal tail has been investigated both in vitro and in vivo. Removal of the C-terminal tail of SM1 by chymotrypsin activates the ATPase of myosin at low Mg2+ but does not change the maximum activity. Addition of peptides, mimicking C-terminal tail regions specific to the SM1 and SM2 isoforms, to permeabilized taenia coli smooth muscle fibers inhibits maximum shortening velocity (Vm) and decreases Ca2+ sensitivity but has no effect on maximum force. The inhibition of Vm by the SM1-peptide was not reversed on washout, whereas Vm inhibition by the SM2-peptide is reversible. We demonstrated that the SM1 peptide specifically bound to myosin at the subfragment 2-light meromyosin (S2-LMM) junction using crosslinking and immunomicroscopy. Modification at this site could have a direct effect on crossbridge function. The relation between C-terminal myosin isoforms and contractile function in vivo was examined using estrogen administration to ovariectomized rats to increase the relative expression of the SM1 C-terminal isoform in uterine smooth muscle. This increase in SM1 was significantly correlated with an increase in Vm. In contrast, the high ATPase N-terminal isoform was decreased by administration of estrogen to ovariectomized rats. Thus, changes in C-terminal isoform distribution appear to affect contractile function in vivo. We propose a mechanism whereby the interactions between the C-terminal tail of one myosin molecule and the S2-LMM region of another in the thick filament can modulate contractility in an isoform specific manner. Further work is needed to unequivocally identify the function of smooth muscle myosin isoforms. However, our evidence suggests that the C-terminal heavy chain isoforms may be important modulators of smooth muscle contractility.

Myosin heavy chain isoforms and smooth muscle function.

Using isoform specific antibodies we have verified the presence of two distinct muscle type myosin heavy chain isoforms in rat uterine muscle. We have shown that an endogenous protease can cleave a small 4 kDa region from the C-terminal of the SM1 isoform which generates a pSM1 species which comigrates with the SM2 isoform on low density SDS gels. While this cleavage can complicate isoform identification, more importantly, this cleavage was associated with a substantial increase in the actomyosin ATPase. Thus we have identified a domain at the C-terminal which may be involved in regulation of the ATPase activity. Interestingly, it is at this C-terminal, tail region of the smooth muscle myosin molecule where the only known isoform specific sequence differences are located. In skinned smooth muscle fibers of rat uterine muscle, we have also shown that differences in myosin heavy chain distribution, induced by beta-estradiol treatment of ovariectomized rats, are correlated with changes in unloaded shortening velocity. Thus our work suggests that the functional significance of myosin heavy chain isoforms in smooth muscle may be similar to that observed in striated muscle.

[Gonadoblastoma in Swyer syndrome]. / Gonadoblastoma en un síndrome de Swyer.

Swyer's syndrome is a pure gonadal dysgenesis with female external genitalia. A likely complication is the appearance of tumour's dysgenetic gonads. This paper studies a case report of gonadoblastoma in a female patient with this syndrome.

Gait analysis of the lower limb in patients with rheumatoid arthritis: a systematic review.

INTRODUCTION: In rheumatoid arthritis (RA), signs and symptoms of feet and ankle are common. To evaluate the dynamic function of feet and ankles, namely walking, a variety of gait studies have been published. In this systematic review, we provide a systematic overview of the available gait studies in RA, give a clinimetrical assignment, and review the general conclusions regarding gait in RA. METHODS: A systematic literature search within the databases PubMed, CINAHL, sportdiscus, Embase, and Scopus was described and performed and delivered 78 original gait studies that were included for further data extraction. RESULTS: The clinimetrical quality of the 78 included RA gait studies measured according a tailored QUADAS item list and proposed clinimetrical criteria by Terwee and coworkers are moderate. General conclusions regarding the walking abnormalities of RA patients point to a slower walk, longer double support time, and avoidance of extreme positions. Frequently found static features in RA are hallux valgus, pes planovalgus, and hind foot abnormalities. CONCLUSIONS: Gait studies in RA patients show moderate clinimetrical properties, but are a challenging way of expressing walking disability. Future gait research should focus on more uniformity in methodology. When this need is satisfied, more clinical applicable conclusions can be drawn.

Magnetic resonance imaging of the rheumatic foot according to the RAMRIS system is reliable.

OBJECTIVE: In rheumatology, magnetic resonance imaging (MRI) is predominantly applied in the assessment and outcome measurement of rheumatoid arthritis (RA) in hands and wrists, leading to the development of the RAMRIS (RA-MRI-Scoring) system. It was initiated by the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT). The RAMRIS system has not been applied widely in the measurement of feet. We investigated the interreader and intrareader agreement of the RAMRIS scoring system in the assessment of feet in RA. METHODS: Twenty-nine patients with RA who had radiological damage and/or arthritis underwent MRI. Two experienced readers independently read both complete sets. One reader read 6 random sets after the initial session, in order to assess the intrareader agreement. For evaluation of the intrareader and interreader reliability, quadratic-weighted κ scores were calculated per joint and lesion. RESULTS: For the forefeet, interreader scores were excellent, ranging from 0.77 (bone edema) to 0.95 (bone erosion). Hindfoot interreader agreement scores were highest for erosion (0.90) and synovitis global score (0.88), but edema and synovial thickness agreement were also acceptable (0.83 and 0.86). Intrareader scores were on the whole slightly lower, but excellent. CONCLUSION: Reliability (interreader and intrareader agreement) in the assessment of the rheumatoid foot according to the RAMRIS method is excellent.

Cost-effectiveness of intensive exercise therapy directly following hospital discharge in patients with arthritis: results of a randomized controlled clinical trial.

OBJECTIVE: To estimate the cost-utility and cost-effectiveness of a 3-week intensive exercise training (IET) program directly following hospital discharge in patients with rheumatic diseases. METHODS: Patients with arthritis who were admitted to the hospital because of a disease activity flare or for elective hip or knee arthroplasty were randomly assigned to either the IET group or usual care (UC) group. Followup lasted 1 year. Quality-adjusted life years (QALYs) were derived from Short Form 6D scores and a visual analog scale (VAS) rating personal health. Function-related outcome was measured using the Health Assessment Questionnaire, the McMaster Toronto Arthritis (MACTAR) Patient Preference Disability Questionnaire, and the Escola Paulista de Medicina Range of Motion scale (EPMROM). Costs were reported from a societal perspective. Differences in costs and incremental cost-effectiveness ratios (ICERs) were estimated. RESULTS: Data from 85 patients (50 IET and 35 UC) could be used for health-economic analysis. VAS personal health-based QALYs were in favor of IET. Function-related outcome showed statistically significant improvements in favor of IET over the first 6 months, according to the MACTAR (P < 0.05) and the EPMROM (P < 0.01). At 1-year followup, IET was euro718 less per patient. The ICER showed a reduction in mean total costs per QALY. In 70% of cases the intervention was cost-saving. CONCLUSION: IET results in better quality of life at lower costs after 1 year. Thus, IET is the dominant strategy compared with UC. This highlights the need for implementation of IET after hospital discharge in patients with arthritis.

Turnover of cardiac troponin subunits. Kinetic evidence for a precursor pool of troponin-I.

The turnover of troponin-T, troponin-I, and troponin-C, under conditions closely approximating a steady state, has been determined from the rate of incorporation of L-[4,5-3H]leucine into the polypeptides. Isotope was administered to rats by constant infusion for a period of 4 h and the rate of equilibration of radioactive leucine in the serum was determined. The specific radioactivity of leucine was measured in both the protein and the precursor pools. Troponin subunits were separated from other proteins by polyacrylamide gel electrophoresis. The turnover rates of other myofibrillar proteins, tropomyosin, actin, and myosin heavy and light chains, were also measured. Troponin-T and troponin-I had similar half-lives of 3.5 and 3.2 days, respectively, which were significantly different from that of troponin-C (5.3 days). The rates of turnover of troponin-T and troponin-I were greater than those of myosin heavy chain, but the turnover of troponin-C was not significantly different from that of myosin heavy chain. These findings indicate that the subunits of cardiac troponin turn over nonuniformly. In addition, evidence from kinetic experiments indicates the presence of a precursor pool of unassembled troponin-I but not for troponin-T or troponin-C.

Perinatal nutritional modification of weanling rat heart contractile protein.

The present study ascertained the influence of litter-size-induced perinatal nutritional modification on cardiac contractile protein enzymatic activity and isomyosin composition. Myofibrillar enzyme activities for Mg2+ -ATPase, Ca2+ -ATPase, and creatine kinase (CK) in the weanling heart were unaltered by nutritional modification. However, these enzyme activities were all significantly augmented in the adult heart. Hill plot analyses of Mg2+ -ATPase activities indicated that myofibrillar calcium regulation was not influenced by either nutritional modification or the weanling-to-adult developmental progression. Isomyosin V1 composition (90 +/- 1%) correlated with plasma thyroid hormone level in normal-growth (8/litter) weanlings. Undernutrition retarded conversion of V3 isomyosin to the V1 species while overnutrition enhanced isomyosin conversion. Isomyosin composition in weanling rats subjected to perinatal nutritional modification was independent of thyroid status. In the adult rat, plasma thyroxine levels were increased, whereas V1 isomyosin remained unchanged (88 +/- 2%) compared with that of the weanling groups. Discrepancies in the relationship between contractile protein enzymatic activities, myosin composition, and heart function are apparent between both the litter-size-adjusted weanling rats and between weanling and adult animals. These discrepancies indicate the complex relationship between heart function and contractile protein properties.

Cardiac myofibrillar creatine kinase is not influenced by hypothyroidism.

The cardiac myofibrillar component of the phosphorylcreatine shuttle mechanism enzymatically couples the functionally significant processes of energy utilization (ATPase) with substrate regeneration by creatine kinase (CK). Both components have isoenzyme forms that are transcriptionally regulated. Propylthiouracil-induced (PTU) hypothyroidism reduced rat cardiac contractile protein ATPase activity by shifting isomyosin predominance from the V1 to the V3 form. However, neither CK specific activity or CK isoenzyme composition was altered by PTU treatment. Thus, myofibrillar components of the phosphorylcreatine shuttle, ATPase and CK, are not coordinately regulated under hypothyroid conditions.

Molecular cloning and developmental expression of the rat cardiac-specific isoform of troponin I.

Troponin I is the subunit of the troponin complex in striated muscle which inhibits actomyosin ATPase activity. We have isolated a full-length cDNA clone for rat cardiac troponin I and determined its nucleic acid sequence. The amino acid sequence deduced from this clone shows 88%-92% similarity with previously reported amino acid sequences for rabbit (Wilkinson and Grand, 1978) and bovine (Leszyk et al.) cardiac troponin I. Examination of cardiac troponin I mRNA abundance during development revealed a 15-fold induction in its expression in the adult heart compared to that in embryonic (14 day) heart muscle. Furthermore, expression of cardiac troponin I mRNA was restricted to heart muscle and was not detected in skeletal muscle at any developmental stage.