OBJECTIVE: To develop evidence-based recommendations for the non-pharmacological and pharmacological management of Raynaud\'s phenomenon (RP) and digital ulcers (DUs) in patients with systemic sclerosis and other immune-mediated connective tissue diseases (CTDs).
METHODS: A task force comprising 21 rheumatologists, two surgeons (vascular and plastic), two nurses, and one patient representative was established. Following a systematic literature review performed to inform the recommendations, statements were formulated and discussed during two meetings (one online and one in-person). Levels of evidence, grades of recommendation (GoR), and level of agreement (LoA) were determined.
RESULTS: Five overarching principles and 13 recommendations were developed. GoR ranged from A to D. The mean ± standard difference (SD) LoA with the overarching principles and recommendations ranged from 7.8±2.1 to 9.8±0.4. Briefly, the management of RP and DUs in patients with CTDs should be coordinated by a multidisciplinary team and based on shared decisions with patients. Nifedipine should be used as first-line therapy for RP and/or DUs. Sildenafil, tadalafil, and/or iloprost IV are second-line options for severe and/or refractory patients with RP and/or DUs. Sildenafil, tadalafil and/or Iloprost IV, should be prescribed for healing and prevention (also including bosentan) of DUs. In patients with RP and/or DUs, non-pharmacological interventions might be considered as add-ons, but there is limited quality and quantity of scientific evidence supporting their use.
CONCLUSIONS: These recommendations will inform rheumatologists, specialist nurses, other healthcare professionals, and patients about a comprehensive and personalized management of RP and DUs. A research agenda was developed to address unmet needs, particularly for non-pharmacologic interventions.

The 2D:4D digit ratio is commonly used as a surrogate possibly reflecting prenatal testosterone levels. Indirect evidence comes from studies investigating the association between 2D:4D and human characteristics that likely relate to prenatal testosterone. In children, sex-typed play reveals large sex differences early in development and an influence of prenatal testosterone is likely. Findings on the association between 2D:4D and children\'s sex-typed play are heterogeneous and other influences on the development of sex-typed play have been suggested, most of all social influences like siblings, their sex and birth order. The current study examined the association between right and left 2D:4D, a proposed surrogate for prenatal testosterone exposure, which was assessed in right and left hands of N = 505 6-month-old children, and sex-typed play behavior, which was evaluated 3.5 years later using the Pre-School Activities Inventory (PSAI), and the influence of siblings. To capture differential effects of siblings\' sex and birth order, dummy-coded variables were used reflecting having no siblings as well as older or younger sisters or brothers. Multiple regression models were used to investigate the association between PSAI scores and sex, right and left 2D:4D, being a singleton as well as having an older or younger sister or brother. It was shown that sex and having an older brother were significant predictors for sex-typed play. Effects were further disentangled by conducting separate regression analyses in boys and girls. In boys, a significant association between PSAI scores and having an older brother was revealed, in girls, no significant associations were found. Results are discussed highlighting the non-significant association between 2D:4D and children\'s sex-typed play, which weakens the applicability of 2D:4D as a surrogate reflecting influences of prenatal T. Further, the importance of social factors like siblings on children\'s sex-typed play is discussed.

Ventrointermediate thalamic stimulation (VIM-DBS) modulates oscillatory activity in a cortical network including primary motor cortex, premotor cortex, and parietal cortex. Here we show that, beyond the beneficial effects of VIM-DBS on motor execution, this form of invasive stimulation facilitates production of sequential finger movements that follow a repeated sequence. These results highlight the role of thalamo-cortical activity in motor learning.

This study was performed to analyze fingertip capillary blood sampling in pediatric patients using microcapillary blood collection tubes and microhematocrit tubes and to compare the blood cell analysis results obtained via these two blood collection methods. Finger capillary blood was collected from 110 outpatients using microcapillary blood collection tubes and microhematocrit tubes and complete blood count analysis was performed with a Sysmex XS-900i hematology analyzer and manual microscopy for blood cell morphology. Paired data was evaluated for agreement and bias using the microhematocrit samples as the reference group and the samples from the microcapillary blood collection tubes as the observation group. The two blood collection methods demonstrated good agreement for measuring red blood cell (RBC) parameters (i.e., RBC, Hb, Hct, MCV, MCH and MCHC), wherein the relative bias was > allowable total error (TEa) in 0.91%, 1.82%, 11.82%, 1.82%, 0.91% and 8.18% of the parameter measures, respectively. According to industry requirements, the proportion of samples meeting the acceptable bias level should be > 80%. Additionally, the estimated biases at each medical decision level were within clinically acceptable levels for RBC, Hb, Hct, and MCV. However, the proportion of WBC and PLT counts with relative bias > TEa was 25.45% and 35.45%, respectively. Furthermore, the relative bias of the WBC count at the medical decision level of 0.5 × 109/L and that of the PLT counts at the medical decision levels of 10 × 109/L and 50 × 109/L were clinically significant. Bland-Altman analysis further showed a mean bias of 0.66 × 109/L (95% LoA, - 0.79 to 2.11) for the WBC count and 39 × 109/L (95% LoA, - 46 to 124) for the PLT count from the blood samples collected in the microcapillary blood collection tubes compared with the counts of those collected in the microhematocrit tubes. Neutrophil, monocyte, lymphocyte, eosinophil, and PLT counts increased significantly in the microcapillary blood collection tubes compared with those in the microhematocrit tubes, along with an elevated number of instrument false alarms (P < 0.05). The two capillary blood collection devices exhibit performance differences. Therefore, clinicians should pay attention to the variation in results caused by different blood collection methods.

Tactile Imagery (TI) remains a fairly understudied phenomenon despite growing attention to this topic in recent years. Here, we investigated the effects of TI on corticospinal excitability by measuring motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation (TMS). The effects of TI were compared with those of tactile stimulation (TS) and kinesthetic motor imagery (kMI). Twenty-two participants performed three tasks in randomly assigned order: imagine finger tapping (kMI); experience vibratory sensations in the middle finger (TS); and mentally reproduce the sensation of vibration (TI). MEPs increased during both kMI and TI, with a stronger increase for kMI. No statistically significant change in MEP was observed during TS. The demonstrated differential effects of kMI, TI and TS on corticospinal excitability have practical implications for devising the imagery-based and TS-based brain-computer interfaces (BCIs), particularly the ones intended to improve neurorehabilitation by evoking plasticity changes in sensorimotor circuitry.

BACKGROUND: Parkinson\'s disease (PD) is characterized by motor symptoms whose progression is typically assessed using clinical scales, namely the Movement Disorder Society-Unified Parkinson\'s Disease Rating Scale (MDS-UPDRS). Despite its reliability, the scale is bounded by a 5-point scale that limits its ability to track subtle changes in disease progression and is prone to subjective interpretations. We aimed to develop an automated system to objectively quantify motor symptoms in PD using Machine Learning (ML) algorithms to analyze videos and capture nuanced features of disease progression.
METHODS: We analyzed videos of the Finger Tapping test, a component of the MDS-UPDRS, from 24 healthy controls and 66 PD patients using ML algorithms for hand pose estimation. We computed multiple movement features related to bradykinesia from videos and employed a novel tiered classification approach to predict disease severity that employed different features according to severity. We compared our video-based disease severity prediction approach against other approaches recently introduced in the literature.
RESULTS: Traditional kinematics features such as amplitude and velocity changed linearly with disease severity, while other non-traditional features displayed non-linear trends. The proposed disease severity prediction approach demonstrated superior accuracy in detecting PD and distinguishing between different levels of disease severity when compared to existing approaches.

OBJECTIVE: The aim of the study is measuring the magnitude and determining the method of finger pressure exerted by doctors on ceramic veneers during their fixation.
METHODS: A simulation model was designed in order to measure the volume of finger pressure. Veneers were produced for 2 central incisors. Doctors alternately placed veneers on the model and applied pressure on them for 20 seconds simulating the clinical stage of cementing. The operator recorded the maximum readings of the scales and entered the result on the research protocol. In addition, it was recorded which finger the doctor exerts on the veneer during its cementing to ensure a tight fit: thumb or index finger.
RESULTS: The values obtained during cementation of 54% doctors ranged up to 1 kg, 27% of doctors from 1 to 2 kg and only 19% more than 2 kg. 80% of doctors applied the main pressure on the veneer using their thumb, while the pressure force was 1.4 kg. For those doctors who pressed the veneer to the tooth with their index finger, the impact value was 0.8 kg.
CONCLUSIONS: The finger pressure on the veneer during cementation applied by dentists varies, the average pressure on the veneers was about 1.5 kg. The amount of pressure on cement during laboratory tests of cements for fixing veneers differs from clinical values many times. The development of a veneers fixation protocol, taking into account the conducted research, will ensure a reliable and accurate fit of the veneer at the stage of its cementing.
UNASSIGNED: Измерение величины и определение способа пальцевого давления, оказываемого врачами на керамические виниры во время их фиксации.
UNASSIGNED: Для измерения величины пальцевого давления была спроектирована симуляционная модель. На 2 центральных резца были изготовлены виниры. Врачи поочередно устанавливали виниры на модель и в течение 20 с на них оказывали давление, имитируя клинический этап цементирования. Оператор регистрировал максимальные показания весов и заносил полученный результат в протокол исследования. Кроме того, фиксировали, каким именно пальцем врач оказывает воздействие на винир во время его цементирования для обеспечения плотной посадки: большим или указательным.
UNASSIGNED: Установлено, что 54% врачей во время цементирования оказывают давление на винир до 1 кг, 27% врачей — от 1 до 2 кг, и только 19% врачей — более 2 кг; 80% врачей оказывали основное давление на винир, используя большой палец, при этом сила прижимного давления составила 1,4 кг. У врачей, которые прижимали винир к зубу указательным пальцем, величина воздействия была 0,8 кг.
UNASSIGNED: Пальцевое давление на винир во время его цементирования у разных врачей имеет существенные различия, в среднем давление на виниры составило около 1,5 кг. Давление на цемент во время лабораторных испытаний цементов для фиксации виниров отличается от клинических величин многократно. Разработка протокола фиксации виниров с учетом поведенных исследований обеспечит надежную и точную посадку винира на этапе его цементирования.

UNASSIGNED: Clinically amyopathic dermatomyositis (CADM) is a rare subtype of dermatomyositis that presents with cutaneous features and no muscle involvement. This case report describes a 26-year-old woman with recurrent and multiple digital ulcerations coinciding with the start of winter each year. There was no evidence of myopathy, and antibody testing yielded negative results. A diagnosis of CADM was ultimately made based on clinicopathologic correlation. The patient\'s ulcers demonstrated excellent response to a combination therapy of hydroxychloroquine and potent topical and systemic steroids. Herein, the authors discuss the pathologic and immunologic characteristics of CADM.

Placental DNA methylation (DNAm) may be a potential mechanism underlying the effects of prenatal bisphenol analogues (BPs) exposure on reproductive health. Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes with prenatal BPs exposure and children\'s digit ratios at age 4 using multiple linear regression models, and mediation analysis was further used to examine the mediating role of placental DNAm in the associations between prenatal BPs exposure and digit ratios among 345 mother-child pairs. Prenatal exposure to bisphenol A (BPA) was associated with hypermethylation at Protocadherin 8 (PCDH8), RBMX Like 2 (RBMXL2), and Sperm Acrosome Associated 1 (SPACA1), while bisphenol F (BPF) exposure was associated with higher methylation levels of Fibroblast Growth Factor 13 (FGF13). Consistent patterns were found in associations between higher DNAm at the 4 genes and increased digit ratios. Further mediation analysis showed that about 15% of the effect of BPF exposure on increased digit ratios was mediated by placental FGF13 methylation. In conclusion, the altered placental DNAm status might be a mediator underlying the feminizing effect of prenatal BPs exposure.

BACKGROUND: Dupuytren\'s contractures (DC) are fibrous cords under the skin of the hand that cause one or more fingers to curl gradually and irreversibly towards the palm. These contractures are usually painless but can cause a loss of hand function. Two treatments for Dupuytren\'s contractures are widely used within the National Health Service (NHS) in the UK: removal of the contractures via surgery (limited fasciectomy) and division of the contractures via a needle inserted through the skin (needle fasciotomy). This study aims to establish the clinical and cost-effectiveness of needle fasciotomy (NF) versus limited fasciectomy (LF) for the treatment of DC in the NHS, in terms of patient-reported hand function and resource utilisation.
METHODS: Hand-2 is a national multi-centre, two-arm, parallel-group randomised, non-inferiority trial. Patients will be eligible to join the trial if they are aged 18 years or older, have at least one previously untreated finger with a well-defined Dupuytren\'s contracture of 30° or greater that causes functional problems and is suitable for treatment with either LF or NF. Patients with a contracture of the distal interphalangeal joint only are ineligible. Eligible consenting patients will be randomised 1:1 to receive either NF or LF and will be followed up for 24 months post-treatment. A QuinteT Recruitment Intervention will be used to optimise recruitment. The primary outcome measure is the participant-reported assessment of hand function, assessed by the Hand Health Profile of the Patient Evaluation Measure (PEM) questionnaire at 12 months post-treatment. Secondary outcomes include other patient-reported measures, loss of finger movement, and cost-effectiveness, reported over the 24-month post-treatment. Embedded qualitative research will explore patient experiences and acceptability of treatment at 2 years post-surgery.
CONCLUSIONS: This study will determine whether treatment with needle fasciotomy is non-inferior to limited fasciectomy in terms of patient-reported hand function at 12 months post-treatment.
BACKGROUND: International Standard Registered Clinical/soCial sTudy ISRCTN12525655. Registered on 18th September 2020.