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Introduction: This study aimed to investigate the influence of neglect and the effect of prism adaptation (PA) combined with continuous Theta-burst transcranial magnetic stimulation (cTBS) on the art constructive errors in painting rehabilitation of stroke patients with neglect. Methods: Fourteen patients with neglect and art constructive errors in painting secondary to stroke were randomly assigned to the rehabilitation group and received PA combined with the inhibitory protocol of cTBS over the intact parietal cortex; the control group received PA combined with sham cTBS for two weeks in ten daily sessions. Patients were assessed for art constructive errors in painting in figure copying test (FCT), and coloring test (CT) before and after the intervention. Art constructive errors in painting were classified into omission, deformation, size, neglect of warm colors, and perseveration of errors. Neglect was evaluated using the line bisection task (LBT), figure copying test (FCT), and coloring test (CT). Results: All patients showed a significant improvement in art constructive errors in painting (measured using the pattern of painting’ errors in FCT and CT), and neglect (measured using LBT, FCT, and CT) (p

OBJECTIVE To summarize the existing literature for several promising minimally invasive tests to measure disease activity in eosinophilic esophagitis (EoE). DATA SOURCES Literature searches were performed using PubMed. Keyword combinations included eosinophilic esophagitis and minimally invasive techniques, including the esophageal string test, Cytosponge, transnasal endoscopy, technetium-labeled heparin, and noninvasive biomarkers. STUDY SELECTIONS Retrospective and prospective observational studies, peer-reviewed reviews, and systematic reviews were selected. Data were reviewed and summarized. RESULTS Various techniques have been developed in recent years to measure disease activity in EoE without the need for conventional endoscopy. Our review summarizes the data on these techniques, the benefits and limitations, and future directions for implementation in both research and clinical care. CONCLUSION Tremendous progress has been made toward developing minimally invasive techniques to measure disease activity in EoE. Each of the techniques mentioned in this review has advantages and disadvantages, and some are closer to widespread use than others.

Stereotactic ablative radiotherapy (SABR), or stereotactic body radiotherapy (SBRT), has recently been applied in the field of arrhythmia management. It has been most widely assessed in the treatment of ventricular tachycardia (VT) but may also have potential in the treatment of other arrhythmias as well, often termed stereotactic arrhythmia radiotherapy (STAR). The non-invasive delivery of treatment for VT has the potential to spare an often physiologically vulnerable group of patients the burden of long catheter ablation procedures with the potential for prolonged periods of hemodynamic instability. Cardiac SABR also has the capacity to direct ablative therapy at substrate that is inaccessible using current transchatheter techniques. For these reasons cardiac SABR has generated significant enthusiasm as an emerging treatment modality for VT. We consider in review the pre-clinical data pertaining to the use of SABR in cardiac tissue and recent clinical evidence regarding the application of SABR in the field of arrhythmia management.

Purpose: The present study investigated the association between Systematic COronary Risk Evaluation (SCORE)-estimated cardiovascular risk and carotid stiffening in a middle-aged population using ultrafast pulse wave velocity (ufPWV).Methods: This study enrolled 683 participants without known cardiovascular disease or diabetes mellitus who underwent ufPWV measurements. Clinical interviews, physical examinations, laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity (PWV) at the beginning of systole (PWV-BS), and PWV at the end of systole (PWV-ES) were assessed. Each participant underwent an assessment of SCORE risk based on major cardiovascular risk factors (CVRFs), including age, sex, smoking, systolic blood pressure (SBP), and total cholesterol (TC). Crude and adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression were used. Overall CVRFs were adjusted to assess ORs.Results: cIMT and carotid stiffening in PWV-BS and PWV-ES were significantly different between sex subgroups (all P0.05).Conclusion: Carotid stiffening quantified by ufPWV is linked to SCORE categories, and elevated PWV-ES may aid in cardiovascular risk stratification.

We appreciate the interest in our study by Majumdar and Tsochatzis1 and welcome the opportunity to provide some clarifications. The literature to date has examined non-invasive test (NIT) algorithms to rule-in and rule-out advanced fibrosis (AF). The main use of such algorithms is to identify those at low risk of AF who can be managed in primary care. We propose an algorithm2 where the rule-out cut-offs remain optimised for AF, whereas the rule-in cut-offs are optimised for cirrhosis. The false-negative (FN) rate of 10% in our proposed algorithm refers to the FN rate for AF and not cirrhosis as Majumdar and Tsochatzis state in their letter.1 Only 18/570 (3%) of patients with cirrhosis are missed using our proposed algorithm (table 1). View this table: Table 1 Number of patients with fibrosis stage F0–2, F3 and F4 according to LSM cut-offs recommended by the Baveno 6 consensus (10 and 15 kPa) and our previous paper (8 and 20, and 8 and 28 kPa) We also argue2 that patients with NITs above the rule-in cut-off for AF should undergo liver biopsy to identify those with cirrhosis who should undergo …

Novel treatment modalities, such as non-invasive brain stimulation (NIBS), typically focus on patient groups that have failed multiple treatment interventions. Despite its promise, the clinical translation of NIBS in schizophrenia has been limited. One important obstacle to implementation is the inconsistent reporting of treatment resistance in the clinical trial literature contributing to heterogeneity in reported effects. In response, we develop a numerical approach to synthesize quality of assessment of Treatment-Resistant Schizophrenia (TRS) and apply this to studies investigating therapeutic response to NIBS in patients with schizophrenia. Literature search conducted through PubMed database identified 119 studies investigating Transcranial Magnetic Stimulation and Transcranial Electrical Stimulation in treating resistant schizophrenia symptoms. A quality score out of 11 was assigned to each study based on adherence to the international consensus guidelines for TRS developed by the Treatment Response and Resistance in Psychosis (TRRIP) group. Results revealed an overall paucity of studies with thorough assessment and/or reporting of TRS phenomenon, as evidenced by a mean quality score of 3.38/11 (SD: 1.01) for trials and 5.16/11 (SD: 1.57) for case reports, though this improved minimally since the publication of consensus criteria. Most studies considered treatment-resistance as a single dimensional construct by reporting resistance of a single symptom, and failed to establish treatment adherence, resistance time course and functional impairment. We conclude that the current NIBS literature in schizophrenia do not reflect its true effects on treatment-resistance. There is an urgent need to improve assessment and reporting standards of clinical trials that target TRS.

Purpose: The use of swimming goggles (SG) has demonstrated to alter different ocular parameters, however, the impact of wearing SG on the tear film stability remains unknown. The main objective of this study was to determine the short-term effects of wearing SG on tear film surface quality break-up time (TFSQ-BUT). Methods: Twenty-eight young healthy adults (14 men and 14 women) wore a drilled SG, and TFSQ-BUT was measured before, during and after SG use. Dynamic-area high-speed videokeratoscopy was used for the non-invasive assessment of TFSQ-BUT. Results: TFSQ-BUT was significantly reduced while SG wear in comparison to the baseline measurement (4.8 ± 4.5 s vs. 8.8 ± 6.9 s; corrected p-value = 0.017, d = 0.57, mean difference = 4.0 [0.6, 7.3]; 45% reduction). Immediately after SG removal, TFSQ-BUT rapidly recovered baseline levels (8.2 ± 5.9 s vs. 8.8 ± 6.9 s; corrected p-value = 0.744). The impact of wearing SG on TFSQ-BUT were independent of the gender of the participants (p = 0.934). Conclusion: The use of SG induces a TFSQ-BUT reduction, with these changes returning to baseline levels immediately after SG removal. These data may be of relevance for the management of dry eye patients, who need to avoid circumstances that exacerbate tear film instability. Nevertheless, these results must be interpreted with caution since the experiment did not entirely mimic real-life conditions (e.g., eye cup piece drilled, time of exposure, environmental conditions). Future studies should consider the inclusion of dry eye patients and older individual in order to explore the generalizability of these findings.

In vivo studies on association between wall shear stress (WSS) and intracranial plaque are deficient. Based on the three-dimensional T1-weighted high-resolution magnetic resonance imaging (3DT1 HR-MRI) data of patients with low-grade stenotic (

It has been demonstrated that acute vagus nerve stimulation (VNS) improves word recognition memory in epilepsy patients. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained interest as a non-invasive alternative to improve cognition. In this prospective randomized cross-over study, we investigated the effect of both invasive VNS and taVNS on verbal memory performance in 15 patients with drug-resistant epilepsy. All patients conducted a word recognition memory paradigm in 3 conditions: VNS ON, VNS OFF and taVNS (3-period 3-treatment cross-over study design). For each condition, patients memorized 21 highlighted words from text paragraphs. Afterwards, the intervention was delivered for 30 s. Immediate recall and delayed recognition scores were obtained for each condition. This memory paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON and VNS OFF (2-period 2-treatment cross-over study design). Acute VNS and taVNS did not improve verbal memory performance. Immediate recall and delayed recognition scores were significantly improved after 6 weeks of VNS treatment irrespective of the acute intervention. We can conclude that the previously described positive effects of invasive VNS on verbal memory performance could not be replicated with invasive VNS and taVNS. An improved verbal memory performance was seen after 6 weeks of VNS treatment, suggesting that longer and more repetitive stimulation of the vagal pathway is required to modulate verbal memory performance.Clinical trial registration number: NCT05031208.

BACKGROUND: Lowering kVp affects the image contrast and computed tomography (CT) attenuation values of low kVp CT is different from those of conventional 120-kVp scans. The purpose of this study is to determine the diagnostic performance and to establish the reference range of low-kVp unenhanced CT for the assessment of hepatic steatosis in liver transplantation donors using magnetic resonance (MR) spectroscopy as a reference standard. METHODS: This retrospective study included 165 potential donors (male:female =114:51, 36.5±12.0 years old) who underwent 100-kVp single-slice unenhanced CT scan and MR spectroscopy. The difference between hepatic and splenic attenuation (CT(L-S)) and liver-to-spleen attenuation ratio (CT(L/S)) were calculated. Reference standard was the fat signal fraction measured by MR spectroscopy. Limits of agreement between CT measurements and the reference standard were calculated. Areas under receiver operating characteristic curves (AUROCs) of CT(L-S) and CT(L/S) were compared for the diagnosis of moderate to severe steatosis. Cut-off values of CT(L-S) and CT(L/S) that provided a balance between sensitivity and specificity and the highest specificity using the lower limit of the reference range were calculated. RESULTS: Eighty-seven subjects had a non-steatotic liver. Sixty-one subjects had mild steatosis and 17 subjects had moderate to severe steatosis based on MR spectroscopy. CT(L-S) and CT(L/S) values were negatively correlated with the fat signal fraction (P

У статті викладені сучасні можливості та власний досвід використання неінвазивного моніторингу центральної гемодинаміки esCCO (estimated Continuous Cardiac Output — розрахунковий безперервний вимір серцевого викиду) в анестезіологічній практиці при проведенні лапароскопічної холецистектомії.

Intracoronary physiology testing has emerged as a valuable diagnostic approach in the management of patients with chronic coronary syndrome, circumventing limitations like inferring coronary function from anatomical assessment and low spatial resolution associated with angiography or non-invasive tests. The value of hyperaemic translesional pressure ratios to estimate the functional relevance of coronary stenoses is supported by a wealth of prognostic data. The continuing drive to further simplify this approach led to the development of non-hyperaemic pressure-based indices. Recent attention has focussed on estimating physiology without even measuring coronary pressure. However, the reduction in procedural time and ease of accessibility afforded by these simplifications needs to be counterbalanced against the increasing burden of physiological assumptions, which may impact on the ability to reliably identify an ischaemic substrate, the ultimate goal during catheter laboratory assessment. In that regard, measurement of both coronary pressure and flow enables comprehensive physiological evaluation of both epicardial and microcirculatory components of the vasculature, although widespread adoption has been hampered by perceived technical complexity and, in general, an underappreciation of the role of the microvasculature. In parallel, entirely non-invasive tools have matured, with the utilization of various techniques including computational fluid dynamic and quantitative perfusion analysis. This review article appraises the strengths and limitations for each test in investigating myocardial ischaemia and discusses a comprehensive algorithm that could be used to obtain a diagnosis in all patients with angina scheduled for coronary angiography, including those who are not found to have obstructive epicardial coronary disease., Graphical Abstract Graphical AbstractIllustration of hierarchy of coronary indices and optimal coronary indices by coronary artery disease substrate. CFR, coronary flow reserve; CT, computed tomography; FFR, fractional flow reserve; hMR, hyperaemic microvascular resistance; hSR, hyperaemic stenosis resistance; iFR, instantaneous wave-free ratio; IMR, index of microvascular resistance; NHPR, non-hyperaemic pressure ratio; Pd/Pa, resting distal to aortic pressure ratio; QFR, quantitative flow reserve.

Background People with COPD have been reported to bear a distinct airway microbiota from healthy individuals based on bronchoalveolar lavage (BAL) and sputum samples. Unfortunately, the collection of these samples involves relatively invasive procedures and is resource-demanding, limiting its regular use. Non-invasive samples from the upper airways could constitute an interesting alternative, but its relationship with COPD is still underexplored. We examined the merits of saliva to identify the typical profile of COPD oral bacteria and test its association with the disease. Methods Outpatients with COPD and age-sex matched healthy controls were recruited and characterised based on clinical parameters and 16S rRNA profiling of oral bacteria. A clustering analysis based on patients’ oral bacteria beta-diversity and logistic regressions were performed to evaluate the association between oral bacteria composition and COPD. Results 128 individuals participated (70 patients and 58 controls). Differential abundance analyses showed differences in patients comparable to the ones previously observed in samples from the lower respiratory tract, i.e., an increase in Proteobacteria (particularly Haemophilus) and loss of microbiota diversity. An unsupervised clustering analysis separated patients in two groups based on microbiota composition differing significantly in the frequency of patients hospitalized due to severe acute exacerbation of COPD (AECOPD) and in the frequency of GOLD D patients. Furthermore, a low frequency of Prevotella was associated with a significantly higher risk of recent severe AECOPD and of being GOLD D. Conclusion Salivary bacteria showed an association with COPD, particularly with severe exacerbations, supporting the use of this non-invasive specimen for future studies of heterogeneous respiratory diseases like COPD.

Background Iron deficiency anemia (IDA) is a public health problem in children and adolescents that is characterized by reduced hemoglobin (Hb) levels. Non-invasive monitoring devices can measure Hb levels continuously without pain or discomfort; however, little is known about their accuracy in children and adolescents. This study estimated the accuracy of a non-invasive Hb monitor in this age group. Methods Participants were outpatients visiting the Tokyo Metropolitan Children's Medical Center for blood tests between January and March 2019. Hb levels were measured using both non-invasive Astrim Fit monitoring devices and invasive blood collection followed by automated analysis. Bland–Altman analysis assessed the agreement between the two measurements. Results Overall, 120 schoolchildren (9–15 years old, 51 % female) were enrolled. The non-invasive measuring device recorded Hb levels of 13.5 ± 1.6 g/dL (mean ± standard deviation [SD]), while the mean Hb level obtained from the collected blood was 13.7 ± 1.7 g/dL. Therefore, the mean difference of bias and SD of precision was 0.17 ± 1.95 g/dL. Values of lower and upper limits of agreement were −3.65 and 3.99, respectively. There was no systematic fixed or proportion bias. Fifty-nine participants (49 %) had a relative error of ± 0.10. Conclusion The Astrim Fit non-invasive Hb monitor can be used to evaluate Hb levels among schoolchildren for health promotion or research purposes because of its extremely low bias (or precision), no systematic biases (including fixed or proportion biases), and positive correlation between non-invasive monitoring and blood drawing. However, it is difficult to assess Hb levels in children and adolescents using the Astrim Fit device for diagnostic purposes.

Objective: To record and characterize features of levator ani muscles (LAM) activity in pregnancy and postpartum using non-invasive and novel Magnetomyography (MMG) technique with amplitude and spectral parameters. Methods: Nulliparous women with uncomplicated pregnancies participated in the MMG data collection during rest and voluntary LAM contractions (Kegels) with modulated intensity in third trimester and approximately 2 months postpartum (PP). Simultaneous surface electromyography was recorded to document the recruitment of accessory muscles. Moderate strength Kegel (MK) MMG trials were analyzed. Amplitude and spectral parameters including root-mean square (RMS) amplitude, power spectrum density (PSD) and normalized PSD (rPSD) in three frequency bands (low, middle, high) were computed on MK epochs. Statistical comparisons between pregnancy and postpartum were calculated. Results: MMG recordings were measured from 10 pregnant women. Results showed decreased RMS and power between third trimester and postpartum, trending towards significance. rPSD values in the low frequency band decreased significantly (p = 0.028) from third trimester to postpartum, while significant increase was observed in the middle frequency band (p = 0.018). Conclusions: This study shows that MMG as non-invasive tool has the ability to detect and characterize changes of LAM activity with amplitude and spectral parameters during pregnancy and postpartum.

In recent years, statistical studies highlighted an increasing incidence of cardiovascular diseases (CVD) which reflected on additional costs on the healthcare systems worldwide. Pulse wave velocity (PWV) measurement is commonly considered a CVD predictor factor as well as a marker of Arterial Stiffness (AS), since it is closely related to the mechanical characteristics of the arterial wall. An increase in PWV is due to a more rigid arterial system. Because of the prevalence of the elastic component, in young people the PWV is lower than in the elderly. Nowadays, invasive and non-invasive methods for PWV assessment are employed: there is an increasing attention in the development of non-invasive devices which mostly perform a regional PWV measurement (over a long arterial portion) rather than local (over a short arterial portion). The accepted gold-standard for non-invasive AS measurement is the carotid-femoral PWV used to evaluate the arterial damage, the corresponding cardiovascular risk and to adapt the proper therapy. This review article considers the main commercially available devices underlining their operating principles in terms of sensors, execution mode, pulse waveform acquired, site of measurement, distance and time estimation methods, as well as their main limitations in clinical practice.

Oocyte and embryo grading is one of the most important steps in assisted reproductive technology to identify the best among cultured embryos for transfer or vitrification. The most commonly used non-invasive method is morphological assessment of gametes and embryos using a microscope. This method despite being simple and cost-effective has interobserver and intraobserver variability and subjectivity and has little to offer about the physiological state of embryos. This review sourced research articles and reviews pertaining to other non-invasive assessment methodologies from Medline and PubMed to collate latest technologies in vogue and identify novel methodologies of the future. The review assesses the current understanding in oocyte and embryo grading and touches upon novel non-invasive techniques and potential biomarkers to identify the best embryo. The latest available literature on time-lapse imaging, hierarchical algorithms, omics (consisting of proteomics and secretomes), miRNAs, mitochondrial RNAs and artificial intelligence has been accessed to summarize the enormous information available, to identify gaps in current interpretations, to identify emerging technologies and to provide direction for future research. This review will greatly benefit anyone practicing assisted reproduction and clinical embryology.

Background and Objective: Diabetic problems are more common in the lower extremity and linked with high mortality rate which affects public health system. The present study focused on monitoring the changes in tissue oxygenation concentrations using Near infrared spectroscopy system along with temperature and hardness of the foot tissues. Methods: Control subjects (without diabetes) and diabetic patients without neuropathy were selected for this study and three standard foot risk areas were considered. Standard induced ischemic stimulus was given to assess the response of the designed system and to analyze the changes in oxyhemoglobin and deoxyhemoglobin levels during venous occlusion. Results: Results showed significant differences in the tissue oxygenation index value in all three standard areas where oxygenation value at the foot areas were significantly low ( p < 0.05) in diabetic group as compared to control group. Also, significant difference were found in tissue hardness value when comparing between groups, where the diabetic group had significantly high ( p < 0.05) tissue hardness at area 5 and area 8 as compared to control groups. Conclusion: Therefore, the present study concludes that high tissue hardness had significant effect on tissue oxygenation index that affects vascular circulation and this condition could be assessable using NIRS technique in order to find risky areas at the foot sole.

Background: Malignant Mesothelioma (MM) is a rare but aggressive tumor that arises in the lungs. Commonly, costly imaging and laboratory resources, i.e. (X-rays imaging, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) scans, biopsies, and blood tests) have already been utilized for the diagnosis of MM. Even though these diagnostic measures are expensive and unavailable in distant areas, some of these diagnosis methods are also very painful for the patient, i.e., biopsy and cytology of pleural fluid. Objective: In this study, we proposed a diagnosis model for early identification of MM via machine learning techniques. We explored the health records of 324 Turkish patients, which show the symptoms related to MM. The data of patients include socio-economic, geographical, and clinical features. Methods: Different feature selection methods have been employed for the selection of significant features. To overcome the data imbalance problem, various data-level resampling techniques have been utilized to obtain efficient results. The Gradient Boosted Decision Tree (GBDT) method has been used to develop the diagnostic model. The performance of the GBDT model is also compared with traditional machine learning algorithms. Results : Our model's results outperformed other models, both on balance and imbalance data. The results clearly show that undersampling techniques outperformed by imbalanced data even without resampling based on accuracy and Receiving Operating Characteristic (ROC) value. Conversely, it has also been observed that oversampling techniques outperformed undersampling and imbalanced data based on accuracy and ROC. All classifiers employed in this study achieved efficient results utilizing feature selection-based methods (OneR, information gain, and Relief-F), but the results of the other two methods (gain ratio and Correlation) were not entirely promising. Finally, when the combination of Synthetic Minority Oversampling Technique (SMOTE) and OneR was applied with GBDT, it gave the most favorable results based on accuracy, F-measure, and ROC. Conclusion: The diagnosis model has also been deployed to assist doctors, patients, medical practitioners, and other healthcare professionals for early diagnosis and better treatment of MM.

Background: The study involved a female patient diagnosed with late-stage dementia, with chronic daytime somnolence (CDS) as a prominent symptom. Objective: To explore whether her dementia resulted from Type 3 diabetes, and whether it could be reversed through ketosis therapy. Methods: A ketogenic diet (KD) generating low-dose 100 μM Blood Ketone Levels (BKL) enhanced by a brief Ketone Mono Ester (KME) regimen with high-dose 2–4 mM BKLs was used. Results: Three sets of data describe relief (assessed by % days awake) from CDS: 1) incremental, slow, time-dependent KD plus KME-induced sigmoid curve responses which resulted in partial wakefulness (0–40% in 255 days) and complete wakefulness (40–85% in 50 days); 2) both levels of wakefulness were shown to be permanent; 3) initial permanent relief from CDS with low-dose ketosis from 6.7% to 40% took 87 days. Subsequent low-dose recovery from illness-induced CDS (6.9% to 40%) took 10 days. We deduce that the first restoration involved permanent repair, and the second energized the repaired circuits. Conclusion: The results suggest a role for ketosis in the elimination of CDS with the permanent functional restoration of the awake neural circuits of the Sleep-Wake cycle. We discuss whether available evidence supports ketosis-induced bioenergetics alone or whether other mechanisms of functional renewal were the basis for the elimination of CDS. Given evidence for permanent repair, two direct links between ketosis and neurogenesis in the adult mammalian brain are discussed: Ketosis-induced 1) brain-derived neurotrophic factor, resulting in neural progenitor/stem cell proliferation, and 2) mitochondrial bioenergetics-induced stem cell biogenesis.

Background/Aims: Esophageal variceal bleeding (EVB) is an important cause of mortality and morbidity in liver cirrhosis. In this study, we aimed to predict the possibility of EVB in patients with cirrhosis using a non-invasive score.Methods: A total of 359 patients with cirrhosis were divided into two groups based on the presence or absence of EVB. ChildTurcotte-Pugh (CTP) score, a model for end-stage liver disease, aspartate aminotransferase to alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4-index (FIB-4), aspartate aminotransferase to alanine aminotransferase ratio/platelet ratio index (AARPRI), and S-index were measured for all participants. Receiver operating characteristic curves were obtained for all parameters, and the optimal cut-off value was determined in predicting EVB.Results: In patients with EVB, the number of platelets (PLT) were low (p

AIMS: Non-invasive myocardial work (MW) is a validated index of left ventricular (LV) systolic performance, incorporating afterload and myocardial metabolism. The role of MW in predicting the first hospitalization for de novo heart failure with preserved ejection fraction (HFpEF) is still unknown. We aim to investigate the diagnostic performance of MW to predict the first de novo HFpEF hospitalization in ambulatory individuals with preserved LV ejection fraction. METHODS AND RESULTS: Twenty-nine patients with transthoracic echocardiography performed at least 6 months before the first HFpEF hospitalization were compared with 29 matched controls. MW was derived as the area of pressure-strain loop using speckle-tracking and brachial artery blood pressure. Global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE) were collected. First HFpEF hospitalization and its combination with cardiovascular death [major adverse cardiovascular events (MACE)] and all-cause of death [major adverse events (MAE)] were assessed. At baseline, future HFpEF patients showed lower global work index, global constructive work, GWE, and higher GWW than controls (all P 170 mmHg% was associated with a 4-fold increase of MACE (HR = 4.5, 95% CI 1.59-13.12, P = 0.005) and a 3-fold higher risk of MAE (HR = 2.9, 95% CI 1.24-6.6, P = 0.014). CONCLUSIONS: In ambulatory patients with preserved LV ejection fraction and risk factors, GWW showed high accuracy to predict the first HFpEF hospitalization and its combination with mortality. The GWW routine assessment may be clinically helpful in patients with dyspnoea. ispartof: ESC HEART FAILURE vol:9 issue:1 pages:373-384 ispartof: location:England status: published

Hepatic steatosis is a key histological feature of nonalcoholic fatty liver disease (NAFLD). The non-invasive quantification of liver fat is now possible due to advances in imaging modalities. Emerging data suggest that high levels of liver fat and its temporal change, as measured by quantitative non-invasive methods, might be associated with NAFLD progression. Ultrasound-based modalities have moderate diagnostic accuracy for liver fat content and are suitable for screening. However, of the non-invasive imaging modalities, MRI-derived proton density fat fraction (MRI-PDFF) has the highest diagnostic accuracy and is used for trial enrolment and to evaluate therapeutic effects in early-phase clinical trials in nonalcoholic steatohepatitis (NASH). In patients with NAFLD without advanced fibrosis, high levels of liver fat are associated with rapid disease progression. Furthermore, changes on MRI-PDFF (≥30% decline relative to baseline) are associated with NAFLD activity score improvement and fibrosis regression. However, an inverse association exists between liver fat and complications of cirrhosis. Liver fat decreases as liver fibrosis progresses towards cirrhosis, and the clinical importance of quantitative measurements of liver fat differs by NAFLD status. As such, patients with NAFLD should be stratified by fibrosis severity to investigate the utility of quantitative measurements of liver fat for assessing NAFLD progression and prognosis.

Background Despite the invention of various non-invasive bioengineering tools, skin-type analysis has largely been based on subjective assessments. However, advancements in the functional cosmetic industry and artificial intelligence-assisted dermatology are creating a greater demand for an objective skin-type classification system. Objectives To propose an objective skin-type classification system solely based on non-invasive, bioengineering devices; provide reference values applicable to the Korean population; and compare our reference values with those of published studies. Methods Biophysical parameter measurements were obtained from the 2018 International Skin Characteristics Data Bank Project conducted by the Foundation of Korea Cosmetic Industry Institute. The participants were 434 healthy South Korean adults. Each participant was assessed using eight bioengineering devices (Tewameter® , pH-meter® , Corneometer® , Sebumeter® , Cutometer® , Spectrophotometer® , PRIMOS® lite, and Janus® ). The measurements were divided into tertiles to determine reference points. Results Our objective skin-type classification consists of five main categories (sensitivity, hydration, oiliness, elasticity, and skin tone) and five corresponding subcategories (erythema, roughness, pores, wrinkles, and pigmentation, respectively). Each skin type was assigned based on the reference point of the biophysical parameter, which was established as the tertile value associated with 'unfavourable' skin characteristics. Individuals were categorized as having sensitive skin when the TEWL scores were over 18.0 g/m2 /h or the pH was over 5.45; dehydrated skin when the corneometric value measured below 47.17 A.U.; oily skin when the sebumetric value exceeded 70 μg/cm2 ; and loose skin when the cutometric R2 value was below 0.68 E/mm. Conclusions This study is the first to provide a comprehensive skin-type classification system based solely on non-invasive biophysical parameters. As measurement data accumulate, the reference points will progress to become more accurate, and they will be subdivided according to gender, age, and ethnic group. Therefore, our classification system serves as a basis for artificial intelligence-based skin-type analysis.

Стаття продовжує цикл публікацій, присвячених пам’яті фундатора рефлексотерапії (РТ) в Україні — професора Мачерет Євгенії Леонідівни з нагоди її 90-річчя. У статті розглядаються актуальні питання медичної реабілітації хворих у клінічній практиці, де провідна увага приділяється методам РТ, сама назва яких має походження від слова «рефлекс». Констатовано загальновизнану пріоритетність давньосхідної медицини як основи РТ, де класичними методами є акупунктура і припікання. Водночас зроблено огляд історичних фактів щодо використання рефлекторних методів у широкому розумінні цього поняття на території України та у вжитку слов’янських народів. На основі здійсненого огляду вітчизняної та зарубіжної літератури й особистого досвіду представлено наукове обґрунтування дії методів РТ. Нейрофізіологічні аспекти полягають у трирівневому впливі на спінальному, стовбуровому, таламокортикальному рівнях центральної нервової системи. Саногенетичні аспекти РТ значною мірою пояснюються феноменом нейропластичності. Заразом згадуються новітні дані щодо виявленої анатомічної структури — первино-васкулярної системи, яка пояснює наявність енергетичних каналів і їх зв’язків (Stefanov M., Potroz M., Kim J.). Головний акцент у статті робиться на неінвазивних методах РТ, тобто способах впливу на точки та рефлексогенні зони, що не порушують шкірний покрив, серед яких точковий та вакуумний масажі, вакуумпунктура, натискування на точки (шіатсу), прогрівання моксами (цзю-терапія), поверхнева голкоаплікація багатоголчастими різнометалевими та полімерними аплікаторами, мей-хуа-чжень тощо. Подано інформацію стосовно менш відомих як неінвазивна РТ методів, за яких рефлекторна відповідь організму забезпечується шляхом стимуляції рецепторів органів чуття (арома-, світло-, смако-, звукотерапія). Пропонується авторська класифікація неінвазивних методів РТ. Акцентується увага на перспективах подальшого впровадження методів неінвазивної РТ у загальноклінічну та неврологічну практику, що базується на її перевагах (ефективність, технічна та матеріальна доступність, майже відсутність протипоказань, можливість широкого вибору одного з методів, а також виконання як лікарем, медичним працівником середньої ланки, так і безпосередньо самими хворими).

Background/Aims Beginning in April 2019, non-invasive vagus nerve stimulation was included in the NHS Innovation and Technology Payment programme. The programme guaranteed reimbursement of at least a 3-month course of treatment using gammaCore, through a prescription refill card, authorised by a headache specialist for patients with cluster headache who reported a clinically meaningful benefit. This study evaluated prescribing and refill trends to assess the use of gammaCore in England since the beginning of this programme. Methods Data regarding gammaCore prescriptions and refills from 1 April 2019 to 31 December 2020 were collected and tabulated. Patients were categorised into three groups: those who initiated gammaCore therapy under the programme (new starters), those who were prescribed ≥1 refill, and those who were prescribed ≥2 refills. One refill corresponds to 3 months of gammaCore therapy. Results In total, 52 NHS sites submitted 2092 prescriptions for gammaCore devices, including 655 for new starters. Among new starters, 46.3% received ≥1 refill and 30.9% received ≥2 refills. Those who started using gammaCore after its inclusion in the Innovation and Technology Payment programme received up to seven refills during the data collection period, representing 21 months of therapy. Conclusions This is one of the largest clinical audits of patients with cluster headache. Patients' continued use of gammaCore treatment through multiple 3-month refills in this audit suggests that non-invasive vagus nerve stimulation is efficacious, tolerable and practical for patients with cluster headache.

Background Diagnosis of pigmentary skin disorders, pre-cancerous and cancerous skin diseases is traditionally relied on visual assessment. The most widely applied invasive diagnostic technique is the skin biopsy. There have been significant technological advances in non-invasive diagnostic methods for skin disorders. Objective The objective of this article is to discuss different non-invasive diagnostic modalities, used in the diagnosis of pigmentary skin disorders and cutaneous cancers. Methods Comprehensive literature search was performed to screen articles related to non-invasive diagnostic techniques in pigmentary skin disorders and cutaneous cancers. Articles published in journals indexed in PubMed were searched along with those in Google Scholar. Clinical trials, review articles, case series, case reports and other relevant articles were considered for review. References of relevant articles were also considered for review. Results Dermoscopy and ultrasonography were the only non-invasive diagnostic and imaging techniques available to dermatologists for many years. The advent of computed tomography (CT) and magnetic resonance imaging (MRI) augmented the visualization of deeper structures. Confocal laser microscopy (CLM) and reflectance spectrophotometers have showed promising results in the non-invasive detection of pigmented lesions. Optical coherence tomography (OCT), electrical impedance spectroscopy (EIS), multispectral imaging, high frequency ultrasonography (HFUS) and adhesive patch biopsy aid in the accurate diagnosis of benign, as well as neoplastic skin diseases. Conclusion There have been significant advancements in non-invasive methods for diagnosis of dermatological diseases. These techniques can be repeatedly used in a comfort manner for the patient, and may offer an objective way to follow the course of a disease.

Non-invasive monitoring of temperature elevations inside tumor tissue is imperative for the oncological thermotherapy known as hyperthermia. In the present study, two cancer patients, one with a developing right renal cell carcinoma and the other with pseudomyxoma peritonei, underwent hyperthermia. The two patients were irradiated with radiofrequency current for 40 min during hyperthermia. We report the results of our clinical trial study in which the temperature increases inside the tumor tissues of patients with right renal cell carcinoma and pseudomyxoma peritonei induced by radiofrequency current irradiation for 40 min could be detected by statistical analysis of ultrasonic scattered echoes. The Nakagami shape parameter m varies depending on the temperature of the medium. We calculated the Nakagami shape parameter m by statistical analysis of the ultrasonic echoes scattered from the tumor tissues. The temperature elevations inside the tumor tissues were expressed as increases in brightness on 2-D hot-scale maps of the specific parameter αmod, indicating the absolute values of the percentage changes in m values. In the αmod map for each tumor tissue, the brightness clearly increased with treatment time. In quantitative analysis, the mean values of αmod were calculated. The mean value of αmod for the right renal cell carcinoma increased to 1.35 dB with increasing treatment time, and the mean value of αmod for pseudomyxoma peritonei increased to 1.74 with treatment time. The increase in both αmod brightness and the mean value of αmod implied temperature elevations inside the tumor tissues induced by the radiofrequency current; thus, the acoustic method is promising for monitoring temperature elevations inside tumor tissues during hyperthermia.

Introduction: The presence of an unbalanced familial translocation can be reliably assessed in the cytotrophoblast of chorionic villi. However, carriers of a balanced translocation often decline invasive testing. This study aimed to investigate whether an unbalanced translocation can also be diagnosed in cell free DNA by whole-genome non-invasive prenatal screening (NIPS). Material and methods: Pregnant women carrying a fetus with an unbalanced familial translocation, for whom NIPS as well as microarray data were available, were included in this retrospective assessment. NIPS was performed in the course of the TRIDENT study. Results: In 12 cases, both NIPS and microarray data were available. In 10 of 12 cases the unbalanced translocation was correctly identified by NIPS without prior knowledge on parental translocation. One was missed because the fetal fraction was too low. One was missed because of technical restrictions in calling 16p gains. Conclusions: This study supports the hypothesis that routine NIPS may be used for prenatal diagnosis of unbalanced inheritance of familial translocations, especially with prior knowledge of the translocation allowing focused examination of the involved chromosomal regions. Our study showed that routine shallow sequencing designed for aneuploidy detection in cell free DNA may be sufficient for higher resolution NIPS, if specialized copy number software is used and if sufficient fetal fraction is present.

Introduction: The study aimed to analyse the clinical response and short-term outcomes with the use of high-flow oxygen therapy (HFOT), non-invasive mechanical ventilation (NIMV) with bilevel positive airway pressure, or continuous positive airway pressure (CPAP) in severe COVID-19 patients. Methods: We conducted an observational, prospective, single-center study, approved by Ethics Committee of “Instituto de Investigación Sanitaria Fundación Jiménez Díaz” (EO102-20-HRJC). We included a total of 130 patients ≥18 years-old, with proved SARS-CoV-2 infection and secondary Acute Respiratory Failure (ARF) that required treatment with Non-invasive Respiratory Support (NIRS). We collected data about population demographic characteristics, clinical factors, and evolution during the incoming. A baseline of patients treated with HFO, CPAP and NIMV were compared with one-way ANOVA test, while categorical variables were expressed as numbers and percentages and were compared using the chi-square test or Fisher’s exact test when appropriate. Results: The cohort was distributed as follows: CPAP 54.6% (n = 71), NIMV 30% (n = 39), HFO 15.4% (n = 20). There were no differences between NIRS subgroups regarding age, comorbidity, or functional status. At the beginning of NIRS treatment, PaO2/FiO2 value was 149.3 ± 69.7. After 24 hours, PaO2/FiO2 was significantly higher in the CPAP group (CPAP vs NIMV, p-value = 0.0042; CPAP vs HFO, p-value = 0.000169). The overall ICU admission evaded rate was 69.1% and TF rate was 43.8%, without differences between the three therapies (p-value = 0.281). The mortality rate was 37.2%, without significant differences between subgroups. Conclusions: Our data suggest that CPAP versus treatment with NIMV or HFO improves PaO2/FiO2 rate in severe ARF patients, significantly reducing ICU admission. No differences were observed in mortality or therapeutic failure.

Resumen La incidencia de la enfermedad del hígado graso asociada al metabolismo (MAFLD) ha aumentado en los últimos años debido al estilo de vida actual. La biopsia de hígado sigue siendo la herramienta estándar de oro para detectar y estadificar MAFLD. Por otro lado, se están desarrollando múltiples biomarcadores y pruebas no invasivas para superar las limitaciones de la biopsia hepática, incluidos el costo y la invasividad. Las pruebas no invasivas se centran principalmente en la esteatosis y, en particular, en la fibrosis hepática y se pueden clasificar en pruebas patentadas y no patentadas. Si bien hepatic steatosis index y fatty liver index son las pruebas más comunes utilizadas para la detección de esteatosis, Hepamet Fibrosis Score, NAFLD fibrosis score, FIB-4, OWLiver®, y ELF® son las más utilizadas para la fibrosis hepática. Sin embargo, las pruebas no invasivas también tienen limitaciones que conviene resaltar ya que sus resultados podrían verse afectados por la presencia de diabetes, obesidad o por edades extremas que podrían dar lugar a falsos positivos o negativos. Para maximizar la precisión de los tests no invasivos, se han propuesto diferentes combinaciones integradas en algoritmos escalonados. Esta revisión tiene como objetivo destacar las fortalezas y limitaciones de dichos tests para detectar y estadificar MAFLD.

Purpose. The experimental study aimed to study the effects of stereotaxic radioablation of various doses on the myocardium of the atria, ventricles and atrioventricular (AV) node in the long term (up to 6 months); as well as assessment of collateral damage during radioablation.Methods. The study comprised 4 domestic pigs. The animals were 10-12 weeks old, the average weight was 30±2.7 kg. A linear accelerator was used for the experiment. Each animal underwent radiation exposure in different areas: 1st animal - AV node (dose 35 Gy), 2nd animal - AV node and the apex of the left ventricle (LV) (dose 40/35 Gy, respectively), 3rd animal - pulmonary veins (PV) and left atrium (dose 30 Gy), 4th - AV node and LV free wall (dose 45/40 Gy). Under intravenous sedation with hemodynamic monitoring, contrast-based CT of the heart was performed to assess the degree of displacement of the heart chambers in one respiratory and cardiac cycle and to assess the anatomy of the chambers of the heart and adjacent organs. The allocation and the contouring of the target zones were carried out in three projections: axial, frontal and sagittal. For electrocardiographic control, a loop recorder was implanted in each animal. The average exposure time was 11±7 minutes. After a follow-up period, morphological examination of the autopsy material was performed.Results. The average follow-up period after ablation was 134.75±77.34 days. The electrophysiological effect of the ablation was achieved in cases of complete AV-block development. This effect was developed in 2 out of 3 animals, where AV-node was exposed: 2nd animal - 40 Gy on 108th day of observation and 4th animal - 45 Gy on 21st day of observation. No cardiac tachyarrhythmia was recorded in the animals. The results of myocardium macro- and microscopic examination showed significant changes in the target zones. These areas had precise but uneven damage boundaries, which were within the planned ones (conformal exposure with a high degree of precision). The transmural nature of the changes was noted as well. Massive fields of fibrous tissue of various degrees of maturity (with a predominance of subepicardial localization) with focal hemorrhages of various ages and granulations were detected, which were surrounded by cardiomyocytes with coagulated and vacuolated cytoplasm.Conclusion. The use of non-invasive stereotactic treatment of tachyarrhythmias has high prospects in modern electrophysiology as an alternative ablation method.

Recent insights into the pathophysiologic underlying mechanisms of obesity have led to the discovery of several promising drug targets and novel therapeutic strategies to address the global obesity epidemic and its comorbidities. Current pharmacologic options for obesity management are largely limited in number and of modest efficacy/safety profile. Therefore, the need for safe and more efficacious new agents is urgent. Drugs that are currently under investigation modulate targets across a broad range of systems and tissues, including the central nervous system, gastrointestinal hormones, adipose tissue, kidney, liver, and skeletal muscle. Beyond pharmacotherapeutics, other potential antiobesity strategies are being explored, including novel drug delivery systems, vaccines, modulation of the gut microbiome, and gene therapy. The present review summarizes the pathophysiology of energy homeostasis and highlights pathways being explored in the effort to develop novel antiobesity medications and interventions but does not cover devices and bariatric methods. Emerging pharmacologic agents and alternative approaches targeting these pathways and relevant research in both animals and humans are presented in detail. Special emphasis is given to treatment options at the end of the development pipeline and closer to the clinic (ie, compounds that have a higher chance to be added to our therapeutic armamentarium in the near future). Ultimately, advancements in our understanding of the pathophysiology and interindividual variation of obesity may lead to multimodal and personalized approaches to obesity treatment that will result in safe, effective, and sustainable weight loss until the root causes of the problem are identified and addressed.

Maternal alloimmunisation against red blood cell antigens can cause haemolytic disease of the fetus and newborn (HDFN). Although most frequently caused by anti-D, since the implementation of rhesus D (RhD) immunoglobulin prophylaxis, other alloantibodies have become more prevalent in HDFN. Recent advances in non-invasive prenatal testing (NIPT) have allowed early prediction of HDFN risk in alloimmunised pregnancies and allow clinicians to focus health resources on those pregnancies that require intervention. This article aims to provide updates on the current status of NIPT in Australia as both a diagnostic and screening tool in pregnancy.

AIM To validate an appropriate spleen size measurement technique for the prediction of high-risk esophagogastric varices. METHODS This retrospective cross-sectional study included 369 patients who underwent ultrasonography and computed tomography (CT) of the spleen and esophagogastroduodenoscopy between January 2018 and December 2020. Maximum spleen length, width, and craniocaudal length were measured in a longitudinal view. The two-dimensional (2D) spleen index (maximum length × maximum width in the longitudinal view) was calculated. A three-dimensional (3D) spleen index was then defined as follows: 2D spleen index × maximum length in the transverse view. The similarity in spleen volume measured by CT and ultrasonography (spleen index) was assessed by the correlation coefficient. The diagnostic accuracies of the spleen index, platelet/spleen length, and platelet/spleen index were calculated to determine the overall diagnostic accuracy. RESULTS Compared to the other spleen indices, our 3D spleen index was significantly better correlated with spleen volume on CT (r = 0.91, 95% confidence interval 0.89-0.92, p

To identify a reliable alternative to the full blood [11C]PBR28 quantification method that would be easily replicated in multiple research and clinical settings. Ten [11C]PBR28 scans were acquired from 7 healthy non-human primates (NHP). Arterial input functions (AIFs) were averaged to create a population template input function (TIF). Population-based input functions were created by scaling the TIF with injected activity per body weight (PBIF) or unmetabolized tracer activity in blood at 15-,30-, and 60-min post-injection (PBIF15, PBIF30, and PBIF60). Two additional input functions were used: the native unmetabolized total plasma activity (Totals) and the Totals curve metabolite corrected by a scaled template parent fraction from a 30-min sample (TPF30-IF). Total distribution volumes (VTs) were calculated using PBIF, PBIF30, PBIF15, PBIF60, Totals, TPF30-IF, and the individual AIF (VTAIF). Distribution volume ratios (DVR) were computed using the cerebellum and the centrum semiovale (CSO), as pseudo-reference regions (DVRCereb, DVRCSO). Results obtained with each method were compared to VTAIF. Applicability of these alternative methods was tested on an independent pharmacological challenge dataset of microglial activation and depletion. Evaluation was carried at baseline, immediately after intervention (acute), and weeks post-intervention (post-recovery). VTs computed using PBIF15 and PBIF30 showed the best correlation to VTAIF (r > 0.90), while VT derived from the blood-free-scaled PBIF showed poor correlation (r = 0.46) and DVRCSO correlated the least (r = 0.26). In the pharmacological challenge study, most population-derived VT values were comparable to VTAIF at baseline and showed varied sensitivity to challenges at acute and post-recovery evaluation. DVR values did not detect relevant changes. Population-based input functions scaled with a single blood sample might be a useful alternative to using AIF to compute [11C]PBR28 binding in healthy NHPs or animals with comparable metabolism and overall perform better than pseudo-reference regions approaches.

В данном обзоре представлен ряд литературных источников, описывающих применение церебральной оксиметрии с использованием инфракрасной спектроскопии у детей. Множество клинических исследований показывают, что, несмотря на некоторые недостатки, неинвазивный мониторинг церебральной оксиметрии является важным инструментом защиты мозга, в первую очередь там, где может присутствовать ятрогенная ишемия головного мозга. Возрастает и количество данных об использовании инфракрасной спектроскопии в таких областях, как педиатрическая кардиохирургия, педиатрическая нейрохирургия, педиатрическая и неонатальная интенсивная терапия. В целом исследования показывают возрастающую роль мониторинга церебральной и соматической оксиметрии. Этот метод представляется полезным как при анестезии, так и в отделениях интенсивной терапии. Однако в настоящее время недостаточно клинических данных о критических уровнях измеряемых переменных, которые необходимы для безопасного ведения периоперационного периода у восприимчивых к церебральной ишемии пациентов, в частности в педиатрии.

The widely use of non-invasive prenatal testing (NIPT) may lead to accidental findings and the discovery of malignancy in pregnancy, often in asymptomatic patients. Diagnosis of such subclinical malignancy during pregnancy in the asymptomatic patient poses a predicament for both doctor and patient. The risks and benefits of possible treatment for both mother and child have to be weighted, and there is often limited scientific evidence available. We present a case of an abnormal NIPT result, leading to the diagnosis of acute myeloid leukemia (AML) in an asymptomatic pregnant patient. After multiple multidisciplinary meetings and an elaborate shared decision making (SDM) process, a watch and wait strategy was implemented, in contradiction with general treatment recommendations. Following this approach, it was possible to achieve a near term pregnancy before delivery of a healthy baby girl. The patient could subsequently commence treatment of her AML and is still in complete remission after a follow-up of 25 months. Our case report highlights the possibility of watch and wait strategy in selected cases and the importance of multidisciplinary collaboration and SDM, when faced with the accidental finding of AML through NIPT. J Hematol. 2021;10(5):228-231 doi: https://doi.org/10.14740/jh908

Urolithiasis is a common urological disease, and treatment strategy options vary between different stone types. However, accurate detection of stone composition can only be performed in vitro. The management of infection stones is particularly challenging with yet no effective approach to pre-operatively identify infection stones from non-infection stones. Therefore, we aimed to develop a radiomic model for preoperatively identifying infection stones with multicenter validation. In total, 1198 eligible patients with urolithiasis from three centers were divided into a training set, an internal validation set, and two external validation sets. Stone composition was determined by Fourier transform infrared spectroscopy. A total of 1316 radiomic features were extracted from the pre-treatment Computer Tomography images of each patient. Using the least absolute shrinkage and selection operator algorithm, we identified a radiomic signature that achieved favorable discrimination in the training set, which was confirmed in the validation sets. Moreover, we then developed a radiomic model incorporating the radiomic signature, urease-producing bacteria in urine, and urine pH based on multivariate logistic regression analysis. The nomogram showed favorable calibration and discrimination in the training and three validation sets (area under the curve [95% confidence interval], 0.898 [0.840-0.956], 0.832 [0.742-0.923], 0.825 [0.783-0.866], and 0.812 [0.710-0.914], respectively). Decision curve analysis demonstrated the clinical utility of the radiomic model. Thus, our proposed radiomic model can serve as a non-invasive tool to identify urinary infection stones in vivo, which may optimize disease management in urolithiasis and improve patient prognosis.

Background 5q spinal muscular atrophy (SMA) is a disabling and life-limiting neuromuscular disease. In recent years, novel therapies have shown to improve clinical outcomes. Yet, the absence of reliable biomarkers renders clinical assessment and prognosis of possibly already affected newborns with a positive newborn screening result for SMA imprecise and difficult. Therapeutic decisions and stratification of individualized therapies remain challenging, especially in symptomatic children. The aim of this proof-of-concept and feasibility study was to explore the value of 1H-nuclear magnetic resonance (NMR)-based metabolic profiling in identifying non-invasive diagnostic and prognostic urinary fingerprints in children and adolescents with SMA. Results Urine samples were collected from 29 treatment-naïve SMA patients (5 pre-symptomatic, 9 SMA 1, 8 SMA 2, 7 SMA 3), 18 patients with Duchenne muscular dystrophy (DMD) and 444 healthy controls. Using machine-learning algorithms, we propose a set of prediction models built on urinary fingerprints that showed potential diagnostic value in discriminating SMA patients from controls and DMD, as well as predictive properties in separating between SMA types, allowing predictions about phenotypic severity. Interestingly, preliminary results of the prediction models suggest additional value in determining biochemical onset of disease in pre-symptomatic infants with SMA identified by genetic newborn screening and furthermore as potential therapeutic monitoring tool. Conclusions This study provides preliminary evidence for the use of 1H-NMR-based urinary metabolic profiling as diagnostic and prognostic biomarker in spinal muscular atrophy.

Respiratory diseases are leading causes of death and disability in the world. The recent COVID-19 pandemic is also affecting the respiratory system. Detecting and diagnosing respiratory diseases requires both medical professionals and the clinical environment. Most of the techniques used up to date were also invasive or expensive. Some research groups are developing hardware devices and techniques to make possible a non-invasive or even remote respiratory sound acquisition. These sounds are then processed and analysed for clinical, scientific, or educational purposes. We present the literature review of non-invasive sound acquisition devices and techniques. The results are about a huge number of digital tools, like microphones, wearables, or Internet of Thing devices, that can be used in this scope. Some interesting applications have been found. Some devices make easier the sound acquisition in a clinic environment, but others make possible daily monitoring outside that ambient. We aim to use some of these devices and include the non-invasive recorded respiratory sounds in a Digital Twin system for personalized health. Ministerio de Ciencia, Innovación y Universidades PGC2018-102145-B-C21 Ministerio de Ciencia, Innovación y Universidades PGC2018-102145-B-C22

Aim: to investigate effect of different treatment modalities of white spot lesions on microhardness of human enamel. Materials and methods: twenty-four recently extracted sound human maxillary incisor teeth were collected. Teeth were divided at random into six groups (10 each) that were summarized as follows: Group 1: sound unprepared teeth (base line control); Groups 2: demineralized enamel (negative control), Group 3: Demineralized enamel treated by resin infiltration (ICON), Group 4: demineralized enamel treated by bioactive glass (Sylc powder) as remineralizing agent, Group 5: demineralized enamel treated by fluoride varnish ( positive control), Group 6: Demineralized enamel treated by microabrasion. Teeth were embedded in the acrylic blocks with their labial surface flushed with the flat surface of the mold. All specimens except the base line control specimens were demineralized. Each group was treated with the assigned treatment according to manufacturer’s recommendations. The microhardness measurements were performed using a Vickers Microhardness Tester with a Vickers diamond indenter and a 20X objective lens. Results: showed that there was a statistically significant difference in MH values between different study groups (P

BackgroundThe current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is unacceptably long, causing loss of quality-adjusted life years and excess mortality. Validated screening strategies for early CTEPH diagnosis are lacking. Echocardiographic screening among all PE survivors is associated with overdiagnosis and cost-ineffectiveness. We aimed to validate a simple screening strategy for excluding CTEPH early after acute PE, limiting the number of performed echocardiograms.MethodsIn this prospective, international, multicentre management study, consecutive patients were managed according to a screening algorithm starting 3 months after acute PE to determine whether echocardiographic evaluation of pulmonary hypertension (PH) was indicated. If the ‘CTEPH prediction score’ indicated high pretest probability or matching symptoms were present, the ‘CTEPH rule-out criteria’ were applied, consisting of ECG reading and N-terminalpro-brain natriuretic peptide. Only if these results could not rule out possible PH, the patients were referred for echocardiography.Results424 patients were included. Based on the algorithm, CTEPH was considered absent in 343 (81%) patients, leaving 81 patients (19%) referred for echocardiography. During 2-year follow-up, one patient in whom echocardiography was deemed unnecessary by the algorithm was diagnosed with CTEPH, reflecting an algorithm failure rate of 0.29% (95% CI 0% to 1.6%). Overall CTEPH incidence was 3.1% (13/424), of whom 10 patients were diagnosed within 4 months after the PE presentation.ConclusionsThe InShape II algorithm accurately excluded CTEPH, without the need for echocardiography in the overall majority of patients. CTEPH was identified early after acute PE, resulting in a substantially shorter diagnostic delay than in current practice.

The aim of this review was to compare the effectiveness of natural and invasive therapy in the removal of viral warts of the foot skin. A research was conducted based on 25 studies on wart removal with salicylic acid, pyruvic acid and formic acid, retinoids, 5-fluorouracil, phenol, occlusion, lasers: CO2, KTP, Nd:Yag, Er:Yag, pulse-dye, cryotherapy, electrocoagulation and surgical method. When comparing natural and invasive treatments, similar effectiveness was concluded, and the presented studies did not show any advantage one over the other.

Objectives To develop and validate a radiomics model for evaluating treatment response to immune-checkpoint inhibitor plus chemotherapy (ICI + CT) in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods A total of 64 patients with advance ESCC receiving first-line ICI + CT at two centers between January 2019 and June 2020 were enrolled in this study. Both 2D ROIs and 3D ROIs were segmented. ComBat correction was applied to minimize the potential bias on the results due to different scan protocols. A total of 788 features were extracted and radiomics models were built on corrected/uncorrected 2D and 3D features by using 5-fold cross-validation. The performance of the radiomics models was assessed by its discrimination, calibration and clinical usefulness with independent validation. Results Five features and support vector machine algorithm were selected to build the 2D uncorrected, 2D corrected, 3D uncorrected and 3D corrected radiomics models. The 2D radiomics models significantly outperformed the 3D radiomics models in both primary and validation cohorts. When ComBat correction was used, the performance of 2D models was better (p = 0.0059) in the training cohort, and significantly better (p Conclusions The easy-to-use 2D corrected radiomics model could facilitate noninvasive preselection of ESCC patients who would benefit from ICI + CT.

Introduction: The anaerobic threshold (AT) determination is important for individualizing the aerobic training prescription. Objective: To compare and verify the agreement between oxygen uptake (VO2), heart rate (HR), and rate of perceived exertion (RPE) at the AT determined by the ventilatory threshold (VT) and heart rate deflection point (HRDP) methods during an aquatic incremental test in trained older women. Methods: Nine elderly women (64.3 ± 4.4 years) engaged in a water-based training program in the last three months performed a maximum incremental test using the water-based stationary running exercise. The test started at a 70 bpm cadence for 2 min, followed by 15 bpm increments every 2 min until exhaustion. VO2, HR and RPE were measured throughout the test and the AT was identified for each method (i.e., VT and HRDP) by three experienced physiologists. Paired t-test and Bland-Altman analysis were used for data analysis (I±=0.05). Results: There was no difference between the VT and HRDP methods (p>0.05) and the Bland-Altman analysis showed acceptable agreement between them for all investigated outcomes (VO2: 22.9 ± 5.1 vs. 23.5 ± 4.7 ml.kg-1.min-1, IC95%: -3-+4 ml.kg-1.min-1; HR: 147 ± 11 vs. 147 ± 11 bpm, IC95%: -9-+8 bpm; RPE: 16 ± 1 vs. 16 ± 1, IC95%: -2-+3). Conclusion: Based on these findings, both HR and RPE determined by the HRDP can be used as valid parameters and practical tools for field prescription of intensity during water-based exercises in elderly trained women.Keywords: exercise, aging, exercise test, hydrotherapy, oxygen consumption.Â