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This article provides information on the diagnosis and management of smouldering myeloma, a precursor condition to multiple myeloma. It discusses various diagnostic tests and imaging techniques used to identify smouldering myeloma and emphasizes the importance of restaging if there is evidence of progression. The article also provides recommendations for screening and initial investigations for suspected myeloma. Additionally, it discusses risk stratification models and treatment options for smouldering myeloma, including the use of lenalidomide. The article concludes by highlighting ongoing clinical trials and the need for further research in the treatment of smouldering myeloma. [Extracted from the article]

This article summarizes several studies on various topics. The first study examines the relationship between internalizing symptoms and problematic pornography use in college students, finding that higher levels of internalizing symptoms are associated with higher levels of problematic pornography use. The second study focuses on sleep-wake disorders among veterans with opioid use disorder, revealing that 24.4% of veterans with opioid use disorder have a sleep disorder, with obstructive sleep apnea being the most common type. The third study explores the association between cannabis use and lifetime suicidal ideation and attempts, finding that cannabis use is associated with an increased risk of suicidal ideation and attempts. Another study examines the impact of mandatory buprenorphine training and the removal of the X-waiver on prescribing patterns for physicians, showing that while there was an increase in knowledge and a decrease in concern about legal consequences after training, there were no significant differences in buprenorphine prescribing patterns. The fifth study focuses on emergency department patients with illicit fentanyl use and co-occurring psychiatric disorders, highlighting the prevalence of illicit fentanyl use and the need for routine assessments and treatment for mental health and substance misuse in this population. Lastly, a study examines the burden of emergency admissions and hospitalizations for nonfatal acute iatrogenic events in people with sickle cell disease and opioid dependence or tolerance, emphasizing the need for improved interventions and better access to care for this population. The first article also highlights the need for further research to improve opioid treatment strategies and [Extracted from the article]

Paper-based electrochemical analytical devices (ePADs) have gained significant interest as promising analytical units in recent years because they can be fabricated in simple ways, are low-cost, portable, and disposable platforms that can be applied in various fields. In this sense, paper-based electrochemical biosensors are attractive analytical devices since they can promote diagnose several diseases and potentially allow decentralized analysis. Electrochemical biosensors are versatile, as the measured signal can be improved by using mainly molecular technologies and nanomaterials to attach biomolecules, resulting in an increase in their sensitivity and selectivity. Additionally, they can be implemented in microfluidic devices that drive and control the flow without external pumping and store reagents, and improve the mass transport of analytes, increasing sensor sensitivity. In this review, we focus on the recent developments in electrochemical paper-based devices for viruses' detection, including COVID-19, Dengue, Zika, Hepatitis, Ebola, AIDS, and Influenza, among others, which have caused impacts on people's health, especially in places with scarce resources. Also, we discuss the advantages and disadvantages of the main electrode's fabrication methods, device designs, and biomolecule immobilization strategies. Finally, the perspectives and challenges that need to be overcome to further advance paper-based electrochemical biosensors' applications are critically presented. [ABSTRACT FROM AUTHOR]

Paracetamol overdose is a leading cause of acute liver failure that can prove fatal. Establishing paracetamol concentration accurately and quickly is critical. Current detection methods are invasive, time-consuming and/or expensive. Non-invasive, rapid and cost-effective techniques are urgently required. To address this challenge, a novel approach, called Paper-Arrow Mass Spectrometry (PA-MS) has been developed. This technique combines sample collection, extraction, enrichment, separation and ionisation onto a single paper strip, and the entire analysis process, from sample to result, can be carried out in less than 10 min requiring only 2 μL of raw human saliva. PA-MS achieved a LOQ of 185 ng mL−1, mean recovery of 107 ± 7%, mean accuracy of 11 ± 8% and precision ≤5% using four concentrations, and had excellent linearity (r2 = 0.9988) in the range of 0.2–200 μg mL−1 covering the treatment concentration range, surpassing the best-in-class methods currently available for paracetamol analysis. Furthermore, from a panel of human saliva samples, inter-individual variability was found to be <10% using this approach. This technique represents a promising tool for rapid and accurate emergency diagnosis. [ABSTRACT FROM AUTHOR]

To improve the storage and transport of clinical specimens for the diagnosis of Neisseria meningitidis (Nm) infections in resource-limited settings, we have evaluated the performance of dried blood spot (DBS) and dried cerebrospinal fluid spot (DCS) assays. DBS and DCS were prepared on filter paper from liquid specimens previously tested for Nm in the United Kingdom. Nm was detected and genogrouped by real-time PCR performed on crude genomic DNA extracted from the DBS (n = 226) and DCS (n = 226) specimens. Targeted whole-genome sequencing was performed on a subset of specimens, DBS (n = 4) and DCS (n = 6). The overall agreement between the analysis of liquid and dried specimens was (94.2%; 95% CI 90.8–96.7) for blood and (96.4%; 95% CI 93.5–98.0) for cerebrospinal fluid. Relative to liquid specimens as the reference, the DBS and DCS assays had sensitivities of (89.1%; 95% CI 82.7–93.8) and (94.2%; 95% CI 88.9–97.5), respectively, and both assays had specificities above 98%. A genogroup was identified by dried specimen analysis for 81.9% of the confirmed meningococcal infections. Near full-length Nm genome sequences (>86%) were obtained for all ten specimens tested which allowed determination of the sequence type, clonal complex, presence of antimicrobial resistance and other meningococcal genotyping. Dried blood and CSF filter spot assays offer a practical alternative to liquid specimens for the molecular and genomic characterisation of invasive meningococcal diseases in low-resource settings. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present consensus paper was to provide recommendations for clinical practice considering the use of visual examination, dental radiography and adjunct methods for primary caries detection. Materials and methods: The executive councils of the European Organisation for Caries Research (ORCA) and the European Federation of Conservative Dentistry (EFCD) nominated ten experts each to join the expert panel. The steering committee formed three work groups that were asked to provide recommendations on (1) caries detection and diagnostic methods, (2) caries activity assessment and (3) forming individualised caries diagnoses. The experts responsible for “caries detection and diagnostic methods” searched and evaluated the relevant literature, drafted this manuscript and made provisional consensus recommendations. These recommendations were discussed and refined during the structured process in the whole work group. Finally, the agreement for each recommendation was determined using an anonymous Delphi survey. Results: Recommendations (N = 8) were approved and agreed upon by the whole expert panel: visual examination (N = 3), dental radiography (N = 3) and additional diagnostic methods (N = 2). While the quality of evidence was found to be heterogeneous, all recommendations were agreed upon by the expert panel. Conclusion: Visual examination is recommended as the first-choice method for the detection and assessment of caries lesions on accessible surfaces. Intraoral radiography, preferably bitewing, is recommended as an additional method. Adjunct, non-ionising radiation methods might also be useful in certain clinical situations. Clinical relevance: The expert panel merged evidence from the scientific literature with practical considerations and provided recommendations for their use in daily dental practice. [ABSTRACT FROM AUTHOR]

Background: Congenital hypothyroidism (CH) is one of the most preventable causes of mental retardation throughout the world. The aim of this study was to evaluate the sensitivity and specificity of filter paper in screening for congenital hypothyroidism and to determine an appropriate cut-off point for filter TSH for recalling screened neonates. Methods: In this cross-sectional study (descriptive analytic), the records of 2739 neonates who had been recalled during the CH screening program in the east of Tehran, Iran (health care centers of the Iran University of Medical Sciences), from March 2011 to March 2015, were studied. According to the CH screening program in Iran, the TSH on filter paper>5 is the current cut-off point for recalling the neonates. The data was analyzed with SPSS software, version 21. The ROC curve was used to determine the TSH cut-off point and the sensitivity and specificity of the filter test. The relationship between the filter and serum TSH was also determined. The study was approved by the Ethics Committee of the Iran University of Medical Sciences. Results: The recall rate was 5.4%. The prevalence of hypothyroidism was 3/1000 neonates (164). The prevalence in males and females was 51.1% and 48.9%, respectively, with no significant difference. The number of recalled neonates diagnosed as patients with congenital hypothyroidism based on the filter TSH level was 5

This ENETS guidance paper, developed by a multidisciplinary working group, provides up‐to‐date and practical advice on the diagnosis and management of digestive neuroendocrine carcinoma, based on recent developments and study results. These recommendations aim to pave the road for more standardized care for our patients resulting in improved outcomes. Prognosis is generally poor for digestive NEC, most are advanced at diagnosis and median survival in metastatic disease is 11–12 months. Surgery can be of benefit for localized disease after extensive preoperative imaging. Carboplatin in combination with etoposide is recommended as first‐line treatment for metastatic disease. Irinotecan with fluoropyrimidines has the best evidence as second‐line treatment. Immunotherapy plays a minor role in biomarker‐unselected patients. Molecular profiling if available is encouraged to identify new targets. More prospective clinical trials are highly needed to fulfil the unmet needs in this field, especially on new predictive and prognostic biomarkers and to improve survival of patients with advanced disease. [ABSTRACT FROM AUTHOR]

Gastro‐oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA‐associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA‐associated GORD and medical and dietary management. The task force (TF) on non‐IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web‐based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA‐associated GORD. [ABSTRACT FROM AUTHOR]

Background and Purpose: Multiple sclerosis (MS) is an unpredictable disease characterised by a highly variable disease onset and clinical course. Three main clinical phenotypes have been described. However, distinguishing between the two progressive forms of MS can be challenging for clinicians. This article examines how the diagnostic definitions of progressive MS impact clinical research, the design of clinical trials and, ultimately, treatment decisions. Methods: We carried out an extensive review of the literature highlighting differences in the definition of progressive forms of MS, and the importance of assessing the extent of the ongoing inflammatory component in MS when making treatment decisions. Results: Inconsistent results in phase III clinical studies of treatments for progressive MS, may be attributable to differences in patient characteristics (e.g., age, clinical and radiological activity at baseline) and endpoint definitions. In both primary and secondary progressive MS, patients who are younger and have more active disease will derive the greatest benefit from the available treatments. Conclusions: We recommend making treatment decisions based on the individual patient's pattern of disease progression, as well as functional, clinical and imaging parameters, rather than on their clinical phenotype. Because the definition of progressive MS differs across clinical studies, careful selection of eligibility criteria and study endpoints is needed for future studies in patients with progressive MS. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis remains a serious public health issue, and Brazil was among the seven countries with the highest prevalence of this disease worldwide. The measures to control this disease are not easily developed, and the improvement of its diagnosis, surveillance, and control is still needed. This study aimed to carry out the polymerase chain reaction (PCR) diagnosis of Leishmania infantum in vector samples in some municipalities of the State of São Paulo, which included two municipalities with human disease transmission and two with dog transmission only. Vectors were collected in traps with luminous bait. Next, they were killed at −4 °C and kept in 70% alcohol. Groups of ten female insects (pools) were mashed on cation exchange paper (fine cellulose phosphate with 18 µEq/cm² ionic exchange capacity) for DNA extraction. The PCR was carried out to identify the natural infection of the Leishmania genus in female Lutzomyia longipalpis (Lu. Longipalpis). Out of the 3,880 Lu. longipalpis phlebotomines, 1060 were female and 2820 were male (3:1). The method used to extract the DNA in pools of ten phlebotomines and the PCR resulted in sensitivity, specificity, practicality, and faster analyses when compared to the individual analysis method. The procedure described can be used on a large scale in the leishmaniasis epidemiological surveillance, enabling a higher number of analyses and the optimization of human resources because the traditional diagnostic method is carried out via desiccation of the insect digestive system and microscopic examination, which is time-demanding and there is the need of manual skills. [ABSTRACT FROM AUTHOR]

Allergy and respiratory disorders are common in young athletic individuals. In the context of elite sport, it is essential to secure an accurate diagnosis in order to optimize health and performance. It is also important, however, to consider the potential impact or consequences of these disorders, in recreationally active individuals engaging in structured exercise and/or physical activity to maintain health and well‐being across the lifespan. This EAACI Task Force was therefore established, to develop an up‐to‐date, research‐informed position paper, detailing the optimal approach to the diagnosis and management of common exercise‐related allergic and respiratory conditions. The recommendations are informed by a multidisciplinary panel of experts including allergists, pulmonologists, physiologists and sports physicians. The report is structured as a concise, practically focussed document, incorporating diagnostic and treatment algorithms, to provide a source of reference to aid clinical decision‐making. Throughout, we signpost relevant learning resources to consolidate knowledge and understanding and conclude by highlighting future research priorities and unmet needs. [ABSTRACT FROM AUTHOR]

Point-of-care testing (POCT) biosensors are rapidly developing in recent years because of the urgent needs for rapid test and home test. Among various types of POCT biosensors, paper-based biosensors have occupied large market share owing to the advantages of cost-effectiveness, portability and simplicity. To further meet the increasing requirement of POCT in various application scenes, the functionalization of paper is highly demanded. Metal-organic framework (MOF), a multifunctional porous material, is introduced in the design of paper-based biosensors, significantly improving the sensing property and application potential. This review provides a summary of the recent advances and emerging trends of MOF-functionalized paper-based biosensors (MOF@paper), including different types of substrates, fabrication methods, detection mechanisms and applications. On account of the multifunctionality and superior performance of MOF@paper biosensors, this field should possess promising prospect in scientific researches, translational medicine and clinical applications. • Multifunctional MOF endows paper-based biosensors with diverse detection properties. • The substrates and fabrication methods for MOF@paper biosensors are reviewed. • Various detection mechanisms are summarized and discussed. • MOF@paper biosensors are promising in diagnosis, food, environment and other related applications. [ABSTRACT FROM AUTHOR]

Molecularly imprinted polymers are efficient and selective adsorbents which act as artificial receptors for desired compounds with the ability to recognize the size, shape, and functional groups of the compounds simultaneously. A molecularly imprinted polymer is prepared by the polymerization of functional monomers around a template (analyte) molecule. Afterward, the removal of the template from the polymer matrix leaves a selective cavity behind. The fabrication and development of molecularly imprinted polymers grew rapidly, due to their low cost, simple preparation, selectivity, sensitivity, and stable physicochemical properties. Traditionally, molecularly imprinted polymers can be synthesized using two main methods, namely bulk and surface imprinting. For more efficient use of the latter method, researchers have developed molecularly imprinted polymers grafted on the solid-phase matrix (substrate). This grafting technique would be particularly useful for surface imprinting of macromolecules, such as proteins. Cellulose fibers of papers with unique properties such as being abundant, retaining a porous structure, having good adsorption properties, and possessing hydroxyl groups naturally have gained much attention as substrate. The goal of this review is to introduce molecularly imprinted polymer-grafted or molecularly imprinted polymer-coated paper, as an interesting, simple, and efficient method in the detection and separation of small and large molecules. Therefore, in the present paper, several recent preparation techniques and applications of molecularly imprinted polymer-grafted paper are reviewed and discussed in detail. [ABSTRACT FROM AUTHOR]

Cardiomyopathies (CMPs) are myocardial diseases in which the heart muscle is structurally and functionally abnormal in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality. Thought for a long time to be rare diseases, it is now clear that most of the CMPs can be easily observed in clinical practice. However, there is a group of specific heart muscle diseases that are rare in nature whose clinical/echocardiographic phenotypes resemble those of the four classical morphological subgroups of hypertrophic, dilated, restrictive, arrhythmogenic CMPs. These rare CMPs, often but not solely diagnosed in infants and paediatric patients, should be more properly labelled as specific CMPs. Emerging consensus exists that these conditions require tailored investigation and management. Indeed, an appropriate understanding of these conditions is mandatory for early treatment and counselling. At present, however, the multisystemic and heterogeneous presentation of these entities is a challenge for clinicians, and time delay in diagnosis is a significant concern. The aim of this paper is to define practical recommendations for diagnosis and management of the rare CMPs in paediatric or adult age. A modified Delphi method was adopted to grade the recommendations proposed by each member of the writing committee. The inherited and rare cardiomyopathy team. The multidisciplinary team, with specific expertise in inherited and rare CMPs, has the potential to improve diagnostic work-up and explore the available treatment options. The expertise required involves adult and paediatric cardiologists, genetic counsellors, electrophysiologists, geneticists, psychologists, intensive care specialists, cardiac surgeons and electrophysiologists [Display omitted] • Rare cardiomyopathies (CMPs) require tailored investigation and management. • A multidisciplinary team is essential to improve diagnosis and management of rare CMPs. • A step-by-step clinical evaluation is required to reach aetiological diagnosis. [ABSTRACT FROM AUTHOR]

Background and objectives: Microscopic agglutination test is the gold standard sero-diagnostic method for detection of leptospirosis. Moreover, it helps identify serovars and their titers in serum samples. For obtaining accurate titer results, proper sampling, collection, storage, and transportation of samples are crucial while maintaining the cold chain. Since storage for long periods and the subsequent deterioration of samples may affect the final titers, we proposed an alternative method of MAT testing using filter paper-dried serum samples. We also evaluated sensitivity and specificity of the MAT test by using filtered-dried serum samples compared with the conventional MAT test. Methods: This experimental study was performed on human and animal serum samples that were sent to a reference leprospirosis laboratory in 2020. Overall, 142 positive samples (with 289 titers for different strains) and 15 negative samples were used for MAT test using filtered-dried serum. For this purpose, each sample was dried on a filter paper (Whatman 903, GE Healthcare) at room temperature (20-30 °C) and kept for four days. On the fifth day, the filter papers were cut into small pieces, soaked in phosphate buffer saline, vortexed, and slowly mixed on shaker for two hours to elute antibodies. The MAT tests were performed simultaneously and under the same environmental conditions. Results: The new MAT test using dried serum samples showed 79% sensitivity and 100% specificity. The test also had positive predictive value of 92% and negative predictive value of 24% when compared with the gold standard MAT test. Conclusion: Filter-dried serum can be used for MAT test to overcome serum storage and transportation problems. [ABSTRACT FROM AUTHOR]

Identifying the genes and mutations that drive the emergence of tumors is a critical step to improving our understanding of cancer and identifying new directions for disease diagnosis and treatment. Despite the large volume of genomics data, the precise detection of driver mutations and their carrying genes, known as cancer driver genes, from the millions of possible somatic mutations remains a challenge. Computational methods play an increasingly important role in discovering genomic patterns associated with cancer drivers and developing predictive models to identify these elements. Machine learning (ML), including deep learning, has been the engine behind many of these efforts and provides excellent opportunities for tackling remaining gaps in the field. Thus, this survey aims to perform a comprehensive analysis of ML-based computational approaches to identify cancer driver mutations and genes, providing an integrated, panoramic view of the broad data and algorithmic landscape within this scientific problem. We discuss how the interactions among data types and ML algorithms have been explored in previous solutions and outline current analytical limitations that deserve further attention from the scientific community. We hope that by helping readers become more familiar with significant developments in the field brought by ML, we may inspire new researchers to address open problems and advance our knowledge towards cancer driver discovery. [ABSTRACT FROM AUTHOR]

When it affects the daily life of the patient or causes complications, it is known as gastroesophageal reflux disease (GORD). GRAPH Rosan Meyer Gastroesophageal reflux (GOR) is a common condition, especially in the first year of life. Editorial comments on: "Diagnosis and management of food allergy associated gastroesophageal reflux disease in young children - EAACI position paper". [Extracted from the article]

Drawing from research on 'paper technologies' conducted by medical historians Volker Hess and Andrew Mendelsohn, among others, this article explores how Adolf Meyer (1866–1950) and his staff at the Phipps Psychiatric Clinic used customized punch cards to develop an alternative conceptualization of schizophrenia: 'parergasia.' It begins by examining 'dementia praecox,' the conceptual precursor to both schizophrenia and parergasia, to explain how earlier paper technologies used to track patients transferred to asylums generated prognostic assumptions that precluded deinstitutionalization and community-based care. It then describes how Meyer's staff modified these technologies to define parergasia in opposition to dementia praecox and other diagnoses that resulted in prolonged hospitalization, primarily by conducting follow-up studies on discharged patients that correlated outcomes with various social factors. After demonstrating how the standardized forms used in these studies limited the possible metrics of recovery, it concludes by suggesting how Meyer's research influenced leaders of the community mental health movement, and prefigured later trends in psychiatric services. [ABSTRACT FROM AUTHOR]

Aβ42 is one of the most extensively studied blood and Cerebrospinal fluid (CSF) biomarkers for the diagnosis of symptomatic and prodromal Alzheimer's disease (AD). Because of the heterogeneity and transient nature of Aβ42 oligomers (Aβ42Os), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aβ42 monomers (Aβ42Ms) and Aβ42Os is essential for the accurate diagnosis of AD. The currently commonly used Aβ42 ELISA test kits usually mis-detected the elevated Aβ42Os, leading to incomplete analysis and underestimation of soluble Aβ42, resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aβ42 monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of Aβ42Ms and Aβ42Os in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of Aβ42Ms or/and Aβ42Os in dLFI was 154 pg/mL. The test results for dLFI were similar to those observed in the enzyme-linked immunosorbent assay (ELISA). Therefore, this paper-based dLFI provides a practical and rapid method for the on-site detection of two biomarkers in blood or CSF samples without the need for additional expertise or equipment. [ABSTRACT FROM AUTHOR]

The use of microfluidic paper-based analytical devices (μPADs) for aiding medical diagnosis is a growing trend in the literature mainly due to their low cost, easy use, simple manufacturing, and great potential for application in low-resource settings. Many important biomarkers (proteins, ions, lipids, hormones, DNA, RNA, drugs, whole cells, and more) and biofluids are available for precise detection and diagnosis. We have reviewed the advances μPADs in medical diagnostics have achieved in the last few years, focusing on the most common human biofluids (whole blood/plasma, sweat, urine, tears, and saliva). The challenges of detecting specific biomarkers in each sample are discussed, along with innovative techniques that overcome such limitations. Finally, the difficulties of commercializing μPADs are considered, and future trends are presented, including wearable devices and integrating multiple steps in a single platform. • μPADs can be applied for simple and low-cost diagnosis in low-resource settings. • The challenges of applying μPADs to human biofluids are analyzed. • Recent advancements to overcome specific drawbacks for each fluid are discussed. • Difficulties in commercializing μPADs and future tendencies are presented. [ABSTRACT FROM AUTHOR]

Background: Brucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable. Methodology/Principal findings: In this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen. Conclusions: B cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations. Author summary: Brucellosis is one of the most important zoonosis in the world and has caused tremendous economic losses in agriculture and animal husbandry in many countries. Developing rapid, sensitive and specific diagnostic methods is very important for early detection and treatment of brucellosis patients. In this study, a novel diagnostic technique, nano-ZnO modified paper ELISA, was established. The antigen used in this technique was a fusion protein containing multiple B cell epitopes, which were predicted from Brucella major outer membrane proteins such as Bp26, Omp31, Omp16, Omp2b and Omp25. Comparing to traditional LPS antigen, this multiepitope based antigen displayed considerably higher sensitivity and higher specificity in laboratory. With the strategy described in this paper, more efficient epitopes and protein antigen can be identified in the future. Currently, LPS antigen is only prepared from live Brucella, while protein antigen can be produced in large quantities in prokaryotic expression system. In addition to nano-p-ELISA, this protein antigen can also be used for development other methods such as fluorescent polarization assay (FPA) and immunochromatographic assay (ICA) to meet the varied demand for brucellosis testing. [ABSTRACT FROM AUTHOR]

Blood can be a window to health, and as a result, is the most intensively studied human biofluid. Blood tests can diagnose diseases, monitor therapeutic drugs, and provide information about the health of an individual. Rapid response blood tests are becoming increasingly essential, especially when subsequent treatment is required. Toward this need, paper-based devices have been excellent tools for performing blood tests due to their ability to conduct rapid and low-cost diagnostics and analyses in a non-laboratory environment. In this Perspective, we review recent advances in paper-based blood tests, particularly focusing on the specific techniques and assays applied. Additionally, we discuss the future of these paper-based devices, such as how the signal intensity can be enhanced and how the in situ synthesis of nanomaterials can be used to improve the sensitivity, functionality, and operational simplicity. With these advances, paper-based devices are becoming increasingly valuable tools for point-of-care blood tests in various practical scenarios. [ABSTRACT FROM AUTHOR]

Leukocyte esterase (LE) is a useful marker that can be used in establishing a diagnosis of urinary tract infections (UTIs). The development of a UTI diagnostic method with quantitative determinations of biomarkers across all age groups is becoming more important. In this report, microfluidic resistance sensors based on silver ink (Ag ink) and silver ink mixed with ZnO nanoparticles (Ag-ZnO ink) were synthesized and coated on cellulose paper, namely LE-Ag-μPADs and LE-Ag-ZnO-μPADs, respectively, for the sensitive detection of LE. The microfluidic design increases the precision of data and further allows for quantitative determination and early detection of LE in human urine. The quantification of LE relies on the change in the resistance readout coating with Ag ink as well as Ag-ZnO ink in the detection zone. A mixture of 3-(N-tosyl- L -alaninyloxy)-5-phenylpyrrole (PE) and 1-diazo-2-naphthol-4-sulfonic acid (DAS) was deposited in the sample zone to selectively recognize LE, and the resulting nonconductive products, i.e., azo compounds, further reacted with the Ag ink and Ag-ZnO ink to increase resistance. The quantitative detectable LE concentrations between 2 to 32 (×5.2 U mL−1), i.e. ≈12 to 108 μg L−1, cover the commercial dipstick range of trace, +1 and +2. The minimum detectable concentration of LE in urine was 1 (×5.2 U mL−1). The lower concentrations of LE detectable by LE-Ag-μPADs (1–8 × 5.2 U mL−1) are below the value achieved with the ELISA LE kit. Urine samples from inpatients with indwelling urinary catheters were used, and the LE levels measured by the present device were highly correlated with those determined by a commercial urine analyser. [ABSTRACT FROM AUTHOR]

The cost-effective rapid diagnosis of infectious diseases is an essential and important factor for curing such diseases in the global public health care picture. Owing to poor infrastructure and lack of sanitation, these diseases have an extreme impact on remote and rural areas, especially in developing countries, and there are unresolved challenges. Molecular diagnosis, such as nucleic acid analysis, plays a key role in the significant treatment of numerous infectious diseases. Current molecular diagnostic assays require a sophisticated laboratory setup with expensive components. Molecular diagnosis on a microfluidic point-of-care (POC) platform is attractive to researchers for disease detection with proper prevention. Compared to various microfluidic substrate materials, paper-based POC technologies offer significant cost-effective solutions over high-cost clinical instruments to fill the gap between the needs of users and affordability. Low-cost paper-based microfluidic POC technologies provide portable and disposable diagnostic systems for multiple disease detection that may be extremely useful in remote areas. This article presents a critical review of paper-based microfluidic device technology which has become an imminent platform to adjust the current health scenario for the detection of diseases using different stages of nucleic acid analysis, such as extraction, amplification and detection of nucleic acid, with future perspectives for paper substrates. [ABSTRACT FROM AUTHOR]

Personalized Medicine is a challenge for healthcare systems in Central and Eastern Europe if they are to provide patients with personalized diagnosis and treatment. Personalized medicine (PM) is about tailoring a treatment as individualized as the disease. [1] Integrated care involves receiving care along a continuum of health promotion, disease prevention, diagnosis, treatment, disease-management, rehabilitation and palliative care services, coordinated across the different levels and sites of care within and beyond the health sector, and according to the needs of patients throughout the life course. Personalized Medicine and Integrated Care are among the most important concepts related to the management and organization of healthcare systems. This article intends to identify challenges to the adoption of personalized medicine and stimulate fruitful dialogue and debate about the evaluation of barriers and facilitators within the implementation of personalized medicine interventions, identify the barriers and take systematic actions to remove as many of them as possible to create a future where PM is fully integrated into real-life settings. [ABSTRACT FROM AUTHOR]

The highly sensitive and selective determination of Escherichia coli (E. coli) in urine was achieved using a SYBR™ safe loop-mediated isothermal amplification (LAMP) method with a distance-based paper device. New primers set specific to multi-copy the 16s rRNA gene of E. coli were designed and used in this study. The detection sensitivity of these primers was higher than in related work and they could be incorporated with a low-cost paper-based device to quantify E. coli in urine at a concentration lower than 101 CFU mL−1. Regarding standard artificial urine, a linear range of a 10-fold dilution of E. coli concentration (105–100 CFU mL−1) with an R-square value (R2) = 0.9823 was observed directly using a fluorescent migratory distance of the 4 μL reaction mixture in the detection zone under blue light without the need for postreaction staining process. Based on the device, E. coli infection could be significantly categorized into 3 groups; none, light, and heavy levels, which is beneficial for UTI diagnosis. Hence, this paper-based device is suitable for use with the SYBR™ Safe-LAMP assay to semi-quantify E. coli, especially in resource-limited settings due to advantages of low cost, simple fabrication and operation, and no requirement for sophisticated instruments, as well as its disposability and portability. [ABSTRACT FROM AUTHOR]

Purpose of review: To give an overview of the current knowledge regarding the diagnosis, treatment, and follow-up of laryngeal dysplasia (LD) and to highlight the contributions of recent literature. Summary: The diagnosis of LD largely relies on endoscopic procedures and on histopathology. Diagnostic efficiency of endoscopy may be improved using videolaryngostroboscopy (VLS) and bioendoscopic tools such as Narrow Band Imaging (NBI) or Storz Professional Image Enhancement System (SPIES). Current histological classifications are not powerful enough to clearly predict the risk to carcinoma evolution and technical issues such as sampling error, variation in epithelial thickness and inflammation hamper pathological examination. Almost all dysplasia grading systems are effective in different ways. The 2017 World Health Organization (WHO) system should prove to be an improvement as it is slightly more reproducible and easier for the non-specialist pathologist to apply. To optimize treatment decisions, surgeons should know how their pathologist grades samples and preferably audit their transformation rates locally. Whether carcinoma in situ should be used as part of such classification remains contentious and pathologists should agree with their clinicians whether they find this additional grade useful in treatment decisions. Recently, different studies have defined the possible utility of different biomarkers in risk classification. The main treatment modality for LD is represented by transoral laser microsurgery. Radiotherapy may be indicated in specific circumstances such as multiple recurrence or wide-field lesions. Medical treatment currently does not have a significant role in the management of LD. Follow-up for patients treated with LD is a fundamental part of their care and investigations may be supported by the same techniques used during diagnosis (VLS and NBI/SPIES). [ABSTRACT FROM AUTHOR]

A rapid and low-cost method of diagnosis is becoming important for detecting fetal inherited diseases, including single-gene disorders and chromosomal abnormalities. Here, we demonstrated an innovation that use paper-dried cord blood (PCB) as the starting material for PCR and whole genome amplification without any DNA extraction step at a very low cost. A novel PCR buffer named "DDB buffer" containing ammonium sulfate and glycerol were used instead of the conventional 10× PCR buffer. The amplicons were directly analyzed through microchip electrophoresis and whole genome sequencing. Inhibitory substances in filter paper were effectively inactivated using DDB buffer. Direct PCR amplification of DNA fragments ranging from 100 to 900 bp using filter paper spotted with 0.5 to 5 μL of cord blood and various anticoagulants was successful. We were able to determine fetal single-gene disorders and chromosomal diseases in all 46 chromosomes using PCB samples successfully. Compared with prenatal diagnosis using purified DNA, the proposed method is simple, fast, less prone to cross-contamination at minimal cost. Researchers and clinical and healthcare workers may employ this method for genetic diagnosis using cord blood samples with minimum laboratory resources. This method is very promising for a variety of genetic diagnosis applications in underserved communities at the point of need in developing areas. [ABSTRACT FROM AUTHOR]

In this article, using the integration of paper microfluidics within laser-inscribed commercial contact lenses, we demonstrate the multiplexed detection of clinically relevant analytes including hydrogen ions, proteins, glucose, nitrites and L -ascorbic acid, all sampled directly from model tears. In vitro measurements involved the optimization of colorimetric assays, with readouts collected, stored and analyzed using a bespoke Tears Diagnostics smartphone application prototype. We demonstrate the potential of the device to perform discrete measurements either for medical diagnosis or disease screening in the clinic or at the point-of-care (PoC), with future applications including monitoring of ocular infections, uveitis, diabetes, keratopathies and assessing oxidative stress. [ABSTRACT FROM AUTHOR]

Writing with ink on a paper and the rapid diagnostics of diseases using paper cartridge, despite their remarkable diversities from application perspective, both involve the motion of a liquid from a source on a porous hydrophilic substrate. Here we bring out a generalization in the pertinent dynamics by appealing to the concerned ensemble-averaged transport with reference to the underlying molecular picture. Our results reveal that notwithstanding the associated complexities and diversities, the resultant liquid transport characteristics on a paper matrix, in a wide variety of applications, resemble universal diffusive dynamics. Agreement with experimental results from diversified applications is generic and validates our unified theory. [ABSTRACT FROM AUTHOR]

Paper is a common material that is promising for constructing microfluidic chips (lab-on-a-paper) for diagnostics and drug delivery for biomedical applications. In the past decade, extensive research on paper-based microfluidics has accumulated a large number of scientific publications in the fields of biomedical diagnosis, food safety, environmental health, drug screening and delivery. This review focuses on the recent progress on paper-based microfluidic technology with an emphasis on the design, optimization and application of the technology platform, in particular for medical diagnostics and drug delivery. Novel advances have concentrated on engineering paper devices for point-of-care (POC) diagnostics, which could be integrated with nucleic acid-based tests and isothermal amplification experiments, enabling rapid sample-to-answer assays for field testing. Among the isothermal amplification experiments, loop-mediated isothermal amplification (LAMP), an extremely sensitive nucleic acid test, specifically identifies ultralow concentrations of DNA/RNA from practical samples for diagnosing diseases. We thus mainly focus on the paper device-based LAMP assay for the rapid infectious disease diagnosis, foodborne pathogen analysis, veterinary diagnosis, plant diagnosis, and environmental public health evaluation. We also outlined progress on paper microfluidic devices for drug delivery. The paper concludes with a discussion on the challenges of this technology and our insights into how to advance science and technology towards the development of fully functional paper devices in diagnostics and drug delivery. Unlabelled Image [ABSTRACT FROM AUTHOR]

Non-radiologist point-of-care ultrasonography (US) is increasingly implemented in paediatric care because it is believed to facilitate a timely diagnosis, such as in ascites or dilated renal pelvicalyceal systems, and can be used to guide interventional procedures. To date, all policy statements have been published by non-radiologic societies. The European Society of Paediatric Radiology hereby issues a position statement on paediatric non-radiologist point-of-care US from the point of view of those leading on children's imaging, i.e. paediatric radiologists. In this position statement, we will address the boundaries, education, credentialing, quality control, reporting and storage of images in paediatric practice. [ABSTRACT FROM AUTHOR]

Highlights • A cellulose-based cationic (Q) paper is a convenient platform to collect, preserve, and store nucleic acids (NA). • Factors that affected arboviral RNA adsorbance on Q-paper were evaluated. • Q-paper produced by optimized technology is an efficient tool for downstream infected mosquito surveillance. • Viral RNA could be recovered from infected mosquito saliva follow feeding on Q-paper treated with honey. Abstract Previously (Glushakova et al. 2017), a cellulose-based cationic (Q) paper derivatized with quaternary ammonium groups was shown to be a convenient platform to collect, preserve, and store nucleic acids (NAs) derived from mosquito vectors infected with pathogens for surveillance. NAs bind electrostatically to Q-paper, but the quantity of NA bound depends on the paper’s binding capacity. To optimize the original technology for mosquito surveillance, factors that affected NA absorbance on Q-paper were evaluated. Sixteen variations of Q-paper were prepared with modifications of the derivatizing reagents and derivatization temperature. The binding capacities of these variations were determined first with 1,3,5-benzenetricarboxylic (BTCA), then viral RNA (purified or in infected mosquito samples) was used for validation. For this, samples with Zika (ZIKV) and chikungunya (CHIKV) RNA or virus-infected Aedes aegypti mosquito bodies were applied to sixteen Q-paper variants. Washing the paper samples with water versus elution with aqueous salt (1 M) gave samples that were analyzed for viral RNA by a PCR-based direct Luminex hybridization assay. The comparison ranked the Q-paper binding capacities from the lowest to the highest. The Q-paper with the highest RNA binding capability was further validated with ZIKV- and CHIKV-infected mosquito saliva. [ABSTRACT FROM AUTHOR]

Monitoring of human serum albumin (HSA) in a point‐of‐care fashion is urgently needed in particular for elderly or chronically ill patients. Herein, a dual‐state emissive chalcone probe having the feature of aggregation‐induced emission was designed and synthesized. The concentration of HSA can be evaluated by the ratios of emission from probes in aggregated and monomeric state, which gives a visually discernible red‐to‐green color change. A simple, portable paper‐based analytical device have been fabricated by integration of the recognition probe in the detection pad and employed for HSA test using the whole blood samples. This paper‐based assay shows the analytical capability comparable to the standard testing methods but is in a point‐of‐care fashion, providing a promising tool for at‐home HSA detection and HSA‐related disease diagnosis. [ABSTRACT FROM AUTHOR]

Background The recent emergence of Chikungunya Virus (CHIKV) in the Americas constitutes a major public health problem on this continent, where the mosquito vector is widespread. The rapid diagnosis of suspected cases is essential for the monitoring and control of this ongoing outbreak. However, this requires reliable tools that are difficult to establish in areas without specialized laboratories. Objectives The aim was to evaluate the performances of serum samples spotted onto filter paper for molecular and serological diagnosis of Chikungunya infection. Study design Analyses were performed from frozen sera and serum spotted onto filter paper provided from 121 Chikungunya suspected cases collected at a biological laboratory on Saint-Martin Island. Results This approach performed well in comparisons with standard methods, with a sensitivity of 100% and a specificity of 93.6% for the combined technical approaches (RT-PCR and serological results). Comparisons of serum samples spotted onto filter paper and frozen samples showed a concordance rate of 94.8% in molecular tests and 98.2% in serological tests. Conclusions This simple sampling technique could overcome the problems of the lack of efficient CHIKV diagnosis tools in remote regions, providing good results regardless of the molecular or serological approach used. This simple filter paper-based method can be used to diagnose both chikungunya and dengue infections, as previously demonstrated following transport at ambient temperature to specialized laboratories. Given the set-up costs and high performance of this method, it could be recommended for the monitoring and control of Chikungunya virus expansion in the Americas and in other affected regions. [ABSTRACT FROM AUTHOR]

Since Internal Medicine (IM) is the most frequent setting of hospitalization for both patients with advanced liver disease and those with comorbidities and risk factors for infection, through this position paper FADOI aims to promote and disseminates its vision regarding the current and potential role of IM in managing hepatitis C virus (HCV) infection (screening, diagnosis, linkage-to-care, treatment). The Internist plays an important role in identifying new cases, in selecting the appropriate diagnostic work-up for liver disease staging and prognosis, and in initiating antiviral therapy, coordinating care and communication with other specialists, the Hepatology outpatient clinic and General Practitioners. Since the Internist is naturally accustomed to the management of multiple comorbidities, he has a fundamental role in the identification of extrahepatic diseases associated with HCV infection and in the diagnosis of comorbidities, some of which are potential factors of liver disease progression. Moreover, in the prescription of the antiviral therapy, it is important to consider the possible drug interactions, and this ideally fits the role of the Internist who can weigh the risk/benefit ratio of possible alternatives, by considering the patient's clinical situation, especially in case of multiple comorbidities. Moreover, it seems appropriate that the ability to prescribe antiviral therapy is guaranteed to all IM hepatology clinics, favoring a spread of awareness as well as an increase in national coverage and therefore patient access to therapies. The network of IM can also contribute to homogenizing the management policies of HCV treatment, which sometimes differ between Italian Regions. [ABSTRACT FROM AUTHOR]

Background Executive skills refer to a set of cognitive skills that allow individuals to engage in goal directed behavior. They encompass planning, initiation, inhibition, monitoring and flexibility in approach to tasks, and are necessary for functional competence. Executive skills are vulnerable to disruption with damage to the brain, as occurs with dementia. Methods Participants were recruited from a tertiary memory assessment and support Service. The Assessment of Motor & Process Skills (AMPS), a standardised observational assessment of occupational performance (1Fischer, 2003) was administered by trained Occupational Therapists. In addition, the EXIT-25, a pen & paper based assessment of executive skills (2Royall et al, 1992) was administered. Process scores from the AMPS, and overall score from the EXIT 25 were utilised for correlation analysis. Results 22 participants, 12 male and 10 females, age range 60-91 (mean 75.5 years), was analysed using Spearman's Rho correlation (-.2). Results did not identify a strong correlation Conclusion Dementia is commonly regarded as a disorder of memory. However, diagnosis is dependent on functional decline related to cognitive decline. The AMPS provides a formal assessment of functional skills, in terms of motor & process skills with cut off scores regarding safe independent living. The results of this study indicate that the AMPS is not associated with executive scores on formal cognitive assessments, highlighting the value of an extensive multi-component MDT approach (also incorporating history taking, imaging, bio marker testing etc.) in assessing and diagnosing a dementia. [ABSTRACT FROM AUTHOR]

The lack of sensitivity is a major problem among microfluidic paper-based analytical devices (μPADs) for early disease detection and diagnosis. Accordingly, the present study presents a method for improving the enrichment factor of low-concentration biomarkers by using shallow paper-based channels realized through a double-sided wax-printing process. In addition, the enrichment factor is further enhanced by exploiting the ion concentration polarization (ICP) effect on the cathodic side of the nanoporous membrane, in which a stationary sample plug is obtained. The occurrence of ICP on the shallow-channel μPAD is confirmed by measuring the current–voltage response as the external voltage is increased from 0 to 210 V (or the field strength from 0 to 1.05 × 104 V m−1) over 600 s. In addition, to the best of our knowledge, the electroosmotic flow (EOF) speed on the μPAD fabricated with a wax-channel is measured for the first time using a current monitoring method. The experimental results show that for a fluorescein sample, the concentration factor is increased from 130-fold in a conventional full-thickness paper channel to 944-fold in the proposed shallow channel. Furthermore, for a fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) sample, the proposed shallow-channel μPAD achieves an 835-fold improvement in the concentration factor. The concentration technique presented here provides a novel strategy for enhancing the detection sensitivity of μPAD applications. [ABSTRACT FROM AUTHOR]

The performance of Whatman 3-MM filter papers for the collection, drying, shipment and long-term storage of blood at ambient temperature, and for the detection of African swine fever virus and antibodies was assessed. Conventional and real-time PCR, viral isolation and antibody detection by ELISA were performed on paired samples (blood/tissue versus dried-blood 3-MM filter papers) collected from experimentally infected pigs and from farm pigs in Madagascar and Côte d'Ivoire. 3-MM filter papers were used directly in the conventional and real-time PCR without previous extraction of nucleic acids. Tests that performed better with 3-MM filter papers were in descending order: virus isolation, real-time UPL PCR and conventional PCR. The analytical sensitivity of real-time UPL PCR on filter papers was similar to conventional testing (virus isolation or conventional PCR) on organs or blood. In addition, blood-dried filter papers were tested in ELISA for antibody detection and the observed sensitivity was very close to conventional detection on serum samples and gave comparable results. Filter papers were stored up to 9 months at 20-25°C and for 2 months at 37°C without significant loss of sensitivity for virus genome detection. All tests on 3-MM filter papers had 100% specificity compared to the gold standards. Whatman 3-MM filter papers have the advantage of being cheap and of preserving virus viability for future virus isolation and characterization. In this study, Whatman 3-MM filter papers proved to be a suitable support for the collection, storage and use of blood in remote areas of tropical countries without the need for a cold chain and thus provide new possibilities for antibody testing and virus isolation. [ABSTRACT FROM AUTHOR]

A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta‐lactam (BL) hypersensitivity demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost‐effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross‐reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible. Furthermore, the update addresses availability and concentrations of skin test (ST) reagents, ST and drug provocation test (DPT) protocols, and diagnostic algorithms and administration of alternative BL in allergic subjects. Specifically, distinct diagnostic algorithms are suggested depending on risk stratification of the patient into high and low risk based on the morphology and chronology of the reaction, immediate (ie, occurring within 1‐6 hours after the last administered dose) or nonimmediate (ie, occurring more than 1 hour after the initial drug administration), and the reaction severity. Regarding the allergy workup, the main novelty of this document is the fact that in some low‐risk nonimmediate reactions ST are not mandatory, especially in children. For DPT, further studies are necessary to provide data supporting the standardization of protocols, especially of those regarding nonimmediate reactions, for which there is currently no consensus. [ABSTRACT FROM AUTHOR]

Background. Establishing a valid communication is not only a basic clinical need to be met but also a relevant ethical commitment. Methods. On the basis of the relevant literature, ethical issues arising from specific, important situations in clinical practice were identified. Results. The main ethical problems regarding communication about the disorder, both in general and in relation to prodromal stages, were described and discussed together with those regarding communication about voluntary and involuntary treatments, "dual roles" enacted in clinical practice, genetic counseling, and end-of-life conditions; on the basis of what emerged, ethically driven indications and suggestions were provided. Conclusions. Several situations put the psychiatrist in front of relevant dilemmas and doubts which are no easy to face with; an ethically driven approach based upon the principle of the best interest of patients may support clinicians in their decisions. [ABSTRACT FROM AUTHOR]

• Ablative radiotherapy is an effective treatment for oligometastatic prostate cancer. • The lack of randomized phase III trials hampers the generalization of this therapy. • In clinical practice, ablative radiotherapy should be adopted in some cases only. • This position paper explores available literature and proposes some recommendations. Oligometastatic prostate cancer comprises a wide spectrum of conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which are distinct entities in terms of biology and prognosis. In order to clarify and standardize the clinical role of ablative radiotherapy in oligometastatic prostate cancer, the Italian Association of Radiotherapy and Clinical Oncology (AIRO) formed an expert panel to review the current literature and develop a formal consensus. Oligometastatic prostate cancer was defined as the presence of up to three metastatic lesions involving bones or nodes outside pelvis. Thereafter, four clinical scenarios were explored: metastatic castration-sensitive disease at diagnosis and after primary treatment, and metastatic castration-resistant disease at diagnosis and during treatment, where the role of ablative radiotherapy was defined either in conjunction with systemic therapy or as the only treatment in selected cases. This paper summarizes the current literature about these issues and the proposed recommendations. [ABSTRACT FROM AUTHOR]

Mobility can be defined as the ability to move or be moved freely and easily. In older adults, mobility impairments are common and associated with risk for additional loss of function. Mobility loss is particularly common in these individuals during acute illness and hospitalization, and it is associated with poor outcomes, including loss of muscle mass and strength, long hospital stays, falls, declines in activities of daily living, decline in community mobility and social participation, and nursing home placement. Thus, mobility loss can have a large effect on an older adult's health, independence, and quality of life. Nevertheless, despite its importance, loss of mobility is not a widely recognized outcome of hospital care, and few hospitals routinely assess mobility and intervene to improve mobility during hospital stays. The Quality and Performance Measurement Committee of the American Geriatrics Society has developed a white paper supporting greater focus on mobility as an outcome for hospitalized older adults. The executive summary presented here focuses on assessing and preventing mobility loss in older adults in the hospital and summarizes the recommendations from that white paper. The full version of the white paper is available as Text S1. J Am Geriatr Soc 67:11–16, 2019. [ABSTRACT FROM AUTHOR]

This paper introduces the concept of rough fermatean neutrosophic sets and investigates their properties. Additionally, a cosine similarity measure between these sets is proposed. By applying this measure to a medical diagnosis example, the paper illustrates how the method can be used in practical situations, highlighting its effectiveness in complex decision-making scenarios. This innovation holds promise for improving decision-making processes, especially in critical areas like medical diagnosis, where making accurate assessments amidst uncertainty is crucial. [ABSTRACT FROM AUTHOR]

The clinician who adopts a psychoanalytic approach in a psychiatric context often regards the encounter between two individuals as an interplay of subjectivities, whose mode of being-in-the-world is shaped by their unique historical experiences. Despite some psychoanalytic authors exploring the concept of "contact", it has often been reduced to its similarity with transference and countertransference, with little attention given to its distinctive qualities. This limits psychoanalysis in its ability to conceptualize an unmediated, preverbal encounter between two individuals. In this article, we argue that the dimension of "contact" cannot be equated with transference, and that it constitutes a vital tool for diagnosing and guiding therapy for various clinical conditions commonly encountered in psychiatry. This article is based on theoretical considerations. We first worked on the history of the concept of contact, then of Praecox Gefühl in the works of H.C. Rümke, to which we added the findings of current studies on the relevance of Praecox Gefühl in the diagnosis of schizophrenia and the study of the works of the great phenomenological psychiatrists. In so doing, we aimed to show that contact could be a tool of great use for psychiatric diagnosis, insofar that it allows for a typification of the forms of existence of different patients. H.C. Rümke's investigation of the concept of Praecox Gefühl highlights the unique mode of contact observed in schizophrenia. It is distinct from the feeling of strangeness and involves an intuitive observation of a perceived distance within the clinical relationship. Given that many psychiatric pathologies can cause patients to withdraw from the shared world, we suggest that the notion of Praecox Gefühl , beyond its original designation of the clinician's experience of schizophrenic dissociation and the particularities of the schizophrenic mode of being-in-the-world, may be applicable to other pathologies studied in psychiatric phenomenology. We propose four main forms of contact: the loss of vitality in schizophrenia, the untraceable authenticity of the hysteric, the impossible fluidity in the melancholic, and the failure of anchorage in mania. By approaching contact as a fractal form that reveals the entire mode of the subject's being-in-the-world, this typifying approach goes beyond a purely semiological or etiological reflection and can be diagnostically useful in guiding therapeutic efforts to enhance the subject's capacity to truly engage with others. Our paper focuses on the relationship between contact and what clinicians commonly refer to as an "encounter." It is important to recognize that contact is not always equivalent to an encounter, and that assuming otherwise risks overlooking the possibility that certain relational modalities could actively prevent such an encounter from taking place. These "anti-contact" modalities, exemplified by the Praecox Gefühl , necessitate a focus on the very possibility of being in a therapeutic relationship with the clinician. Therefore, we suggest that clinicians should work to establish the possibility of being in a relation with the patient, prior to attempting to create an encounter. This approach allows for a more nuanced understanding of the ways in which patients can either facilitate or hinder the development of an encounter, and highlights the importance of working on establishing the possibility of a real encounter and being-with the clinician. This paper has sought to challenge the prevailing assumption among psychoanalytically oriented clinicians that contact is merely a sub-dimension of the transferential dynamic. Instead, we have argued that contact warrants specific attention as a tool for both diagnosis and therapy in psychiatry. By examining the example of the Praecox Gefülh , we have proposed a typifying approach that could be applied to the most common clinical entities encountered in psychiatry, based on the clinician's perception of specific modalities of contact within the therapeutic consultation. This reflection on contact and anti-contact is a necessary and contemporary contribution to the psychiatric field, which is increasingly embracing a dimensional approach to psychological pathologies. By prioritizing the dimension of contact, we can deepen our understanding of the nuances of the therapeutic relationship and can enhance our ability to help patients overcome barriers to connection and encounter. [ABSTRACT FROM AUTHOR]

Background: A huge amount of research is carried out nowadays in Artificial Intelligence to propose automated ways to analyse medical data with the aim to support doctors in delivering medical diagnoses. However, a main issue of these approaches is the lack of transparency and interpretability of the achieved results, making it hard to employ such methods for educational purposes. It is therefore necessary to develop new frameworks to enhance explainability in these solutions. Results: In this paper, we present a novel full pipeline to generate automatically natural language explanations for medical diagnoses. The proposed solution starts from a clinical case description associated with a list of correct and incorrect diagnoses and, through the extraction of the relevant symptoms and findings, enriches the information contained in the description with verified medical knowledge from an ontology. Finally, the system returns a pattern-based explanation in natural language which elucidates why the correct (incorrect) diagnosis is the correct (incorrect) one. The main contribution of the paper is twofold: first, we propose two novel linguistic resources for the medical domain (i.e, a dataset of 314 clinical cases annotated with the medical entities from UMLS, and a database of biological boundaries for common findings), and second, a full Information Extraction pipeline to extract symptoms and findings from the clinical cases and match them with the terms in a medical ontology and to the biological boundaries. An extensive evaluation of the proposed approach shows the our method outperforms comparable approaches. Conclusions: Our goal is to offer AI-assisted educational support framework to form clinical residents to formulate sound and exhaustive explanations for their diagnoses to patients. [ABSTRACT FROM AUTHOR]

Anderson–Fabry disease is a lysosomal storage disorder caused by mutations in the GLA gene, which encodes the enzyme α-galactosidase A. The GLA gene is located on the X-chromosome, causing an X-linked pathology: due to lyonization, female patients usually manifest a variable symptomatology, ranging from asymptomatic to severe phenotypes. The confirmation of the clinical diagnosis of Fabry disease, achieved by measuring α-galactosidase A activity, which is usually the first test used, shows differences between male and female patients. This assay is reliable in male patients with causative mutations in the GLA gene, in whom the enzymatic activity is lower than normal values; on the other hand, in female Fabry patients, the enzymatic activity is extremely variable between normal and pathological values. These fluctuations are also found in female patients' blood levels of globotriaosylsphingosine (LysoGb3) for the same reason. In this paper, we present a retrospective study conducted in our laboratories on 827 Fabry patients with causative mutations in the GLA gene. Our results show that 100% of male patients had α-galactosidase A activity below the reference value, while more than 70% of female patients had normal values. It can also be observed that almost half of the female patients with pathogenic mutations in the GLA gene showed normal values of LysoGb3 in blood. Furthermore, in women, blood LysoGb3 values can vary over time, as we show in a clinical case presented in this paper. Both these tests could lead to missed diagnoses of Fabry disease in female patients, so the analysis of the GLA gene represents the main diagnostic test for Fabry disease in women to date. [ABSTRACT FROM AUTHOR]

Introduction Nerve agents have emerged as a global threat since their discovery in the 1930s, posing severe risks due to their inhibition of acetylcholinesterase and the subsequent accumulation of acetylcholine in nerve synapses. Despite the enforcement of the Chemical Weapon Convention to control chemical weapons, including nerve agents, recent events, such as the Novichok attacks on Sergei Skripal and Alexei Navalny, have highlighted the persistent threat. Novichok, a distinct class of nerve agents, raises specific concerns regarding its management due to limited understanding. This article aims to comprehensively analyze existing literature. Materials and Methods A scoping review was employed to comprehensively assess the current state of knowledge on managing patients poisoned with Novichok. Following the PRISMA-ScR guidelines, relevant literature was identified in peer-reviewed journals covering symptoms, diagnosis, treatment, decontamination, and long-term effects. Searches were conducted on February 1, 2023, across four electronic databases (PubMed, EMBASE, MEDLINE, and Web of Science) using "Novichok" as a keyword. No restrictions were applied, and additional studies were sought from the references of identified papers. Eligible papers included discussions on Novichok or its specific properties impacting management, regardless of study type, language, or publication date, while those unrelated to the study's conceptual framework were excluded. Results A total of 170 records were identified from the initial database search, with 86 studies screened after removing duplicates. Among these, 28 publications met the eligibility criteria and were included in the analysis. An additional relevant study was identified from the citation lists of included studies, bringing the total to 29. The review encompasses studies published from 2018 onwards, indicating the growing interest in this topic. While most studies are reviews on Novichok or nerve agents in general, several theoretical and experimental investigations were also found. Conclusion This review highlights the significant uncertainties and knowledge gaps surrounding the management of patients poisoned with Novichok. While some aspects align with other nerve agents, limited research likely due to safety and ethical challenges leads to assumptions and uncertainties in patient care. The review identifies areas with ongoing research, such as decontamination and biomarker recognition, while other aspects remain understudied. The possible inefficacy of current treatment options and the need for further research on oximes, bioscavengers, and long-term effects emphasize the necessity for increased research to optimize patient outcomes. More studies are essential to clarify the actual threat and toxicity of Novichok. Moreover, raising awareness among medical staff is crucial for early diagnosis, prompt treatment, and safety. This review offers valuable insights into managing Novichok-poisoned patients and calls for increased research and awareness in this critical area. [ABSTRACT FROM AUTHOR]