Point-of-Care Platform for Diagnosis of Venous Thrombosis by Simultaneous Detection of Thrombin Generation and D-Dimer in Human Plasma.

Venous thromboembolism (VTE) refers to a blood clot that starts in a vein. The risk of developing VTE is highest after major surgery or a major injury, or when someone has heart failure, cancer, or infectious disease (e.g., COVID-19). Without prompt treatment to break up clots and prevent more from forming, VTE can restrict or block blood flow and oxygen, which can damage the body tissue or organs. VTE can occur without any obvious signs, and imaging technologies are used. Alternatively rapid measurement of thrombin generation (TG) and D-dimer could be used to make a fast, portable, and easy-to-use diagnostic platform for VTE. Here, we have demonstrated a diagnostic sensing platform with the ability of simultaneous detection of TG and D-dimer in human plasma. Modifications were made to both the assay protocols to eliminate the need for sample dilution and incubation steps. Using a substantially reduced sample volume, the measurement results show comparable performance to the gold standard method. Our platform is able to deliver accurate and cost-effective results for both TG and D-dimer assays when using undiluted plasma in under 15 min. The assays presented are therefore a good candidate technology for use in a point-of-care platform to diagnose VTE.

A Cybersecure P300-Based Brain-to-Computer Interface against Noise-Based and Fake P300 Cyberattacks.

In a progressively interconnected world where the Internet of Things (IoT), ubiquitous computing, and artificial intelligence are leading to groundbreaking technology, cybersecurity remains an underdeveloped aspect. This is particularly alarming for brain-to-computer interfaces (BCIs), where hackers can threaten the user's physical and psychological safety. In fact, standard algorithms currently employed in BCI systems are inadequate to deal with cyberattacks. In this paper, we propose a solution to improve the cybersecurity of BCI systems. As a case study, we focus on P300-based BCI systems using support vector machine (SVM) algorithms and EEG data. First, we verified that SVM algorithms are incapable of identifying hacking by simulating a set of cyberattacks using fake P300 signals and noise-based attacks. This was achieved by comparing the performance of several models when validated using real and hacked P300 datasets. Then, we implemented our solution to improve the cybersecurity of the system. The proposed solution is based on an EEG channel mixing approach to identify anomalies in the transmission channel due to hacking. Our study demonstrates that the proposed architecture can successfully identify 99.996% of simulated cyberattacks, implementing a dedicated counteraction that preserves most of BCI functions.

Shaping the Nonlinear Emission Pattern of a Dielectric Nanoantenna by Integrated Holographic Gratings.

We demonstrate the shaping of the second-harmonic (SH) radiation pattern from a single AlGaAs nanodisk antenna using coplanar holographic gratings. The SH radiation emitted from the antenna toward the-otherwise forbidden-normal direction can be effectively redirected by suitably shifting the phase of the grating pattern in the azimuthal direction. The use of such gratings allows increasing the SH power collection efficiency by 2 orders of magnitude with respect to an isolated antenna and demonstrates the possibility of intensity-tailoring for an arbitrary collection angle. Such reconstruction of the nonlinear emission from nanoscale antennas represents the first step toward the application of all-dielectric nanostructures for nonlinear holography.

Comparison of three Bacillus amyloliquefaciens strains growth behaviour and evaluation of the spoilage risk during bread shelf-life.

This study aims at the characterisation of growth behaviour of three strains of Bacillus amyloliquefaciens, isolated from ropy bread (ATCC8473), wheat grain (ISPA-S109.3) and semolina (ISPA-N9.1) to estimate rope spoilage risk in pan bread during shelf-life using the Sym'Previus tool. Cardinal values and growth/no growth boundaries were determined in broth, while artificial spore inoculations were performed in dough for various pan bread recipes to compare experimental counts with in silico growth simulations. Finally, two storage scenarios were tested to determine the probability to reach a spoilage threshold during bread shelf-life. Similarly to the safety criteria fixed for Listeria monocytogenes contamination in foodstuff complying with EC regulation, a potential rope spoilage threshold was arbitrary fixed at 5 log CFU/g for B. amyloliquefaciens. This study further underlines a higher rope spoilage potential of the ISPA strains as compared to the ATCC strain, thus emphasizing the interest to characterise both wild strains and reference strain to account for biological variability. In conclusion, this study showed that available decision making tools which are largely recognized to predict behaviour of pathogenic strains, shall also be used with spoilage strains to help maintain food quality and extend shelf-life.

Indoor pollution and burning practices in wood stove management.

This study evaluates effects of good burning practice and correct installation and management of wood heaters on indoor air pollution in an Italian rural area. The same study attests the role of education in mitigating wood smoke pollution. In August 2007 and winters of 2007 and 2008, in a little mountain village of Liguria Apennines (Italy), indoor and outdoor benzene, toluene, ethylbenzene, and xylene (BTEX) concentrations were measured in nine wood-heated houses. During the first sampling, several mistakes in heating plant installations and management were found in all houses. Indoor BTEX concentrations increased during use of wood burning. Low toluene/benzene ratios were in agreement with wood smoke as main indoor and outdoor pollution source. Other BTEX sources were identified as the indoor use ofsolvents andpaints and incense burning. Results obtained during 2007 were presented and discussed with homeowners. Following this preventive intervention, in the second winter sampling all indoor BTEX concentrations decreased, in spite of the colder outdoor air temperatures. Information provided to families has induced the adoption of effective good practices in stoves and fire management. These results highlight the importance ofeducation, supported by reliable data on air pollution, as an effective method to reduce wood smoke exposures.

Incidence of primary and second cancers in renal transplant recipients: a multicenter cohort study.

Limited data exist about cancer prognosis and the development of second cancers in renal transplant recipients. In a retrospective cohort study on 3537 patients incidence rates of the first and, if any, of a second cancer, and standardized incidence ratios [SIR (95% CI)] were computed. Two hundred and sixty-three (7.5%) patients developed a NMSC, and 253 (7.2%) another type of cancer after a median follow-up of 6.5 and 9.0 years, respectively. A statistically significant excess risk, if compared to an age- and sex-matched reference general population, was observed for Kaposi sarcoma and NMSC, followed by non-Hodgkin lymphoma and carcinoma of cervix uteri; a small number of unusual cancers such as tumors of the salivary glands, small intestine and thyroid also were detected at a level worthy of additional scrutiny. Ten-year survival rate of all noncutaneous cancers was 71.3%, with lower rates for lung carcinoma and non-Hodgkin lymphoma (0% and 41.7%, respectively). Patients with NMSC had an increased risk of developing a second NMSC [SIR 8.3 (7.0-10.0)], and patients with a primary noncutaneous cancer had increased risk of developing a second noncutaneous cancer [SIR 1.8 (1.2-2.8)], if compared to the whole cohort. Our study underscore that the high risk of primary and second cancer in renal transplant recipients, including unusual cancers.

An Edible Rechargeable Battery.

Edible electronics is a growing field that aims to produce digestible devices using only food ingredients and additives, thus addressing many of the shortcomings of ingestible electronic devices. Edible electronic devices will have major implications for gastrointestinal tract monitoring, therapeutics, as well as rapid food quality monitoring. Recent research has demonstrated the feasibility of edible circuits and sensors, but to realize fully edible electronic devices edible power sources are required, of which there have been very few examples. Drawing inspiration from living organisms, which use redox cofactors to power biochemical machines, a rechargeable edible battery formed from materials eaten in everyday life is developed. The battery is realized by immobilizing riboflavin and quercetin, common food ingredients and dietary supplements, on activated carbon, a widespread food additive. Riboflavin is used as the anode, while quercetin is used as the cathode. By encapsulating the electrodes in beeswax, a fully edible battery is fabricated capable of supplying power to small electronic devices. The proof-of-concept battery cell operated at 0.65 V, sustaining a current of 48 µA for 12 min. The presented proof-of-concept will open the doors to new edible electronic applications, enabling safer and easier medical diagnostics, treatments, and unexplored ways to monitor food quality.

Factor VIII companion diagnostic for haemophilia.

Haemophilia is predominantly an inherited disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. The condition of this disease is complex to manage, but many patients do so through home therapy and often only see their core multidisciplinary healthcare team annually. There is an increasing need for patients to be able to monitor their condition efficiently at home while staying connected with their healthcare team. As a consequence, a low-cost handheld self-monitoring solution for clotting factor is required. Here we have demonstrated a suitable one-step Factor VIII companion diagnostic sensing approach based on a chromogenic assay for haemophilia A. The results show comparable performance to the gold standard method. Our approach is able to deliver accurate cost-effective results in under 5 min from undiluted human plasma. It has the potential to be able to reduce the human and monetary costs of over- or under-medication for haemophiliacs.

Role of the probiotic strain Lactobacillus paracasei LMGP22043 carried by artichokes in influencing faecal bacteria and biochemical parameters in human subjects.

AIMS: To evaluate the positive influence of the probiotic strain Lactobacillus paracasei LMGP22043 carried by artichokes into the human gut with special reference to faecal bacterial balance, short-chain fatty acid concentrations and enzyme activities in a randomized, double-blind human trial in comparison with probiotic-free artichokes (control). METHODS: Twenty subjects were randomized into two groups, which consumed daily 180 g of the artichoke product (probiotic or control) during two 15-day study periods (periods 1 and 2) separated by a 15-day washout in a crossover manner. Faecal samples were subjected to microbiological and biochemical analyses, and a strain-specific PCR was performed to monitor the probiotic strain. RESULTS: The probiotic strain, transported by the vegetable matrix, transiently colonized the gut of 17/20 subjects (median 6·87 log CFU g⁻¹ faeces), antagonized Escherichia coli and Clostridium spp. and increased the genetic diversity of lactic population based on REP-PCR profiles, mainly after period 1. CONCLUSIONS: The probiotic L. paracasei LMGP22043 successfully colonized the human gut and positively influenced faecal bacteria and biochemical parameters. SIGNIFICANCE AND IMPACT OF THE STUDY: The association of the probiotic L. paracasei with a food carrier rich in fibre can represent a new strategy for favouring a daily supply of probiotics and attracting more consumers to vegetable food fortified with probiotic strains.

Air pollution and related respiratory diseases: the experience of a local health authority in Liguria (north Italy).

BACKGROUND: Numerous epidemiological studies have shown that air pollution due to both industry and heavy traffic has short- and long-term effects on health. The study was carried out in an industrial area with heavy urban and motorway traffic in the Province of Genoa (Italy). METHODS: The study was carried out from June 2005 to July 2008. An epidemiologic study was conducted by monitoring an elementary/middle school situated in an area of recent industrial development and an elementary/middle school located in an area free from sources of industrial pollution. Furthermore, we conducted an investigation of workers in commercial premises situated in one area of heavy vehicular traffic. In the study areas, environmental monitoring campaigns were carried out in order to determine the association between indoor and outdoor pollution and respiratory disorders. RESULTS AND DISCUSSION: The study did not bring to light any specific health problems attributable with certainty to industrial emissions. The impact of pollution caused by motor traffic proved to be greater than that due to industrial emissions. More exhaustive sampling campaigns should be implemented in order to quantify the effects of specific sources of emissions and to correlate these sources with pollutants (industry, urban traffic, motorway traffic).

Stress and Maladaptive Coping of Italians Health Care Professionals during the First Wave of the Pandemic.

Stress during the pandemic has had an impact on the mental health of healthcare professionals (HCPs). However, little is known about coping and "maladaptive" coping behaviours of this population. This study investigates "maladaptive" coping behaviours and their correlation with stress, anxiety and insomnia of Italian HCPs during the pandemic. It reports on a cross-sectional, descriptive and correlational study based on a survey of 1955 Italian HCPs. Overall participants reported increases in cigarette smoking, time spent online and video playing. Overall reported alcohol consumption decreased but increased in those reporting drinking more than once a week. Those reporting starting smoking during the pandemic were found to have higher SAS and PSS scores. Those reporting being online for 3 or more hours were found to have higher ISS scores. Doctors who reported playing video games were found to have higher PSS, ISS and SAS scores whilst nurses who reported playing video games were found to have higher ISS scores. Doctors who reported playing for longer than one hour had higher PSS scores. Online behaviours may be a coping behaviour of HCPs affected by the pandemic. However, this is an underexplored area for the wellbeing of HCPs. These deficits need to be addressed going forward.

A monolithic single-chip point-of-care platform for metabolomic prostate cancer detection.

There is a global unmet need for rapid and cost-effective prognostic and diagnostic tools that can be used at the bedside or in the doctor's office to reduce the impact of serious disease. Many cancers are diagnosed late, leading to costly treatment and reduced life expectancy. With prostate cancer, the absence of a reliable test has inhibited the adoption of screening programs. We report a microelectronic point-of-care metabolite biomarker measurement platform and use it for prostate cancer detection. The platform, using an array of photodetectors configured to operate with targeted, multiplexed, colorimetric assays confined in monolithically integrated passive microfluidic channels, completes a combined assay of 4 metabolites in a drop of human plasma in under 2 min. A preliminary clinical study using l-amino acids, glutamate, choline, and sarcosine was used to train a cross-validated random forest algorithm. The system demonstrated sensitivity to prostate cancer of 94% with a specificity of 70% and an area under the curve of 0.78. The technology can implement many similar assay panels and hence has the potential to revolutionize low-cost, rapid, point-of-care testing.

Lifestyle Risk Factors for Type 2 Diabetes Mellitus and National Diabetes Care Systems in European Countries.

BACKGROUND: Diabetes is increasing by 3.09% per year in males and 1.92% in females. Lifestyle risk factors are related to diabetes. The aim of this work is to highlight within EU-28 countries the distribution percentages of some lifestyle risk factors and some components of diabetes health care. METHODS: A literature search was conducted to highlight the presence of diabetes registries, which are fundamental tools for disease surveillance and health planning; the presence of a national diabetes plan (NDP); the care setting; and methods used for reimbursement of drugs, devices, and coverage of any comorbidities associated with diabetes. A multiple correspondence analysis (MCA) was carried out to evaluate the possible associations between the variables considered. RESULTS: The highest percentages of diabetes (>10%) are registered in Bulgaria, Malta, and Hungary. Concerning the prevalence of overweight, no European country shows overall percentages of less than 50%. Regarding obesity, 57% of countries show prevalence rates of 25%. The record for physical inactivity belongs to Malta, with 45% of individuals being inactive. The percentage of physical inactivity for females is higher than for males across Europe. In total, 57% of the countries have an insurance-based health system, while 12 countries have public national health systems. Further, 57% of countries have an NDP, while 42% of the EU countries have established a prevalence register for diabetes. Conclusions. Prevalence rates for type 2 DM in the range of 8-9% are noted in 50% of EU-28 countries. In total, 21 out of EU countries show a high prevalence rate for overweight, while 7% of EU-28 countries have an obesity prevalence rate of 25%. Diabetes treatment is entrusted to general practitioners in most countries. The results of this work highlight the differences between countries, but also between genders.

Disposable Paper-on-CMOS Platform for Real-Time Simultaneous Detection of Metabolites.

OBJECTIVE: Early stage diagnosis of sepsis without overburdening health services is essential to improving patient outcomes. METHODS: A fast and simple-to-use platform that combines an integrated circuit with paper microfluidics for simultaneous detection of multiple-metabolites appropriate for diagnostics was presented. Paper based sensors are a primary candidate for widespread deployment of diagnostic or test devices. However, the majority of devices today use a simple paper strip to detect a single marker using the reflectance of light. However, for many diseases such as sepsis, one biomarker is not sufficient to make a unique diagnosis. In this work multiple measurements are made on patterned paper simultaneously. Using laser ablation to fabricate microfluidic channels on paper provides a flexible and direct approach for mass manufacture of disposable paper strips. A reusable photodiode array on a complementary metal oxide semiconductor chip is used as the transducer. RESULTS: The system measures changes in optical absorbance in the paper to achieve a cost-effective and easily implemented system that is capable of multiple simultaneous assays. Potential sepsis metabolite biomarkers glucose and lactate have been studied and quantified with the platform, achieving sensitivity within the physiological range in human serum. CONCLUSION: We have detailed a disposable paper-based CMOS photodiode sensor platform for real-time simultaneous detection of metabolites for diseases such as sepsis. SIGNIFICANCE: A combination of a low-cost paper strip with microfluidic channels and a sensitive CMOS photodiode sensor array makes our platform a robust portable and inexpensive biosensing device for multiple diagnostic tests in many different applications.

Multimodal Integrated Sensor Platform for Rapid Biomarker Detection.

Precision metabolomics and quantification for cost-effective rapid diagnosis of disease are the key goals in personalized medicine and point-of-care testing. At present, patients are subjected to multiple test procedures requiring large laboratory equipment. Microelectronics has already made modern computing and communications possible by integration of complex functions within a single chip. As More than Moore technology increases in importance, integrated circuits for densely patterned sensor chips have grown in significance. Here, we present a versatile single complementary metal-oxide-semiconductor chip forming a platform to address personalized needs through on-chip multimodal optical and electrochemical detection that will reduce the number of tests that patients must take. The chip integrates interleaved sensing subsystems for quadruple-mode colorimetric, chemiluminescent, surface plasmon resonance, and hydrogen ion measurements. These subsystems include a photodiode array and a single photon avalanche diode array with some elements functionalized to introduce a surface plasmon resonance mode. The chip also includes an array of ion sensitive field-effect transistors. The sensor arrays are distributed uniformly over an active area on the chip surface in a scalable and modular design. Bio-functionalization of the physical sensors yields a highly selective simultaneous multiple-assay platform in a disposable format. We demonstrate its versatile capabilities through quantified bio-assays performed on-chip for glucose, cholesterol, urea, and urate, each within their naturally occurring physiological range.

[Atheroembolic renal disease]. / La malattia renale ateroembolica.

Atheroembolic renal disease can be defined as renal failure due to occlusion of the renal arterioles by cholesterol crystal emboli usually dislodged from ulcerated atherosclerotic plaques of the aorta. Atheroembolic renal disease is part of multisystem disease, since the embolization usually involves other organ systems such as the gastrointestinal system, central nervous system, and lower extremities. The kidney is frequently involved because of the proximity of the renal arteries to the abdominal aorta, where erosion of atheromatous plaques is most likely to occur. Embolization may occur spontaneously or after angiographic procedures, vascular surgery, and anticoagulation. In the last decade, atheroembolic renal disease has become a recognizable cause of renal disease. An ante-mortem diagnosis of the disease is possible in a significant proportion of cases as long as the level of diagnostic suspicion is high. The disease can severely affect kidney and patient survival. Although no specific treatment has been proven efficacious, use of statins may be justifiable and such therapy would be a reasonable choice for future treatment trials.

HPV-vaccination and cancer cervical screening in 53 WHO European Countries: An update on prevention programs according to income level.

Human papillomavirus (HPV) is the most common sexually transmitted disease in the world. The aim of our study is to describe the differences in HPV-vaccination coverage and screening programs in WHO European Countries notably according to income levels. Multiple correspondence analysis was applied to examine the association among the following variables: Gross National Income (GNI) levels (Lower-Middle Income, LMI; Upper-Middle Income, UMI; and High Income, HI); type of CC screening program (coverage; opportunistic/organized); vaccination payment policies (free or partial or total charge); mortality rates/100 000 (≤3; >3-6; >6-9; >9); incidence rates/100 000 (≤7; >7-15; >15-21; >21). Data HPV-vaccination start (years) (2006-2008; 2009-2011; 2012-2014; >2014; no program); coverage HPV-vaccination percentage (≤25; 26-50; 51-75; >75); data screening start (years) (<1960; 1960-1980; 1981-2000; >2000); primary screening test (HPV, cytology), and screening coverage percentage (≤25; >25-50; >50-75; >75). A high income is associated with: start of screening before 1960, medium-high screening coverage, organized screening, start of vaccination in the periods 2009-2011 and 2012-2014 and high immunization coverage. On the other hand, lower-middle income is associated with: late start of vaccination and screening programs with cytology as primary test, high mortality and incidence rates and lower-medium vaccination coverage. Our results show a useful scenario for crucial support to public health decision-makers. Public health authorities should monitor the HPV-vaccinated population in order to determine more precisely the effects on short- and long-term incidence and mortality rates. In fact, the greater the vaccination coverage, the greater will be the efficacy of the program for the prevention of CC and other HPV-related diseases.

Differences in colorectal cancer surveillance epidemiology and screening in the WHO European Region.

The aim of this study was to describe the Colorectal Cancer (CRC) burden and prevention actions in 53 countries of the World Health Organization (WHO) European Region (ER). Multiple correspondence analysis was applied to examine the association among the following variables: Measures of occurrence; type of screening programme; existence of cancer registries; data quality and; and gross national income (GNI) level. The study demonstrated clear differences according to GNI: low-middle income (LMI) countries show low mortality rates and unorganized screening programme; upper-middle income (UMI) countries show no test offered, incomplete or absent data mortality, and low quality of the method used to estimate incidence and mortality rates; high income (HI) countries show high mortality rates, test offered (FOBT and colonoscopy), the existence of a national registry, screening population-based, insurance of payment policy, and high quality of the method used to estimate incidence and mortality rates. HI countries reflect a strong interest in epidemiological monitoring and produce accurate indicators of disease occurrence. On the other hand, surveillance strategies need to be improved in UMI and LMI countries: As national vital statistics are unavailable, partial or inaccurate, the coverage and completeness of the mortality data are frequently poor, there is a less efficient general organization. In conclusion, it is important to underline that the resources available (as measured by GNI) appear to be major factors in the Colorectal Cancer Surveillance Epidemiology and Screening in the WHO European Region.

[Treatment of post-transplant glomerulonephritis]. / Il trattamento delle glomerulonefriti de novo e recidivate come causa di disfunzione cronica del rene trapiantato.

The treatment of recurrent glomerulonephritis (GN) is often empirical. Plasmapheresis has received the largest consensus for the treatment of focal glomerular sclerosis (FGS), whether associated with cyclophosphamide and steroids or not. To be effective, such therapy needs to be started as quickly as possible after the onset of proteinuria, and prolonged for months when recovery is delayed. Plasmapheresis and cyclophosphamide have also been used to treat GNs with glomerular crescents. However, there has been no consensus on the efficacy of such therapy. The recently introduced rituximab is the most innovative drug but also the most experimental. So far, it has been used for the treatment of ANCA-associated vasculitis, FGS and membranous GN, with results that are still under debate. Cyclophosphamide has been used in patients with severe recurrent GN, but the anedoctal cases described prevent us from drawing any firm conclusions. Steroids have been used for the treatment of many recurrent GNs, but yet again, without any standard protocol. They have been used both in children with FGS and in adults with aggressive GN or severe proteinuria. Both ACE inhibitors and angiotensinreceptor blockers have been suggested as first-line therapy in recurrent GN with proteinuria. This therapy is safe and can be even more effective than others. Finally, it must be kept in mind that the addition of immunosuppression in transplant patients can dramatically increase the risk of infective complications. Moreover, recurrent GNs are often associated with chronic allograft diseases that can cause graft worsening independently of any therapy.

[Choosing the right treatment approach in focal and segmental glomerular sclerosis with chronic renal failure]. / Il trattamento della glomerulosclerosi focale e segmentaria con insufficienza renale cronica: quale approccio?

Focal and segmental glomerular sclerosis (FSGS) is a heterogeneous disease from a clinical, etiological and clinical point of view. FSGS may be idiopathic, usually associated with nephrotic syndrome, which requires an ''etiological'' treatment approach. In addition, hereditary and secondary forms of FSGS have been described. The response to therapy, including steroids, cytotoxic drugs and calcineurin inhibitors, is considered the best clinical indicator of outcome. Many uncertainties exist regarding the best therapeutic approach to FSGS in patients presenting with chronic renal failure. In this setting, before planning any treatment, the physician should always assess the presence of superimposed functional renal insufficiency and evaluate the severity of the renal impairment, the histological picture, previous immunosuppressive treatments, and the individual patient's risk for side effects. Keeping in mind these considerations and in the absence of appropriate studies, we can formulate the following suggestions: 1. there is no absolute contraindication to the use of full-dose prednisone as initial therapy, although the likelihood of a good response is low; 2. the use of cytotoxic drugs is not recommended unless the patient presents with a steroid-responsive form of the disease; 3. in patients with a glomerular filtration rate of less than 40 mL/min, the use of calcineurin inhibitors should be avoided.