Sensing Devices for Detecting and Processing Acoustic Signals in Healthcare.

Acoustic signals are important markers to monitor physiological and pathological conditions, e.g., heart and respiratory sounds. The employment of traditional devices, such as stethoscopes, has been progressively superseded by new miniaturized devices, usually identified as microelectromechanical systems (MEMS). These tools are able to better detect the vibrational content of acoustic signals in order to provide a more reliable description of their features (e.g., amplitude, frequency bandwidth). Starting from the description of the structure and working principles of MEMS, we provide a review of their emerging applications in the healthcare field, discussing the advantages and limitations of each framework. Finally, we deliver a discussion on the lessons learned from the literature, and the open questions and challenges in the field that the scientific community must address in the near future.

Experimental Assessment of Cuff Pressures on the Walls of a Trachea-Like Model Using Force Sensing Resistors: Insights for Patient Management in Intensive Care Unit Settings.

The COVID-19 outbreak has increased the incidence of tracheal lesions in patients who underwent invasive mechanical ventilation. We measured the pressure exerted by the cuff on the walls of a test bench mimicking the laryngotracheal tract. The test bench was designed to acquire the pressure exerted by endotracheal tube cuffs inflated inside an artificial model of a human trachea. The experimental protocol consisted of measuring pressure values before and after applying a maneuver on two types of endotracheal tubes placed in two mock-ups resembling two different sized tracheal tracts. Increasing pressure values were used to inflate the cuff and the pressures were recorded in two different body positions. The recorded pressure increased proportionally to the input pressure. Moreover, the pressure values measured when using the non-armored (NA) tube were usually higher than those recorded when using the armored (A) tube. A periodic check of the cuff pressure upon changing the body position and/or when performing maneuvers on the tube appears to be necessary to prevent a pressure increase on the tracheal wall. In addition, in our model, the cuff of the A tube gave a more stable output pressure on the tracheal wall than that of the NA tube.

Sensors and Sensing Technologies for Indoor Positioning and Indoor Navigation.

The last 10 years have seen enormous technical progress in the field of indoor positioning and indoor navigation; yet, in contrast with outdoor well-established GNSS solutions, no technology exists that is cheap and accurate enough for the general market. The potential applications of indoor localization are all-encompassing, from home to wide public areas, from IoT and personal devices to surveillance and crowd behavior applications, and from casual use to mission-critical systems. This special issue is focused on the recent developments within the sensors and sensing technologies for indoor positioning and indoor navigation networks domain. The papers included in this special issue provide useful insights to the implementation, modelling, and integration of novel technologies and applications, including location-based services, indoor maps and 3D building models, human motion monitoring, robotics and UAV, self-contained sensors, wearable and multi-sensor systems, privacy and security for indoor localization systems.

"Hi This Is NESTORE, Your Personal Assistant": Design of an Integrated IoT System for a Personalized Coach for Healthy Aging.

In the context of the fourth revolution in healthcare technologies, leveraging monitoring and personalization across different domains becomes a key factor for providing useful services to maintain and promote well-being. This is even more crucial for older people, with aging being a complex multi-dimensional and multi-factorial process which can lead to frailty. The NESTORE project was recently funded by the EU Commission with the aim of supporting healthy older people to sustain their well-being and capacity to live independently. It is based on a multi-dimensional model of the healthy aging process that covers physical activity, nutrition, cognition, and social activity. NESTORE is based on the paradigm of the human-in-the-loop cyber-physical system that, exploiting the availability of Internet of Things technologies combined with analytics in the cloud, provides a virtual coaching system to support healthy aging. This work describes the design of the NESTORE methodology and its IoT architecture. We first model the end-user under several domains, then we present the NESTORE system that, analyzing relevant key-markers, provides coaching activities and personalized feedback to the user. Finally, we describe the validation strategy to assess the effectiveness of NESTORE as a coaching platform for healthy aging.

Comparing the Performance of Indoor Localization Systems through the EvAAL Framework.

In recent years, indoor localization systems have been the object of significant research activity and of growing interest for their great expected social impact and their impressive business potential. Application areas include tracking and navigation, activity monitoring, personalized advertising, Active and Assisted Living (AAL), traceability, Internet of Things (IoT) networks, and Home-land Security. In spite of the numerous research advances and the great industrial interest, no canned solutions have yet been defined. The diversity and heterogeneity of applications, scenarios, sensor and user requirements, make it difficult to create uniform solutions. From that diverse reality, a main problem is derived that consists in the lack of a consensus both in terms of the metrics and the procedures used to measure the performance of the different indoor localization and navigation proposals. This paper introduces the general lines of the EvAAL benchmarking framework, which is aimed at a fair comparison of indoor positioning systems through a challenging competition under complex, realistic conditions. To evaluate the framework capabilities, we show how it was used in the 2016 Indoor Positioning and Indoor Navigation (IPIN) Competition. The 2016 IPIN competition considered three different scenario dimensions, with a variety of use cases: (1) pedestrian versus robotic navigation, (2) smartphones versus custom hardware usage and (3) real-time positioning versus off-line post-processing. A total of four competition tracks were evaluated under the same EvAAL benchmark framework in order to validate its potential to become a standard for evaluating indoor localization solutions. The experience gained during the competition and feedback from track organizers and competitors showed that the EvAAL framework is flexible enough to successfully fit the very different tracks and appears adequate to compare indoor positioning systems.

Interferon-gamma promoter hypomethylation and increased expression in chronic periodontitis.

AIM: The goal of this investigation was to determine whether epigenetic modifications in the IFNG promoter are associated with an increase of IFNG transcription in different stages of periodontal diseases. MATERIALS AND METHODS: DNA was extracted from gingival biopsy samples collected from 47 total sites from 47 different subjects: 23 periodontally healthy sites, 12 experimentally induced gingivitis sites and 12 chronic periodontitis sites. Levels of DNA methylation within the IFNG promoter containing six CpG dinucleotides were determined using pyrosequencing technology. Interferon gamma mRNA expression was analysed by quantitative polymerase chain reactions using isolated RNA from part of the biological samples mentioned above. RESULTS: The methylation level of all six analysed CpG sites within the IFNG promoter region in the periodontitis biopsies {52% [interquartile range, IQR (43.8%, 63%)]} was significantly lower than periodontally healthy samples {62% [IQR (51.3%, 74%)], p=0.007} and gingivitis biopsies {63% [IQR (55%, 74%)], p=0.02}. The transcriptional level of IFNG in periodontitis biopsies was 1.96-fold and significantly higher than tissues with periodontal health (p=0.04). Although the mRNA level from experimental gingivitis samples exhibited an 8.5-fold increase as compared with periodontally healthy samples, no significant methylation difference was observed in experimental gingivitis sample. CONCLUSIONS: A hypomethylation profile within IFNG promoter region is related to an increase of IFNG transcription present in the chronic periodontitis biopsies, while such an increase of IFNG in experimentally induced gingivitis seems independent of promoter methylation alteration.

Role of environmental and genetic factor interaction in age-related disease development: the gastric cancer paradigm.

The association of Helicobacter pylori (Hp) infection with gastric cancer is well known and might be considered a paradigmatic example of the role that interaction among environmental factors and individual background might play in inducing age-associated disease. To evaluate the role of interaction of Hp infection with genetic background, gastric cancer and chronic gastritis patients as well as random selected controls were typed for five inflammation-related polymorphisms of IL-1 and IL-10 cytokine genes. No association among IL-10 or IL-1 variants with an increased risk of gastric cancer was found, whereas an Hp-independent association of IL-1beta -511T positive genotypes to an increased risk of chronic gastritis was found (Hp-/511T+ OR 1.89, 95% CI: 1.01-3.54; Hp+/-511T+ OR 1.83, 95% CI: 1.05-3.19). Stratification of gastric cancer group according to Hp infection does not allow finding a statistically significant association of Hp+ to the higher histological grading (G3) of gastric cancer (OR 1.54, 95% CI: 0.46-5.11). Our findings seem to confirm that cytokine genetic variants might contribute to determining the background for inflammaging in which H. pylori infection might facilitate cancer development.

Apolipoprotein E genotypic frequencies among Down syndrome patients imply early unsuccessful aging for ApoE4 carriers.

Down syndrome (DS) might be considered a model for unsuccessful and early aging, possibly accelerated for those who carry the APOE4 allele associated with common age-related diseases, e.g., Alzheimer's disease and a poor prognosis after acute myocardial infarction, causing lower ApoE4 frequencies among the very old in general populations. We compared ApoE genotypic frequencies found for healthy adults (n = 211, age < 40; n = 79, ages 70-79; n = 71, ages > 90) to those found for DS patients (n = 106, mean age 9 years), all living in western Sicily. We found that the frequency of the ApoE23 genotype increased with age among the healthy adults (8.5%, 6.4%, 19.7%; p = 0.024) while ApoE34 frequency decreased (16.1%, 12.6%, 4.1%; p = 0.012). DS patients had APOE34 genotypic frequencies very similar to those found in septuagenarians (9%; p = 0.005). Analyzing results according to surviving rate of persons with DS, an age-related reduction of ApoE3/4 genotype frequency was found comparing =5 years old to >5 years old DS subjects. These results highlight DS as a model to understand the role of APOE4 allele in unsuccessful ageing considering that a number of proinflammatory supernumerary genes (Cu/Zn superoxide dismutase, Ets-2 transcription factors, Down syndrome critical region 1, stress-inducible factor, interferon-alpha receptor and the amyloid precursor protein) are located on chromosome 21 and are implied in the pathologic processes of DS.

Tumor necrosis factor-alpha -308A/G polymorphism is associated with age at onset of Alzheimer's disease.

Pro-inflammatory cytokines and acute-phase proteins play an important role in Alzheimer's disease (AD) neurodegeneration, and common polymorphisms of genes controlling their production have been shown to be associated with AD. Tumor necrosis factor (TNF)-alpha is an inflammatory cytokine involved in the local immune response occurring in the central nervous system of AD patients. Genetic variation could contribute to the risk of developing AD or influence the age at the onset of the disease. We genotyped 222 patients (152 women, 70 men; age range 60-87) and 240 non-demented age-matched healthy controls for TNF-alpha -308 G/A single nucleotide polymorphism (SNP). No significant differences were observed in genotyped frequencies between patients and controls, whereas carriers of -308A showed a significantly lower mean age at onset than non-carriers of this allele. This difference was more evident taking into account ApolipoproteinE (ApoE) status since the lowest age at onset was observed in patients carrying the -308ATNF+/APOE4+ genotypes. In conclusion, our data support previous suggestions that, at least in Caucasians, the TNF gene is a disease modifier gene in patients in which AD is rising, bringing to light the importance of genetic variation at the pro-inflammatory components in the progression of AD.

Regulatory cytokine gene polymorphisms and risk of colorectal carcinoma.

It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori-associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease-associated colorectal cancer. Growing evidence suggests that these associations might be not casual findings. Focusing on individual cytokines has generated evidence that anti-inflammatory cytokine interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) may have a complex role in gastrointestinal carcinogenesis. As an example, IL-10-deficient mice develop severe atrophic gastritis and a chronic enterocolitis, developing colorectal cancer similar to human inflammatory bowel disease-associated neoplasia. TGF-beta1 is a multifunctional signaling molecule with a wide array of roles. Animal experiments suggest that TGF-beta1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting a significant stimulation of tumor growth invasion and metastasis during tumor progression. We assessed association of functional polymorphisms (-1082G/A; -592C/A) and TGF-beta1 (-509C/T; +869C/T) influencing the IL-10 production to colorectal cancer risk in a case-control study of 62 patients and 124 matched controls. No significant differences were observed among cancer patients and controls for IL-10 -1082G/A; -592C/A genotype frequencies. Evaluation of odds ratios (OR) for the TGF-beta1 +869C/T genotypes showed a significant increased risk for individuals bearing +869CC genotype compared to +869CT- and +869TT-positive individuals. These results suggest that the +869C allele, responsible for a Leu-->Pro substitution in the signal peptide sequence of the TGF-beta1 protein, may have a predisposing role in the development of colorectal cancer.

Cytokine gene polymorphisms and breast cancer susceptibility.

Human breast cancer (BC) is characterized by a considerable clinical heterogeneity. Steroid hormone receptor expression and growth factor receptor expression have been considered suitable diagnostic and prognostic markers, whereas mutations of oncosuppressor and gatekeeper genes have been found associated with an increased risk for this malignancy. To evaluate the role that polymorphisms of genes involved in the regulation of inflammatory response might play in BC susceptibility, we investigated associations between cytokine functionally relevant polymorphisms in 84 BC patients compared to 110 age- and sex-matched controls. TNF-alpha (-308G/A), TGF-beta1 (+869C/T), IL-10 (-1117G/A; -854C/T; -627C/A), and IFN-gamma (874T/A) single nucleotide polymorphisms (SNPs) were identified by sequence-specific primers (SSP)-PCR or restriction fragment length polymorphism (RFLP)-PCR. Genotype or haplotype distributions for each polymorphisms were consistent with the HWE in these populations. We were unable to demonstrate differences in genotype or allele frequencies between patient and control groups. Data obtained in this study indicate that none of the cytokine SNPs studied is likely to have predisposing or protective effects on BC susceptibility. On the other hand, both positive and negative association with BC have been reported for some of the studied genotypes by different research groups. In conclusion, further studies involving larger numbers of subjects are required.

Association between platelet glycoprotein Ib-alpha and myocardial infarction: results of a pilot study performed in male and female patients from Sicily.

Myocardial infarction (AMI) is a complex multifactorial disorder. Platelet adhesion and thrombosis are pivotal events in the development of atherosclerotic lesions. Occlusive thrombus is almost exclusively initiated by plaque rupture and adhesion of platelets to subendothelial von Willebrand factor (vWf) by its specific platelet receptor, the alpha-chain of glycoprotein (GP) Ib-IX-V complex of the human platelet-specific antigens (HPA). Two polymorphisms have been reported in the sequence of GPIb-alpha. The first, a C/T transition at nucleotide 1018 results in an amino acid dimorphism (Thr/Met) at residue 145 of GPIb-alpha, which is located within the vWF-binding domain of the receptor. The second is a T/C polymorphism in the Kozak sequence at position -5 from the initiator ATG. This affects the receptor density on the platelet surface. We assessed 1018 C/T and -5 T/C Kozak polymorphisms to see whether they are associated with AMI in homogeneous populations of Sicilian patients with AMI. To this end, we have analyzed the distribution of 1018 C/T and -5 T/C Kozak polymorphisms in 105 young Sicilian patients (<46 years) and 110 healthy age-related controls, by PCR-SSP and PCR-RFLP. Our results demonstrate no significant differences in the frequency of 1018 C/T and -5 T/C Kozak polymorphism between patients with AMI and controls. Stratifying by gender, there is no difference between male and female patients and control data. Thus, our results indicate that the HPA-2 polymorphisms are not associated with an increased risk for AMI at early onset (< 46 years) both in men and in women.