Detection of NT-proBNP Using Optical Fiber Back-Reflection Plasmonic Biosensors.

Heart failure (HF) is a clinical entity included in cardiovascular diseases affecting millions of people worldwide, being a leading cause of hospitalization of older adults, and therefore imposing a substantial economic burden on healthcare systems. HF is characterized by dyspnea, fatigue, and edema associated with elevated blood levels of natriuretic peptides, such as N Terminal pro-B-type Natriuretic Peptide (NT-proBNP), for which there is a high demand for point of care testing (POCT) devices. Optical fiber (OF) biosensors offer a promising solution, capable of real-time detection, quantification, and monitoring of NT-proBNP concentrations in serum, saliva, or urine. In this study, immunosensors based on plasmonic uncladded OF tips were developed using OF with different core diameters (200 and 600 µm). The tips were characterized to bulk refractive index (RI), anddetection tests were conducted with NT-proBNP concentrations varying from 0.01 to 100 ng/mL. The 200 µm sensors showed an average total variation of 3.6 ± 2.5 mRIU, an average sensitivity of 50.5 mRIU/ng·mL-1, and a limit of detection (LOD) of 0.15 ng/mL, while the 600 µm sensors had a response of 6.1 ± 4.2 mRIU, a sensitivity of 102.8 mRIU/ng·mL-1, and an LOD of 0.11 ng/mL. Control tests were performed using interferents such as uric acid, glucose, and creatinine. The results show the potential of these sensors for their use in biological fluids.

Aerobic exercise improves central blood pressure and blood pressure variability among patients with resistant hypertension: results of the EnRicH trial.

Central blood pressure (BP) and BP variability are associated with cardiovascular disease risk. However, the influence of exercise on these hemodynamic parameters is unknown among patients with resistant hypertension. The EnRicH (The Exercise Training in the Treatment of Resistant Hypertension) was a prospective, single-blinded randomized clinical trial (NCT03090529). Sixty patients were randomized to a 12-week aerobic exercise program or usual care. The outcome measures include central BP, BP variability, heart rate variability, carotid-femoral pulse wave velocity, and circulating cardiovascular disease risk biomarkers including high-sensitivity C-reactive protein, angiotensin II, superoxide dismutase, interferon gamma, nitric oxide, and endothelial progenitor cells. Central systolic BP decreased by 12.22 mm Hg (95% CI, -1.88 to -22.57, P = 0.022) as did BP variability by 2.85 mm Hg (95% CI, -4.91 to -0.78, P = 0.008), in the exercise (n = 26) compared to the control group (n = 27). Interferon gamma -4.3 pg/mL (95%CI, -7.1 to -1.5, P = 0.003), angiotensin II -157.0 pg/mL (95%CI, -288.1 to -25.9, P = 0.020), and superoxide dismutase 0.4 pg/mL (95%CI, 0.1-0.6, P = 0.009) improved in the exercise compared to the control group. Carotid-femoral pulse wave velocity, heart rate variability, high-sensitivity C-reactive protein, nitric oxide, and endothelial progenitor cells were not different between groups (P > 0.05). In conclusion, a 12-week exercise training program improved central BP and BP variability, and cardiovascular disease risk biomarkers in patients with resistant hypertension. These markers are clinically relevant as they are associated with target organ damage and increased cardiovascular disease risk and mortality.

Cost-Effective Fiber Optic Solutions for Biosensing.

In the last years, optical fiber sensors have proven to be a reliable and versatile biosensing tool. Optical fiber biosensors (OFBs) are analytical devices that use optical fibers as transducers, with the advantages of being easily coated and biofunctionalized, allowing the monitorization of all functionalization and detection in real-time, as well as being small in size and geometrically flexible, thus allowing device miniaturization and portability for point-of-care (POC) testing. Knowing the potential of such biosensing tools, this paper reviews the reported OFBs which are, at the moment, the most cost-effective. Different fiber configurations are highlighted, namely, end-face reflected, unclad, D- and U-shaped, tips, ball resonators, tapered, light-diffusing, and specialty fibers. Packaging techniques to enhance OFBs' application in the medical field, namely for implementing in subcutaneous, percutaneous, and endoscopic operations as well as in wearable structures, are presented and discussed. Interrogation approaches of OFBs using smartphones' hardware are a great way to obtain cost-effective sensing approaches. In this review paper, different architectures of such interrogation methods and their respective applications are presented. Finally, the application of OFBs in monitoring three crucial fields of human life and wellbeing are reported: detection of cancer biomarkers, detection of cardiovascular biomarkers, and environmental monitoring.

Label-free plasmonic immunosensor for cortisol detection in a D-shaped optical fiber.

Measuring cortisol levels as a stress biomarker is essential in many medical conditions associated with a high risk of metabolic syndromes such as anxiety and cardiovascular diseases, among others. One technology that has a growing interest in recent years is fiber optic biosensors that enable ultrasensitive cortisol detection. Such interest is allied with progress being achieved in basic interrogation, accuracy improvements, and novel applications. The development of improved cortisol monitoring, with a simplified manufacturing process, high reproducibility, and low cost, are challenges that these sensing mechanisms still face, and for which solutions are still needed. In this paper, a comprehensive characterization of a D-shaped fiber optic immunosensor for cortisol detection based on surface plasmon resonance (SPR) enabled by gold coating is reported. Specifically, the sensor instrumentation and fabrication processes are discussed in detail, and a simulation with its complete mathematical formalism is also presented. Moreover, experimental cortisol detection tests were performed for a detection range of 0.01 to 100 ng/mL, attaining a logarithmic sensitivity of 0.65 ± 0.02 nm/log(ng/mL) with a limit of detection (LOD) of 1.46 ng/mL. Additionally, an investigation of signal processing is also discussed, with the main issues addressed in order to highlight the best way to extract the sensing information from the spectra measured with a D-shaped sensor.

Respiratory and heart rate monitoring using an FBG 3D-printed wearable system.

This work proposes a 3D-printed sensor based on fiber Bragg grating (FBG) technology for respiratory rate (RR) and heart rate (HR) monitoring. Each sensor is composed of a single FBG fully encapsulated into a 3D-printable Flexible, during the printing process. Sensors with different material thicknesses and infill densities were tested. The sensor with the best metrological properties was selected and preliminary assessed in terms of capability of monitoring RR and HR on three users. Preliminary results proved that the developed sensor can be a valuable easy-to-fabricate solution, with high reproducibility and high strain sensitivity to chest wall deformations due to breathing and heart beating.

Esophagomediastinal fistula: a rare case of gastrointestinal tuberculosis.

A 40-year-old male with history of HIV infection was admitted to the hospital with a one-month history of productive cough, vespertine fever, night sweats, loss of appetite and unintentional 10-Kg weight loss. Physical exam was remarkable for cachexia. Blood tests revealed a CD4+ T lymphocyte count of 23 cells/mm3 and HIV viral load of 837,678 copies/ml. Bacilloscopies were positive. Chest computed thomography (CT) showed multiple mediastinal lymph nodes, signs of esophagomediastinal fistula, pericardial effusion and multiple micronodular pulmonary opacities. Endoscopy (EGD) revealed a 10 mm deep ulcer-like lesion in the middle esophagus with pus overflow, but no bubbles were seen. The diagnosis of stage C3 HIV infection with disseminated tuberculosis was made and the patient underwent standard antituberculosis (RIPE) and antiretroviral therapy. Given the mediastinitis risk a percutaneous endoscopic gastrostomy (PEG) tube was placed for nutritional purposes.

Relevance of the Spectral Analysis Method of Tilted Fiber Bragg Grating-Based Biosensors: A Case-Study for Heart Failure Monitoring.

Optical fiber technology has rapidly progressed over the years, providing valuable benefits for biosensing purposes such as sensor miniaturization and the possibility for remote and real-time monitoring. In particular, tilted fiber Bragg gratings (TFBGs) are extremely sensitive to refractive index variations taking place on their surface. The present work comprises a case-study on the impact of different methods of analysis applied to decode spectral variations of bare and plasmonic TFBGs during the detection of N-terminal B-type natriuretic peptide (NT-proBNP), a heart failure biomarker, namely by following the most sensitive mode, peaks of the spectral envelopes, and the envelopes' crossing point and area. Tracking the lower envelope resulted in the lowest limits of detection (LOD) for bare and plasmonic TFBGs, namely, 0.75 ng/mL and 0.19 ng/mL, respectively. This work demonstrates the importance of the analysis method on the outcome results, which is crucial to attain the most reliable and sensitive method with lower LOD sensors. Furthermore, it makes the scientific community aware to take careful attention when comparing the performance of different biosensors in which different analysis methods were used.

When needles are not enough, forceps delivers!

A 35-year-old male with a history of recurrent pleuritic chest pain was referred for evaluation of a mediastinal mass detected on CT. MRI showed a 10.5 x 7 x 3 cm lesion in the posterior mediastinum. EUS revealed a multicystic lesion with thin septa and clear anechoic content that extended from the lower posterior mediastinum to the upper retroperitoneum. EUS-FNA was performed using a 22-gauge needle with aspiration of a serosanguineous fluid. Fluid analysis showed low values of amylase, triglycerides, CEA, and CA19-9. Cytology tests identified small mature lymphocytes without malignancy.

Fulminant Haemolysis Following Endoscopic Retrograde Cholangiopancreatography.

We report the case of a 77-year-old-man with a history of type 2 diabetes mellitus who underwent endoscopic retrograde cholangiopancreatography (ERCP) because of a gallstone in the common bile duct. Thirty-six hours after the procedure, the patient developed persistent fever and epigastric pain associated with de novo jaundice. Massive haemolysis (with exuberant spherocytosis) occurred and patient died in 3 hours. Clostridium perfringens was isolated in the blood cultures. Massive haemolysis associated with C. perfringens has a high mortality rate. Management involves a high index of suspicion after gastrointestinal procedures like ERCP, surgical consultation, antibiotic therapy, transfusion of red cell concentrates and, potentially, hyperbaric oxygen therapy. LEARNING POINTS: Endoscopic retrograde cholangiopancreatography (ERCP) can be complicated by Clostridium perfringens bacteraemia with devastating consequences.C. perfringens infection should be suspected in an icteric, febrile patient with abdominal pain, especially if intravascular haemolysis is present.Management of intravascular haemolysis and inflammation in a patient following ERCP should be multidisciplinary, involving surgery when needed and potentially hyperbaric oxygen therapy; penicillin or penicillin-derived antibiotics associated with clindamycin or metronidazole are the mainstays of antibiotic therapy.

Immunosensing Based on Optical Fiber Technology: Recent Advances.

The evolution of optical fiber technology has revolutionized a variety of fields, from optical transmission to environmental monitoring and biomedicine, given their unique properties and versatility. For biosensing purposes, the light guided in the fiber core is exposed to the surrounding media where the analytes of interest are detected by different techniques, according to the optical fiber configuration and biofunctionalization strategy employed. These configurations differ in manufacturing complexity, cost and overall performance. The biofunctionalization strategies can be carried out directly on bare fibers or on coated fibers. The former relies on interactions between the evanescent wave (EW) of the fiber and the analyte of interest, whereas the latter can comprise plasmonic methods such as surface plasmon resonance (SPR) and localized SPR (LSPR), both originating from the interaction between light and metal surface electrons. This review presents the basics of optical fiber immunosensors for a broad audience as well as the more recent research trends on the topic. Several optical fiber configurations used for biosensing applications are highlighted, namely uncladded, U-shape, D-shape, tapered, end-face reflected, fiber gratings and special optical fibers, alongside practical application examples. Furthermore, EW, SPR, LSPR and biofunctionalization strategies, as well as the most recent advances and applications of immunosensors, are also covered. Finally, the main challenges and an outlook over the future direction of the field is presented.

Physical Activity is Associated With Lower Arterial Stiffness in Patients With Resistant Hypertension.

BACKGROUND: Physical activity is associated with reduced arterial stiffness, although such a relationship has not been reported in those with resistant hypertension. Therefore, this study aimed to determine the association between daily physical activity and arterial stiffness in patients with resistant hypertension. METHODS: Fifty-seven (57) patients with resistant hypertension (50.9% men), aged 58.8±9.4 years, were consecutively recruited. Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). Daily physical activity was objectively assessed with accelerometers during 7 consecutive days. RESULTS: Patients had a body mass index of 29.0±4.0 kg/m2 (84.3% overweight/obese) and were taking an average 4.5 antihypertensive medications. Overall, the cf-PWV was 9.2±2.4 m/s and the majority of participants (n=41, 71.9%) presented a cf-PWV <10 m/s. The cf-PWV showed an inverse correlation with light-intensity physical activity (r = -0.290, p=0.029) and total daily physical activity (r = -0.287, p=0.030). The correlation between light physical activity and cf-PWV remained significant after adjustment for systolic and diastolic blood pressure, but lost significance when further adjusted for age. CONCLUSIONS: Higher daily levels of light-intensity and total physical activity were associated with lower arterial stiffness. Nonetheless, this association is weak and attenuated or abolished when adjusted for blood pressure and age. These results suggest that physical activity may play an important role as a lifestyle intervention for patients with resistant hypertension. Future studies with larger samples sizes are necessary to confirm this preliminary data.

Cortisol AuPd plasmonic unclad POF biosensor.

This paper presents the development and feasibility tests of a cortisol immunosensor. The sensor is based on surface plasmon resonance (SPR) using an unclad plastic optical fiber (POF) in which the SPR is used as sensitivity enhancer, promoted by a gold/palladium (AuPd) alloy coating. The AuPd coated fibers were functionalized with an anti-cortisol antibody and passivated with bovine serum albumin (BSA) to be tested in the presence of cortisol as target analyte. The antibody-antigen binding reaction caused a variation of the refractive index on the surface of the AuPd coating, which leads to a shift of the SPR signature wavelength. The sensor was tested for different cortisol concentrations, ranging from 0.005 to 10 ng/mL. The reported biosensor presented a total wavelength shift of 15 nm for the testing range, putting in evidence a high sensitivity. Control tests for selectivity assessment were also performed. Concentrations as high as 10 ng/mL of cortisol, in a sensor functionalized with anti-hCG antibodies, only resulted in 1 nm variation of the resonance wavelength, 15 times lower than the one functionalized with the anti-cortisol antibodies, which indicates a high selectivity for the proposed approach. For this sensing approach the limit of detection (LOD) was determined to be 1 pg/mL. The proposed SPR based POF sensor has a low-cost interrogation method, high sensitivity and low LOD, straightforward signal processing and find important applications in different biological fields.

Exercise training reduces arterial stiffness in adults with hypertension: a systematic review and meta-analysis.

OBJECTIVE: Arterial stiffness, namely pulse wave velocity (PWV), is an emerging biomarker in the assessment of vascular health. This meta-analysis aims to determine the effects of exercise training on PWV in patients with hypertension, and to identify the possible moderator variables (e.g. type of exercise) of the effect of exercise on PWV. METHODS: MEDLINE, EMBASE, Cochrane and Web of Science were searched up until July 2019 for randomized controlled trials assessing the effect of exercise interventions lasting 4 or more weeks on PWV in adults with hypertension. Random-effects modelling was used to compare changes from pre to postintervention in PWV between exercise and control groups. Data were reported as weighted mean difference (WMD) and 95% confidence interval (95% CI). Protocol registration: PROSPERO registration number CRD42019138658. RESULTS: We included 14 trials (15 interventions), involving five aerobic, two dynamic resistance, six combined and two isometric resistance groups, totalling 642 participants with hypertension. PWV was significantly reduced by exercise training [(WMD (95% CI) = -0.76 m/s (-1.05 to -0.47)]. Analysis of moderator variables showed that aerobic exercise [WMD (95% CI) = -0.70 m/s (-1.20 to -0.19)], combined exercise [WMD (95% CI) = -0.74 m/s (-1.41 to -0.08)] and isometric resistance exercise [WMD (95% CI) = -0.98 m/s (-1.24 to -0.73)] reduced PWV. There was no significant reduction in PWV in participants undertaking dynamic resistance training [WMD (95% CI) = -0.58 (-1.58 to 0.42)]. CONCLUSION: This meta-analysis supports that exercise interventions based on aerobic, combined or isometric exercise are suitable to improve PWV in adults with hypertension.

Hepatic osteodystrophy in cirrhosis due to alcohol-related liver disease.

INTRODUCTION: hepatic osteodystrophy, including osteoporosis, is an abnormal bone metabolism related with chronic liver diseases. Osteoporosis is associated with an increased risk of bone fractures, with a significant impact on morbidity, mortality and healthcare costs. Nevertheless, bone disorders tend to be undervalued in cirrhosis due to alcohol-related liver disease (ALD cirrhosis). This study aimed to assess the prevalence of hepatic osteodystrophy and osteoporosis in ALD cirrhosis. METHODS: a prospective observational study was performed that included patients with ALD cirrhosis, between September 2017 and December 2018. Bone mineral density was determined by dual energy X-ray absorptiometry at the lumbar spine and the femoral neck. Hepatic osteodystrophy was defined as a T-score below -1 SD and osteoporosis as a T-score below -2.5 SD. RESULTS: ninety-four patients were included; 24.5 % (n = 23) had prior fragility fractures and ten patients suffered new osteoporotic fractures during the study period. Hepatic osteodystrophy was diagnosed in 79.8 % (n = 75) and osteoporosis in 21.3 % (n = 20) of cases. Patients with hepatic osteodystrophy presented significantly worse Child-Turcotte-Pugh (p < 0.05) and Model for End-Stage Liver Disease (MELD-sodium) scores (p = 0.01). According to the multivariate analysis, lower body mass index (BMI) (OR = 0.787, 95 % CI: 0.688-0.901, p = 0.001) and vitamin D deficiency (OR = 6.798, 95 % CI: 1.775-26.038, p = 0.005) were significantly and independently associated with hepatic osteodystrophy. Patients with osteoporosis also had a lower BMI (p = 0.01). Female patients and those with prior fragility fractures were more likely to suffer from osteoporosis (p < 0.05). CONCLUSION: our study revealed a high prevalence of hepatic osteodystrophy and osteoporosis in patients with ALD cirrhosis (particularly in those with a lower BMI) and a concerning high rate of fragility fractures. Bone mineral density should be assessed in order to allow for an early diagnosis and the implementation of preventive measures.

Polymer optical fibers for mechanical wave monitoring.

This Letter presents the development of a low-cost polymer optical fiber (POF) sensor for mechanical wave monitoring. The POF is fabricated using the light polymerization spinning process (LPS-POF) with Bisphenol-A as its main component, resulting in a highly flexible fiber. The proposed LPS-POF sensor is applied on the assessment of squared waves with different amplitudes, where the amplitude and dynamic responses are compared to the ones of a piezoelectric transducer (PZT). In static conditions, a determination coefficient (R2) of 0.990 is obtained between the reference (PZT) and proposed sensors for the amplitude assessment of the wave. In dynamic analysis, the LPS-POF viscoelasticity is compensated using viscoelastic constitutive models, resulting in a R2 of 0.988 between the sensor responses, which indicate a mean error reduction of 21% when compared to the uncompensated responses in the amplitudes of different square waves. The dynamic analysis also shows the sensor capability of operating in frequencies as high as 25 Hz. Then, the sensor's responses, compared to the input squared wave, show the possibility of wave velocity measurement. Therefore, with a LPS-POF sensor array, it is possible to monitor these parameters in practical applications.

Knowledge and use of evidence-based medicine in daily practice by health professionals: a cross-sectional survey.

OBJECTIVES: Healthcare professionals are expected to firmly ground their practice in sound evidence. That implies that they know and use evidence-based medicine (EBM). In this study, our aim was to know how often health professionals actually made use of EBM in their daily practice. DESIGN: A questionnaire survey of healthcare professionals. PARTICIPANTS: Healthcare professionals who attended six university postgraduate courses. 226 answered the questionnaire (144 physicians, 64 nurses and 24 pharmacists; response rate 63.3%). SETTING: 56.5% of respondents worked in hospitals (mostly non-teaching), 25.0% in nursing homes and 10.2% in primary care. All participants were French-speaking and lived in France or Switzerland. MEASURES: Declared degree of knowledge and use of EBM, use of EBM-related information sources. RESULTS: Overall, 14.2% of respondents declared to use EBM regularly in their daily practice and 15.6% declared to use EBM only occasionally. The remaining respondents declared they: knew about EBM but did not use it (33.1%), had just heard about EBM (31.9%) or did not know what EBM is (4.0%). Concerning the use of EBM-related information sources, 83.4% declared to use at least monthly (or more often) clinical guidelines, 47.1% PubMed, 21.3% the Cochrane Library and 6.4% other medical databases.Fewer pharmacists (12%) declared to use EBM in their practice than nurses (22%) or doctors (36%). No difference appeared when analysed by gender, work setting or years after graduation. The most frequent obstacles perceived for the practice of EBM were: lack of general knowledge about EBM, lack of skills for critical appraisal and lack of time. CONCLUSIONS: Only a minority of health professionals-with differences between physicians, nurses and pharmacists-declare to regularly use EBM in their professional practice. A larger proportion appears to be interested in EBM but seems to be deterred by their lack of knowledge, skills and personal time.