Evaluation of self-sampling-based cervical cancer screening strategy using HPV Selfy CE-IVD test coupled with home-collection kit: a clinical study in Italy.

BACKGROUND: Primary human papillomaviruses (HPV) cervical cancer screening can be strengthened by offering home-collection of biological specimen as a valuable option to increase screening coverage. As recommended by World Health Organization (WHO), screening programs should consider whether the inclusion of HPV self-sampling as a complementary option within their existing screening algorithms could address the gaps in current coverage. However, few HPV screening tests are validated for self-sampling according to international guidelines. This study aimed to test a self-sampling-based screening strategy, complementary to the main screening program based on clinician-collected cervical samples. The study took place in Trieste, Italy, and it aimed to evaluate the feasibility of self-testing at home under an opt-in system during COVID-19 pandemic in order to exploit self-sampling to reduce the screening delay generated by the lockdown. METHODS: 500 women, who should have received the screening call in 2020, were asked, via phone call, to participate in the study. To whom agreed, a home-collection kit, including a vaginal dry swab for specimen collection, was sent. The recipients performed the sample self-collection and sent back the swab through traditional mail using a prepaid envelope. Once received by the hospital, the samples were analyzed with HPV Selfy (Ulisse BioMed, Italy), a CE-IVD HPV screening test specifically validated for self-collection. Results were further compared using cobas® 4800 HPV (Roche, Switzerland). RESULTS: 80% women sent back their swab, showing one of the highest return rate obtained in comparable studies. 34 HPV-positive women were followed up and underwent the Pap test, that revealed 8 low squamous intraepithelial lesions (LSIL) cases, later triaged to colposcopy. HPV Selfy was confirmed to be an adequate test for self-sampling-based screening. CONCLUSIONS: This study further confirmed the feasibility of self-test at home screening strategy based on self-sampling with an opt-in system as a support method to enhance cervical cancer screening coverage in Italy. Enrolled women showed a high appreciation for this approach. HPV Selfy test demonstrated to be a valuable assay for cervical cancer screening based on home self-collection. TRIAL REGISTRATION: ASUGI Trieste n. 16008/2018 and amendment 02-11/09/2020.

Usability and utility of a remote monitoring system to support physiotherapy for people with Parkinson's disease.

Background: Physiotherapy for persons with Parkinson's disease (PwPD) could benefit from objective and continuous tracking of physical activity and falls in daily life. Objectives: We designed a remote monitoring system for this purpose and describe the experiences of PwPD and physiotherapists who used the system in daily clinical practice. Methods: Twenty-one PwPD (15 men) wore a sensor necklace to passively record physical activity and falls for 6 weeks. They also used a smartphone app to self-report daily activities, (near-)falls and medication intake. They discussed those data with their PD-specialized physiotherapist (n = 9) during three regular treatment sessions. User experiences and aspects to be improved were gathered through interviews with PwPD and physiotherapists, resulting in system updates. The system was evaluated in a second pilot with 25 new PwPD (17 men) and eight physiotherapists. Results: We applied thematic analysis to the interview data resulting in two main themes: usability and utility. First, the usability of the system was rated positively, with the necklace being easy to use. However, some PwPD with limited digital literacy or cognitive impairments found the app unclear. Second, the perceived utility of the system varied among PwPD. While many PwPD were motivated to increase their activity level, others were not additionally motivated because they perceived their activity level as high. Physiotherapists appreciated the objective recording of physical activity at home and used the monitoring of falls to enlarge awareness of the importance of falls for PwPD. Based on the interview data of all participants, we drafted three user profiles for PwPD regarding the benefits of remote monitoring for physiotherapy: for profile 1, a monitoring system could act as a flagging dashboard to signal the need for renewed treatment; for profile 2, a monitoring system could be a motivational tool to maintain physical activity; for profile 3, a monitoring system could passively track physical activity and falls at home. Finally, for a subgroup of PwPD the burdens of monitoring will outweigh the benefits. Conclusions: Overall, both PwPD and physiotherapists underline the potential of a remote monitoring system to support physiotherapy by targeting physical activity and (near-)falls. Our findings emphasize the importance of personalization in remote monitoring technology, as illustrated by our user profiles.

Chemokine-Decorated Nanoparticles Target Specific Subpopulations of Primary Blood Mononuclear Leukocytes.

Specific cell targeting to deliver nanoparticles can be achieved by tailored modifications of the material surface with chemical moieties. The selection of the cell targets can be optimized by covering the nanoparticle with molecules, the receptor expression of which is restricted to particular cell subsets. Chemokines perform their biological action through 7-TM Gi-protein-coupled receptors differently expressed in all tissues. We decorated the surface of biocompatible polymer nanoparticles with full-length CCL5, an inflammatory chemokine that attracts leukocytes by binding CCR5, which is highly expressed in blood-circulating monocytes. Our observations showed that CCL5 functionalization does not affect the nanoparticle biocompatibility. Notably, CCL5 NPs delivered to PBMCs are selectively internalized by CCR5+ monocytes but not by CCR5- lymphocytes. The efficacy of PBMC subpopulation targeting by chemokine-decorated nanoparticles establishes an easy-to-use functionalization for specific leukocyte delivery.

Clinical validation of full HR-HPV genotyping HPV Selfy assay according to the international guidelines for HPV test requirements for cervical cancer screening on clinician-collected and self-collected samples.

BACKGROUND: According to international guidelines, Human Papillomavirus (HPV) DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more (CIN2+) lesions. The study aimed to assess whether HPV Selfy (Ulisse BioMed - Trieste, Italy), a full-genotyping HPV DNA test that detects and differentiates 14 high-risk HPV (HR-HPV) types, meets the criteria for primary cervical cancer screening described in the international guidelines, on clinician-collected as well as on self-collected samples. METHODS: For each participant woman, consecutively referring to Azienda Sanitaria Universitaria Giuliano Isontina (Trieste, Italy) and CRO-National Cancer Institute (Aviano, Italy) for the cervical cancer screening program, the following samples were tested: (a) a clinician-collected cervical specimen, analyzed with the reference test (Hybrid Capture®2 test, HC2) and HPV Selfy; and (b) a self-collected vaginal sample, analyzed with HPV Selfy. Enrolled women were also asked to fulfill a questionnaire about self-sampling acceptability. As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with its reference test. RESULTS: HPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.92 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population. CONCLUSIONS: HPV Selfy fulfills all the requirements of the international Meijer's guidelines and has been clinically validated for primary cervical cancer screening purposes. Moreover, HPV Selfy has also been validated for self-sampling according to VALHUDES guidelines. Therefore, at date, HPV Selfy is the only full-genotyping test validated both for screening purposes and for self-sampling. Trial registration ASUGI Trieste n. 16008/2018; CRO Aviano n.17149/2018.

Combining Incompatible Processes for Deracemization of a Praziquantel Derivative under Flow Conditions.

An efficient deracemization method for conversion of the racemate to the desirable (R)-enantiomer of Praziquantel has been developed by coupling incompatible racemization and crystallization processes. By a library approach, a derivative that crystallizes as a conglomerate has been identified. Racemization occurs via reversible hydrogenation over a palladium on carbon (Pd/C) packed column at 130 °C, whereas deracemization is achieved by alternating crystal growth/dissolution steps with temperature cycling between 5-15 °C. These incompatible processes are combined by means of a flow system resulting in complete deracemization of the solid phase to the desired (R)-enantiomer (98 % ee). Such an unprecedented deracemization by a decoupled crystallization/racemization approach can readily be turned into a practical process and opens new opportunities for the development of essential enantiomerically pure building blocks that require harsh methods for racemization.

Estimation of Stride Time Variability in Unobtrusive Long-Term Monitoring Using Inertial Measurement Sensors.

Stride time variability is an important indicator for the assessment of gait stability. An accurate extraction of the stride intervals is essential for determining stride time variability. Peak detection is a commonly used method for gait segmentation and stride time estimation. Standard peak detection algorithms often fail due to additional movement components and measurement noise. A novel algorithm for robust peak detection in inertial sensor signals was proposed in a previous contribution. In this work, we present a novel approach for estimation of stride time variability based on the formerly proposed peak detection algorithm applied to an unobtrusive sensor setup for motion monitoring. The unobtrusive sensor setup includes a wrist sensor, a pocket or belt sensor, and a necklace sensor, all equipped with both accelerometer and gyroscope. The goal of this work is to implement a generalized approach for accurate and robust stride interval determining algorithm for different sensor locations. Therefore, treadmill and level ground walking experiments were conducted with ten healthy subjects at increasing walking speeds and an age-simulating suit. With the proposed algorithm, we achieved a RMSE of 0.07 s for the stride interval estimation during treadmill walking experiments. The results give promising indications that detection of variation of stride time variability is possible using the proposed unobtrusive sensor setup.

Home-based monitoring of falls using wearable sensors in Parkinson's disease.

INTRODUCTION: Falling is among the most serious clinical problems in Parkinson's disease (PD). We used body-worn sensors (falls detector worn as a necklace) to quantify the hazard ratio of falls in PD patients in real life. METHODS: We matched all 2063 elderly individuals with self-reported PD to 2063 elderly individuals without PD based on age, gender, comorbidity, and living conditions. We analyzed fall events collected at home via a wearable sensor. Fall events were collected either automatically using the wearable falls detector or were registered by a button push on the same device. We extracted fall events from a 2.5-year window, with an average follow-up of 1.1 years. All falls included were confirmed immediately by a subsequent telephone call. The outcomes evaluated were (1) incidence rate of any fall, (2) incidence rate of a new fall after enrollment (ie, hazard ratio), and (3) 1-year cumulative incidence of falling. RESULTS: The incidence rate of any fall was higher among self-reported PD patients than controls (2.1 vs. 0.7 falls/person, respectively; P < .0001). The incidence rate of a new fall after enrollment (ie, hazard ratio) was 1.8 times higher for self-reported PD patients than controls (95% confidence interval, 1.6-2.0). CONCLUSION: Having PD nearly doubles the incidence of falling in real life. These findings highlight PD as a prime "falling disease." The results also point to the feasibility of using body-worn sensors to monitor falls in daily life. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Quality Sleep Is Associated With Overnight Metabolic Rate in Healthy Older Adults.

BACKGROUND: Increasing age is associated with an increase in overnight metabolic rate. OBJECTIVE: To determine the relationship between quality sleep, sleep efficiency, and overnight metabolic rate as measured in a respiration chamber in older participants. METHODS: The study design was cross sectional. Forty participants, aged 50 to 83 years (17 males, age 63±7 years, body mass index 25.7±2.3kg/m2) spent one night in a respiration chamber to measure sleep stages by polysomnography and overnight metabolic rate (OMR). Data were collected between 23:00 and 07:00. Subsequently basal metabolic rate (BMR) was measured under a ventilated hood. Quality sleep was calculated as time spent in rapid-eye movement (REM) sleep and slow wave sleep divided by total sleep time, and sleep efficiency was calculated as total sleep time divided by the sleep period time. Body movement was measured between 23:00 and 07:00 with an accelerometer on the wrist. Overnight metabolic rate was adjusted for body size by dividing by basal metabolic rate (OMR/BMR). RESULTS: OMR/BMR was positively associated with age (r = 0.48, p < .001), and quality sleep was negatively associated with age (r = -0.51, p < .001). The variance of OMR/BMR was significantly explained by quality sleep (r = -0.58, p < 0.001). Body movement was negatively related to sleep efficiency (r = -0.38, p<0.01) with no effect on OMR/BMR. When OMR/BMR was adjusted for quality sleep, the effect of age was non significant. CONCLUSION: Quality sleep is inversely associated with the age-related rise in overnight metabolic rate, suggesting that increased overnight metabolic rate is a biological sign of ageing as a consequence of diminished quality sleep.

Diurnal Patterns of Physical Activity in Relation to Activity Induced Energy Expenditure in 52 to 83 Years-Old Adults.

BACKGROUND: Ageing is associated with a declining physical activity level (PAL) and changes in the diurnal activity pattern. Changes in the activity pattern might help explaining the age-associated reduction of physical activity. OBJECTIVE: The aims were to investigate diurnal activity patterns within groups of older adults classified by PAL, to investigate diurnal activity patterns within age-groups and to investigate the association between the drop in activity and aerobic fitness. METHODS: Thirty-one healthy subjects aged between 52 and 83y were recruited for the study. Subjects were divided in sedentary (PAL<1.75), moderately active (1.75

Walking as a Contributor to Physical Activity in Healthy Older Adults: 2 Week Longitudinal Study Using Accelerometry and the Doubly Labeled Water Method.

BACKGROUND: Physical activity is recommended to promote healthy aging. Defining the importance of activities such as walking in achieving higher levels of physical activity might provide indications for interventions. OBJECTIVE: To describe the importance of walking in achieving higher levels of physical activity in older adults. METHODS: The study included 42 healthy subjects aged between 51 and 84 years (mean body mass index 25.6 kg/m(2) [SD 2.6]). Physical activity, walking, and nonwalking activity were monitored with an accelerometer for 2 weeks. Physical activity was quantified by accelerometer-derived activity counts. An algorithm based on template matching and signal power was developed to classify activity counts into nonwalking counts, short walk counts, and long walk counts. Additionally, in a subgroup of 31 subjects energy expenditure was measured using doubly labeled water to derive physical activity level (PAL). RESULTS: Subjects had a mean PAL of 1.84 (SD 0.19, range 1.43-2.36). About 20% of the activity time (21% [SD 8]) was spent walking, which accounted for about 40% of the total counts (43% [SD 11]). Short bouts composed 83% (SD 9) of walking time, providing 81% (SD 11) of walking counts. A stepwise regression model to predict PAL included nonwalking counts and short walk counts, explaining 58% of the variance of PAL (standard error of the estimate=0.12). Walking activities produced more counts per minute than nonwalking activities (P<.001). Long walks produced more counts per minute than short walks (P=.001). Nonwalking counts were independent of walking counts (r=-.05, P=.38). CONCLUSIONS: Walking activities are a major contributor to physical activity in older adults. Walking activities occur at higher intensities than nonwalking activities, which might prevent individuals from engaging in more walking activity. Finally, subjects who engage in more walking activities do not tend to compensate by limiting nonwalking activities. TRIAL REGISTRATION: ClinicalTrials.gov NCT01609764; https://clinicaltrials.gov/ct2/show/NCT01609764 (Archived by WebCite at http://www.webcitation.org/6grls0wAp).

Multicomponent Fitness Training Improves Walking Economy in Older Adults.

BACKGROUND: Walking economy declines with increasing age, possibly leading to mobility limitation in older adults. Multicomponent fitness training could delay the decline in walking economy. PURPOSE: This study aimed to determine the effect of multicomponent fitness training on walking economy in older adults. METHODS: Participants were untrained adults, age 50 to 83 yr (N = 26, 10 males, age = 63 ± 6 yr, BMI = 25.6 ± 2.1 kg·m, mean ± SD). A control group was also recruited (N = 16, 9 males, age = 66 ± 10 yr, BMI = 25.4 ± 3.0 kg·m), matching the intervention group for age, weight, body composition, and fitness. The intervention group followed a multicomponent fitness program of 1 h, twice per week during 1 yr. The control group did not take part in any physical training. Fat-free mass, walking economy, and maximal oxygen uptake (V˙O2max) were measured in both groups before and after the year. Walking economy was measured with indirect calorimetry as the lowest energy needed to displace 1 kg of body mass for 1 m while walking on a treadmill. The data were compared between the two groups with repeated-measures ANOVA. RESULTS: Thirty-two subjects completed all measurements. There was an interaction between the effects of time and group on V˙O2max (P < 0.05) and walking economy (P < 0.05), whereas fat-free mass did not change significantly (P = 0.06). V˙O2max decreased by 1.8 mL·kg·min in the control group and increased by 1.3 mL·kg·min in the intervention group. The lowest energy needed to walk increased by 0.12 J·kg·m in the control group and decreased in the intervention group by 0.13 J·kg·m. CONCLUSION: Multicomponent fitness training decreases walking cost in older adults, preserving walking economy. Thus, training programs could delay mobility limitation with increasing age.

Body Acceleration as Indicator for Walking Economy in an Ageing Population.

BACKGROUND: In adults, walking economy declines with increasing age and negatively influences walking speed. This study aims at detecting determinants of walking economy from body acceleration during walking in an ageing population. METHODS: 35 healthy elderly (18 males, age 51 to 83 y, BMI 25.5±2.4 kg/m2) walked on a treadmill. Energy expenditure was measured with indirect calorimetry while body acceleration was sampled at 60Hz with a tri-axial accelerometer (GT3X+, ActiGraph), positioned on the lower back. Walking economy was measured as lowest energy needed to displace one kilogram of body mass for one meter while walking (WCostmin, J/m/kg). Gait features were extracted from the acceleration signal and included in a model to predict WCostmin. RESULTS: On average WCostmin was 2.43±0.42 J/m/kg and correlated significantly with gait rate (r2 = 0.21, p<0.01) and regularity along the frontal (anteroposterior) and lateral (mediolateral) axes (r2 = 0.16, p<0.05 and r2 = 0.12, p<0.05 respectively). Together, the three variables explained 46% of the inter-subject variance (p<0.001) with a standard error of estimate of 0.30 J/m/kg. WCostmin and regularity along the frontal and lateral axes were related to age (WCostmin: r2 = 0.44, p<0.001; regularity: r2 = 0.16, p<0.05 and r2 = 0.12, p<0.05 respectively frontal and lateral). CONCLUSIONS: The age associated decline in walking economy is induced by the adoption of an increased gait rate and by irregular body acceleration in the horizontal plane.

Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe.

We describe the synthesis of 1-amino-2,5-anhydro-D-mannose ("mannitolamine"), a key intermediate to the 7-nitro-1,2,3-benzadiazole conjugate (NBDM), using commercially available fluidic devices to increase the throughput. The approach is the first example of a flow-based Tiffeneau-Demjanov rearrangement. Performing this step in flow enables a ~64-fold throughput enhancement relative to batch. The flow process enables the synthesis to be accomplished three times faster than the comparable batch route. The high throughput enabled the production of larger quantities of the fluorescent fructose transport probe NBDM, enabling us to measure key photophysical properties that will facilitate future uptake studies.