Flexible neural probes: a review of the current advantages, drawbacks, and future demands. / 柔性神经探针：当前的优点、缺点及未来需求.

Brain diseases affect millions of people and have a huge social and economic impact. The use of neural probes for studies in animals has been the main approach to increasing knowledge about neural network functioning. Ultimately, neuroscientists are trying to develop new and more effective therapeutic approaches to treating neurological disorders. The implementation of neural probes with multifunctionalities (electrical, optical, and fluidic interactions) has been increasing in the last few years, leading to the creation of devices with high temporal and spatial resolution. Increasing the applicability of, and elements integrated into, neural probes has also led to the necessity to create flexible interfaces, reducing neural tissue damage during probe implantation and increasing the quality of neural acquisition data. In this paper, we review the fabrication, characterization, and validation of several types of flexible neural probes, exploring the main advantages and drawbacks of these devices. Finally, future developments and applications are covered. Overall, this review aims to present the currently available flexible devices and future appropriate avenues for development as possible guidance for future engineered devices.

Effect of Preoperative Home-Based Exercise Training on Quality of Life After Lung Cancer Surgery: A Multicenter Randomized Controlled Trial.

BACKGROUND: Preoperative exercise training is recommended for improvement of clinical outcomes after lung cancer (LC) surgery. However, its effectiveness in preventing postoperative decline in quality of life (QoL) remains unknown. This study investigated the effect of preoperative home-based exercise training (PHET) on QoL after LC surgery. METHODS: Patients awaiting LC resection were randomized to PHET or a control group (CG). The PHET program combined aerobic and resistance exercise, with weekly telephone supervision. Primary outcome was QoL-assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) at baseline, before surgery, and 1 month after surgery. The secondary outcomes were hospital length of stay and physical performance. The main analysis included a factorial repeated-measures analysis of variance. Additionally, the proportion of patients experiencing clinical deterioration from baseline to post-surgery was assessed. RESULTS: The study included 41 patients (68.1 ± 9.3 years; 68.3% male) in the intention-to-treat analysis (20 PHET patients, 21 CG patients). A significant group × time interaction was observed for global QoL (p = 0.004). Between-group differences in global QoL were statistically and clinically significant before surgery (mean difference [MD], 13.5 points; 95% confidence interval [CI], 2.4-24.6; p = 0.019) and after surgery (MD, 12.4 points; 95% CI, 1.3-23.4; p = 0.029), favoring PHET. Clinical deterioration of global QoL was reported by 71.4% of the CG patients compared with 30 % of the PHET patients (p = 0.003). Between-group differences in favor of PHET were found in pain and appetite loss as well as in physical, emotional and role functions after surgery (p < 0.05). Compared with CG, PHET was superior in improving preoperative five-times sit-to-stand and postoperative exercise capacity (p < 0.05). No between-group differences in other secondary outcomes were observed. CONCLUSION: The study showed that PHET can effectively prevent the decline in QoL after LC surgery.

Home-Based Preoperative Exercise Training for Lung Cancer Patients Undergoing Surgery: A Feasibility Trial.

BACKGROUND: Clinical guidelines recommend prehabilitation with exercise training to optimize recovery after lung cancer surgery. However, the lack of access to facility-based exercise programs is a major barrier to routine participation. This study aimed to assess the feasibility of a home-based exercise intervention before lung cancer resection. METHODS: We conducted a prospective, two-site feasibility study, including patients scheduled for lung cancer surgery. Exercise prescription involved aerobic and resistance training with telephone-based supervision. The primary endpoint was overall feasibility (recruitment rate, retention rate, intervention adherence and acceptability). Secondary endpoints included safety and effects on health-related quality of life (HRQOL) and physical performance, evaluated at baseline, after the exercise intervention and 4-5 weeks after surgery. RESULTS: Over three months, 15 patients were eligible, and all agreed to participate (recruitment rate: 100%). A total of 14 patients completed the exercise intervention, and 12 patients were evaluated postoperatively (retention rate: 80%). The median length of the exercise intervention was 3 weeks. Patients performed an aerobic and resistance training volume higher than prescribed (median adherence rates of 104% and 111%, respectively). A total of nine adverse events occurred during the intervention (Grade 1, n = 8; Grade 2, n = 1), the most common being shoulder pain. After the exercise intervention, significant improvements were observed in the HRQOL summary score (mean difference, 2.9; 95% confidence interval [CI], from 0.9 to 4.8; p = 0.049) and the five-times sit-to-stand test score (median difference, -1.5; 95% CI, from -2.1 to -0.9; p = 0.001). After surgery, no significant effects on HRQOL and physical performance were observed. CONCLUSION: A short-term preoperative home-based exercise intervention is feasible before lung cancer resection and may enhance accessibility to prehabilitation. Clinical effectiveness should be investigated in future studies.

Role of digital health in pulmonary rehabilitation and beyond: shaping the future.

Pulmonary rehabilitation (PR) is a cost-effective intervention with well-known benefits to exercise capacity, symptoms and quality of life in patients with chronic respiratory diseases. Despite the compelling evidence of its benefits, PR implementation is still suboptimal, and maintenance of PR benefits is challenging. To overcome these pitfalls, there has been a growing interest in developing novel models for PR delivery. Digital health is a promising solution, as it has the potential to address some of the most reported barriers to PR uptake and adherence (such as accessibility issues), help maintain the positive results following a PR programme and promote patients' adherence to a more active lifestyle through physical activity (tele)coaching. Despite the accelerated use of digital health to deliver PR during the coronavirus disease 2019 pandemic, there are still several factors that contribute to the resistance to the adoption of digital health, such as the lack of evidence on its effectiveness, low acceptability by patients and healthcare professionals, concerns about implementation and maintenance costs, inequalities in access to the internet and technological devices, and data protection issues. Nevertheless, the trend towards reducing technology costs and the higher availability of digital devices, as well as the greater ease and simplicity of use of devices, enhance the opportunities for future development of digitally enabled PR interventions. This narrative review aims to examine the current evidence on the role of digital health in the context of PR, including strengths and weaknesses, and to determine possible threats and opportunities, as well as areas for future work.

Flexible Neural Probe Fabrication Enhanced with a Low-Temperature Cured Polyimide and Platinum Electrodeposition.

Polyimide is an emerging and very interesting material for substrate and passivation of neural probes. However, the standard curing temperature of polyimide (350 °C) is critical for the microelectrodes and contact pads of the neural probe, due to the thermal oxidation of the metals during the passivation process of the neural probe. Here, the fabrication process of a flexible neural probe, enhanced with a photosensitive and low-temperature cured polyimide, is presented. Annealing tests were performed with metallic films deposited on polyimide, which led to the reduction of the curing temperature to 250 °C, with no significant irregularities in the metallic sample annealed at that temperature and an effective polyimide curing. The use of a lower curing temperature reduces the thermal oxidation of the metals during the polyimide curing process to passivate the neural probe. Additionally, in this fabrication process, the microelectrodes of the neural probe were coated with electrodeposited platinum (Pt), only after the passivation process, and its electrochemical performance was accessed. At 1 kHz, the impedance of the microelectrodes before Pt electrodeposition was approximately 1.2 MΩ, and after Pt electrodeposition, it was approximately 350 kΩ. Pt electrodeposition changed the equivalent circuit of the microelectrodes and reduced their impedance, which will be crucial for future in-vivo tests to acquire the electrical activity of the neurons with the fabricated neural probe.

What Motivates Patients with COPD to Be Physically Active? A Cross-Sectional Study.

Motivation can be broadly defined as what moves people to act. Low motivation is a frequently reported factor for the reduced physical activity (PA) levels observed in patients with chronic obstructive pulmonary disease (COPD). This study assessed patients' motives to be physically active, according to three pulmonary rehabilitation (PR) participation groups (Never PR, Previous PR and Current PR) and explored whether these motives were related to the PA levels and clinical characteristics. The motives to be physically active were assessed with the Exercise Motivation Inventory-2 (EMI-2, 14 motivational factors, five dimensions) and PA with accelerometry (PA groups: <5000 steps/day vs. ≥5000 steps/day). The clinical variables included symptoms, impact of the disease, exercise capacity and comorbidities. Ninety-two patients (67.4 ± 8.1 years, 82.6% male, forced expiratory volume in 1s (FEV1) 48.3 ± 18.9% predicted; 30.4% Never PR, 51% Previous PR and 18.5% Current PR) participated. The motivational dimensions related to health/fitness presented the highest scores (3.8 ± 1.1; 3.4 ± 1.3). The motives to be active were not significantly different between PA groups (p > 0.05) but having less symptoms and ≥two comorbidities were associated with higher scores in psychological/health and body-related motives, respectively (p < 0.05). The findings may encourage health professionals to actively explore with patients their motives to be physically active to individualise PA promotion.

Differentiation between normal and tumor mammary glands with depth-resolved attenuation coefficient from optical coherence tomography.

Optical coherence tomography (OCT) is a well-established imaging technology for high-resolution, cross-sectional imaging of biological tissues. Imaging processing and light attenuation coefficient estimation allows to further improve the OCT diagnostic capability. In this paper we use a commercial OCT system, Telesto II-1325LR from Thorlabs, and demonstrate its ability to differentiate normal and tumor mammary mouse glands with the OCT attenuation coefficient. Using several OCT images of normal and tumor mammary mouse glands (n = 26), a statistical analysis was performed. The attenuation coefficient was calculated in depth, considering a slope of 0.5 mm. The normal glands present a median attenuation coefficient of 0.403 mm-1, comparatively to 0.561 mm-1obtained for tumor mammary glands. This translates in an attenuation coefficient approximately 39% higher for tumor mammary glands when compared to normal mammary glands. The OCT attenuation coefficient estimation eliminates the subjective analysis provided by direct visualization of the OCT images.

Effect of Exercise Training on Quality of Life after Colorectal and Lung Cancer Surgery: A Meta-Analysis.

Surgical treatment affects health-related quality of life (HRQoL) and increases fatigue symptoms in patients with lung cancer (LC) and colorectal cancer (CRC). We aimed to systematically review the effect of exercise training on HRQoL and fatigue after LC and CRC surgery. Randomized controlled trials published before 21 March 2021, were searched in PubMed, Scopus, Web of Science, SPORTDiscus and PEDro. Eligible trials compared the effect of exercise interventions initiated preoperatively or in the first 3 months after surgery versus usual care on postoperative HRQoL and fatigue. Standardized mean differences (SMD) were pooled using random-effects models. Twelve studies with a total of 777 patients were included. In LC patients (10 studies, n = 651), exercise training in general led to a moderate improvement in the physical domain of HRQoL (0.68: 95% CI: [0.47; 0.89]) and a small reduction in fatigue levels after surgery (SMD = 0.28: 95% CI: [0.02; 0.53]), while no effects were found in other HRQoL domains. In CRC (two studies, n = 126), exercise training showed no effects on HRQoL and fatigue after surgery. Exercise training is an effective intervention to improve physical function and fatigue after LC surgery. Further studies are necessary to clarify the effects of exercise on HRQoL and fatigue after CRC surgery.

Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions.

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that has gained great attention in the past years as a new therapy for cancer treatment. PDT uses photosensitizers that, after being excited by light at a specific wavelength, react with the molecular oxygen to create reactive oxygen species in the target tissue, resulting in cell death. Compared to conventional therapeutic modalities, PDT presents greater selectivity against tumor cells, due to the use of photosensitizers that are preferably localized in tumor lesions, and the precise light irradiation of these lesions. This paper presents a review of the principles, mechanisms, photosensitizers, and current applications of PDT. Moreover, the future path on the research of new photosensitizers with enhanced tumor selectivity, featuring the improvement of PDT effectiveness, has also been addressed. Finally, new applications of PDT have been covered.

Double-Layer Flexible Neural Probe With Closely Spaced Electrodes for High-Density in vivo Brain Recordings.

Flexible polymer neural probes are an attractive emerging approach for invasive brain recordings, given that they can minimize the risks of brain damage or glial scaring. However, densely packed electrode sites, which can facilitate neuronal data analysis, are not widely available in flexible probes. Here, we present a new flexible polyimide neural probe, based on standard and low-cost lithography processes, which has 32 closely spaced 10 µm diameter gold electrode sites at two different depths from the probe surface arranged in a matrix, with inter-site distances of only 5 µm. The double-layer design and fabrication approach implemented also provides additional stiffening just sufficient to prevent probe buckling during brain insertion. This approach avoids typical laborious augmentation strategies used to increase flexible probes' mechanical rigidity while allowing a small brain insertion footprint. Chemical composition analysis and metrology of structural, mechanical, and electrical properties demonstrated the viability of this fabrication approach. Finally, in vivo functional assessment tests in the mouse cortex were performed as well as histological assessment of the insertion footprint, validating the biological applicability of this flexible neural probe for acquiring high quality neuronal recordings with high signal to noise ratio (SNR) and reduced acute trauma.

Phenotyping Adopters of Mobile Applications Among Patients With COPD: A Cross-Sectional Study.

Effectiveness of technology-based interventions to improve physical activity (PA) in people with COPD is controversial. Mixed results may be due to participants' characteristics influencing their use of and engagement with mobile health apps. This study compared demographic, clinical, physical and PA characteristics of patients with COPD using and not using mobile apps in daily life. Patients with COPD who used smartphones were asked about their sociodemographic and clinic characteristics, PA habits and use of mobile apps (general and PA-related). Participants performed a six-minute walk test (6MWT), gait speed test and wore an accelerometer for 7 days. Data were compared between participants using (App Users) and not using (Non-App Users) mobile apps. A sub-analysis was conducted comparing characteristics of PA-App Users and Non-Users. 59 participants were enrolled (73% Male; 66.3 ± 8.3 yrs; FEV1 48.7 ± 18.4% predicted): 59% were App Users and 25% were PA-App Users. Significant differences between App Users and Non-App Users were found for age (64.2 ± 8.9 vs. 69.2 ± 6.3yrs), 6MWT (462.9 ± 91.7 vs. 414.9 ± 82.3 m), Gait Speed (Median 1.5 [Q1-Q3: 1.4-1.8] vs. 2.0 [1.0-1.5]m/s), Time in Vigorous PA (0.6 [0.2-2.8] vs. 0.14 [0.1-0.7]min) and Self-Reported PA (4.0 [1.0-4.0] vs. 1.0 [0.0-4.0] Points). Differences between PA-App Users and Non-Users were found in time in sedentary behavior (764.1 [641.8-819.8] vs. 672.2 [581.2-749.4] min) and self-reported PA (4.0 [2.0-6.0] vs. 2.0 [0.0-4.0] points). People with COPD using mobile apps were younger and had higher physical capacity than their peers not using mobile apps. PA-App Users spent more time in sedentary behaviors than Non-Users although self-reporting more time in PA.

PDMS Microlenses for Focusing Light in Narrow Band Imaging Diagnostics.

Minimally invasive medical devices can greatly benefit from Narrow Band Imaging (NBI) diagnostic capabilities, as different wavelengths allow penetration of distinct layers of the gastrointestinal tract mucosa, improving diagnostic accuracy and targeting different pathologies. An important performance parameter is the light intensity at a given power consumption of the medical device. A method to increase the illumination intensity in the NBI diagnostic technique was developed and applied to minimally invasive medical devices (e.g., endoscopic capsules), without increasing the size and power consumption of such instruments. Endoscopic capsules are generally equipped with light-emitting diodes (LEDs) operating in the RGB (red, green, and blue) visible light spectrum. A polydimethylsiloxane (PDMS) µ-lens was designed for a maximum light intensity at the target area of interest when placed on top of the LEDs. The PDMS µ-lens was fabricated using a low-cost hanging droplet method. Experiments reveal an increased illumination intensity by a factor of 1.21 for both the blue and green LEDs and 1.18 for the red LED. These promising results can increase the resolution of NBI in endoscopic capsules, which can contribute to early gastric lesions diagnosis.

LED Optrode with Integrated Temperature Sensing for Optogenetics.

In optogenetic studies, the brain is exposed to high-power light sources and inadequate power density or exposure time can cause cell damage from overheating (typically temperature increasing of 2 ∘ C). In order to overcome overheating issues in optogenetics, this paper presents a neural tool capable of assessing tissue temperature over time, combined with the capability of electrical recording and optical stimulation. A silicon-based 8 mm long probe was manufactured to reach deep neural structures. The final proof-of-concept device comprises a double-sided function: on one side, an optrode with LED-based stimulation and platinum (Pt) recording points; and, on the opposite side, a Pt-based thin-film thermoresistance (RTD) for temperature assessing in the photostimulation site surroundings. Pt thin-films for tissue interface were chosen due to its biocompatibility and thermal linearity. A single-shaft probe is demonstrated for integration in a 3D probe array. A 3D probe array will reduce the distance between the thermal sensor and the heating source. Results show good recording and optical features, with average impedance magnitude of 371 k Ω , at 1 kHz, and optical power of 1.2 mW·mm - 2 (at 470 nm), respectively. The manufactured RTD showed resolution of 0.2 ∘ C at 37 ∘ C (normal body temperature). Overall, the results show a device capable of meeting the requirements of a neural interface for recording/stimulating of neural activity and monitoring temperature profile of the photostimulation site surroundings, which suggests a promising tool for neuroscience research filed.

High-selectivity neural probe based on a Fabry-Perot optical filter and a CMOS silicon photodiodes array at visible wavelengths.

This paper presents a silicon neural probe with a high-selectivity optical readout function and light emitting diodes for neurons photostimulation and fluorophore excitation. A high-selectivity Fabry-Perot optical filter on the top of a CMOS silicon photodiodes array can read the emitted fluorescence, which indicates the neurons physiological state. The design, fabrication, and characterization of the optical filter are presented. The SiO2 / TiO2 based optical filter thin films were deposited by RF sputtering. The performance of the optical filter deposited on the top of the silicon photodiodes array, implemented in the neural probe, was tested through in-vitro fluorescence measurements. The transmittance peak of the fabricated optical filter is 81.8% at 561 nm, with a full width at half maximum of 28 nm. The peak responsivity of the CMOS silicon photodiode with the optical filter deposited on its top is 273.6 mA / W at 578 nm. The in-vitro fluorescence measurements results show a CMOS photodiode current proportional to the fluorophore concentration with a good linearity (R2 = 0.9361). The results validate the use of the neural probe with the high-selectivity optical readout function to determine the presence of different fluorophore concentrations. The development of the device in a conventional CMOS process allows on-chip electronics readout.

Optical microsystem for analysis of diffuse reflectance and fluorescence signals applied to early gastrointestinal cancer detection.

The detection of cancer at its earliest stage is crucial in order to increase the probability of a successful treatment. Optical techniques, specifically diffuse reflectance and fluorescence, may considerably improve the ability to detect pre-cancerous lesions. These techniques have high sensitivity to some biomarkers present on the tissues, providing morphological and biochemical information of normal and diseased tissue. The development of a chip sized spectroscopy microsystem, based on these techniques, will greatly improve the early diagnosis of gastrointestinal cancers. The main innovation is the detection of the spectroscopic signals using only few, but representative, spectral bands allowing for miniaturization. This paper presents the mathematical models, its validation and analysis for retrieving data of the measured spectroscopic signals. These models were applied to a set of phantoms clearly representative of gastrointestinal tissues, leading to a more accurate diagnostic by a pathologist. Moreover, it was demonstrated that the models can use the reconstructed spectroscopic signals based only on its extraction on those specific spectral bands. As a result, the viability of the spectroscopy microsystem implementation was proved.

Identidade coletiva e política na trajetória de organização das trabalhadoras rurais de Minas Gerais: para uma psicologia política das ações coletivas / Collective and political identity in the trajectory of rural workwomen´s organization in Minas Gerais: toward a political psychology of collective action

O texto apresenta um estudo da organização das trabalhadoras rurais de Minas Gerais, focando sua análise nas práticas e nos discursos grupais que colaboram no processo de constituição da identidade política do grupo, cujo ápice se deu na organização da Comissão Estadual de Mulheres Trabalhadoras Rurais. Com os dados coletados nos documentos históricos, nas entrevistas individuais semi-estruturadas e no diário de campo, procedeu-se uma análise de conteúdo com base em duas categorias, a saber: estratégias de mobilização e processo de conscientizaçã. Os resultados revelam que a identidade política configura-se, assim, como aquele elemento que, ao mesmo tempo, é possibilitado e constituído no interior do processo mobilizatório e revela-se como elemento mediador da consistência interventiva dos grupos envolvidos na luta, e, nessa medida, promove transformações subjetivas e objetivas tanto em indivíduos particulares como nas diversas esferas da vida cotidiana. (AU)

Identidade coletiva e política na trajetória de organização das trabalhadoras rurais de Minas Gerais: para uma psicologia política das ações coletivas / Collective and political identity in the trajectory of rural workwomen´s organization in Minas Gerais: toward a political psychology of collective action

O texto apresenta um estudo da organização das trabalhadoras rurais de Minas Gerais, focando sua análise nas práticas e nos discursos grupais que colaboram no processo de constituição da identidade política do grupo, cujo ápice se deu na organização da Comissão Estadual de Mulheres Trabalhadoras Rurais. Com os dados coletados nos documentos históricos, nas entrevistas individuais semi-estruturadas e no diário de campo, procedeu-se uma análise de conteúdo com base em duas categorias, a saber: estratégias de mobilização e processo de conscientizaçã. Os resultados revelam que a identidade política configura-se, assim, como aquele elemento que, ao mesmo tempo, é possibilitado e constituído no interior do processo mobilizatório e revela-se como elemento mediador da consistência interventiva dos grupos envolvidos na luta, e, nessa medida, promove transformações subjetivas e objetivas tanto em indivíduos particulares como nas diversas esferas da vida cotidiana.

This paper is based on research about rural workwomen’s social movements in Minas Gerais. It focuses on group discourses and practices that collaborated to the process of constitution of the group’s political identity, which culminated in the organization of the Comissão Estadual de Mulheres Trabalhadoras Rurais (StateCommission of Rural Workwomen). Through data collected from historical documents, semi-structured individual interviews and a field diary, a content analysis was made based on two important categories: mobilization strategies and social awareness process.The results show that political identity is a fundamental component of the mobilization process and works as a mediator of the interventive consistency of the groups involved, promoting subjective and objective transformations in daily life at individual and collective levels.