Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2.

We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.

Effects of Hand Motor Interventions on Cognitive Outcomes Post-stroke: A Systematic Review and Bayesian Network Meta-analysis.

OBJECTIVE: To synthetize the evidence on the effects of hand rehabilitation (RHB) interventions on cognition post-stroke and compare their efficacy. DATA SOURCES: PubMed, Embase, Cochrane, Scopus, Web of Science, and CINAHL were searched from inception to November 2022. DATA SELECTION: Randomized controlled trials conducted in adults with stroke where the effects of hand motor interventions on any cognitive domains were assessed. DATA EXTRACTION: Data were extracted by 2 independent reviewers. A Bayesian Network Meta-analysis (NMA) was applied for measures with enough studies and comparisons. Risk of bias was assessed with the Cochrane Risk of Bias tool. DATA SYNTHESIS: Fifteen studies were included in qualitative synthesis, and 11 in NMA. Virtual reality (VR) (n=7), robot-assisted (n=5), or handgrip strength (n=3) training were the experimental interventions and conventional RHB (n=14) control intervention. Two separate NMA were performed with MoCA (n=480 participants) and MMSE (n=350 participants) as outcome measures. Both coincided that the most probable best interventions were robot-assisted and strength training, according to SUCRA and rankogram, followed by conventional RHB and VR training. No significant differences between any of the treatments were found in the MoCA network, but in the MMSE, robot-assisted and strength training were significantly better than conventional RHB and VR. No significant differences between robot-assisted and strength training were found nor between conventional RHB and VR. CONCLUSIONS: Motor interventions can improve MoCA/MMSE scores post-stroke. Most probable best interventions were robot-assisted and strength training. Limited literature assessing domain-specific cognitive effects was found.

Macro level system mapping of the provision of mental health services to young people living in a conflict context in Colombia.

Colombia has one of the longest running internal armed conflicts, which has significantly impacted the mental health of the population. This article is the first to present a national level mapping of the provision of mental health services to young people living in Colombia, through detailed review of documentation, interviews with key stakeholders and quantitative analysis of existing data on mental health and suicide. It explores the existing public mental health provision in the country, focussing on where mental health resources are concentrated and how these are implemented. We use this mapping to understand how the current mental health system in Colombia fits with international approaches to youth mental health. We show that whilst mental health policy is variously framed (biomedical, biosocial, psychologically or through human rights), Colombian policy clearly focusses on a differential approach. This differential approach shapes service provision to target support at those in need, consequently neglecting whole population level mental health support. This means that not all stakeholders were clearly articulated or included in policy and that key institutional stakeholders, such as the education sector, were not linked to implementation plans or activity. Policy approaches were also over-centralised with little cross-institutional collaboration. Youth were specifically missing from services, as was explicit understanding of the intergenerational effects and impact of conflict. This was exacerbated by unequal distribution of mental health care services concentrated in populous, urban areas away from conflict-affected regions. Suicide is the second most prevalent cause of death with 10% of population who were recorded as dying by violence, dying from completed suicide. Triangulation implies a strong relationship between suicide and poorer access to professional support in conflict-affected areas and suggests that international frameworks and policy approaches to supporting youth mental health have been insufficiently adapted for conflict and post conflict contexts.

The emotional management of death and absence by forensic anthropologists in Colombia and Peru.

This article analyzes the experiences of seven forensic anthropologists working on exhumations in cases related to political violence and armed conflict in Colombia and Peru. From a critical social psychology perspective, we investigate the ways in which these professionals manage their emotions in the face of situations of violence, including murder, massacres, and enforced disappearances. We analyze both the emotional impact of confronting mass violence and the coping mechanisms developed by these professionals in order to continue doing their work. The experiences recounted by the forensic anthropologists interviewed for this study oscillate between a marked professional commitment and the need for distance to safeguard their own emotional well-being.

A unilateral robotic knee exoskeleton to assess the role of natural gait assistance in hemiparetic patients.

BACKGROUND: Hemiparetic gait is characterized by strong asymmetries that can severely affect the quality of life of stroke survivors. This type of asymmetry is due to motor deficits in the paretic leg and the resulting compensations in the nonparetic limb. In this study, we aimed to evaluate the effect of actively promoting gait symmetry in hemiparetic patients by assessing the behavior of both paretic and nonparetic lower limbs. This paper introduces the design and validation of the REFLEX prototype, a unilateral active knee-ankle-foot orthosis designed and developed to naturally assist the paretic limbs of hemiparetic patients during gait. METHODS: REFLEX uses an adaptive frequency oscillator to estimate the continuous gait phase of the nonparetic limb. Based on this estimation, the device synchronically assists the paretic leg following two different control strategies: (1) replicating the movement of the nonparetic leg or (2) inducing a healthy gait pattern for the paretic leg. Technical validation of the system was implemented on three healthy subjects, while the effect of the generated assistance was assessed in three stroke patients. The effects of this assistance were evaluated in terms of interlimb symmetry with respect to spatiotemporal gait parameters such as step length or time, as well as the similarity between the joint's motion in both legs. RESULTS: Preliminary results proved the feasibility of the REFLEX prototype to assist gait by reinforcing symmetry. They also pointed out that the assistance of the paretic leg resulted in a decrease in the compensatory strategies developed by the nonparetic limb to achieve a functional gait. Notably, better results were attained when the assistance was provided according to a standard healthy pattern, which initially might suppose a lower symmetry but enabled a healthier evolution of the motion of the nonparetic limb. CONCLUSIONS: This work presents the preliminary validation of the REFLEX prototype, a unilateral knee exoskeleton for gait assistance in hemiparetic patients. The experimental results indicate that assisting the paretic leg of a hemiparetic patient based on the movement of their nonparetic leg is a valuable strategy for reducing the compensatory mechanisms developed by the nonparetic limb.

Cognitive rehabilitation in a case of traumatic brain injury using EEG-based neurofeedback in comparison to conventional methods.

Severe traumatic brain injury residual cognitive impairments significantly impact the quality of life. EEG-based neurofeedback is a technique successfully used in traumatic brain injury and stroke to rehabilitate cognitive and motor sequelae. There are not individualized comparisons of the effects of EEG-based neurofeedback versus conventional neuropsychological rehabilitation. We present a case study of a traumatic brain injury subject in whom eight sessions of a neuropsychological rehabilitation protocol targeting attention, executive functions, and working memory as compared with a personalized EEG-based neurofeedback protocol focused on the electrodes and bands that differed from healthy subjects (F3, F1, Fz, FC3, FC1, and FCz), targeting the inhibition of theta frequency band (3 Hz-7 Hz) in the same number of sessions. Quantitative EEG and neuropsychological testing were performed. Clear benefits of EEG-based neurofeedback were found in divided and sustained attention and several aspects related to visuospatial skills and the processing speed of motor-dependent tasks. Correlative quantitative EEG changes justify the results. EEG-based neurofeedback is probably an excellent complementary technique to be considered to enhance conventional neuropsychological rehabilitation.

Wearable Technology to Detect Motor Fluctuations in Parkinson's Disease Patients: Current State and Challenges.

Monitoring of motor symptom fluctuations in Parkinson's disease (PD) patients is currently performed through the subjective self-assessment of patients. Clinicians require reliable information about a fluctuation's occurrence to enable a precise treatment rescheduling and dosing adjustment. In this review, we analyzed the utilization of sensors for identifying motor fluctuations in PD patients and the application of machine learning techniques to detect fluctuations. The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ten studies were included between January 2010 and March 2021, and their main characteristics and results were assessed and documented. Five studies utilized daily activities to collect the data, four used concrete scenarios executing specific activities to gather the data, and only one utilized a combination of both situations. The accuracy for classification was 83.56-96.77%. In the studies evaluated, it was not possible to find a standard cleaning protocol for the signal captured, and there is significant heterogeneity in the models utilized and in the different features introduced in the models (using spatiotemporal characteristics, frequential characteristics, or both). The two most influential factors in the good performance of the classification problem are the type of features utilized and the type of model.

Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson's Disease: Study Protocol for a Randomized Controlled Trial.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson's. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.

Clinical Effects of Immersive Multimodal BCI-VR Training after Bilateral Neuromodulation with rTMS on Upper Limb Motor Recovery after Stroke. A Study Protocol for a Randomized Controlled Trial.

Background and Objectives: The motor sequelae after a stroke are frequently persistent and cause a high degree of disability. Cortical ischemic or hemorrhagic strokes affecting the cortico-spinal pathways are known to cause a reduction of cortical excitability in the lesioned area not only for the local connectivity impairment but also due to a contralateral hemisphere inhibitory action. Non-invasive brain stimulation using high frequency repetitive magnetic transcranial stimulation (rTMS) over the lesioned hemisphere and contralateral cortical inhibition using low-frequency rTMS have been shown to increase the excitability of the lesioned hemisphere. Mental representation techniques, neurofeedback, and virtual reality have also been shown to increase cortical excitability and complement conventional rehabilitation. Materials and Methods: We aim to carry out a single-blind, randomized, controlled trial aiming to study the efficacy of immersive multimodal Brain-Computer Interfacing-Virtual Reality (BCI-VR) training after bilateral neuromodulation with rTMS on upper limb motor recovery after subacute stroke (>3 months) compared to neuromodulation combined with conventional motor imagery tasks. This study will include 42 subjects in a randomized controlled trial design. The main expected outcomes are changes in the Motricity Index of the Arm (MI), dynamometry of the upper limb, score according to Fugl-Meyer for upper limb (FMA-UE), and changes in the Stroke Impact Scale (SIS). The evaluation will be carried out before the intervention, after each intervention and 15 days after the last session. Conclusions: This trial will show the additive value of VR immersive motor imagery as an adjuvant therapy combined with a known effective neuromodulation approach opening new perspectives for clinical rehabilitation protocols.

Computerized Simple Reaction Time and Balance in Nondemented Parkinson's Patients.

BACKGROUND: Parkinson's disease (PD) patients are known to suffer from subtle cognitive and balance deficits from the early stages although they usually manifest in advanced stages. Postural instability (PI) has been correlated with slower information processing speed. Simple reaction time (SRT) tasks can be used to measure the speed of information processing. The main objective of this study was to examine the usefulness of SRT as a valid predictor of balance in PD, thus providing a simple and complementary assessment method. METHODS: This cross-sectional study included 52 PD patients without dementia who were evaluated for balance using the pull test (PT) maneuver and Biodex® limits of stability (LOS). In addition, a reaction time task was used to measure processing speed. Correlation and linear regression analyses were performed. RESULTS: The performance of SRT tasks was correlated with the evaluation of LOS% and PT, suggesting that the SRT may be a predictor of balance performance. Longer reaction time and poorer postural stability were also associated with disease duration but not with age. CONCLUSIONS: Poor performance in a simple reaction task can predict altered PI and can complement staging and evaluation in PD patients.

Translation and cross-cultural adaptation of the Spanish version of the King's Parkinson's Disease Pain Scale (KPPS).

PURPOSE: To translate and cross-culturally adapt the King's Parkinson's Disease Pain Scale (KPPS) into Spanish. METHODS: The English KPPS was forward translated into Spanish, back translated, and revised by the original developers. Cross-cultural adaptation of relevant target groups was conducted following COSMIN standards. Cognitive pretesting in Spanish people with Parkinson's Disease (PD) and pain was performed via three semi-structured focus group meetings. Changes were implemented based on qualitative and quantitative analyses. A Delphi study (two rounds) of individual assessments by Spanish experts was conducted. Changes were implemented based on the Content Validity Index (CVI) at item and scale levels (I-CVI/S-CVI). RESULTS: Five Spanish professionals performed the initial translation. Thirty-eight inter-translation inconsistencies were identified, and consensus was reached for a unified version. After back translation and confirmation with scale developers, the pre-final Spanish KPPS was obtained. Cognitive pretesting in 30 people with PD-related pain identified 5 items where terminology changes were made to assure comprehensibility. The Delphi study in 14 Spanish experts underlined the necessity to further modify two items. After the second round, all experts agreed on the modifications and I-CVI and S-CVI were satisfactory. CONCLUSIONS: The KPPS was successfully translated and cross-culturally adapted into Spanish.

The King's Parkinson's Disease Pain Scale (KPPS) was translated into Spanish by 5 independent experts.Cross-cultural validity was assessed by Spanish Parkinson's Disease (PD) patients and neurology experts.The Spanish KPPS adaptation was relevant, understandable, and comprehensive.Rehabilitation professionals will have access to the Spanish KPPS version for assessing PD-related pain in Spanish speaking patients.

Combined non-invasive neuromodulation using transcranial direct current stimulation, motor imagery and action observation for motor, cognitive and functional recovery in cortico-basal degeneration: a single case study.

This case report presents a comprehensive assessment and therapeutic intervention using non-invasive motor cortex neuromodulation for a 70-year-old female patient diagnosed with corticobasal degeneration (CBD). The study followed the CARE guidelines. The patient meets the criteria for probable CBD, with neuroimaging evidence of exclusively cortical impairment. The patient underwent a non-invasive neuromodulation protocol involving transcranial direct current stimulation (tDCS) and action observation plus motor imagery (AO+MI). The neuromodulation protocol comprised 20 sessions involving tDCS over the primary motor cortex and combined AO+MI. Anodal tDCS was delivered a 2 mA excitatory current for 20 minutes. AO+MI focused on lower limb movements, progressing over four weeks with video observation and gradual execution, both weekly and monthly. The neuromodulation techniques were delivered online (i.e. applied simultaneously in each session). Outcome measures were obtained at baseline, post-intervention and follow-up (1 month later), and included motor (lower limb), cognitive/neuropsychological and functional assessments. Walking speed improvements were not observed, but balance (Berg Balance Scale) and functional strength (Five Times Sit-to-Stand Test) improved post-treatment. Long-term enhancements in attentional set-shifting, inhibitory control, verbal attentional span, and working memory were found. There was neurophysiological evidence of diminished intracortical inhibition. Functional changes included worsening in Cortico Basal Ganglia Functional Scale score. Emotional well-being and general health (SF-36) increased immediately after treatment but were not sustained, while Falls Efficacy Scale International showed only long-term improvement. The findings suggest potential benefits of the presented neuromodulation protocol for CBD patients, highlighting multifaceted outcomes in motor, cognitive, and functional domains.

TDCS for parkinson's disease disease-related pain: A randomized trial.

OBJECTIVE: To evaluate the effects of transcranial direct current stimulation (tDCS) on Parkinson's disease (PD)-related pain. METHODS: This triple-blind randomized controlled trial included twenty-two patients (age range 38-85, 10 male) with PD-related pain. Eleven subjects received ten sessions of 20 minutes tDCS over the primary motor cortex contralateral to pain at 2 mA intensity. Eleven subjects received sham stimulation. Outcome measures included changes in the Kinǵs Parkinsons Pain Scale (KPPS), Brief Pain Inventory (BPI), widespread mechanical hyperalgesia (WMH), temporal summation of pain (TS), and conditioned pain modulation (CPM). RESULTS: Significant differences were found in KPPS between groups favoring the active-tDCS group compared to the sham-tDCS group at 15-days follow-up (p = 0.014) but not at 2 days post-intervention (p = 0.059). The active-group showed significant improvements over the sham-group after 15 days (p = 0.017). Significant changes were found in CPM between groups in favor of active-tDCS group at 2 days post-intervention (p = 0.002) and at 15 days (p = 0.017). No meaningful differences were observed in BPI or TS. CONCLUSIONS: tDCS of the primary motor cortex alleviates perceived PD-related pain, reduces pain sensitization, and enhances descending pain inhibition. SIGNIFICANCE: This is the first study to test and demonstrate the use of tDCS for improving PD-related pain.

Effects of motor imagery-based neurofeedback training after bilateral repetitive transcranial magnetic stimulation on post-stroke upper limb motor function: an exploratory crossover clinical trial.

OBJECTIVE: To examine the clinical effects of combining motor imagery-based neurofeedback training with bilateral repetitive transcranial magnetic stimulation for upper limb motor function in subacute and chronic stroke. DESIGN: Clinical trial following an AB/BA crossover design with counterbalanced assignment. SUBJECTS: Twenty individuals with subacute (n = 4) or chronic stroke (n = 16). METHODS: Ten consecutive sessions of bilateral repetitive transcranial magnetic stimulation alone (therapy A) were compared vs a combination of10 consecutive sessions of bilateral repetitive transcranial magnetic stimulation with 12 non-consecutive sessions of motor imagery-based neurofeedback training (therapy B). Patients received both therapies (1-month washout period), in sequence AB or BA. Participants were assessed before and after each therapy and at 15-days follow-up, using the Fugl-Meyer Assessment-upper limb, hand-grip strength, and the Nottingham Sensory Assessment as primary outcome measures. RESULTS: Both therapies resulted in improved functionality and sensory function. Therapy B consistently exhibited superior effects compared with therapy A, according to Fugl-Meyer Assessment and tactile and kinaesthetic sensory function across multiple time-points, irrespective of treatment sequence. No statistically significant differences between therapies were found for hand-grip strength. CONCLUSION: Following subacute and chronic stroke, integrating bilateral repetitive transcranial magnetic stimulation and motor imagery-based neurofeedback training has the potential to enhance functional performance compared with using bilateral repetitive transcranial magnetic stimulation alone in upper limb recovery.

AMBER: A Device for Hand Motor and Cognitive Rehabilitation-Development and Proof of Concept.

Stroke survivors usually exhibit concurrent motor and cognitive impairment. Historically, rehabilitation strategies post-stroke occur separately in terms of motor and cognitive functions. However, recent studies show that hand motor interventions can have a positive impact on cognitive recovery. In this work, we introduce AMBER (portAble and Modular device for comprehensive Brain Evaluation and Rehabilitation), a new device developed for the evaluation and rehabilitation of both hand motor function and cognition simultaneously. AMBER is a simple, portable, ergonomic and cheap device based on Force Sensitive Resistors, in which every finger interaction is recorded to provide information about finger strength, processing speed, and memory status. This paper presents the requirements of the device and the design of the system. In addition, a pilot study was conducted with 36 healthy individuals using the evaluation module of the device to assess its psychometric properties, as test-retest reliability and measurement error. Its validity was also evaluated comparing its measurements with three different gold standards for strength, processing speed and memory. The device showed good test-retest reliability for strength (ICC =0.741-0.852), reaction time (ICC =0.715 - 0.900) and memory (ICC =0.556-0.885). These measures were correlated with their corresponding gold standards (r =0.780-890). AMBER shows great potential to impact hand rehabilitation, offering therapists a valid, reliable and versatile tool to comprehensively assess patients. With ongoing advancements and refinements, it has the opportunity to significantly impact rehabilitation practices and improve patient outcomes.

Robotic exoskeleton embodiment in post-stroke hemiparetic patients: an experimental study about the integration of the assistance provided by the REFLEX knee exoskeleton.

Hemiparetic gait is the most common motor-disorder after stroke and, in spite of rehabilitation efforts, it is persistent in 50% of community dwelling stroke-survivors. Robotic exoskeletons have been proposed as assistive devices to support impaired joints. An example of these devices is the REFLEX knee exoskeleton, which assists the gait of hemiparetic subjects and whose action seems to be properly embodied by stroke survivors, who were able to adapt the motion of their non-assisted limbs and, therefore, reduce their compensation mechanisms. This paper presents an experimental validation carried out to deepen into the effects of REFLEX's assistance in hemiparetic subjects. Special attention was paid to the effect produced in the muscular activity as a metric to evaluate the embodiment of this technology. Significant differences were obtained at the subject level due to the assistance; however, the high dispersion of the measured outcomes avoided extracting global effects at the group level. These results highlight the need of individually tailoring the action of the robot to the individual needs of each patient to maximize the beneficial outcomes. Extra research effort should be done to elucidate the neural mechanisms involved in the embodiment of external devices by stroke survivors.

Mapping Essential Tremor to a Common Brain Network Using Functional Connectivity Analysis.

BACKGROUND AND OBJECTIVES: The cerebello-thalamo-cortical circuit plays a critical role in essential tremor (ET). However, abnormalities have been reported in multiple brain regions outside this circuit, leading to inconsistent characterization of ET pathophysiology. Here, we test whether these mixed findings in ET localize to a common functional network and whether this network has therapeutic relevance. METHODS: We conducted a systematic literature search to identify studies reporting structural or metabolic brain abnormalities in ET. We then used 'coordinate network mapping,' which leverages a normative connectome (n = 1,000) of resting-state fMRI data to identify regions commonly connected to findings across all studies. To assess whether these regions may be relevant for the treatment of ET, we compared our network with a therapeutic network derived from lesions that relieved ET. Finally, we investigated whether the functional connectivity of this ET symptom network is abnormal in an independent cohort of patients with ET as compared with healthy controls. RESULTS: Structural and metabolic brain abnormalities in ET were located in heterogeneous regions throughout the brain. However, these coordinates were connected to a common functional brain network, including the cerebellum, thalamus, motor cortex, precuneus, inferior parietal lobe, and insula. The cerebellum was identified as the hub of this network because it was the only brain region that was both functionally connected to the findings of over 90% of studies and significantly different in connectivity compared with a control data set of other movement disorders. This network was strikingly similar to the therapeutic network derived from lesions improving ET, with key regions aligning in the thalamus and cerebellum. Furthermore, positive functional connectivity between the cerebellar network hub and the sensorimotor cortices was significantly reduced in patients with ET compared with healthy controls, and connectivity within this network was correlated with tremor severity and cognitive functioning. DISCUSSION: These findings suggest that the cerebellum is the central hub of a network commonly connected to structural and metabolic abnormalities in ET. This network may have therapeutic utility in refining and informing new targets for neuromodulation of ET.

Revealing cell populations catching the early stages of human embryo development in naive pluripotent stem cell cultures.

Naive human pluripotent stem cells (hPSCs) are defined as the in vitro counterpart of the human preimplantation embryo's epiblast and are used as a model system to study developmental processes. In this study, we report the discovery and characterization of distinct cell populations coexisting with epiblast-like cells in 5iLAF naive human induced PSC (hiPSC) cultures. It is noteworthy that these populations closely resemble different cell types of the human embryo at early developmental stages. While epiblast-like cells represent the main cell population, interestingly we detect a cell population with gene and transposable element expression profile closely resembling the totipotent eight-cell (8C)-stage human embryo, and three cell populations analogous to trophectoderm cells at different stages of their maturation process: transition, early, and mature stages. Moreover, we reveal the presence of cells resembling primitive endoderm. Thus, 5iLAF naive hiPSC cultures provide an excellent opportunity to model the earliest events of human embryogenesis, from the 8C stage to the peri-implantation period.

A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.

It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism.

Components determining the slowness of information processing in parkinson's disease.

INTRODUCTION: Bradyphrenia is a key cognitive feature in Parkinson's disease (PD). There is no consensus on whether information processing speed is impaired or not beyond motor performance. OBJECTIVE: This study aims to explore which perceptual, motor, or cognitive components of information processing are involved in the slowdown affecting cognitive performance. METHODS: The study included 48 patients with PD (age: 63, 3 ± 8, 18; HY I-III; UPDRS 15,46 ± 7,76) and 53 healthy controls (age: 60,09 ± 12,83). Five reaction time (RT) tasks were administered to all participants. The average RT in each of the tasks and the percentage of correct answers were measured. Patients with PD were in "ON state" at the time of the evaluation. Perceptual, motor, and cognitive components were isolated by means of a series of ANCOVAs. RESULTS: As expected, the motor component was slowed down in patients with PD. Moreover, while patients with PD showed slower RT than controls in all tasks, differences between groups did not exponentially increase with the increasing task complexity. ANCOVA analyses also revealed that the perceptual and sustained alert component resulted to be slowed down, with no differences being found in any of the remaining isolated cognitive components (i.e., response strategy-inhibition, decisional, visual search, or interference control). CONCLUSIONS: The results revealed that slowness of information processing in PD was mainly associated with an impaired processing speed of the motor and perceptual-alertness components analyzed. The results may help designing new neurorehabilitation strategies, focusing on the improvement of perceptual and alertness mechanisms.