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Perinatal brain injury is a primary cause of cerebral palsy, a condition resulting in life-long motor impairment. Infancy is an important period of motor system development, including development of the corticospinal tract (CST), the primary pathway for cortical movement control. The interaction between perinatal stroke recovery, CST organization, and resultant motor outcome in infants is not well understood. Here, we present a protocol for multimodal longitudinal assessment of brain development and motor function following perinatal brain injury using transcranial magnetic stimulation and magnetic resonance imaging to non-invasively measure CST functional and structural integrity across multiple timepoints in infants 3 to 24 months of age. We will further assess the association between cortical excitability, integrity, and motor function. This protocol will identify bioindicators of motor outcome and neuroplasticity, and subsequently inform early detection, diagnosis, and intervention strategies for infants with perinatal stroke, brain bleeds and related diagnoses.

Introduction: Cardiovascular disease is the most common cause of death among people with non-alcoholic fatty liver disease (NAFLD) and lifestyle changes can improve health outcomes. A NAFLD digital intervention was designed and here we report retention, engagement and satisfaction results in addition to the program's potential clinical impact on markers of liver- and cardiometabolic health. Hypothesis: We assessed the hypothesis that a digital intervention is feasible for individuals with metabolic derangements and NAFLD to improve cardiometabolic health. Methods: A prospective, open label, single arm, 12 week long study was conducted in Iceland.The intervention was delivered through the Sidekick app, with focus on disease education, low carbohydrate diet, increasing activity levels, reducing stress and healthy lifestyle coaching. Individuals with either BMI>30, metabolic syndrome or type 2 diabetes were screened for NAFLD with a FibroScan assessment. Other potential reasons for liver steatosis were excluded. Following recruitment and collection of demographic data, anthropometric and clinical measurements, MRI-PDFF for liver fat content, dual-energy X-ray absorptiometry for body composition and blood tests, were carried out at baseline and after 12 weeks. Primary outcomes were engagement and retention as measured in-app, and user satisfaction (mHealth App Usability Questionnaire); secondary outcomes were changes in weight, liver fat content and other cardiovascular risk factors. Results: In total, 38 individuals were included in the study and 34 (89%) completed the program (defined as being active 9/12 weeks). The median age was 59.5 [IQR 46.0,69.0] years and 23 (60.5%) were females. The median number of active days was 81 [IQR 45.8, 84.0] and the median user satisfaction score was 6.3 out of 7. The mean weight loss was 3.5 kg (SD=3.7) (p Conclusion: This study suggests that a holistic digital intervention may improve liver-specific and cardiometabolic health in individuals with NAFLD, as indicated by the reduction in liver fat, systolic blood pressure and improvements in body composition. Together with the excellent program engagement, completion and satisfaction, this approach could provide a new tool to improve health outcomes in NAFLD.

Introduction: Patients with peripheral artery disease (PAD) are at increased risk for adverse cardiovascular and limb events and impaired quality of life. Lifestyle factors, such as patient physical activity levels and dietary habits, are known risk factors. Limited data is available on the feasibility and efficacy of tailored PAD digital therapeutic programs, focused on improving lifestyle (e.g. physical activity levels, dietary habits, sleep, stress, energy levels) and medication adherence. Hypothesis: We assessed the hypothesis that a digital therapeutic program is feasible among elderly patients with PAD. Methods: Patients were recruited from two vascular surgery specialty clinics in Sweden. Fourteen patients signed informed consent forms and started a four-week intervention based on the first weeks of the SK-111 digital program (Sidekick Health). Questionnaires were administered at baseline and at the end of the intervention. Data on in-app activity was collected throughout the intervention. Results: Out of the 14 patients (8 men, 6 women) who started the intervention, 11 stayed active within the platform from week 1 through 4. The 11 active participants performed a median of 7.1 activities in the app/day (IQR=3.4-12.9) and logged a median number of 4500 steps/day (IQR=2700-6455). The amount of physical activity logged/day went up from a mean of 21 (SD=39) min/day to 33 (SD=54) min/day from week 1 to week 4 (p=0.201). Seven participants (median age=72, IQR=69-73 years) answered both pre and post questionnaires. No changes were observed from pre to post intervention for either the walking distance domain of the Walking Impairment Questionnaire: 22.7 (SD=0.1) and 24.3 (SD=0.1), (p=0.499) or the Vascular Quality of Life Questionnaire sum score: 15.4 (SD=3.2) and 15.6 (SD=3.4), (p=0.864). For the pre-post medication adherence question (“During the last week, did you ever forget to take your PAD medication?” Rated from 0-10), ratings went down from 2.0 (SD=3.6) before to 0.1 (SD=0.4) after intervention (p=0.048). A post-program question asking whether using the platform helped them remember to take their medication, 5/7 (71%) patients considered it helpful. When asked how likely patients would be to recommend the PSP to others, the average score was 83/100. Conclusions: The findings from this feasibility study indicate that a PAD digital therapeutic program is feasible for elderly patients with PAD. A multicenter RCT is currently ongoing, where the clinical effectiveness of the full SK-111 will be further explored in this patient group.

Introduction: Lifestyle and medication adherence are important factors in secondary coronary artery disease (CAD)-prevention. Furthermore, the mind-heart-body connection is gaining recognition in cardiovascular health management. Hypothesis: We assessed the hypothesis that a CAD-specific digital intervention is feasible for outpatient care in terms of program retention, satisfaction, quality of life, symptom frequency and medication adherence. Methods: A four-week CAD-program (SK-121) delivered via a smart phone was designed in collaboration between the National University Hospital of Iceland (NUHI) and Sidekick Health. Patient recruitment took place at NUHI, and program participation consisted of daily health promoting missions assigned within the digital intervention such as watching educational videos, mindfulness exercises, medication reminders and logging quality of life scores. Pre- and post-intervention questionnaires were administered for the Hospital anxiety and depression scale (HADS), Seattle Angina Questionnaire-7 (SAQ-7) and the Morisky medication adherence scale (MMAS-8). Stress-, energy-levels and quality of sleep were logged on a ten-point scale. Participants were interviewed about their program experience. Results: A total of 33 individuals signed informed consent and completed the baseline survey, of which 25 individuals registered in the app (76% males, mean age 60 years [SD=10]). A total of 23 participants logged a mission during the 4-week intervention, five of those were active a single day. A total of 16 (70%) participants completed the program and both pre- and post-surveys (mean age 60 years [SD=10], range 44-80 years). On average participants logged 7.5 missions/day (10.2 for women and 6.6 for men), completing half of daily missions (women 71%, men 47%). Results for average quality of life scores from week one to four were: for energy 5.5[SD=1.8] to 5.8[SD=1.9], p =0.22, for quality of sleep 6.2[SD=2.5] to 5.9[SD=2.4] p =0.20 and for stress 3.3[SD=2.6] to 3.3[SD=2.4] p =0.71.The proportion of the 16 patients who experienced CAD-symptoms in the last four weeks decreased from 56% at baseline to 38% at program completion, p p =0.03.There were slight non-significant decreases in anxiety scores from 4.3 [SD=3.4] to 4.13[SD=2.9] p =0.88 and depression scores from 3.1 [SD=3.3] to 2.8[SD=3.6] p =0.33.User satisfaction was good as 75% of the 16 participants said it was likely that they would recommend the program, that it had a positive effect on their life, well-being and ability to deal with their disease. Conclusions: In conclusion, a CAD-specific digital intervention is feasible in terms of engagement, user satisfaction and improved treatment adherence. An RCT study is being planned to further test the program.

Unbiased transcriptome profiling and functional genomics approaches identified glucocorticoid-induced transcript 1 (GLCCI1) as being a transcript highly specific for the glomerulus, but its role in glomerular development and disease is unknown. Here, we report that mouse glomeruli express far greater amounts of Glcci1 protein compared with the rest of the kidney. RT-PCR and Western blotting demonstrated that mouse glomerular Glcci1 is approximately 60 kD and localizes to the cytoplasm of podocytes in mature glomeruli. In the fetal kidney, intense Glcci1 expression occurs at the capillary-loop stage of glomerular development. Using gene knockdown in zebrafish with morpholinos, morphants lacking Glcci1 function had collapsed glomeruli with foot-process effacement. Permeability studies of the glomerular filtration barrier in these zebrafish morphants demonstrated a disruption of the selective glomerular permeability filter. Taken together, these data suggest that Glcci1 promotes the normal development and maintenance of podocyte structure and function.

To determine whether automated reminders from 2 contemporary personal digital assistant (PDA) devices produce higher rates of timely task completion in people with traumatic brain injury (TBI).Outpatient and community rehabilitation settings.Thirty-six adults aged 18 to 66 years with TBI and self-determined complaints of memory impairment.Timely completion rates for assigned memory tasks under 4 randomly assigned memory aid conditions.Significantly, higher completion rates were found when using either PDA device when compared with a combined baseline and paper memory aid condition (for Palm OS device, Incidence Rate Ratio [IRR] = 2.14, P.0005, CI [confidence interval] = 1.77-2.59; for Microsoft Pocket PC OS device, IRR = 1.47, P.001, CI = 1.18-1.82). A significant difference in completion rates was also found between the 2 PDA devices (IRR = 1.46, P.0005, CI = 1.26-1.70), with the Palm version producing the better scores.Substantially higher rates of task completion (more than double in some cases) when using either PDA device suggest that rehabilitation clinicians can make productive use of PDA-based memory aids in their TBI patient populations. The strength of the effects of PDA device usage argues for further investigation of the impact of device usage on quality-of-life and costs of care, and of personal and caregiver factors predictive of successful and sustained device usage.

Purpose of review The zebrafish pronephros provides an informative vertebrate model system for studying renal development and function as well as a rapid screening tool for identification of genes important to the physiology and pathophysiology of the vertebrate kidney. To this end, the zebrafish pronephros is continuously being characterized and its relevance for the study of human diseases validated. This review summarizes recent advances in our current knowledge of the zebrafish pronephros as a valuable model system relevant to the study of human kidney biology and nephropathology. Recent findings Recent findings argue for conserved renal gene structure and function in the zebrafish pronephros and also elucidate the role of genes in kidney biology that were not possible to discern in other vertebrate model systems due to early lethality. Summary Abnormalities in podocyte gene function, renal ion channels and transporters, and renal epithelial primary cilia genes lead to defective pronephric kidney function in the zebrafish that mimics human disease. This supports the use of the zebrafish pronephros as a valid system to study kidney physiology and for rapid identification of potential therapeutic drugs and strategies in combating renal disease.

The glomerular capillary tuft is a highly specialized microcapillary that is dedicated to function as a sophisticated molecular sieve. The glomerulus filter has a unique molecular composition, and several essential glomerular proteins are expressed in the kidney exclusively by glomerular podocytes. A catalog of >300 glomerulus-upregulated transcripts that were identified using expressed sequence tag profiling and microarray analysis was published recently. This study characterized the expression profile of five glomerulus-upregulated transcripts/proteins (ehd3, dendrin, sh2d4a, plekhh2, and 2310066E14Rik) in detail. The expression pattern of these novel glomerular transcripts in various mouse tissues was studied using reverse transcriptase-PCR, Northern blotting, and in situ hybridization. For studying the distribution of corresponding proteins, polyclonal antibodies were raised against the gene products, and Western blotting, immunofluorescence, and immunoelectron microscopic analyses were performed. Remarkably, it was discovered that all five transcripts/proteins were expressed in the kidney exclusively by glomerular cells. Ehd3 was expressed only by glomerular endothelial cells. Importantly, ehd3 is the first gene ever shown to be expressed exclusively by glomerular endothelial cells and not by other endothelial cells in the kidney. Dendrin, sh2d4a, plekhh2, and 2310066E14Rik, however, were transcribed solely by podocytes. With the use of polyclonal antibodies, dendrin, sh2d4a, and plekhh2 proteins were localized to the slit diaphragm and the foot process, whereas 2310066E14Rik protein was localized to the podocyte major processes and cell body. This study provides fresh insights into glomerular biology and uncovers new possibilities to explore the role of these novel proteins in the glomerular physiology and pathology.