Polaris Research Articles

The NCCB Case Example: Reflections on a Successful Fourteen-Year CBPR Partnership

The Newark Community Collaborative Board (NCCB) is in its fourteenth year of operation with nine successful research projects and more than six million dollars in funding. The NCCB began with a community needs assessment in Newark, New Jersey, that led to the subsequent establishment of a community collaborative board (CCB) of consumers, researchers, service providers, and residents committed to advocating for health equity through community engagement and research informed by critical thinking. This paper explores the NCCB’s history and processes that allowed conducting community-based participatory research (CBPR) to reduce inequities related to social determinants of health (SDH). This conceptual manuscript draws on data from NCCB meeting minutes and a group interview with three of the five founding members. We detail the collaborative process used to develop and assess Community Wise, a multilevel, group-based intervention designed to reduce substance use among formerly incarcerated men in Newark, funded by the National Institutes of Health. Review of documentation and interview transcripts revealed the following key ingredients for success: 1) Having a north star; 2) Functional diversity; 3) Challenges as learning opportunities; 4) Board structure and healthy relationships; and 5) Funding and resources. The NCCB has undergone multiple transformations, including a name change to the New Jersey Critical Consciousness Collaborative Board (NJ-3CB), representing its growth from being a small local board to becoming part of a network of community collaborative boards across the United States and a chapter of the global campaign against racism. These and future transitions will help sustain the collaborative journey.

Finding a North Star: Lessons in space law for the Nuclear Regime

Finding a North Star: Lessons in space law for the Nuclear Regime

High-Resolution Iodine-Enhanced Micro-Computed Tomography of Intact Human Hearts for Detailed Coronary Microvasculature Analyses.

Identifying the detailed anatomies of the coronary microvasculature remains an area of research; one needs to develop methods for non-destructive, high-resolution, three-dimensional imaging of these vessels for computational modeling. Currently employed Micro-Computed Tomography (Micro-CT) protocols for vasa vasorum analyses require organ dissection and, in most cases, non-clearable contrast agents. Here, we describe a method developed for a non-destructive, economical means to achieve high-resolution images of the human coronary microvasculature without organ dissection. Formalin-fixed human hearts were cannulated using venogram balloon catheters, which were then fixed into the specimen's aortic root. The canulated hearts, protected by a polyethylene bag, were placed in radiolucent containers filled with insulating polyurethane foam to reduce movement. For vasculature staining, iodine potassium iodide (IKI, Lugol's solution; 6.3% Potassium Iodide, 4.1% Iodide) was injected. Contrast distributions were monitored using a North Star Imaging X3000 micro-CT scanner with low-radiation settings, followed by high-radiation scanning (3600 rad, 60 kV, 900 mA) for the final high-resolution imaging. We successfully imaged four intact human hearts presenting with chronic total coronary occlusions of the right coronary artery. This imaging enabled detailed analyses of the vasa vasorum surrounding stenosed and occluded segments. After imaging, the hearts were cleared of iodine and excess polyurethane foam and returned to their initial formalin-fixed state for indefinite storage. Conclusions: the described methodologies allow for the non-destructive, high-resolution micro-CT imaging of coronary microvasculature in intact human hearts, paving the way for detailed computational 3D microvascular reconstructions with a macrovascular context.

Meaningful changes in motor function in Duchenne muscular dystrophy (DMD): A multi-center study.

Evaluations of treatment efficacy in Duchenne muscular dystrophy (DMD), a rare genetic disease that results in progressive muscle wasting, require an understanding of the 'meaningfulness' of changes in functional measures. We estimated the minimal detectable change (MDC) for selected motor function measures in ambulatory DMD, i.e., the minimal degree of measured change needed to be confident that true underlying change has occurred rather than transient variation or measurement error. MDC estimates were compared across multiple data sources, representing >1000 DMD patients in clinical trials and real-world clinical practice settings. Included patients were ambulatory, aged ≥4 to <18 years and receiving steroids. Minimal clinically important differences (MCIDs) for worsening were also estimated. Estimated MDC thresholds for >80% confidence in true change were 2.8 units for the North Star Ambulatory Assessment (NSAA) total score, 1.3 seconds for the 4-stair climb (4SC) completion time, 0.36 stairs/second for 4SC velocity and 36.3 meters for the 6-minute walk distance (6MWD). MDC estimates were similar across clinical trial and real-world data sources, and tended to be slightly larger than MCIDs for these measures. The identified thresholds can be used to inform endpoint definitions, or as benchmarks for monitoring individual changes in motor function in ambulatory DMD.

تحديد عائد الاستثمارات الأمنية للشركات التقنية الناشئة

تعتبر الشركات الناشئة في مجال التكنولوجيا بالغة الأهمية في النهوض بالمبادرات الرقمية في العديد من البلدان التي تخضع لأجندة الدولة الذكية. وبالتالي ، فإن الشركات الناشئة في مجال التكنولوجيا هي بائعون وموردون للخدمات للمنظمات الكبيرة مثل القطاع الحكومي والشركات متعددة الجنسيات والمؤسسات المالية. على هذا النحو ، أصبحت الشركات الناشئة سريعًا نواقل هجوم للجناة الخبثاء للدخول عبر الأبواب الخلفية إلى المؤسسات الكبيرة. ومع ذلك ، لا تزال الشركات الناشئة حكيمة في إنفاقها على الأمن السيبراني لأن نجمها الشمالي هو توليد الإيرادات من خلال تقديم خدماتها والحد الأدنى من المنتجات القابلة للتطبيق (MVP) لعملائها. تقترح هذه الدراسة عائدًا معززًا على الاستثمار الأمني (ROSI) والذي يساعد الشركات الناشئة في مجال التكنولوجيا على حساب العائد على الاستثمار الأمني وتبرير ميزانيتها للإنفاق على الأمن السيبراني على الرغم من وجود نماذج حالية لحساب عائد الاستثمارات المخصصة لنفقات الأمن السيبراني ، إلا أنها معقدة نوعًا ما ولا تعطي وضوحًا للإدارة من حيث القيمة النقدية للإنفاق على الأمن السيبراني. علاوة على ذلك ، لا تلبي النماذج الحالية ديناميكيات وفروق الشركات الناشئة في مجال التكنولوجيا. يوفر النموذج المحسّن أيضًا للشركات الناشئة في مجال التكنولوجيا القدرة على تعديل استثماراتها في مجال الأمن السيبراني بشكل مناسب بناءً على حسابات قيم الحد الأدنى (الأدنى) والحد الأقصى (الأقصى) لمؤشر ROSI. تم التحقق من صحة نموذج ROSI المقترح والمحسّن من قبل 5 من خبراء الأمن السيبراني الذين اتفقوا على أهمية وضرورة النموذج الذي سيتم تطبيقه على الشركات الناشئة في مجال التكنولوجيا. تتيح نتائج دراسة الحالة الخاصة بشركة FinTech الناشئة حساب Min و Max ROSI لتبرير العائد على الاستثمارات الأمنية وتزويد الشركة الناشئة بالقدرة على ضبط الإنفاق على الأمن السيبراني وفقًا لذلك.

WITHIN THESE FOUR WALLS: THE PERILOUSNESS OF ELUSIVE GUARD RAILS AND IMPERMANENCE OF SAFETY

Cognition for better or worse does appear to reside at the feet of spatiality, which in turn constitutes one of the more ossified keystones of reality-carving perception mechanisms the humanoid-coded cohort is invariably endowed with, and it bears repeating that this constellation of epistemic mechanics abides in no small measure owing to societal and culturally-tinted mores incessantly reiterated to the brink of relegation to a metanoia contrived in a borderline ad nauseum fashion. Therein lies the hindrance to one-to-one or at the very least easily elicited correspondence in the transposition and limpid demarcation between structurally inherited and transgenerationally mooted and affirmed cognitive devices garnered from a relatively unbiased source and telegraphed with a gloss of fear into a more pliant and individuated target domain. The unremitting character of moulding an intertextual and ostensibly erroneous meaning-sensitive system is equal parts the north star and a murky nor’easter blanketing the way forward and out. The paper, notwithstanding said constraints, posits an amalgamated theoretical and analytical matrix attuned to the “what works principle” and at the same intent lays the groundwork for a dry-run approach to decipherment at large. This hybridised analytical tool is provisionally put on a metaphorical beta blocker and remains to be further expatiated on and deployed in force on a more comprehensive corpus, however the paper shines a light on cognition, culture and along with grammaring as the “fifth” skill and brings it into synchronous orbit. It would not be misleading to say that this is a spark plug teasing an upcoming in-depth volume. It follows that since the unequivocal assertions concerning cultural and cognitive negotiations populating the domain at the heart of both cogitation and consequent meaningful and workable output show no signs of abating, this zetetic line ought to be further pursued and hopefully illuminated. The propositions were put to the test in an empirically attested and cogently targeted sample study of media-propelled and licenced messaging armature. Last and by no means least, this analytical amalgam seeks to broach the through line of safety, health and wellbeing perpendicular to the shielding tools meant to safeguard their sustained preservation.

Instead of with a rowboat, search for the north star by navigating a sailboat through turbulent times

AbstractWe respond to von Schnurbein and Ahmad's (2019) metaphor of rowing to elucidate the inflexibility of foundations. We suggest that perhaps a sailboat would be more appropriate to finding the north star and add a fifth proposition: a participatory decision‐making process that includes balanced feedback. This approach, though not new, can pose risks such as misaligned priorities and ineffective decisions. To navigate these challenges, the introduction of a "court jester" role is proposed, encouraging open dialogue and critical self‐reflection. The flexibility akin to sailing, where adjustments are made based on feedback, is advocated for effective and dynamic foundation governance.

Appendicular lean mass index and motor function in ambulatory patients with Duchenne muscular dystrophy.

Appendicular lean mass index (ALMI) has been linked to motor function in patients with Duchenne muscular dystrophy (DMD). However, quantification of the relationship between ALMI and disease-specific clinical outcome assessment trajectories is needed. The purpose of this study was to determine associations between dual-energy x-ray absorptiometry (DXA) derived estimates of ALMI and motor function in ambulatory patients with DMD. A retrospective analysis of longitudinal clinical visit data from 137 glucocorticoid-treated patients with DMD collected via structured motor assessment protocol evaluated associations between ALMI and motor function indexed by the North Star Ambulatory Assessment (NSAA) and 10 Meter Walk/run Test (10MWT). Body composition was assessed using DXA. ALMI was calculated by dividing arm and leg lean mass by height in m2; fat mass index (FMI) was calculated by dividing whole body fat mass by height in m2. Linear mixed-effects models were used to estimate associations between ALMI and motor function, controlling for age and FMI. The full prediction model (age, age,2 ALMI, and FMI) explained 57% of the variance in NSAA scores and 63% of the variance in 10MWT speed. A 1 kg/m2 higher ALMI value predicted a 5.4-point higher NSAA score (p < .001) and 0.45 m/s faster 10MWT speed (p < .001). A 1 kg/m2 higher FMI value predicted a 1.5-point lower NSAA score (p < .001) and 0.14 meters/second slower 10MWT speed (p < .001). DXA-derived estimates of ALMI and FMI are associated with motor function in DMD and may explain variation in DMD disease progression.

Neighbours under the North Star: Civil wars in Finland and Korea

The article has two objectives. The first one is to advance the existing studies on civil wars by developing a comparative approach. It explores similarities and differences between the Finnish and Korean experiences. The broader objective of the article is to initiate a project to explore potential connections between the Nordic region and the Korean peninsula. There are various direct and indirect linkages between the Nordic countries and Korea. Finland had long been part of Sweden and then part of Russia. Finland achieved independence, but it was immediately overshadowed by the war. Korea had long been influenced heavily by China and then colonised by Japan. Independence brought sunshine on the peninsula, but it soon disappeared with the Korean War. Against this backdrop, the article investigates the civil wars in Finland and Korea. In order to go beyond the existing research, the article pays attention to popular culture (film) depicting the two wars. The article also sheds light on how Finland and Korea have tried to pave the way to reconciliation. If the war still divides Finland even after 100 years, the reconciliation process in Korea would be much more complex and difficult.

Clinical validation of Northstar Select, a novel liquid biopsy assay for comprehensive genomic profiling of solid tumors.

3072 Background: Comprehensive Genomic Profiling (CGP) liquid biopsy tests are vital tools for oncologists that enable the non-invasive detection of diverse somatic mutations, many of which correspond to targeted therapies, in circulating tumor DNA (ctDNA). However, these tests have less utility when ctDNA signal is low, which is common even in late-stage cancer patients. BillionToOne’s Northstar (NS) Select assay is a novel CGP test that seeks to leverage proprietary technology and novel calling algorithms to address this limitation by achieving higher sensitivity. Methods: Clinical samples for 182 unique patients with stage III or IV solid tumors were obtained via a prospective validation study assessing head-to-head concordance with widely adopted, commercially available ‘comparator’ liquid biopsy CGP assays. The study cohort was recruited from 1 large hospital center and 6 community clinics across the US and was diverse in patient demographics and clinical presentations. Over 15 different cancer types were represented in the cohort, with the majority of patients having either Lung, Breast, Colorectal, or Prostate cancer, all of which are commonly tested using liquid biopsies in the US. Pathogenic (including likely pathogenic) variants called by NS Select and/or the comparator assay were analyzed for concordance. For a subset of samples (N=28), white blood cell-derived genomic DNA was also processed to identify which variants were detected due to clonal hematopoiesis of indeterminate potential (CHIP). Results: In the head-to-head comparison, a large number of variants (N=380) were concordant between the two assays. In addition, NS Select detected 43% (N=147) more pathogenic variants than comparators when controlling for matched coverage regions. The majority of these variants were detected below the reported limit of detection of the comparator assays, but above the limit of detection of NS Select. The rate of CHIP mutations was not significantly different in the variants detected by NS Select (19.0% ± 7.6%) vs. comparators (17.2% ± 9.2%). Finally, the proportion of patients with no pathogenic variants detected was shown to be lower by 45% when using NS Select vs. the comparator assays (20/182 vs. 36/182). Conclusions: NS Select reported clinically useful information about the tumor for most patients. For patients in which ctDNA signal was high, NS Select had very high concordance with comparator tests. Furthermore, additional low-VAF pathogenic mutations identified by NS Select translated to a higher diagnostic yield compared to other CGP assays, and CHIP was ruled out as an explanation for these additional detections. This suggests that some patients with low levels of ctDNA would derive clinical benefit from testing with NS Select due to its high sensitivity.

Factors Associated With Early Motor Function Trajectories in DMD After Glucocorticoid Initiation: Post Hoc Analysis of the FOR-DMD Trial.

Clinical trials in Duchenne muscular dystrophy (DMD) require 3-6 months of stable glucocorticoids, and the primary outcome is explored at 48-52 weeks. The factors that influence the clinical outcome assessment (COA) trajectories soon after glucocorticoid initiation are relevant for the design and analysis of clinical trials of novel drugs. We describe early COA trajectories, associated factors, and the time from glucocorticoid initiation to COA peak. This was a prospective 18-month analysis of the Finding the Optimum Corticosteroid Regimen for Duchenne Muscular Dystrophy study. Four COAs were investigated: rise from supine velocity (RFV), 10-meter walk/run velocity (10MWRV), North Star Ambulatory Assessment (NSAA) total score, and 6-minute walk test distance (6MWT). The relationships of baseline age (4-5 vs 6-7 years), COA baseline performance, genotype, and glucocorticoid regimen (daily vs intermittent) with the COA trajectories were evaluated using linear mixed-effects models. One hundred ninety-six glucocorticoid-naïve boys with DMD aged 4-7 years were enrolled. The mean age at baseline was 5.9 ± 1.0 years, 66% (n = 130) were on daily regimens, 55% (n = 107) showed a 6MWT distance >330 metres; 41% (n = 78) showed RFV >0.2 rise/s; 76% (n = 149) showed 10MWRV >0.142 10m/s, and 41.0% (n = 79) showed NSAA total score >22 points. Mean COA trajectories differed by age at glucocorticoid initiation (p < 0.01 for RFV, 10MWRV, and NSAA; p < 0.05 for 6MWT) and regimen (p < 0.01 for RFV, 10MWRV, and NSAA). Boys younger than 6 years reached their peak performance 12-18 months after glucocorticoid initiation. Boys aged 6 years or older on a daily regimen peaked between months 9 and 12 and those on an intermittent regimen by 9 months. The baseline COA performance was associated with the NSAA (p < 0.01) and the 6MWT trajectory in boys younger than 6 years on a daily regimen (p < 0.01). Differences in the mean trajectories by genotype were not significant. Glucocorticoid regimen, age, duration of glucocorticoid exposure, and baseline COA performance need to be considered in the design and analysis of clinical trials in young boys with DMD.

D.4 Safety and efficacy of delandistrogene moxeparvovec versus placebo in Duchenne muscular dystrophy (EMBARK): Pivotal Phase 3 primary results

Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations. Delandistrogene moxeparvovec is an investigational gene transfer therapy, developed to address the underlying cause of DMD. We report findings from Part 1 (52 weeks) of the two-part EMBARK trial (NCT05096221). Methods: Key inclusion criteria: Ambulatory patients aged ≥4-&lt;8 years with a confirmed DMD mutation within exons 18–79 (inclusive); North Star Ambulatory Assessment (NSAA) score &gt;16 and &lt;29 at screening. Eligible patients were randomized 1:1 to intravenous delandistrogene moxeparvovec (1.33×1014 vg/kg) or placebo. The primary endpoint was change from baseline in NSAA total score to Week 52. Results: At Week 52 (n=125), the primary endpoint did not reach statistical significance, although there was a nominal difference in change from baseline in NSAA total score in the delandistrogene moxeparvovec (2.6, n=63) versus placebo groups (1.9, n=61). Key secondary endpoints (time to rise, micro-dystrophin expression, 10-meter walk/run) demonstrated treatment benefit in both age groups (4-5 and 6-7 years; p&lt;0.05).There were no new safety signals, reinforcing the favorable and manageable safety profile observed to date. Conclusions: Based on the totality of functional assessments including the timed function tests, treatment with delandistrogene moxeparvovec indicates beneficial modification of disease trajectory.

Interpreting the evidence. Reducing subjectivity in appraising the evidence calls for a return to teaching evidence-based medicine.

The interpretation of clinical research evidence is still characterized by wide subjectivity. This subjectivity is also visible when comparing guidelines and recommendations developed by institutions and learned societies. It is often due to bias and conflicts of interest experienced by the members of guideline panels: thus, the role of editors and publishers of journals and scientific media becomes increasingly important, and they should return to careful oversight of the content of what is published. To address the problem, however, it is necessary to return to teaching evidence-based medicine in order to restore its function as a "North star" in clinical practice and public health decision-making.

Variability in the Qualitative and Quantitative Composition of Phenolic Compounds and the In Vitro Antioxidant Activity of Sour Cherry (Prunus cerasus L.) Leaves.

Sour cherry (Prunus cerasus L.) is a deciduous tree belonging to the Rosaceae Juss. family. Cherry leaves are an underutilized source of biologically active compounds. The aim of this study was to determine the composition of the phenolic compounds, as well as the total antioxidant activity, in leaf samples of P. cerasus cultivars and to elucidate the cultivars with particular phytochemical compositions. The phytochemical profiles of P. cerasus leaves vary significantly in a cultivar-dependent manner. The total content of identified phenolic compounds varied from 8.254 to 16.199 mg/g in the cherry leaves. Chlorogenic acid ranged between 1413.3 µg/g ('North Star') and 8028.0 µg/g ('Note'). The total content of flavonols varied from 4172.5 µg/g ('Vytenu zvaigzde') to 9030.7 µg/g ('Tikhonovskaya'). The total content of identified proanthocyanidins varied from 122.3 µg/g ('Note') to 684.8 µg/g ('Kelleris'). The highest levels of phloridzin (38.1 ± 0.9 µg/g) were found in samples of 'Molodezhnaya', while the lowest level of this compound was determined in the leaf samples of 'Turgenevka' (6.7 ± 0.2). The strongest antiradical (138.0 ± 4.0 µmol TE/g, p < 0.05) and reducing (364.9 ± 10.5 µmol TE/g, p < 0.05) activity in vitro was exhibited by the cultivar 'Vytenu zvaigzde' cherry leaf sample extracts. 'Kelleris', 'Note', and 'Tikhonovskaya' distinguish themselves with peculiar phytochemical compositions.

Which direction should we head to get to our North Star?

Which direction should we head to get to our North Star?

The Association Between Physical Activity/Heart Rate Variability Data Obtained Using a Wearable Device and Timed Motor Functional Tests in Patients with Duchenne Muscular Dystrophy: A Pilot Study.

Duchenne muscular dystrophy (DMD) is a devastating X-linked muscle disease. Clinical evaluation of DMD uses patient-intensive motor function tests, and the recent development of wearable devices allows the collection of a variety of biometric information, including physical activity. In this study, we examined differences in physical activity and heart rate variability (HRV) between patients with DMD and healthy subjects using a wearable device, and investigated any association between these parameters and motor function in patients with DMD. Participants were 7 patients with DMD and 8 healthy males, whose physical activity and HRV were provided by a wearable device. These data were used to investigate the relationship between both physical activity and HRV parameters and timed motor functional tests [Time to stand from supine, 10-meter walking time (10MWT), North Star Ambulatory Assessment (NSAA), and 6-minute walking test (6MWT)] in patients with DMD. Results of 24-hours physical activity, fat burning, total number of steps and active distance, average step rate, average exercise intensity during walking, exercise, degree of forward lean during walking, maximum heart rate, normalized low frequency power (LF norm), and maximum exercise intensity in patients with DMD were lower than those in control subjects. Physical activity and HRV parameters did not correlate with the time to stand from supine. The 10MWT positively correlated with average heart rate, while NSAA negatively correlated with average heart rate, total frequency power (TF), and very low frequency power (VLF) during arousal. The 6MWT negatively correlated with ratio LF/high frequency power (HF). Physical activity and HRV indices that differ from those of normal children and that correlate with motor function assessment may serve as digital biomarkers.

Stride Velocity 95th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy.

Stride Velocity 95th Centile (SV95C) is the first wearable device-derived clinical outcome assessment (COA) to receive European Medicines Agency (EMA) qualification as a primary endpoint in ambulant patients with Duchenne muscular dystrophy (DMD) aged ≥4 years. To compare SV95C-in its first-ever clinical trial application as a secondary endpoint-with established motor function COAs used in the trial (Four-Stair Climb [4SC] velocity, North Star Ambulatory Assessment [NSAA], and Six-Minute Walk Distance [6MWD]). SV95C was a secondary endpoint in a subset (n = 47) of participants in the SPITFIRE/WN40227 trial of taldefgrobep alfa, which was discontinued due to lack of clinical benefit. Participants in the ≤48-week SV95C sub-study were 6-11 years old and received corticosteroids for ≥6 months pre-treatment. Pearson correlations were used to compare SV95C with the other COAs. Responsiveness and changes over time were respectively assessed via standardized response means (SRMs) based on absolute changes and mixed models for repeated measures. SV95C change at Week 24 was -0.07 m/s, with limited variability (standard deviation: 0.16, n = 27). The SRM for SV95C indicated moderate responsiveness to clinical change at the earliest timepoint (Week 12, n = 46), while those of the other COAs did not indicate moderate responsiveness until Week 36 (6MWD, n = 33) or Week 48 (4SC velocity, n = 20; NSAA total score, n = 20). Baseline correlations between SV95C and other COAs were strong (r = 0.611-0.695). Correlations between SV95C change from baseline to Week 48 and changes in other COAs were moderate to strong (r = 0.443-0.678).∥. Overall, SV95C demonstrated sensitivity to ambulatory decline over short intervals, low variability, and correlation with established COAs. Although the negative trial precluded demonstration of SV95C's sensitivity to drug effect, these findings support the continued use of SV95C in DMD clinical trials.

Open-label observational study of effectiveness and tolerability of ipidacrine in treatment of patients with diabetic polyneuropathy (DIAMANT study)

Diabetic polyneuropathy (DPN) is one of the most common complications of diabetes mellitus, leading to the development of flaccid paresis, neuropathic pain syndrome, sensitive ataxia, as well as trophic disorders in the distal parts of the lower extremities.The purpose of the randomized, open-label, comparative, prospective study was to evaluate the effectiveness and tolerability of ipidacrine in the complex treatment of patients with DPN.Materials and methods. Patients with DPN (n = 60) were randomized into 2 groups. Both groups received basic therapy (alpha-lipoic acid, B vitamins, gabapentin); in the treatment of patients of the main group (n = 30), in addition, ipidacrine was used (Ipidacrine-SZ, North Star Co., Russia). We have analyzed the intensity of pain syndrome (VAS-P), the average daily dosage of gabapentin, and the results of the neuropathic dysfunctional scale (modified version, NDSm), Pittsburgh Sleep Quality Index, PSQI), Global Rating of Change Scale (GROC), the results of electroneuromyography (ENMG). The total duration of the observation and treatment period was 2 months.Results. After 2 months of therapy in the main group of patients, compared with the control group, there was significantly more complete pain control (VAS-P: 3.0 ± 0.9 vs 3.6 ± 0.8), a decrease in the average daily dosage of gabapentin (390 vs 500 mg/day), reduction in the severity of clinical manifestations of polyneuropathic syndrome (NDSm: 4.4 ± 1.0 vs 4.9 ± 1.0 points) and improvement in sleep quality (PSQI: 6.8 ± 1.3 vs 7.9 ± 1.7). According to ENMG data, patients in the main group showed a significant improvement in the neurophysiological parameters of both motor and sensory fibers, which was significantly more pronounced compared to the control group. A significantly larger proportion of patients in the main group assessed the improvement from the therapy as ‘pronounced’ (GROC: 10/33.3 % vs 6/20.0 %).Conclusions. The use of ipidacrine in complex therapy of patients with DPN can significantly reduce the clinical manifestations of disease and improve the neurophysiological parameters of the peripheral nerves of the lower extremities. Ipidacrine can be considered as a basic drug for the treatment of patients with neurological complications of diabetes mellitus.

Remarkable clinical improvement with oral nucleoside treatment in a patient with adult-onset TK2 deficiency: A case report

ObjectivesThymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms. We present the response to treatment in a patient with adult-onset TK2d. MethodsAn adult with ptosis, ophthalmoplegia, facial, neck, and proximal muscle weakness, non-invasive nocturnal mechanical ventilation, and dysphagia due to biallelic pathogenic variants in TK2 received treatment with 260 mg/kg/day of deoxycytidine (dC) and deoxythymidine (dT) under a Compassionate Use Program. Prospective motor and respiratory assessments are presented. ResultsAfter 27 months of follow-up, the North Star Ambulatory Assessment improved by 11 points, he walked 195 m more in the 6 Minute-Walking-Test, ran 10 s faster in the 100-meter time velocity test, and the Forced Vital Capacity stabilized. Growth Differentiation Factor-15 (GDF15) levels, a biomarker of respiratory chain dysfunction, normalized. The only reported side effect was dose-dependent diarrhea. DiscussionTreatment with dC and dT can significantly improve motor performance and stabilize respiratory function safely in patients with adult-onset TK2d.

“Astronomy for sailors”: a web game to learn physics using the stars and a clock

If you were on a boat in the middle of the sea how could you guess your position using just the stars and a clock? This is the challenge for hundreds of students at our interactive astronomy workshop in the context of the Genoa Science Festival held in Genoa (Italy) in 2021. Visitors played on the web application Astronomy for sailors which we developed from scratch. They could estimate their latitude and longitude in a virtual environment by measuring the altitude of the Sun above the horizon at solar noon and by using a marine chronometer. By recognising the brightest circumpolar constellations, they could learn how to find the North Star. The workshop included also an interdisciplinary section regarding orientation techniques in the animal world, ancient times and modernity. In this contribution we present the workshop’s activities, highlighting their original and innovative aspects. We report on the positive feedback from students and teachers who actively played with celestial navigation during our workshop. Around 600 people have visited us and the web application Astronomy for sailors is still available online for free.