Current and novel infusion therapies for patients with Parkinson's disease

Advanced Parkinson’s disease is characterized by periods of poor mobility, dyskinesia and progressive decline in functional independence of the affected person despite the manipulation of levodopa doses and the introduction of supplemental therapies such as catechol-O-methyl transferase inhibitors, monoamine oxidase-B inhibitors and dopamine agonists. The implementation of drug delivery systems allows to bypass problems related to irregular and often unpredictable intestinal absorption of oral levodopa, which significantly affects its bioavailability and contributes to the development and persistence of motor complications. Subcutaneous apomorphine and levodopa/carbidopa jejunal infusion systems have been available for many years and their efficacy is confirmed by randomized studies and long-term experience in many centers worldwide. Recently, a new formulation of levodopa/carbidopa infusion gel that includes the catechol-O-methyl transferase inhibitor Entacapone has been introduced to the market. The use of entacapone allows to reduce total daily dose of administered levodopa. Two different soluble formulations of levodopa/carbidopa (ND0612 and ABBV-951) have completed clinical development, and both can ensure subcutaneous delivery by a portable pump infusion system. ABBV-951 uses a foslevodopa/foscarbidopa formulation, both prodrugs to improve absorption and tolerability. Both systems provide effective improvement of motor complications and are likely to expand the therapeutic options in advanced patients. Future efforts should focus on the earlier detection of patients who are candidates for device-aided therapies, increasing appropriate referral and broadening the availability of these treatments globally

Planktic foraminiferal response to early Eocene carbon cycle perturbations in the southeast Atlantic Ocean (ODP Site 1263)

At low latitude locations in the northern hemisphere, striking changes in the relative abundances and diversity of the two dominant planktic foraminifera genera, Morozovella and Acarinina, are known to have occurred close to the Early Eocene Climatic Optimum (EECO; ~ 49–53 Ma). Lower Eocene carbonate-rich sediments at Ocean Drilling Program (ODP) Site 1263 were deposited on a bathymetric high (Walvis Ridge) at ~ 40° S, and afford an opportunity to examine such planktic foraminiferal assemblage changes in a temperate southern hemisphere setting. We present here quantified counts of early Eocene planktic foraminiferal assemblages from Hole 1263B, along with bulk sediment stable isotope analyses and proxy measurements for carbonate dissolution. The bulk sediment δ13C record at Site 1263 resembles similar records generated elsewhere, such that known and inferred hyperthermal events can be readily identified. Although some carbonate dissolution has occurred, the well-preserved planktic foraminiferal assemblages mostly represent primary changes in environmental conditions. Our results document the permanent decrease in Morozovella abundance and increase in Acarinina abundance at the beginning of the EECO, although this switch occurred ~ 165 kyr after that at low-latitude northern hemisphere locations. This suggests that unfavourable environmental conditions for morozovellids at the start of the EECO, such as sustained passage of a temperature threshold or other changes in surface waters, occurred at lower latitudes first. The remarkable turnover from Morozovella to Acarinina was widely geographically widespread, although the causal mechanism remains elusive. In addition, at Site 1263, we document the virtual disappearance within the EECO of the biserial chiloguembelinids, commonly considered as inhabiting intermediate water depths, and a reduction in abundance of the thermocline-dwelling subbotinids. We interpret these changes as signals of subsurface water properties, perhaps warming, and the associated contraction of ecological niches

Dextral to sinistral coiling switch in planktic foraminifer Morozovella during the Early Eocene Climatic Optimum

Coiling direction is a basic characteristic of trochospiral planktic foraminifera. Modifications in the coiling direction within ancient planktic foraminiferal populations may reflect important changes in evolution or environment, yet they remain scarcely discussed. Here we investigate fluctuations in the coiling direction within Morozovella assemblages from sections that span the interval of peak Cenozoic warmth, the Early Eocene Climatic Optimum (EECO; ~53-49 million years ago, Ma), at Atlantic Ocean Drilling Program (ODP) sites 1051, 1258 and 1263. The surface-dwelling genus Morozovella is of particular interest because it dominated tropical-subtropical early Paleogene assemblages then suffered an abrupt and permanent decline in abundance and taxonomic diversity at the start of the EECO. At all ODP sites, morozovellids display a dominant dextral coiling preference during the interval preceding the EECO. However, all the Morozovella species at all sites modify their coiling from preferentially dextral to sinistral coiling within the EECO < 200 kyr after the K/X event (~52.8 Ma), providing a new biostratigraphic tool for correlation. We also document that before the major shift in morozovellid coiling, transient excursions to higher abundances of sinistral tests occurred in conjunction with negative carbon isotope excursions. Significantly, carbon isotope data reveal that sinistral morphotypes belonging to the same morphospecies typically have lower 13C values. The dominance of sinistral morphotypes, at the expense of dextral forms within the EECO, coupled with the lower 13C signatures of the former, suggests that the sinistral forms were less dependent on their photosymbiotic partnerships and thus able to adapt more readily to paleoceanographic change at the EECO. The observed sinistral and dextral coiling of morozovellids can be a genetically heritable characteristic that lies within cryptic speciation across multiple morphologically defined species. Alternatively the coiling changes were exclusively ecophenotypic responses whereby different species were able to preferentially adopt sinistral coiling in reaction to the changed conditions in the mixed-layer during the EECO. Previous interpretations of coiling flips in planktic foraminifera in the early Eocene, especially including morozovellids, have favoured a genetic explanation rather than an ecological response. Our present data cannot validate or disprove this idea, but should stimulate renewed thought on the matter

A Fractional Model of Complex Permittivity of Conductor Media with Relaxation: Theory vs. Experiments

Moving from the study of plasmonic materials with relaxation, in this work we propose a fractional Abraham-Lorentz-like model of the complex permittivity of conductor media. This model extends the Ciancio-Kluitenberg, based on the Mazur-de Groot non-equilibrium thermodynamics theory (NET). The approach based on NET allows us to link the phenomenological function of internal variables and electrodynamics variables for a large range of frequencies. This allows us to closer reproduce experimental data for some key metals, such as Cu, Au and Ag. Particularly, our fitting significantly improves those obtained by Rakic and coworkers and we were able to operate in a larger range of energy values. Moreover, in this work we also provide a definition of a substantial fractional derivative, and we extend the fractional model proposed by Flora et al

Un modello semplificato per la previsione dell'incremento di pressione interstiziale indotto da carichi ciclici

Le procedure che consentono la valutazione dell’incremento di pressione interstiziale indotto da azioni sismiche in terreni sabbiosi saturi si basano, tipicamente, sui risultati di prove cicliche di laboratorio a tensione o deformazione controllata. In tali procedure la storia di carico irregolare a cui è sottoposto in terreno in sito deve essere semplificata con una azione equivalente tale che produca, su provini di terreno sottoposti a prove cicliche di laboratorio, lo stesso incremento delle pressioni interstiziali atteso nel sito. In alternativa, nel caso di propagazione monodimensionale, è possibile utilizzare un unico parametro, detto ‘parametro di danno’, per modellare gli incrementi di pressione interstiziale misurati in laboratorio. Questo parametro consente di applicare direttamente i risultati di laboratorio per predire l’incremento di pressione interstiziale generato in sito da storie irregolari di tensione o deformazione dovute all’azione sismica. Tale procedura, per la sua semplicità di applicazione, consente di effettuare analisi della risposta dinamica di depositi sabbiosi saturi senza adottare sofisticati modelli costitutivi del terreno e pertanto si presta all’implementazione in codici di calcolo che operano nel dominio del tempo

Evidence of disorientation towards immunization on online social media after contrasting political communication on vaccines. Results from an analysis of Twitter data in Italy

Background In Italy, in recent years, vaccination coverage for key immunizations as MMR has been declining to worryingly low levels, with large measles outbreaks. As a response in 2017, the Italian government expanded the number of mandatory immunizations introducing penalties to unvaccinated children’s families. During the 2018 general elections campaign, immunization policy entered the political debate with the government in-charge blaming oppositions for fuelling vaccine scepticism. A new government (formerly in the opposition) established in 2018 temporarily relaxed penalties and announced the introduction of forms of flexibility. Objectives and methods First, we supplied a definition of disorientation, as the “lack of well-established and resilient opinions among individuals, therefore causing them to change their positions as a consequence of sufficient external perturbations”. Second, procedures for testing for the presence of both short and longer-term collective disorientation in Twitter signals were proposed. Third, a sentiment analysis on tweets posted in Italian during 2018 on immunization topics, and related polarity evaluations, were used to investigate whether the contrasting announcements at the highest political level might have originated disorientation amongst the Italian public. Results Vaccine-relevant tweeters’ interactions peaked in response to main political events. Out of retained tweets, 70.0% resulted favourable to vaccination, 16.4% unfavourable, and 13.6% undecided, respectively. The smoothed time series of polarity proportions exhibit frequent large changes in the favourable proportion, superimposed to a clear up-and-down trend synchronized with the switch between governments in Spring 2018, suggesting evidence of disorientation among the public. Conclusions The reported evidence of disorientation for opinions expressed in online social media shows that critical health topics, such as vaccination, should never be used to achieve political consensus. This is worsened by the lack of a strong Italian institutional presence on Twitter, calling for efforts to contrast misinformation and the ensuing spread of hesitancy. It remains to be seen how this disorientation will impact future parents’ vaccination decisions

Demise of the Planktic Foraminifer genus Morozovella during the Early Eocene Climatic Optimum: new records from ODP Site 1258 (Demerara Rise, western equatorial Atlantic) and Site 1263 (Walvis Ridge, South Atlantic)

Here we present relative abundances of planktic foraminifera that span the Early Eocene Climatic Optimum (EECO) at Ocean Drilling Program (ODP) Site 1258 in the western equatorial Atlantic. The EECO (~53.3−49.1 Ma) represents peak Cenozoic warmth, probably related to high atmospheric CO2, and when planktic foraminifera, a dominant component of marine sediment, exhibit a major biotic response. Consistent with previous work, the relative abundance of the genus Morozovella, which dominated early Paleogene tropical-subtropical assemblages, markedly and permanently declined from a mean percentage of ~32% to less than ~7% at the beginning of the EECO. The distinct decrease in Morozovella abundance occurred at Site 1258 within ~20 kyr before a negative excursion in δ13C records known as the J event and which defines the beginning of EECO. Moreover, all morozovellid species except M. aragonensis dropped in abundance permanently at Site 1258, and this is related to a reduction in test-size. Comparing our data with that from other locations, the remarkable switch in planktonic foraminifera assemblages appears to have begun first with unfavourable environmental conditions near the Equator and then extended to higher latitudes. Several potential stressors may explain observations, including some combination of algal photosymbiont inhibition (bleaching), a sustained increase in temperature, or an extended decrease in pH

Congenital disorders of glycosylation: narration of a story through its patents

Congenital disorders of glycosylation are a group of more than 160 rare genetic defects in protein and lipid glycosylation. Since the first clinical report in 1980 of PMM2-CDG, the most common CDG worldwide, research made great strides, but nearly all of them are still missing a cure. CDG diagnosis has been at a rapid pace since the introduction of whole-exome/whole-genome sequencing as a diagnostic tool. Here, we retrace the history of CDG by analyzing all the patents associated with the topic. To this end, we explored the Espacenet database, extracted a list of patents, and then divided them into three major groups: (1) Drugs/therapeutic approaches for CDG, (2) Drug delivery tools for CDG, (3) Diagnostic tools for CDG. Despite the enormous scientific progress experienced in the last 30 years, diagnostic tools, drugs, and biomarkers are still urgently needed

Combined flow-based imaging assessment of optimal cardiac resynchronization therapy pacing vector: A case report

Background: There are still many pendent issues about the effective evaluation of cardiac resynchronization therapy impact on functional mitral regurgitation. In order to reduce the intrinsic difficulties of quantification of functional mitral regurgitation itself, an automatic quantification of real-time three-dimensional full-volume color Doppler transthoracic echocardiography was proposed as a new, rapid, and accurate method for the assessment of functional mitral regurgitation severity. Recent studies suggested that images of left ventricle flow by echo-particle imaging velocimetry could be a useful marker of synchrony. Echo-particle imaging velocimetry has shown that regional anomalies of synchrony/synergy of the left ventricle are related to the alteration, reduction, or suppression of the physiological intracavitary pressure gradients. Case summary: We describe a case in which the two technologies are used in combination during acute echocardiographic optimization of left pacing vector in a 63-year-old man, Caucasian, who showed worsening heart failure symptoms a few days after an implant, and the effect of the device\u2019s optimization at 6-month follow-up. Discussion: The degree of realignment of hemodynamic forces, with quantitative analysis of the orientation of blood flow momentum (\u3c6), can represent improvement of fluid dynamics synchrony of the left ventricle, and explain, with a new deterministic parameter, the effects of cardiac resynchronization therapy on functional mitral regurgitation. Realtime three-dimensional color flow Doppler quantification is feasible and accurate for measurement of mitral inflow, left ventricular outflow stroke volumes, and functional mitral regurgitation severity. Conclusion: This clinical case offers an innovative and accurate approach for acute echocardiographic optimization of left pacing vector. It shows clinical utility of combined three-dimensional full-volume color Doppler transthoracic echocardiography/echo-particle imaging velocimetry assessment to increase response to cardiac resynchronization therapy, in terms of reduction of functional mitral regurgitation, improving fluid dynamics synchrony of the left ventricle

Prevention of Secondary Injury after Anterior Cruciate Ligament Reconstruction: Relationship between Pelvic-Drop and Dynamic Knee Valgus.

Background: Optimal neuromuscular, Lumbo-Pelvic-Hip Complex, and lower extremity control are associated with decreased risk factors for secondary anterior cruciate ligament (ACL) injury. This study aimed to analyze any asymmetries and malalignments in the Lumbo-Pelvic-Hip Complex and the lower limbs at 6 months after ACL reconstruction (ACLR). (2) Methods: We conducted an exploratory retrospective observational single-center study in patients during the outpatient postoperative rehabilitation program at ICOT (Latina, Italy). From January 2014 to June 2020, 181 patients were recruited, but only 100 patients (86 male 28 ± 0.6 years, 178 ± 0.5 height; 14 female 24 ± 2.0 years, 178 ± 3.0 height) were eligible for the inclusion criteria and studied 6 months after ACL reconstruction surgery. (3) Statistical analysis: Student's t-tests and Pearson's product-moment correlation coefficient were used to determine significant differences between affected and non-affected limbs and variables' association. (4) Results: The study shows a decrease in neuromuscular control of the Lumbo-Pelvic-Hip Complex and dynamic adaptive valgus of the knee at 6 months after ACLR (mean difference between pathological and healthy limb of dynamic adaptive valgus was -10.11 ± 8.19° 95% CI -14.84 to -9.34; mean value was 16.3 ± 6.8° 95% CI 14.04 to 18.55 for healthy limb and 4.2 ± 3.1° 95% CI 3.15 to 5.21 for pathological limb, p &lt; 0.0001). The results also showed a relationship between dynamic adaptive valgus and contralateral pelvic drop (r = 0.78, 95% CI 0.62 to 0.88, magnitude of correlation very large). (5) Conclusions: The analysis showed an associative correlation between decreased postural control of the pelvic girdle and dynamic adaptive valgus of the knee in 38% of patients; this study highlights the usefulness of the Single-Leg Squat Test (SLST) as a clinical/functional assessment to evaluate the rehabilitation process and as a preventive tool to reduce the risk of second ACL injuries during the return to sport