An abrupt change in the African monsoon at the end of the Younger Dryas

International audienceHigh-resolution studies of variations in the elemental and stable carbon- and nitrogen-isotope composition of organic matter in cores from Lakes Malawi, Tanganyika, and Bosumtwi (tropical Africa) indicate an abrupt change in the wind-driven circulation of these lakes that, within the limits of available chronologies, was contemporaneous with the end of the Younger Dryas in the northern hemisphere. The change was also coincident with shifts in surface winds recorded in cores from off the west and northeast coasts of Africa. A range of other proxies indicate that these changes in wind regime were accompanied by a marked increase in precipitation in the northern tropics. Africa south of ~5°-10°S, on the other hand, initially suffered drought conditions. Together, the evidence suggests an abrupt northward translation of the African monsoon system at circa 11.5 ± 0.25 ka B.P. The data assembled here contribute to a growing body of work showing that the Younger Dryas was a major climatic excursion in tropical Africa. Furthermore, they add substance to recent suggestions that climatic events in the southern hemisphere may have played a significant role in the abrupt demise of the Younger Drya

Is it possible to study paleoenvironmental changes in Alpine spring habitats? A few examples from the south-eastern Alps (NE Italy)

Palaeolimnological techniques were applied to spring habitats in the Trentino Region (NE Italy) as a test in order to reconstruct past environmental changes in these crucial and fragile milieus. Three different sites were selected from a database of more than one hundred on the basis of morphological, geological, and biological factors, including human impact evaluation: Nambrone, Paul and Madonnina Val Lomasona. Sampling was performed by adapting standard lake-sediment coring methods, and the retrieved sediment was described and subsampled following standard "lake" procedures. Field work and sedimentological analyses revealed clear influence from nearby fluvial environment for the Nambrone site, whereas Paul and Madonnina Val Lomasona were selected for further analyses (e.g., dating, diatoms, chironomids). Lead-210 and Caesium-137 dating methods were used to obtain a chronological framework, in addition to historical information on land use and other events in the area. The upper part of the Paul sequence presented organic rich sediment compatible with spring environments, but the lower and essentially detrital part appeared to record alluvial deposition, probably linked to extraordinary flood events (1882, 1966). This interpretation is indirectly confirmed by the records of the fallout nuclides Caesium-137 and Lead-210, that were both unfortunately concentrated in the topmost 1 cm, making it impossible to construct a normal age-depth profile. Madonnina Val Lomasona sedimentological and biological indicators point to a marked change around ca 5 cm, dividing the sequence in two units, corresponding to different environmental conditions. Although the interpretation of the dating results is not completely straightforward, the assembled data suggest that the upper 5 cm of the record represents ca the last 50 years. During this period we found typical limnocrenic, clear-water spring conditions, while before 1960s the coexistence of lotic and lentic chironomid species including several opportunistic ones and the low richness, emphasized the presence of a disturbance (e.g., highly variable flow and/or trophic conditions), as confirmed also by diatom assemblages and sedimentological features. The recorded disturbance is probably linked to a water-level change due to the local land use, as also testified by historical data. The results of this study support the idea that carefully selected spring sites might be approached with adapted palaeolimnological techniques to extract valuable palaeoenvironmental information. However, it also highlighted the low percentage of "good sites" (1%) and considerable difficulties in coring and sampling without disturbing the sediment

Improving the Characterization of Radiologically Isolated Syndrome Suggestive of Multiple Sclerosis

OBJECTIVE: To improve the characterization of asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities highly suggestive of multiple sclerosis (MS), a condition named as "radiologically isolated syndrome" (RIS). METHODS: Quantitative MRI metrics such as brain volumes and magnetization transfer (MT) were assessed in 19 subjects previously classified as RIS, 20 demographically-matched relapsing-remitting MS (RRMS) patients and 20 healthy controls (HC). Specific measures were: white matter (WM) lesion volumes (LV), total and regional brain volumes, and MT ratio (MTr) in lesions, normal-appearing WM (NAWM) and cortex. RESULTS: LV was similar in RIS and RRMS, without differences in distribution and frequency at lesion mapping. Brain volumes were similarly lower in RRMS and RIS than in HC (p<0.001). Lesional-MTr was lower in RRMS than in RIS (p = 0.048); NAWM-MTr and cortical-MTr were similar in RIS and HC and lower (p<0.01) in RRMS. These values were particularly lower in RRMS than in RIS in the sensorimotor and memory networks. A multivariate logistic regression analysis showed that 13/19 RIS had ≥70% probability of being classified as RRMS on the basis of their brain volume and lesional-MTr values. CONCLUSIONS: Macroscopic brain damage was similar in RIS and RRMS. However, the subtle tissue damage detected by MTr was milder in RIS than in RRMS in clinically relevant brain regions, suggesting an explanation for the lack of clinical manifestations of subjects with RIS. This new approach could be useful for narrowing down the RIS individuals with a high risk of progression to MS

Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial

Background and purpose Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. Methods This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. Results Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. Conclusions The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Infiltrative treatment associated with rehabilitation in coxarthrosis: long-term results

This study was performed to obtain clinical evidence, not only about immediate analgesic effect, but also regarding the delay in arthroplasty. Results show that 3 infiltrations every 30 days are well tolerated and they get a high degree of satisfaction for effectiveness for at least 6 months