Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FDT) are progressive neurodegenerative disorders that, in several cases, overlap in clinical presentation, and genetic and ...pathological disease mechanisms. About 10–15% of ALS cases and up to 40% of FTD are familial, usually with dominant traits. ALS and FTD, in several cases, share common gene mutations, such as in C9ORF72, TARDBP, SQSTM-1, FUS, VCP, CHCHD10, and TBK-1. Also, several mechanisms are involved in ALS and FTD pathogenesis, such as protein misfolding, oxidative stress, and impaired axonal transport. In addition, neuroinflammation and neuroinflammatory cells, such as astrocytes, oligodendrocytes, microglia, and lymphocytes and, overall, the cellular microenvironment, have been proposed as pivotal players in the pathogenesis the ALS-FTD spectrum disorders. This review overviews the current evidence regarding neuroinflammatory markers in the ALS/FTD continuum, focusing on the neuroinflammatory pathways involved in the genetic cases, moving from post-mortem reports to in vivo biofluid and neuroimaging data. We further discuss the potential link between genetic and autoimmune disorders and potential therapeutic implications.
Alzheimer’s disease (AD) causes a significant challenge to global healthcare systems, with limited effective treatments available. This review examines the landscape of novel therapeutic strategies ...for AD, focusing on the shortcomings of traditional therapies against amyloid-beta (Aβ) and exploring emerging alternatives. Despite decades of research emphasizing the role of Aβ accumulation in AD pathogenesis, clinical trials targeting Aβ have obtained disappointing results, highlighting the complexity of AD pathophysiology and the need for investigating other therapeutic approaches. In this manuscript, we first discuss the challenges associated with anti-Aβ therapies, including limited efficacy and potential adverse effects, underscoring the necessity of exploring alternative mechanisms and targets. Thereafter, we review promising non-Aβ-based strategies, such as tau-targeted therapies, neuroinflammation modulation, and gene and stem cell therapy. These approaches offer new avenues for AD treatment by addressing additional pathological hallmarks and downstream effects beyond Aβ deposition.
Parkinson's disease (PD) is a neurodegenerative disease characterized by both motor and non-motor symptoms. A progressive neuronal loss and the consequent clinical impairment lead to deleterious ...effects on daily living and quality of life. Despite effective symptomatic therapeutic approaches, no disease-modifying therapies are currently available. Emerging evidence suggests that adopting a healthy lifestyle can improve the quality of life of PD patients. In addition, modulating lifestyle factors can positively affect the microstructural and macrostructural brain levels, corresponding to clinical improvement. Neuroimaging studies may help to identify the mechanisms through which physical exercise, dietary changes, cognitive enrichment, and exposure to substances modulate neuroprotection. All these factors have been associated with a modified risk of developing PD, with attenuation or exacerbation of motor and non-motor symptomatology, and possibly with structural and molecular changes. In the present work, we review the current knowledge on how lifestyle factors influence PD development and progression and the neuroimaging evidence for the brain structural, functional, and molecular changes induced by the adoption of positive or negative lifestyle behaviours.
•Experimental campaign performed to test the operation of a return-to-supply bidirectional substation.•Hardware-in-the-loop technique coupling in real-time realistic thermal load and production ...profiles.•Detailed tests for representative days, three case studies and extended assessment for the entire year.•Daily district heating contribution ranging between 21% and 100%.•Yearly local production contribution reaches 100% of the user’s load, considering the net-metering.
The regulatory European and national policies outline the role of efficient district heating in achieving mid and long-term decarbonization targets. Prosumers could be equipped with bidirectional exchange substations to increase the local production contribution. The present paper evaluates the contribution of a bidirectional substation in maximizing the use of thermal energy produced locally by renewable sources or waste heat in a densely populated area, considering the limitation due to the non-contemporaneity of production and consumption and possibilities to overcome them. The substation prototype and the control system were tested in operational conditions, assuming the district heating network operating at two temperature levels (80 °C/50 °C and 60 °C/30 °C for supply and return) and applying the hardware-in-the-loop technique for coupling the substation in real-time with data-driven thermal loads (multi-family residential building) and production (solar panels and waste heat) profiles. The various energy flows in the substation are presented for representative days, resulting in a district heating contribution to the user’s load ranging between 99.8 % (winter day) and 21.8 % (summer day). The net-metering mechanism was considered, and the assessment extended to the entire year. The local production contribution to the user’s load ranges between 24 % and 100 %, depending on the system configuration considered.
Pediculus humanus, the human body louse, is widespread where overcrowding and lack of hygiene are present, in areas of the world affected by poverty, war, famine and presence of refugees. It has ...recently been considered re-emerging among homeless populations in developed countries. In Italy, it was last reported in 1945. Pediculus humanus is a vector of highly relevant human pathogens.
In October 2018, a woman found small insects on a T-shirt bought second-hand in a local street market in a village 35 km south of Rome (central Italy). Insects were identified both morphologically and by molecular analysis. Moreover, they were analyzed molecularly for the presence of Rickettsia prowazekii, Borrelia recurrentis, Bartonella quintana, Coxiella burnetii and Yersinia pestis.
Morphological and molecular analyses of the insects identified them as 26 lice (12 females, 10 males and 4 nymphs) of the species P. humanus. Many nits were found on the T-shirt seams. DNA of the investigated pathogens was not detected in any of the lice.
The exceptionality of the described case lies both in the report of P. humanus from a country where it had not been reported since 1945, and in its finding from second-hand clothes for sale in a market, constituting a potential source of infection for people buying this type of goods. The question arises, how did adults and nits of P. humanus infest clothes for sale on a market stall in a country where it had not been reported for decades. Given that the body louse requires frequent blood meals to survive and develop, its arrival on clothes imported from abroad is highly improbable. Hence, it must be presumed that people infected with the human body louse are present in Italy. This report points out a serious regulatory problem regarding the management of second-hand clothes prior to sale and, more generally, of controls in street markets.
Management of extracranial internal carotid artery steno-occlusive lesion during endovascular therapy remains debated. Stent occlusion within 24 hours of endovascular therapy is a frequent event ...after acute carotid artery stenting, and we currently lack large population results. We investigated the incidence, predictors, and clinical impact of stent occlusion after acute carotid artery stenting in current clinical practice.
Patients treated by endovascular therapy with acute carotid artery stenting between 2015 and 2019 in 5 large-volume endovascular-capable centers were retrospectively analyzed. Patients were separated in 2 groups according to the stent patency at 24 hours after carotid artery stenting. We compared baseline characteristics, treatment modalities, and clinical outcome depending on 24-hour stent patency. Primary end point was favorable outcome, defined as a modified Rankin Scale score 0-2 at 3 months.
A stent occlusion was observed in 47/225 patients (20.9%). Patients with stent patency had a lower baseline National Institutes of Health Stroke Scale (median interquartile range: 13 7-17 versus 18 12-21) and had more often stroke of atherothrombotic origin (77.0% versus 53.2%). A higher stent patency rate was found for patients treated with P2Y
antagonists at the acute phase (odds ratio OR' 2.95 95% CI' 1.10-7.91;
=0.026) and treated with angioplasty (OR' 2.42 95% CI' 1.24-4.67;
=0.008). A better intracranial angiographic reperfusion was observed in patients with 24-hour stent patency compared with patients without stent patency (OR' 8.38 95% CI' 3.07-22.78;
<0.001). Patients with a stent patency at 24 hours had a higher chance of favorable outcome (OR' 3.29 95% CI, 1.66-6.52;
<0.001) and a lower risk of death (OR' 0.32 95% CI, 0.13-0.76;
=0.009).
One out of 5 patients treated with carotid artery stenting during endovascular therapy presented a stent occlusion within 24 hours. This event was associated with worse functional outcome. Stroke etiology, P2Y
antagonist administration, quality of intracranial reperfusion, and angioplasty were associated with 24-hour stent patency.
Artemisinin combination therapy (ACT) is used worldwide as the first-line treatment against uncomplicated Plasmodium falciparum malaria. Despite the success of ACT in reducing the global burden of ...malaria, the emerging of resistance to artemisinin threatens its use.
This report describes the first case of failure of dihydroartemisinin-piperaquine (DHA-PPQ) for the treatment of P. falciparum malaria diagnosed in Europe. It occurred in an Italian tourist returned from Ethiopia. She completely recovered after the DHA-PPQ treatment but 32 days after the end of therapy she had a recrudescence. The retrospective analysis indicated a correct DHA-PPQ absorption and genotyping demonstrated that the same P. falciparum strain was responsible for the both episodes.
In consideration of the growing number of cases of resistance to ACT, it is important to consider a possible recrudescence, that can manifest also several weeks after treatment.
Background and Purpose- Nonagenarians represent a growing stroke population characterized by a higher frailty. Although endovascular therapy (ET) is a cornerstone of the management of acute ischemic ...stroke related to large vessel occlusion, the benefit of reperfusion among nonagenarians is poorly documented. We aimed to assess the impact of ET-related reperfusion on the functional outcome of reperfusion in this elderly population. Methods- A retrospective analysis of clinical and imaging data from all patients aged over 90 included in the ETIS (Endovascular Treatment in Ischemic Stroke) registry between October 2013 and April 2018 was performed. Association between post-ET reperfusion and favorable (modified Rankin Scale 0-2 or equal to prestroke value) and good (modified Rankin Scale 0-3 or equal to prestroke value) outcome were evaluated. Demographic and procedural predictors of functional outcome, including the first-pass effect, were evaluated. Results were adjusted for center, admission National Institutes of Health Stroke Scale, and use of intravenous thrombolysis. Results- Among the 124 nonagenarians treated with ET, those with successful reperfusion had the lowest 90-day modified Rankin Scale (odds ratio, 3.26; 95% CI, 1.04-10.25). Only patients with successful reperfusion after the first pass (n=53, 56.7%) had a reduced 90-day mortality (odds ratio, 0.15; 95% CI, 0.05-0.45) and an increased rate of good outcome (odds ratio, 4.55; 95% CI, 1.38-15.03). No increase in the rate of intracranial hemorrhage was observed among patients successfully reperfused. Conclusions- Successful reperfusion improves the functional outcome of nonagenarians who should not be excluded from ET. The first-pass effect should be considered in the procedural management of this frail population.
Approximately half of the patients with acute ischemic stroke due to anterior circulation large vessel occlusion do not achieve functional independence despite successful reperfusion. We aimed to ...determine influence of reperfusion strategy (bridging therapy, intravenous thrombolysis alone, or mechanical thrombectomy alone) on clinical outcomes in this population.
From ongoing, prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke registry in France, all patients with anterior circulation large vessel occlusion who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3) following reperfusion therapy were included. Primary end point was favorable outcome, defined as 90-day modified Rankin Scale score ≤2. Patient groups were compared using those treated with bridging therapy as reference. Differences in baseline characteristics were reduced after propensity score-matching, with a maximum absolute standardized difference of 14% for occlusion site.
Among 1872 patients included, 970 (51.8%) received bridging therapy, 128 (6.8%) received intravenous thrombolysis alone, and the remaining 774 (41.4%) received MT alone. The rate of favorable outcome was comparable between groups. Excellent outcome (90-day modified Rankin Scale score 0-1) was achieved more frequently in the bridging therapy group compared with the MT alone (odds ratio after propensity score-matching, 0.70 95% CI, 0.50-0.96). Regarding safety outcomes, hemorrhagic complications were similar between the groups, but 90-day mortality was significantly higher in the MT alone group compared with the bridging therapy group (odds ratio, 1.60 95% CI, 1.09-2.37).
This real-world observational study of patients with anterior circulation large vessel occlusion demonstrated a similar rate of favorable outcome following successful reperfusion with different therapeutic strategies. However, our results suggest that bridging therapy compared with MT alone is significantly associated with excellent clinical outcome and lower mortality.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03776877.
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