Amyotrophic Lateral Sclerosis (ALS) is a fatal, progressive neurodegenerative disease affecting upper and lower motor neurons of the central nervous system that is associated to glial reactivity. ...The pathogenesis of this disease is not entirely clear. Different mechanisms have been postulated, including alterations in RNA processing, protein metabolism, axonal transport and mitochondrial function, increased oxidative stress and excitotoxicity. Astrocytes exhibit processes surrounding the synapse, where glutamate transporters are located to uptake the excess of neurotransmitter during synaptic activity. Alterations in this mechanism have been found in ALS and have highlighted the role of glia in the progression of ALS. Glutamate acts on two receptor families: NMDA and non-NMDA. There is evidence that links glutamate transporters dysfunction to the pathogenesis of the disease. In addition, it has been proven that alteration in the function and availability of the glutamate transporter EAAT2 / GLT1contributes to the increase of extracellular glutamate concentration. In this work, we aim to review the literature on the role of astrocytes and the glutamate transporter EAAT2 / GLT1 in the pathogenesis of ALS, to identify unsolved questions that may guide further research to improve the treatment of these patients.
La Esclerosis Lateral Amiotrófica (ELA) es una enfermedad neurodegenerativa fatal, progresiva que afecta las motoneuronas superiores e inferiores del sistema nervioso central y se acompaña de ...reactividad glial. La patogenia de esta enfermedad no está del todo clara. Se han postulado diferentes mecanismos dentro de los cuales se destacan las alteraciones en el procesamiento del ARN, en el metabolismo proteico, en el transporte axonal y en la función mitocondrial, aumento del estrés oxidativo y excitotoxicidad. Los astrocitos presentan prolongaciones que rodean la sinapsis, donde se localizan los transportadores de glutamato que captan el exceso del neurotransmisor durante la actividad sináptica. En la ELA se han encontrado alteraciones en este mecanismo lo cual ha resaltado la participación de la glía en la progresión de la enfermedad. El glutamato actúa sobre dos familias de receptores: NMDA y no NMDA, cuyas alteraciones se vinculan con la patogenia de la enfermedad. Además, se ha probado que existe una alteración en la función y disponibilidad del transportador de glutamato EAAT2/GLT1, que contribuye al aumento de la concentración de glutamato extracelular. En este trabajo, el objetivo fue revisar la bibliografía sobre el rol de los astrocitos y el transportador de glutamato EAAT2/GLT1 en la patogenia de la ELA, con el fin de identificar algunos interrogantes aún no dilucidados para dirigir nuevas investigaciones que puedan mejorar el tratamiento de estos pacientes.
Enhancing the quality of life of people with a lower limb amputation is critical in prosthetic development and rehabilitation. Yet, no overview is available concerning the impact of passive, ...quasi-passive and active ankle-foot prostheses on quality of life.
To systematically review the therapeutic benefits of performing daily activities with passive, quasi-passive and active ankle-foot prostheses in people with a lower limb amputation.
We searched the Pubmed, Web of Science, Scopus and Pedro databases, and backward citations until November 3, 2021. Only English-written randomised controlled trials, cross-sectional, cross-over and cohort studies were included when the population comprised individuals with a unilateral transfemoral or transtibial amputation, wearing passive, quasi-passive or active ankle-foot prostheses. The intervention and outcome measures had to include any aspect of quality of life assessed while performing daily activities. We synthesised the participants' characteristics, type of prosthesis, intervention, outcome and main results, and conducted risk of bias assessment using the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42021290189.
We identified 4281 records and included 34 studies in total. Results indicate that quasi-passive and active prostheses are favoured over passive prostheses based on biomechanical, physiological, performance and subjective measures in the short-term. All studies had a moderate or high risk of bias.
Compared to passive ankle-foot prostheses, quasi-passive and active prostheses significantly enhance the quality of life. Future research should investigate the long-term therapeutic benefits of prosthetics devices.
Current ankle prostheses for people with unilateral transtibial amputation (TTA) or transfemoral amputation (TFA) are unable to mimic able-bodied performance during daily activities. A new mechanical ...ankle-foot prosthesis was developed to further optimise the gait of people with a lower-limb amputation. This study aimed to evaluate the Talaris Demonstrator (TD) during daily activities by means of performance-related, physiological and subjective outcome measures.
Forty-two participants completed a protocol assessing performance and functional mobility with their current prosthesis and the TD. The protocol comprised the L-test, 2 min of stair climbing, 2 min of inclined treadmill walking, 6 min of treadmill walking at 3 different speeds in consecutive blocks of 2 min, and a 3-m Backward Walk test (3mBWT). Heart rate was measured during each task, and oxygen uptake was collected during all tasks except for the L-test and 3mBWT. Time of execution was recorded on the L-test and 3mBWT, and the rate of perceived exertion (score = 6-20), fatigue and comfort (score = 0-100) were assessed after each task. Paired sample t-tests and Wilcoxon Signed-rank tests were performed to compare outcomes between prosthetic devices. Benjamini-Hochberg corrections were applied to control for multiple comparisons with a level of significance set at α = 0.05.
Subjects with a TTA (N = 28) were faster with their current prosthesis compared to the TD on the L-test and 3mBWT (p = 0.005). In participants with a TFA (N = 14), we observed a tendency towards a higher heart rate during the L-test and towards increased comfort during inclined walking, with the TD compared to the participants' current prosthetic device (0.05 < p < 0.10). Further, no significant results were observed.
The Talaris Demonstrator is a novel state-of-the-art passive ankle-foot prosthesis for both people with a TTA and TFA. Subjective measures indicate the added value of this device, while overall task performance and intensity of effort do not differ between the Talaris Demonstrator and the current prosthesis. Further investigations unravelling both acute and more prolonged adaptations will be conducted to evaluate the TD more thoroughly.
Abstract
Background
Falls are a major problem associated with ageing. Yet, fall-risk classification models identifying older adults at risk are lacking. Current screening tools show limited ...predictive validity to differentiate between a low- and high-risk of falling.
Objective
This study aims at identifying risk factors associated with higher risk of falling by means of a quality-of-life questionnaire incorporating biological, behavioural, environmental and socio-economic factors. These insights can aid the development of a fall-risk classification algorithm identifying community-dwelling older adults at risk of falling.
Methods
The questionnaire was developed by the Belgian Ageing Studies research group of the Vrije Universiteit Brussel and administered to 82,580 older adults for a detailed analysis of risk factors linked to the fall incidence data. Based on previously known risk factors, 139 questions were selected from the questionnaire to include in this study. Included questions were encoded, missing values were dropped, and multicollinearity was assessed. A random forest classifier that learns to predict falls was trained to investigate the importance of each individual feature.
Results
Twenty-four questions were included in the classification-model. Based on the output of the model all factors were associated with the risk of falling of which two were biological risk factors, eight behavioural, 11 socioeconomic and three environmental risk factors. Each of these variables contributed between 4.5 and 6.5% to explaining the risk of falling.
Conclusion
The present study identified 24 fall risk factors using machine learning techniques to identify older adults at high risk of falling. Maintaining a mental, physical and socially active lifestyle, reducing vulnerability and feeling satisfied with the living situation contributes to reducing the risk of falling. Further research is warranted to establish an easy-to-use screening tool to be applied in daily practice.
Abstract
Background
Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5–10% of AYAs worldwide. There is no ...approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers pioglitazone (PIO), metformin (MET) and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue spironolactone (SPI), within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs.
Methods
In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO.
Discussion
The present study will be the first to evaluate—in a randomised, double-blind, placebo-controlled way—the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention.
Trial registration
EudraCT 2021–003177-58. Registered on 22 December 2021.
https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58
.
The use of environmental DNA (eDNA) for monitoring aquatic macrofauna allows the non-invasive species determination and measurement of their DNA abundance and typically involves the analysis of eDNA ...captured from water samples. In this proof-of-concept study, we focused on the novel use of eDNA extracted from archived suspended particulate matter (SPM) for identifying fish species using metabarcoding, which benefits from the prospect of retrospective monitoring and also analysis of fish communities through time. We used archived SPM samples of the German Environmental Specimen Bank (ESB), which were collected using sedimentation traps from different riverine points in Germany. Environmental DNA was extracted from nine SPM samples differing in location, organic content, and porosity (among other factors) using four different methods for the isolation of high-quality DNA. Application of the PowerSoil DNA Isolation Kit with an overnight incubation in lysis buffer, resulted in DNA extraction with the highest purity and eDNA metabarcoding of these eDNA fragments was used to detect a total of 29 fish taxa among the analyzed samples. Here we demonstrated for the first time that SPM is a promising source of eDNA for metabarcoding analysis, which could provide valuable retrospective information (when using archived SPM) for fish monitoring, complementing the currently used approaches.
The intercropping of ryegrass and red clover constitutes a sustainable alternative to mitigate the adverse effects of intensive livestock production on grassland degradation by increasing forage ...yield and quality. The implementation of biofertilization technologies has been widely used to improve soil nutritional properties, and therefore has the potential to ensure the success of this multicrop system. To determine the impact of bioaugmentation on forage growth and quality, as well as the associate changes in the rhizosphere bacterial community, we evaluated the inoculation with two plant growth-promoting bacteria (PGPB) under reduced nitrogen usage. Overall,
Herbaspirillum
sp. AP21 had a larger effect than
Azospirillum brasilense
D7 on plant growth. Inoculation with
Herbaspirillum
sp. AP21 together with 50% of the required nitrogen rate increased shoot dry weight, crude protein, and shoot nitrogen content, and decreased the amount of neutral detergent fiber. PGPB inoculation changed the rhizosphere bacterial community structure, which associated with forage growth and quality. We conclude that PGPB inoculation has the potential to improve the growth of the ryegrass-red clover system, decreasing the requirements for nitrogen fertilization.
Patients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. SPS inherited genetic basis is mostly unknown. We aimed to ...identify new germline predisposition factors for SPS by functionally evaluating a candidate gene and replicating it in additional SPS cohorts.
After a previous whole-exome sequencing in 39 SPS patients from 16 families (discovery cohort), we sequenced specific genes in an independent validation cohort of 211 unrelated SPS cases. Additional external replication was also available in 297 SPS cases. The
gene was disrupted in HT-29 cells by gene editing, and
variants were transfected using a lentiviral delivery system. Cells were analysed by immunoblots, real-time PCR and functional assays monitoring the mitogen-activated protein kinase (MAPK) pathway, cell cycle progression, survival and adhesion.
We identified 2 rare germline variants in the
gene in the discovery cohort, 3 additional variants in the validation cohort and 10 other variants in the external cohorts. Variants c.2105C>T (p.Pro702Leu), c.4820C>T (p.Ala1607Val) and c.6157G>A (p.Val2053Ile) were functionally characterised, displaying higher levels of phospho-PAK1/2, phospho-ERK1/2, CCND1, clonogenic capacity and MMP2.
After whole-exome sequencing in SPS cases with familial aggregation and replication of results in additional cohorts, we identified rare germline variants in the
gene. Functional studies suggested germline
variants affect protein function in the context of the MAPK pathway, a molecular hallmark in this disease.
The consumption of Caesalpinia coriaria dry ground fruit (Ccgf) and a Duddingtonia flagrans chlamydospore suspension (DfchS) either individually or in combination for the control of gastrointestinal ...nematodes (GIN) was assessed in sheep. Forty-five lambs infected with GIN were distributed into five groups (n = 9): Group 1: DfChS at 5 × 10
5
chlamydospores /kg BW; Group 2: Ccgf at 10% of the total diet; Group 3: Combination of both treatments; Group 4: Levamisole at 6 mg/kg BW; and Group 5: Control. The DfChS was orally administered every third day for 15 days; while the Ccgf, was daily offered during the same period. Faecal egg counts and coprocultures were established. Mean faecal egg accounts (EPG) and infective larvae from coprocultures were recorded. The highest EPG reductions were obtained on the 17th day with the treated group (72.1%); followed by Ccgf group (69.1%) at day 13 and DfchS group (62.6%) also on the 17th day; though, no significant differences were found among treatments. The highest larval reductions were observed with the combined treatment 97.7% (day 17); followed by DfchS group: 96.2% (day 11) and Ccgf group: 70% (day 11). The EPG and larvae reductions achieved with DfchS and Ccgf could be associated to the anthelmintic compounds present in both fungi and plants. The combined use of DfchS and Ccgf against GIN in sheep under grazing conditions seems to be a promising alternative for GIN control in sheep.
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