La velocidad de acortamiento de los telómeros predice la longevidad de las especies

Telomere shortening rate predicts species life span

Significance

The exact causes of aging are still not understood, and it is unclear why some species live less than 1 d, while others can live more than 400 y. Research suggests that telomeres are related to the aging process, but a clear relationship between the life span of a species and initial telomere length has not been observed. Here, we measure the telomere lengths of a variety of different species. We find that, in fact, there is no strong correlation between the life span of a species and initial telomere length. However, we find a strong correlation between the telomere shortening rate and the life span of a species.

Abstract

Telomere shortening to a critical length can trigger aging and shorter life spans in mice and humans by a mechanism that involves induction of a persistent DNA damage response at chromosome ends and loss of cellular viability. However, whether telomere length is a universal determinant of species longevity is not known. To determine whether telomere shortening can be a single parameter to predict species longevities, here we measured in parallel the telomere length of a wide variety of species (birds and mammals) with very different life spans and body sizes, including mouse (Mus musculus), goat (Capra hircus), Audouin’s gull (Larus audouinii), reindeer (Rangifer tarandus), griffon vulture (Gyps fulvus), bottlenose dolphin (Tursiops truncatus), American flamingo (Phoenicopterus ruber), and Sumatran elephant (Elephas maximus sumatranus). We found that the telomere shortening rate, but not the initial telomere length alone, is a powerful predictor of species life span. These results support the notion that critical telomere shortening and the consequent onset of telomeric DNA damage and cellular senescence are a general determinant of species life span.


Keywords

telomere

life span

species

Identifican una nueva mutación en una familia con enfermedad de Alzheimer de inicio tardío

A novel mutation in PSEN1 (p.T119I) in an Argentine family with early- and late-onset Alzheimer's disease

Abstract 

Mutations in PSEN1 are the most common cause of early-onset Alzheimer's disease (AD). In this article, we present an Argentine family with autosomal dominant early- and late-onset AD. The proband and 6 family members were available for genetic testing and clinical and neuropsychological assessments. Cerebrospinal fluid biomarkers were analyzed in the proband and a cousin (mutation carrier), who also underwent positron emission tomography using F-18-2-fluoro-2-deoxy-D-glucose and Pittsburgh compound B. Exon sequencing of PSEN1, PSEN2, and APP revealed a novel heterozygous variant in PSEN1 (c.356C>T; p.T119I). Median age of onset in the family was 56 years. However, the proband's uncle showed initial symptoms at age 71. Although no DNA was available, he was an obligate carrier because his daughter (proband's cousin) carried the mutation. Both the proband and his cousin exhibited biomarker evidence (cerebrospinal fluid or imaging) of underlying Alzheimer's pathology. Overall, our results support that the PSEN1 p.T119I variant is likely pathogenic. 

Keywords: Latin America Sequencing Biomarker Cognitive impairment Imaging Genetics

Diferentes perfiles clínicos de la enfermedad de Huntington se asocian con dos firmas neurales específicas

Specific patterns of brain alterations underlie distinct clinical profiles in Huntington's disease

Abstract

Huntington's disease (HD) is a genetic neurodegenerative disease which involves a triad of motor, cognitive and psychiatric disturbances. However, there is great variability in the prominence of each type of symptom across individuals. The neurobiological basis of such variability remains poorly understood but would be crucial for better tailored treatments. Multivariate multimodal neuroimaging approaches have been successful in disentangling these profiles in other disorders. Thus we applied for the first time such approach to HD. We studied the relationship between HD symptom domains and multimodal measures sensitive to grey and white matter structural alterations. Forty-three HD gene carriers (23 manifest and 20 premanifest individuals) were scanned and underwent behavioural assessments evaluating motor, cognitive and psychiatric domains. We conducted a multimodal analysis integrating different structural neuroimaging modalities measuring grey matter volume, cortical thickness and white matter diffusion indices – fractional anisotropy and radial diffusivity. All neuroimaging measures were entered into a linked independent component analysis in order to obtain multimodal components reflecting common inter-subject variation across imaging modalities. The relationship between multimodal neuroimaging independent components and behavioural measures was analysed using multiple linear regression. We found that cognitive and motor symptoms shared a common neurobiological basis, whereas the psychiatric domain presented a differentiated neural signature. Behavioural measures of different symptom domains correlated with different neuroimaging components, both the brain regions involved and the neuroimaging modalities most prominently associated with each type of symptom showing differences. More severe cognitive and motor signs together were associated with a multimodal component consisting in a pattern of reduced grey matter, cortical thickness and white matter integrity in cognitive and motor related networks. In contrast, depressive symptoms were associated with a component mainly characterised by reduced cortical thickness pattern in limbic and paralimbic regions. In conclusion, using a multivariate multimodal approach we were able to disentangle the neurobiological substrates of two distinct symptom profiles in HD: one characterised by cognitive and motor features dissociated from a psychiatric profile. These results open a new view on a disease classically considered as a uniform entity and initiates a new avenue for further research considering these qualitative individual differences.

Graphical abstract

La neuropatía periférica inducida por quimioterapia, una reacción adversa frecuente en la terapia diaria del cáncer

Prevalence of peripheral neuropathy associated with chemotherapy in four oncology centers of Colombia

Purpose

To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors.

Methods

A systematic literature search identified relevant, randomized controlled trials (RCTs) for the

treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life.

Results

A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms.

Recommendations:

On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a com-pounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted.

La exposición materna a disolventes en el trabajo se vincularía con un mayor riesgo de autismo en los niños

The CHARGE study: an assessment of parental occupational exposures and autism spectrum disorder.

Abstract

OBJECTIVES:

The aim of this study is to determine if parental occupational exposure to 16 agents is associated with autism spectrum disorder (ASD).

METHODS:

Demographic, health and parental occupational data were collected as part of the CHildhood Autism Risks from Genetics and Environment study. The workplace exposure assessment was conducted by two experienced industrial hygienists for the parents of 537 children with ASD and 414 typically developing (TD) children. For each job, frequency and intensity of 16 agents were assessed and both binary and semi-quantitative cumulative exposure variables were derived. Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) to assess associations between parental occupational exposures 3 months pre-pregnancy until birth.

RESULTS:

The OR of ASD in the children of mothers exposed to any solvents was 1.5 times higher than the mothers of TD children (95% CI=1.01-2.23). Cumulative exposure indicated that the OR associated with a moderate level of solvent exposure in mothers was 1.85 (95% CI=1.09, 3.15) for children with ASD compared with TD children. No other exposures were associated with ASD in mothers, fathers or the parents combined.

CONCLUSION:

Maternal occupational exposure to solvents may increase the risk for ASD. These results are consistent with a growing body of evidence indicating that environmental and occupational exposures may be associated with ASD. Future research should consider specific types of solvents, larger samples and/or different study designs to evaluate other exposures for potential associations with ASD.

KEYWORDS:

autism spectrum disorder, paternal exposure, maternal exposure, occupational, solvents

Pacientes ancianos con lumbalgia tendrían más riesgo de sufrir depresión

Depression Symptoms Among Older Adults With and Without Subacute Low Back Pain.

Abstract

PURPOSE:

Lumbago, or low back pain (LBP), is a common musculoskeletal complaint among older adults that may also be associated with depression. The study objective was to investigate differences in Beck Depression Inventory depression symptoms scores among older adult patients with and without LBP.

DESIGN:

This was a case-control study.

METHODS:

A total of 152 older adult patients, recruited at an outpatient healthcare clinic (47 men, 105 women; 74.81 ± 6.9 years), were classified as having subacute LBP (n = 76) or non-LBP (n = 76) according to clinic records.

FINDINGS:

Beck Depression Inventory scores (mean ± SD) among LBP patients (10.93 ± 6.18) were significantly higher compared to the non-LBP group (7.62 ± 5.70; p = .000085), whose scores indicated no depression symptoms.

CONCLUSION:

Subacute LBP may represent a potential risk for increased depression among older adults.

CLINICAL RELEVANCE:

Early detection of depression will assist rehabilitation nurses in prescribing the beneficial physical rehabilitation and exercise programs or provide the information and treatment recommendations to older adults with subacute LBP and their families. Also, it should be part of a nursing staff prevention strategy for patients who suffer this common musculoskeletal disorder.

Estimulación magnética transcraneal sobre la espasticidad en pacientes con esclerosis múltiple recurrente

Effects of intermittent theta burststimulation on spasticity after spinalcord injury

Abstract. 

Purpose: Spasticity is a common disorder in patients with spinal cord injury (SCI). The aim of this study was to investigate whether intermittent theta burst stimulation (iTBS), a safe, non-invasive and well-tolerated protocol of excitatory repetitive transcranial magnetic stimulation (rTMS), is effective in modulating spasticity in SCI patients. Methods: In this randomized, double-blind, crossover, sham-controlled study, ten subjects with incomplete cervical or thoracic SCI received 10 days of daily sessions of real or sham iTBS. The H/M amplitude ratio of the Soleus H reflex, the amplitude of the motor evoked potentials (MEPs) at rest and during background contraction, as well as Modified Ashworth Scale (MAS) and the Spinal Cord Injury Assessment Tool for Spasticity (SCAT) were compared before and after the stimulation protocols. Results: Patients receiving real iTBS showed significant increased resting and active MEPs amplitude and a significant reduction of the H/M amplitude ratio. In these patients also the MAS and SCAT scores were significantly reduced after treatment. These changes persisted up to 1 week after the end of the iTBS treatment, and were not observed under the sham-TBS condition. Conclusion: These findings suggest that iTBS may be a promising therapeutic tool for the spasticity in SCI patients. 

Keywords: 

Intermittent theta burst stimulation, spinal cord injury, spasticity, motor evoked potential, H/M amplitude ratio, Modified Ashworth Scale, Spinal Cord Injury Assessment Tool for Spasticity.

Effects of intermittent theta burst stimulation on spasticity after spinal cord injury

Neuropsicología del trastorno de ansiedad generalizada

Neuropsychology of generalized anxiety disorders: a systematic review

Abstract 

The present study aimed to provide a comprehensive review of psycho-education in adults with formally diagnosed anxiety disorders, assessing its effectiveness in reducing the severity of anxiety symptoms, psychological distress, depression and pain, and improving quality of life and satisfaction with treatment. A systematic search was conducted using a narrative approach for extraction and synthesis of the data. Searches were undertaken between April and May 2017 in the following databases: Scopus, PubMed, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The studies included had been published between 2000 and 2017. 2804 references were identified, but the final sample of this review only considered five studies involving 490 participants. Three of the studies used a randomized design. Most of the interventions used a face-to-face format. In addition, the internet and the telephone were delivery resources used in available interventions addressed to anxiety disorders. All intervention protocols included an educational component and anxiety symptom control skills. Psycho-education improved the psychological distress, pain and quality of life of the patients with anxiety disorders and these effects remained over time. The interventions and therapists received a good evaluation. However, we emphasize the need to develop more research with sophisticated design to test the effect of psycho-educational interventions in this setting.

Psycho-Education for Anxiety Disorders in Adults_ A Systematic Review of

Bloquean en modelos de ratón una proteína fundamental en el desarrollo de la enfermedad de Alzheimer

Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aβ. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2–DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD.

Keywords

Alzheimer’s disease (AD) Galectin-3 TREM2 Microglia Inflammation Amyloid aggregation 

Antecedentes familiares de enfermedad de Alzheimer podrían influir en un riesgo futuro de problemas de memoria

Family history of Alzheimer’s disease alters cognition and is modified by medical and genetic factors

Abstract

In humans, a first-degree family history of dementia (FH) is a well-documented risk factor for Alzheimer’s disease (AD); however, the influence of FH on cognition across the lifespan is poorly understood. To address this issue, we developed an internet-based paired-associates learning (PAL) task and tested 59,571 participants between the ages of 18–85. FH was associated with lower PAL performance in both sexes under 65 years old. Modifiers of this effect of FH on PAL performance included age, sex, education, and diabetes. The Apolipoprotein E ε4 allele was also associated with lower PAL scores in FH positive individuals. Here we show, FH is associated with reduced PAL performance four decades before the typical onset of AD; additionally, several heritable and non-heritable modifiers of this effect were identified.

Infecciones del tracto urinario podrían ser desencadenantes de ictus

Infection as a Stroke Trigger

Associations Between Different Organ System Infection Admissions and Stroke Subtypes

Abstract

Background and Purpose—

The relationships between different infection types and stroke subtype are not well-characterized. We examined exposure to infections in different organ systems in different time periods before the acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

Methods—

We used the New York State Inpatient Databases and Emergency Department Databases (2006–2013). Validated International Classification of Diseases, Ninth Edition definitions identified index hospitalizations for acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, and emergency department visits and hospitalizations for infection (skin, urinary tract infection, septicemia, abdominal, and respiratory). We used case cross-over analysis with conditional logistic regression to estimate odds ratios (OR) for the association between each infection type during case periods compared with control periods 1 year before.

Results—

Every infection type was associated with an increased likelihood of acute ischemic stroke. The greatest association was for urinary tract infection, with OR of 5.32 (95% CI, 3.69–7.68) within the 7-day window. The magnitude of association between urinary tract infection and intracerebral hemorrhage was of lesser magnitude, with OR of 1.80 (1.04–3.11) in the 14-day exposure period and OR of 1.54 (1.23–1.94) in the 120-day exposure period. Only respiratory infection was associated with subarachnoid hemorrhage, with OR of 3.67 (1.49–9.04) in the 14-day window and 1.95 (1.44–2.64) in the 120-day window.

Conclusions—

All infection types were associated with subsequent acute ischemic stroke, with the greatest association for urinary tract infection. Stroke triggers are conditions that precipitate the acute occurrence of stroke. Acute infections have been studied as potential triggers of stroke.1–3 However, infections in different organ systems have been rarely examined comparatively in the same study, and studies failed to differentiate subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH).2 We sought to examine the differential associations between infection in different body systems and risk of stroke (ischemic, SAH, and ICH), hypothesizing that there would be a gradient of association, with a greater magnitude of association between infection and stroke during shorter time intervals before the stroke event.

Avances en interfaces cerebro-máquina para restablecer el movimiento de personas con discapacidad neuromotora

Decoding Movements from Cortical Ensemble Activity Using a Long Short-Term Memory Recurrent Network

Abstract

Although many real-time neural decoding algorithms have been proposed for brain-machine interface (BMI) applications over the years, an optimal, consensual approach remains elusive. Recent advances in deep learning algorithms provide new opportunities for improving the design of BMI decoders, including the use of recurrent artificial neural networks to decode neuronal ensemble activity in real time. Here, we developed a long-short term memory (LSTM) decoder for extracting movement kinematics from the activity of large (N = 134–402) populations of neurons, sampled simultaneously from multiple cortical areas, in rhesus monkeys performing motor tasks. Recorded regions included primary motor, dorsal premotor, supplementary motor, and primary somatosensory cortical areas. The LSTM's capacity to retain information for extended periods of time enabled accurate decoding for tasks that required both movements and periods of immobility. Our LSTM algorithm significantly outperformed the state-of-the-art unscented Kalman filter when applied to three tasks: center-out arm reaching, bimanual reaching, and bipedal walking on a treadmill. Notably, LSTM units exhibited a variety of well-known physiological features of cortical neuronal activity, such as directional tuning and neuronal dynamics across task epochs. LSTM modeled several key physiological attributes of cortical circuits involved in motor tasks. These findings suggest that LSTM-based approaches could yield a better algorithm strategy for neuroprostheses that employ BMIs to restore movement in severely disabled patients.

Los supervivientes al cáncer podrían tener unas probabilidades más bajas de demencia

Rate of Memory Change Before and After Cancer Diagnosis

Abstract

Importance  Patients with a history of cancer, even nonfatal cancers, have lower subsequent Alzheimer disease incidence. An inverse biological link between carcinogenesis and neurodegeneration has been hypothesized, although survival and detection biases are possible explanations.

Objective  To compare long-term memory trajectories before and after incident cancer with memory trajectories of similarly aged individuals not diagnosed with cancer.

Design, Setting, and Participants  This population-based cohort study included 14 583 US adults born before 1949 with no cancer history from the Health and Retirement Study. Biennial assessments were performed for up to 16 years from 1998 to 2014. Data analysis was performed from January 8 to October 5, 2018.

Exposures  Self-reported physician diagnosis of any cancer (excluding nonmelanoma skin cancer) during follow-up.

Main Outcomes and Measures  A composite memory score standardized to a mean (SD) of 0 (1) at baseline was based on immediate and delayed word-list recall and proxy assessments. The rate of memory change among people diagnosed with cancer during follow-up before and after diagnosis was compared with rate of memory change in individuals who remained cancer free during follow-up using linear mixed-effect models with random intercepts and slopes.

Results  A total of 14 583 participants were included in the sample (mean [SD] age, 66.4 [10.4] years; 8453 [58.0%] female). The mean (SD) follow-up was 11.5 (5.1) years; 2250 had a cancer diagnosis during follow-up, and 12 333 had no cancer diagnosis during follow-up. The rate of memory decline in the decade before a cancer diagnosis was 10.5% (95% CI, 6.2%-14.9%), which was slower than memory decline in similarly aged cancer-free individuals. For individuals diagnosed at 75 years of age, mean memory function immediately before diagnosis was 0.096 SD units (95% CI, 0.060-0.133 SD units) higher compared with that among similarly aged cancer-free individuals. A new cancer diagnosis was associated with a short-term decline in memory of −0.058 (95% CI, −0.084 to −0.032) SD units compared with memory before diagnosis. After diagnosis, the rate of memory decline was 3.9% (95% CI, 0.9%-6.9%) slower in individuals with cancer than in those without a cancer diagnosis.

Conclusions and Relevance  In this study, older individuals who developed cancer had better memory and slower memory decline than did similarly aged individuals who remained cancer free. These findings support the possibility of a common pathologic process working in opposite directions in cancer and Alzheimer disease.