The provenance of the stones in the Menga dolmen reveals one of the greatest engineering feats of the Neolithic.

The technical and intellectual capabilities of past societies are reflected in the monuments they were able to build. Tracking the provenance of the stones utilised to build prehistoric megalithic monuments, through geological studies, is of utmost interest for interpreting ancient architectures as well as to contribute to their protection. According to the scarce information available, most stones used in European prehistoric megaliths originate from locations near the construction sites, which would have made transport easier. The Menga dolmen (Antequera, Malaga, Spain), listed in UNESCO World Heritage since July 2016, was designed and built with stones weighting up to nearly 150 tons, thus becoming the most colossal stone monument built in its time in Europe (c. 3800-3600 BC). Our study (based on high-resolution geological mapping as well as petrographic and stratigraphic analyses) reveals key geological and archaeological evidence to establish the precise provenance of the massive stones used in the construction of this monument. These stones are mostly calcarenites, a poorly cemented detrital sedimentary rock comparable to those known as 'soft stones' in modern civil engineering. They were quarried from a rocky outcrop located at a distance of approximately 1 km. In this study, it can be inferred the use of soft stone in Menga reveals the human application of new wood and stone technologies enabling the construction of a monument of unprecedented magnitude and complexity.

Kinetic modulation of bacterial hydrolases by microbial community structure in coastal waters.

In this study, we hypothesized that shifts in the kinetic parameters of extracellular hydrolytic enzymes may occur as a consequence of seasonal environmental disturbances and would reflect the level of adaptation of the bacterial community to the organic matter of the ecosystem. We measured the activities of enzymes that play a key role in the bacterial growth (leucine aminopeptidase, ß- and α-glucosidases) in surface coastal waters of the Eastern Cantabrian Sea and determined their kinetic parameters by computing kinetic models of distinct complexity. Our results revealed the existence of two clearly distinct enzymatic systems operating at different substrate concentrations: a high-affinity system prevailing at low substrate concentrations and a low-affinity system characteristic of high substrate concentrations. These findings could be the result of distinct functional bacterial assemblages growing concurrently under sharp gradients of high-molecular-weight compounds. We constructed an ecological network based on contemporaneous and time-delayed correlations to explore the associations between the kinetic parameters and the environmental variables. The analysis revealed that the recurring phytoplankton blooms registered throughout the seasonal cycle trigger the wax and wane of those members of the bacterial community able to synthesize and secrete specific enzymes.

The health status: the ignored risk factor in dementia incidence. NEDICES cohort.

BACKGROUND: The causes of the dementia decrease in affluent countries are not well known but health amelioration could probably play a major role. Nevertheless, although many vascular and systemic disorders in adult life are well-known risk factors (RF) for dementia and Alzheimer disease (AD), health status is rarely considered as a single RF. AIM: To analyse whether the health status and the self-perceived health (SPH) could be RF for dementia and AD and to discuss its biological basis. METHODS: We analysed different objective health measures and SPH as RF for dementia and AD incidence in 4569 participants of the NEDICES cohort by means of Cox-regression models. The mean follow-up period was 3.2 (range: 0.03-6.6) years. RESULTS: Ageing, low education, history of stroke, and "poor" SPH were the main RF for dementia and AD incidence, whereas physical activity was protective. "Poor" SPH had a hazard ratio = 1.66 (95% CI 1.17-2.46; p = 0.012) after controlling for different confounders. DISCUSSION: According to data from NEDICES cohort, SPH is a better predictor of dementia and AD than other more objective health status proxies. SPH should be considered a holistic and biologically rooted indicator of health status, which can predict future development of dementia and AD in older adults. CONCLUSIONS: Our data indicate that it is worthwhile to include the SPH status as a RF in the studies of dementia and AD incidence and to explore the effect of its improvement in the evolution of this incidence.

Enhanced Viral Activity in the Surface Microlayer of the Arctic and Antarctic Oceans.

The ocean surface microlayer (SML), with physicochemical characteristics different from those of subsurface waters (SSW), results in dense and active viral and microbial communities that may favor virus-host interactions. Conversely, wind speed and/or UV radiation could adversely affect virus infection. Furthermore, in polar regions, organic and inorganic nutrient inputs from melting ice may increase microbial activity in the SML. Since the role of viruses in the microbial food web of the SML is poorly understood in polar oceans, we aimed to study the impact of viruses on prokaryotic communities in the SML and in the SSW in Arctic and Antarctic waters. We hypothesized that a higher viral activity in the SML than in the SSW in both polar systems would be observed. We measured viral and prokaryote abundances, virus-mediated mortality on prokaryotes, heterotrophic and phototrophic nanoflagellate abundance, and environmental factors. In both polar zones, we found small differences in environmental factors between the SML and the SSW. In contrast, despite the adverse effect of wind, viral and prokaryote abundances and virus-mediated mortality on prokaryotes were higher in the SML than in the SSW. As a consequence, the higher carbon flux released by lysed cells in the SML than in the SSW would increase the pool of dissolved organic carbon (DOC) and be rapidly used by other prokaryotes to grow (the viral shunt). Thus, our results suggest that viral activity greatly contributes to the functioning of the microbial food web in the SML, which could influence the biogeochemical cycles of the water column.

Is milk and dairy intake a preventive factor for elderly cognition (dementia and Alzheimer's)? A quality review of cohort surveys.

Milk and dairy (M&D) is a longstanding human food with widespread use. Many studies showed the preventive capacity of M&D in several human health disorders, but its utility in others is under discussion. Aging has been associated to elderly cognitive decline including dementia-Alzheimer syndrome (Dem-AD). The absence of a therapy to impede or postpone Dem-AD determines the need for its prevention, including nutritional factors. To evaluate the preventive capacity of M&D consumption in elderly Dem-AD we performed a systematic review in the main biomedical databases and information resources, but we present this study as a narrative review to discuss better the complexity of this subject. The elderly Dem-AD has a long pre-symptomatic period and the M&D intake has a widespread use. These determinants and the quality flaws of published studies impeach us to answer whether M&D consumption is preventive for Dem-AD. Moreover, two long Japanese cohorts suggest that M&D intake could prevent Dem-AD. Prospective cohorts beginning in midlife (or early life) could answer this question in the future.

Genetic study of neurexin and neuroligin genes in Alzheimer's disease.

The interaction between neurexins and neuroligins promotes the formation of functional synaptic structures. Recently, it has been reported that neurexins and neuroligins are proteolytically processed by presenilins at synapses. Based on this interaction and the role of presenilins in familial Alzheimer's disease (AD), we hypothesized that dysfunction of the neuroligin-neurexin pathway might be associated with AD. To explore this hypothesis, we carried out a meta-analysis of five genome-wide association studies (GWAS) comprising 1, 256 SNPs in the NRXN1, NRXN2, NRXN3, and NLGN1 genes (3,009 cases and 3,006 control individuals). We identified a marker in the NRXN3 gene (rs17757879) that showed a consistent protective effect in all GWAS, however, the statistical significance obtained did not resist multiple testing corrections (OR = 0.851, p = 0.002). Nonetheless, gender analysis revealed that this effect was restricted to males. A combined meta-analysis of the former five GWAS together with a replication Spanish sample consisting of 1,785 cases and 1,634 controls confirmed this observation (rs17757879, OR = 0.742, 95% CI = 0.632-0.872, p = 0.00028, final meta-analysis). We conclude that NRXN3 might have a role in susceptibility to AD in males.

Síndrome mielodisplásico en el paciente mayor: valoración geriátrica integral y recomendaciones terapéuticas / Myelodysplastic syndrome in the elderly: comprehensive geriatric assessment and therapeutic recommendations

La edad de presentación de los síndromes mielodisplásicos (SMD) suele ser alrededor de los 70 años. A pesar de esto, la mayor parte de los ensayos clínicos se restringen a sujetos más jóvenes, con lo cual el tratamiento de los pacientes mayores con SMD no siempre es el mejor. El paciente mayor presenta características fisiológicas que lo diferencian del adulto, y esto condiciona el tratamiento farmacológico. En este sentido, la valoración geriátrica integral (VGI) cobra especial importancia. Este artículo recoge las conclusiones de la I Reunión de Especialistas de la Sociedad Española de Medicina Geriátrica y de la Sociedad Española de Hematología y Hemoterapia, y propone la implantación de instrumentos de la VGI que ayuden en el proceso de toma de decisiones del paciente mayor con SMD. Los resultados se centrarán en el diagnóstico, pronóstico, tratamiento y manejo de los efectos adversos en este grupo de pacientes (AU)

The onset of myelodysplastic syndromes (MDS) is usually around the age of 70. Despite this, most clinical trials are restricted to younger subjects. Thus, the management of elderly patients with MDS is not always optimal. Physiologically, elderly patients show characteristics that differ from those of younger patients and that condition their pharmacological treatment. In this regard, the comprehensive geriatric assessment (CGA) becomes particularly important. This document gathers conclusions from the 1st Meeting of Members of the Sociedad Española de Medicina Geriátrica and the Sociedad Española de Hematología y Hemoterapia, with the objective of proposing the establishment of CGA instruments to assist in the decision-making process of elderly patients with MDS. The results of this consensus document will focus on the diagnosis, prognosis, treatment and management of adverse events in this age group (AU)

[Myelodysplastic syndrome in the elderly: comprehensive geriatric assessment and therapeutic recommendations]. / Síndrome mielodisplásico en el paciente mayor: valoración geriátrica integral y recomendaciones terapéuticas.

The onset of myelodysplastic syndromes (MDS) is usually around the age of 70. Despite this, most clinical trials are restricted to younger subjects. Thus, the management of elderly patients with MDS is not always optimal. Physiologically, elderly patients show characteristics that differ from those of younger patients and that condition their pharmacological treatment. In this regard, the comprehensive geriatric assessment (CGA) becomes particularly important. This document gathers conclusions from the 1(st) Meeting of Members of the Sociedad Española de Medicina Geriátrica and the Sociedad Española de Hematología y Hemoterapia, with the objective of proposing the establishment of CGA instruments to assist in the decision-making process of elderly patients with MDS. The results of this consensus document will focus on the diagnosis, prognosis, treatment and management of adverse events in this age group.

Prospective one-year cost-of-illness study in a cohort of patients with dementia of Alzheimer's disease type in Spain: the ECO study.

In this study, we analyzed the economic impact of one-year healthcare and non-healthcare resources utilization by patients with dementia of Alzheimer's disease (AD) under usual medical practice in Spain. A one-year, prospective, naturalistic, multicenter cohort study was designed to recruit patients with mild, moderate to severe, and severe AD according to Clinical Dementia Rating scale: the ECO study. Healthcare resources (medical visits, drugs and concomitant treatments, complementary and diagnostic tests, institutionalization and use of home-nursing facilities) and non-healthcare resources (inventory materials, consumables, professional and non-professional caregivers' time for care and supervision) were recorded and valued at 2006 prices. A total of 560 patients with possible/probable AD by DSM-IV-NINCDS-ADRDA criteria were included in the study: 68% women, 77 +/- 6 years old, 29% treatment naïve. Monthly average cost per patient was 1,425.73 euro, and increased 10.08% at the end of the study (baseline monthly cost; 1,316.22 euro). Non-healthcare costs 1059.00 euro, 74.30% of total cost) decreased 4.30 euro/month (0.40%) at the end of the year, while healthcare costs, which presented a total average of 366.66 euro, grew by 136.94 euro in the period (54.06%), mainly due to cost of drugs, nursing home utilization, and institutionalization. The 87.26% of the overall cost (1,244.22 euro) was not financed by National Health Service (NHS), and the majority of this cost corresponded to caregiver-associated cost. The caregiver's total burden represented 70.86% of the overall cost-of-illness. In conclusion, monthly overall mean cost of dementia of AD type was high in Spain (1,412.73 euro). Almost 88% of the cost-of-illness is funded by the patient's own family, adding a financial burden to the suffering of these families.

Beneficios clínicos de la memantina en las alteraciones de la capacidad para realizar actividades de la vida diaria en pacientes con enfermedad de Alzheimer. Revisión sistemática de la bibliografía médica / Efficacy of memantine in improving activities of daily living in patients with Alzheimer's disease

Revisión sistemática de ensayos clínicos controlados y aleatorizados con memantina en el tratamiento de la enfermedad de Alzheimer (EA) en fase moderada y avanzada, en la que se analiza la efectividad de este fármaco en el área funcional. De siete ensayos clínicos, cuatro de ellos incluían a pacientes con demencia vascular y EA y el resto sólo esta última patología. La revisión incluye 1.439 pacientes de edad media 72 años. La dosis de memantina habitual fue 20 mg/día. La duración de los ensayos varió entre 6 y 28 semanas. Al usar la escala ADCS-ADL se encontró una diferencia estadísticamente significativa a favor de memantina (diferencia de medias, 1,70; intervalo de confianza del 95%, 0,63-2,76; p = 0,002) y de 3,4 puntos a favor de memantina (p = 0,003) con la versión ADCS-ADLsev. El tratamiento con memantina parece mejorar las actividades de la vida diaria en la EA, precisa un tiempo menor de cuidado y utilización de recursos asistenciales y retrasa la institucionalización

We performed a systematic review of randomized, controlled clinical trials of memantine in the treatment of moderate and advanced Alzheimer's disease to analyze the effectiveness of this drug in producing functional improvement. Of seven clinical trials, four included patients with vascular dementia and Alzheimer's disease and the remainder included patients with Alzheimer's disease only. The review included 1439 patients with a mean age of 72 years. The usual dose of memantine was 20 mg/day. The clinical trials lasted between 6 and 28 weeks. Statistically significant differences were found in favor of memantine when the ADCS-ADL scale was used (mean difference 1.70, 95% confidence interval 0.63 to 2.76, p = 0.002) and a difference of 3.4 points in favor of memantine (p = 0.003) was found when the ADCS-ADLsev was used. Memantine therapy seems to improve activities of daily living in Alzheimer's disease, reducing the amount of