Combining traceological analysis and ZooMS on Early Neolithic bone artefacts from the cave of Coro Trasito, NE Iberian Peninsula: Cervidae used equally to Caprinae.

Few studies have combined the analysis of use-wear traces, traceology, and the proteomic taxonomic identification method Zooarchaeology by Mass Spectrometry (ZooMS). Traceology provides information on the usage, in this case, of bone artefacts, while ZooMS allows for taxonomic identifications where diagnostic features are otherwise gone. The approaches therefore offer complementary information on bone artefacts, allowing for insights into species selection strategies in bone tool manufacture and their subsequent use. Here we present a case study of 20 bone artefacts, mainly bone points, from the Early Neolithic cave site of Coro Trasito located on the southern slope of the Central Pyrenees. Hitherto, studies on Early Neolithic bone artefacts from the Iberian Peninsula have suggested based on morphological assessments that Ovis aries/Capra hircus constituted the majority of the bone material selected for bone tool production. However, the taxonomic identification in this study suggests that, at this site, Cervidae was selected equally to that of O. aries/C. hircus. Furthermore, bone artefacts made from Cervidae specimens seem to be utilised in a wider range of artefact types compared to O. aries/C. hircus. Coro Trasito's bone artefact species composition is probably site-specific to some degree, however, morphological assessments of bone artefacts might not be representative and could be biased towards certain species. Therefore, research on bone artefacts' usage could possibly gain new insights by implementing ZooMS in combination with traceology.

Improvement of non-adherence and reduction of BP values in patients with difficult-to-treat hypertension: the ATHAN clinical trial.

Hypertension treatment and blood pressure (BP) control reduce cardiovascular disease burden. However, prevalence of controlled BP is overall insufficient and lack of adherence to treatment is a suggested major contributor. This prospective, randomized clinical trial was designed to evaluate whether a specific 3-month (m) action plan to improve therapeutic adherence results in a decrease in BP. Patients with ambulatory 24 h-BP ≥ 130/80 mmHg despite receiving ≥2 antihypertensive drugs and with therapeutic non-compliance confirmed by antihypertensive drugs analyzed in urine were randomized (1:1) to receive a specific 3 m program to improve adherence (INT = intervention) or routine follow-up (C = control). Antihypertensive treatment was not modified and knowledge of non-adherence was only notified to patients randomized to the intervention group. Before randomization and at 3 m all patients underwent urinary screening for antihypertensive drugs and 24 h-ambulatory-BP monitoring. Forty-five patients (36% women, mean age: 58 ± 13 yr) were randomized. At 3 m, mean (95% CI) BP differences (INT vs. C) were 12.2 mmHg (4.3-20.8), adjusted-p = 0.032 and 8.7 mmHg (2.5-14.8), adjusted-p = 0.018 for 24 h-systolic and 24 h-diastolic BP, respectively. Differences (INT vs. C) for office SBP and DBP were 18.4 mmHg (6.8-30.1), adjusted-p = 0.005 and 15.7 mmHg (7.2-24.2), adjusted-p < 0.001. Non-detected antihypertensive drugs were median [IQR]: 40% [25-100] and 0% [0-20] at baseline and 3 m, respectively, in the INT group, and 33.3% [25-63.7] and 33.3% [23.8-57.9], in the C group (p < 0.001 for the 3-month between-group comparison). A combined action plan of notifying knowledge of non-adherence plus a 3-month specific nursing intervention to improve therapeutic adherence results in BP reduction in patients with inadequate therapeutic compliance.

Office measurement vs. ambulatory blood pressure monitoring: associations with mortality in patients with or without diabetes.

BACKGROUND AND AIMS: Guidelines suggest similar blood pressure (BP) targets in patients with and without diabetes and recommend ambulatory BP monitoring (ABPM) to diagnose and classify hypertension. It was explored whether different levels of ambulatory and office BP and different hypertension phenotypes associate with differences of risk in diabetes and no diabetes. METHODS: This analysis assessed outcome data from the Spanish ABPM Registry in 59 124 patients with complete available data. The associations between office, mean, daytime, and nighttime ambulatory BP with the risk in patients with or without diabetes were explored. The effects of diabetes on mortality in different hypertension phenotypes, i.e. sustained hypertension, white-coat hypertension, and masked hypertension, compared with normotension were studied. Analyses were done with Cox regression analyses and adjusted for demographic and clinical confounders. RESULTS: A total of 59 124 patients were recruited from 223 primary care centres in Spain. The majority had an office systolic BP >140 mmHg (36 700 patients), and 23 128 (40.6%) patients were untreated. Diabetes was diagnosed in 11 391 patients (19.2%). Concomitant cardiovascular (CV) disease was present in 2521 patients (23.1%) with diabetes and 4616 (10.0%) without diabetes. Twenty-four-hour mean, daytime, and nighttime ambulatory BP were associated with increased risk in diabetes and no diabetes, while in office BP, there was no clear association with no differences with and without diabetes. While the relative association of BP to CV death risk was similar in diabetes compared with no diabetes (mean interaction P = .80, daytime interaction P = .97, and nighttime interaction P = .32), increased event rates occurred in diabetes for all ABPM parameters for CV death and all-cause death. White-coat hypertension was not associated with risk for CV death (hazard ratio 0.86; 95% confidence interval 0.72-1.03) and slightly reduced risk for all-cause death in no diabetes (hazard ratio 0.89; confidence interval 0.81-0.98) but without significant interaction between diabetes and no diabetes. Sustained hypertension and masked hypertension in diabetes and no diabetes were associated with even higher risk. There were no significant interactions in hypertensive phenotypes between diabetes and no diabetes and CV death risk (interaction P = .26), while some interaction was present for all-cause death (interaction P = .043) and non-CV death (interaction P = .053). CONCLUSIONS: Diabetes increased the risk for all-cause death, CV, and non-CV death at every level of office and ambulatory BP. Masked and sustained hypertension confer to the highest risk, while white-coat hypertension appears grossly neutral without interaction of relative risk between diabetes and no diabetes. These results support recommendations of international guidelines for strict BP control and using ABPM for classification and assessment of risk and control of hypertension, particularly in patients with diabetes. CLINICAL TRIAL REGISTRATION: Not applicable.

New therapeutic targets in hypertension. / Nuevas dianas terapéuticas en hipertensión.

Even though a large number of antihypertensive drugs are suitable for hypertension treatment, some new therapeutic targets are recently under development. Most are focused in the treatment of resistant hypertension, added to the drugs currently available for treating such condition. Others have specific particularities in their duration of action, which allows their use once per month or every six months and could become alternatives to the current antihypertensive treatment. Most interesting therapeutic targets are the renin-angiotensin-aldosterone system, through interference with the RNA of the angiotensinogen, the inhibition of brain aminopeptidase III, the inhibition of aldosterone synthase, and new non-steroidal aldosterone receptor antagonists. In addition, dual endothelin receptor antagonists or agonists of the NPR1 receptor, the main effector of natriuretic peptides are other new interesting therapeutic possibilities. In this paper, we review clinical data on the development of the most interesting molecules acting through these new therapeutic targets.

Blood pressure measurement and assessment of arterial structure and function: an expert group position paper.

Measuring blood pressure (BP) and investigating arterial hemodynamics are essential in understanding cardiovascular disease and assessing cardiovascular risk. Several methods are used to measure BP in the doctor's office, at home, or over 24 h under ambulatory conditions. Similarly, several noninvasive methods have been introduced for assessing arterial structure and function; these methods differ for the large arteries, the small ones, and the capillaries. Consequently, when studying arterial hemodynamics, the clinician is faced with a multitude of assessment methods whose technical details, advantages, and limitations are sometimes unclear. Moreover, the conditions and procedures for their optimal implementation, and/or the reference normality values for the parameters they yield are not always taken into sufficient consideration. Therefore, a practice guideline summarizing the main methods and their use in clinical practice is needed. This expert group position paper was developed by an international group of scientists after a two-day meeting during which each of the most used methods and techniques for blood pressure measurement and arterial function and structure evaluation were presented and discussed, focusing on their advantages, limitations, indications, normal values, and their pragmatic clinical application.

Clinic and ambulatory blood pressures, blood pressure phenotypes and mortality in patients with a previous stroke.

There is scarce evidence of the role of clinic and ambulatory BP indices, as well as blood pressure phenotypes in the prognosis of stroke survivors. We aimed to evaluate the association between ambulatory BP indices and mortality in patients with a previous stroke. Our study was an observational cohort study from individuals included in the Spanish Ambulatory Blood Pressure Registry from March 2004 to December 2014. The Cox model was used to estimate associations between usual clinic and ambulatory BP and mortality, adjusted for confounders and additionally for alternative measures of BP. Two thousand one hundred and eighty-three patients with a previous stroke were included. During a median of 9.2 years, 632 (28.9%) patients died: 236 (10.8%) from cardiovascular causes. In the confounder-adjusted model, clinic systolic BP was not associated with the risk of all-cause or cardiovascular mortality. In contrast, systolic BP indices obtained through ABPM (24 h, day and night) were all associated with all-cause and cardiovascular death. In the simultaneous adjustment of daytime and night-time systolic BP, only night-time systolic BP remained significantly associated with all-cause and cardiovascular death: HR 1.35 (95% CI 01.21-1.51) and 1.44 (1.20-1.72), respectively. For diastolic BP, only night-time BP was associated with all-cause and cardiovascular mortality: HR 1.32 (1.18-1.48) and 1.57 (1.31-1.88), respectively. According to the circadian pattern, a riser pattern was associated with all-cause and cardiovascular mortality: HR 1.49 (1.18-1.87) and 1.70 (1.14-2.52), respectively. In conclusion, in patients who have suffered a stroke, night-time BP is the BP estimate most closely associated with all-cause and cardiovascular mortality.

Cardio-ankle vascular index for predicting cardiovascular morbimortality and determinants for its progression in the prospective advanced approach to arterial stiffness (TRIPLE-A-Stiffness) study.

BACKGROUND: The cardio-ankle vascular index (CAVI) measure of arterial stiffness is associated with prevalent cardiovascular risk factors, while its predictive value for cardiovascular events remains to be established. The aim was to determine associations of CAVI with cardiovascular morbimortality (primary outcome) and all-cause mortality (secondary outcome), and to establish the determinants of CAVI progression. METHODS: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years. FINDINGS: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI. INTERPRETATION: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments. FUNDING: International Society of Vascular Health (ISVH) and Fukuda Denshi, Japan.

Ambulatory blood pressure monitoring. Current status and future perspectives. / Monitorización ambulatoria de la presión arterial. Situación actual y perspectivas futuras.

Ambulatory Blood Pressure Monitoring (ABPM) is considered the best method for obtaining a reliable estimation of the true blood pressure. Average values obtained during the whole 24-hour period, or during daytime and nighttime periods are better correlated with the risk of mortality and cardiovascular disease compared to clinic or office blood pressure. Indeed, nighttime blood pressure, a measure only obtained through ABPM, is the most powerful risk predictor. ABPM is complementary to clinic blood pressure measurement and allows the definition of blood pressure phenotypes, such as "white-coat or masked hypertension, when clinic and ABPM measurements show discrepancy in normal values. Additional potentially relevant features include blood pressure variability, such as nocturnal blood pressure decline, morning surge or short-term variability, as determined by standard deviation or the coefficient of variation.

Assessment and management of exaggerated blood pressure response to standing and orthostatic hypertension: consensus statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability.

Recent evidence suggests that an exaggerated blood pressure (BP) response to standing (ERTS) is associated with an increased risk of adverse outcomes, both in young and old individuals. In addition, ERTS has been shown to be an independent predictor of masked hypertension. In the vast majority of studies reporting on the prognostic value of orthostatic hypertension (OHT), the definition was based only on systolic office BP measurements. This consensus statement provides recommendations on the assessment and management of individuals with ERTS and/or OHT. ERTS is defined as an orthostatic increase in SBP at least 20 mmHg and OHT as an ERTS with standing SBP at least 140 mmHg. This statement recommends a standardized methodology to assess ERTS, by considering body and arm position, and the number and timing of BP measurements. ERTS/OHT should be confirmed in a second visit, to account for its limited reproducibility. The second assessment should evaluate BP changes from the supine to the standing posture. Ambulatory BP monitoring is recommended in most individuals with ERTS/OHT, especially if they have high-normal seated office BP. Implementation of lifestyle changes and close follow-up are recommended in individuals with ERTS/OHT and normotensive seated office BP. Whether antihypertensive treatment should be administered in the latter is unknown. Hypertensive patients with ERTS/OHT should be managed as any other hypertensive patient. Standardized standing BP measurement should be implemented in future epidemiological and interventional studies.

Shepherding the past: High-resolution data on Neolithic Southern Iberian livestock management at Cueva de El Toro (Antequera, Málaga).

The feeding strategies of the first domesticated herds had to manage the risks arising from the novelty of livestock practices in territories often distant from the animals' primary habitats. The Iberian Peninsula is characterised by a great diversity of environments, which undoubtedly influenced these dynamics. At the beginning of the Neolithic period these led the possibility to combine diverse livestock farming practices based on different animal feeding habits. This variability is also consistent with the rythms of adoption of domesticated animals, being later on the northern area. In order to address this issue, this work focuses on the dietary regimes of early sheep herds from southern Iberia, an area for which information is currently scarce. This study utilises high-resolution radiocarbon dating and stable isotope data on teeth to investigate sheep husbandry management strategies in Cueva de El Toro (Antequera, Málaga). The radiocarbon dates on the analysed remains evidenced they were deposited at the site over a short period, supporting the recurrent use of the cave. The sequential analysis of oxygen and carbon isotopes in tooth enamel reveals distinct livestock management strategies, reproduction patterns, feeding habits, and mobility during this short period. This variability demonstrates that livestock management practices in the western Mediterranean are more diverse than previously considered. Furthermore, these findings support the hypothesis that early Neolithic communities in the southern Iberian Peninsula were able to adopt different feeding strategies within the same herd, depending on their ecological and productive needs.

Artificial Intelligence-Derived Risk Prediction: A Novel Risk Calculator Using Office and Ambulatory Blood Pressure.

BACKGROUND: Quantification of total cardiovascular risk is essential for individualizing hypertension treatment. This study aimed to develop and validate a novel, machine-learning-derived model to predict cardiovascular mortality risk using office blood pressure (OBP) and ambulatory blood pressure (ABP). METHODS: The performance of the novel risk score was compared with existing risk scores, and the possibility of predicting ABP phenotypes utilizing clinical variables was assessed. Using data from 59 124 patients enrolled in the Spanish ABP Monitoring registry, machine-learning approaches (logistic regression, gradient-boosted decision trees, and deep neural networks) and stepwise forward feature selection were used. RESULTS: For the prediction of cardiovascular mortality, deep neural networks yielded the highest clinical performance. The novel mortality prediction models using OBP and ABP outperformed other risk scores. The area under the curve achieved by the novel approach, already when using OBP variables, was significantly higher when compared with the area under the curve of the Framingham risk score, Systemic Coronary Risk Estimation 2, and Atherosclerotic Cardiovascular Disease score. However, the prediction of cardiovascular mortality with ABP instead of OBP data significantly increased the area under the curve (0.870 versus 0.865; P=3.61×10-28), accuracy, and specificity, respectively. The prediction of ABP phenotypes (ie, white-coat, ambulatory, and masked hypertension) using clinical characteristics was limited. CONCLUSIONS: The receiver operating characteristic curves for cardiovascular mortality using ABP and OBP with deep neural network models outperformed all other risk metrics, indicating the potential for improving current risk scores by applying state-of-the-art machine learning approaches. The prediction of cardiovascular mortality using ABP data led to a significant increase in area under the curve and performance metrics.

A blunted nocturnal blood pressure decline is associated with all-cause and cardiovascular mortality.

OBJECTIVE: It has been suggested that a blunted nocturnal blood pressure (BP) decline is associated with a poor prognosis. Nevertheless, it remains unclear if an abnormal dipping is deleterious per se or it merely reflects an elevated BP during sleep. We aimed to assess the prognostic value of nocturnal BP decline, with or without concomitant elevated nocturnal BP. METHODS: Vital status and cause of death were obtained from death certificates in 59 124 patients, enrolled in the Spanish ABPM Registry between 2004 and 2014 (median follow-up: 10 years). The association between night-to-day ratio (NDR) and dipping patterns (extreme dippers, dippers, reduced dippers, and risers) with all-cause and cardiovascular mortality were evaluated by Cox-proportional models adjusted for clinical confounders and 24 h blood pressure. RESULTS: NDR was associated with all-cause mortality [hazard ratio for 1SD change: 1.15; 95% confidence interval (CI) 1.13-1.17]. Reduced dippers (1.13; 1.06-1.20) and risers (1.41; 1.32-1.51) were associated with an increased risk of all-cause death, whereas extreme dippers (0.90; 0.79-1.02) were not. Elevated NDR (≥0.9) in the absence of elevated night SBP (<120 mmHg) was associated with an increased risk of death (1.13; 1.04-1.22), as well as elevated night SBP but normal NDR (1.38; 1.26-1.50), and the combination of both abnormalities (1.56; 1.46-1.66). Similar results were obtained for cardiovascular mortality. CONCLUSION: Abnormalities in the circadian pattern are associated with an increased risk of all-cause and cardiovascular mortality. This is maintained even in the absence of nocturnal BP elevation.

Prognostic Relevance of Short-Term Blood Pressure Variability. The Spanish ABPM Registry.

BACKGROUND: The prognostic relevance of short-term blood pressure (BP) variability in hypertension is not clearly established. We aimed to evaluate the association of short-term BP variability, with all-cause and cardiovascular mortality in a large cohort of patients with hypertension. METHODS: We selected 59 124 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry from 2004 to 2014 (median follow-up: 9.7 years). Systolic and diastolic BP SD and coefficient of variation from daytime and nighttime, weighted SD, weighted coefficient of variation, average real variability (mean of differences between consecutive readings), and BP variability ratio (ratio between systolic and diastolic 24-hour SD) were calculated through baseline 24-hour ambulatory BP monitoring. Association with all-cause and cardiovascular mortality were assessed by Cox regression models adjusted for clinical confounders and BP. RESULTS: Patients who died during follow-up had higher values of BP variability compared with those remaining alive. In adjusted models systolic and diastolic daytime and weighted SD and coefficient of variation, average real variability, as well as systolic nighttime SD and BP variability ratio were all significantly associated with all-cause and cardiovascular mortality. Hazard ratios for 1-SD increase in the systolic components ranged from 1.05 to 1.12 for all-cause mortality and from 1.07 to 1.17 for cardiovascular mortality. A daytime SD≥13 mm Hg, a nighttime and a weighted SD≥12 mm Hg, and an average real variability ≥10 mm Hg, all systolic, were independently associated with mortality. CONCLUSIONS: Short-term blood pressure variability shows a relatively weak but significant association with all-cause and cardiovascular mortality in patients with hypertension.

Impact of timing of antihypertensive treatment on mortality: an observational study from the Spanish Ambulatory Blood Pressure Monitoring Registry.

BACKGROUND AND AIMS: Whether bedtime versus morning administration of antihypertensive therapy is beneficial on outcomes is controversial. We evaluated the risk of total and cardiovascular mortality in a very large observational cohort of treated hypertensive patients, according to the timing of their usual treatment administration (morning versus evening). METHODS: Vital status and cause of death were obtained from death certificates of 28 406 treated hypertensive patients (mean age 62 years, 53% male individuals), enrolled in the Spanish Ambulatory Blood Pressure Monitoring (ABPM) Registry between 2004 and 2014. Among the 28 406 patients, most (86%) received their medication exclusively in the morning; whilst 13% were treated exclusively in the evening or at bedtime. Follow-up was for a median of 9.7 years and 4345 deaths occurred, of which 1478 were cardiovascular deaths. RESULTS: Using Cox-models adjusted for clinical confounders and 24-h SBP, and compared with patients treated in the morning (reference group), all-cause mortality [hazard ratio 1.01; 95% CI 0.93-1.09) and cardiovascular mortality (hazard ratio 1.04; 95% CI 0.91-1.19) was not significantly different in those receiving evening medication dosing. The results were consistent in all the subgroups of patients analysed. CONCLUSION: In this very large observational study, morning versus bedtime dosing of antihypertensive medication made no difference to the subsequent risk of all-cause or cardiovascular mortality. These findings are in accordance with results from a recent randomized controlled trial and do not support the hypothesis of a specific beneficial effect of night-time antihypertensive treatment dosing on risk of all-cause or cardiovascular death.

From molecular mechanisms of prostate cancer to translational applications: based on multi-omics fusion analysis and intelligent medicine.

Prostate cancer is the most common cancer in men worldwide and has a high mortality rate. The complex and heterogeneous development of prostate cancer has become a core obstacle in the treatment of prostate cancer. Simultaneously, the issues of overtreatment in early-stage diagnosis, oligometastasis and dormant tumor recognition, as well as personalized drug utilization, are also specific concerns that require attention in the clinical management of prostate cancer. Some typical genetic mutations have been proved to be associated with prostate cancer's initiation and progression. However, single-omic studies usually are not able to explain the causal relationship between molecular alterations and clinical phenotypes. Exploration from a systems genetics perspective is also lacking in this field, that is, the impact of gene network, the environmental factors, and even lifestyle behaviors on disease progression. At the meantime, current trend emphasizes the utilization of artificial intelligence (AI) and machine learning techniques to process extensive multidimensional data, including multi-omics. These technologies unveil the potential patterns, correlations, and insights related to diseases, thereby aiding the interpretable clinical decision making and applications, namely intelligent medicine. Therefore, there is a pressing need to integrate multidimensional data for identification of molecular subtypes, prediction of cancer progression and aggressiveness, along with perosonalized treatment performing. In this review, we systematically elaborated the landscape from molecular mechanism discovery of prostate cancer to clinical translational applications. We discussed the molecular profiles and clinical manifestations of prostate cancer heterogeneity, the identification of different states of prostate cancer, as well as corresponding precision medicine practices. Taking multi-omics fusion, systems genetics, and intelligence medicine as the main perspectives, the current research results and knowledge-driven research path of prostate cancer were summarized.

Effect of salivary fluid characteristics on the physical features of in vitro bread bolus: From the absence of saliva to artificially simulated hypersalivation.

Saliva facilitates food oral processing, bolus formation, swallowing, and sensory perception, in addition to contributing to oral health and phonation. Ageing, health affections, and polymedication are among many causes altering salivary production, modifying the mastication process, the food impregnation ratio, and in turn altering the characteristics of the bolus, swallowing, and digestion. In this in vitro work, using the AM2 masticator apparatus, which replicates the mechanical actions taking place while chewing solid foods and produces realistic food bolus in various oral conditions, we investigated the effect of salivary fluid characteristics, i.e., composition, quantity (from absence to hypersalivation), temperature, and enzymatic action, on the physical characteristics (i.e., particle size distribution (PSD), bolus mass, salivary fluid content) of in vitro boluses of Traditional French baguette. A ready-to-swallow bolus of baguette displayed on average a d50 value (median particle size by mass) of 4.1 ± 0.4 mm, with saliva fluid constituting âˆ¼ 35 % of the final bolus mass. The absence of saliva in mouth led to a deficient oral processing, forming bread boluses constituted by extremely big particles (ca. 80 % of particles had a size > 7.1 mm) that likely cannot be swallowed safely. On the contrary, an excess of saliva favoured an excessive breaking down of bread, leading to bread boluses constituted by smaller particles than those formed under healthy salivary conditions (d50 decreased from 4.1 mm to 3.1 mm), having a higher salivary fluid content (+10 %). On the other hand, the salivary fluid temperature did not affect PSD, d50, bolus mass, or salivary fluid content of in vitro bread boluses, however, the addition of human salivary α-amylase did, favouring particle size reduction (d50 decreased to 2.6 mm). Therefore, beyond the correlation between bolus hydration by saliva and food properties such as hardness and moisture content, our findings indicate that the quantity of salivary fluid present in the oral cavity and the enzymatic activity of salivary α-amylase during bread mastication significantly influence both the particle size distribution and the fluid content of bread boluses, ultimately determining the physical properties of the bolus and, therefore, potentially impacting the subsequent swallowing process.

Benchmarking of a microgel-reinforced hydrogel-based aqueous lubricant against commercial saliva substitutes.

Xerostomia, the subjective sensation of 'dry mouth' affecting at least 1 in 10 adults, predominantly elders, increases life-threatening infections, adversely impacting nutritional status and quality of life. A patented, microgel-reinforced hydrogel-based aqueous lubricant, prepared using either dairy or plant-based proteins, has been demonstrated to offer substantially enhanced lubricity comparable to real human saliva in in vitro experiments. Herein, we present the benchmarking of in vitro lubrication performance of this aqueous lubricant, both in its dairy and vegan formulation against a range of widely available and employed commercial saliva substitutes, latter classified based on their shear rheology into "liquids", "viscous liquids" and "gels", and also had varying extensional properties. Strikingly, the fabricated dairy-based aqueous lubricant offers up to 41-99% more effective boundary lubrication against liquids and viscous liquids, irrespective of topography of the tested dry mouth-mimicking tribological surfaces. Such high lubricity of the fabricated lubricants might be attributed to their limited real-time desorption (7%) from a dry-mouth mimicking hydrophobic surface unlike the tested commercial products including gels (23-58% desorption). This comprehensive benchmarking study therefore paves the way for employing these microgel-based aqueous lubricant formulations as a novel topical platform for dry mouth therapy.

Blood Pressure Variability as a Risk Factor for Cardiovascular Disease: Which Antihypertensive Agents Are More Effective?

Blood pressure oscillations during different time scales, known as blood pressure variability (BPV), have become a focus of growing scientific interest. BPV can be measured at long-term (seasonal variability or visit-to-visit), at mid-term (differences in consecutive days or weeks) or at short-term (day-night differences or changes induced by other daily activities and conditions). An increased BPV, either at long, mid or short-term is associated with a poor cardiovascular prognosis independently of the amount of blood pressure elevation. There is scarce evidence on the effect of different antihypertensive treatments on BPV, but some observational and interventional studies suggest that calcium channel blockers in general, and particularly amlodipine, either in monotherapy or combined with renin-angiotensin system blockers, can reduce BPV more efficiently than other antihypertensive drugs or combinations. Nevertheless, there are several aspects of the relationship between BPV, antihypertensive treatment, and clinical outcomes that are still unknown, and more work should be performed before considering BPV as a therapeutical target in clinical practice.

Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure.

Clinical and cognitive progression in alpha-synucleinopathies is highly heterogeneous. While some patients remain stable over long periods of time, other suffer early dementia or fast motor deterioration. Sleep disturbances and nocturnal blood pressure abnormalities have been identified as independent risk factors for clinical progression but a mechanistic explanation linking both aspects is lacking. We hypothesize that impaired glymphatic system might play a key role on clinical progression. Glymphatic system clears brain waste during specific sleep stages, being blood pressure the motive force that propels the interstitial fluid through brain tissue to remove protein waste. Thus, the combination of severe sleep alterations, such as REM sleep behavioral disorder, and lack of the physiological nocturnal decrease of blood pressure due to severe dysautonomia may constitute the perfect storm for glymphatic failure, causing increased abnormal protein aggregation and spreading. In Lewy body disorders (Parkinson's disease and dementia with Lewy bodies) the increment of intraneuronal alpha-synuclein and extracellular amyloid-ß would lead to cognitive deterioration, while in multisystemic atrophy, increased pathology in oligodendroglia would relate to the faster and malignant motor progression. We present a research model that may help in developing studies aiming to elucidate the role of glymphatic function and associated factors mainly in alpha-synucleinopathies, but that could be relevant also for other protein accumulation-related neurodegenerative diseases. If the model is proven to be useful could open new lines for treatments targeting glymphatic function (for example through control of nocturnal blood pressure) with the objective to ameliorate cognitive and motor progression in alpha-synucleinopathies.