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Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2., Materials and Methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic., Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future., Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients., (© Dustri-Verlag Dr. K. Feistle.)

Vaccination is the main public health intervention to prevent influenza. We aimed to evaluate the efficacy and safety of influenza vaccination including systematic reviews and meta-analyses of observational studies and randomized controlled trials (RCTs). Peer-reviewed systematic reviews with meta-analyses of prospective studies that investigated the association of influenza vaccination with any health-related outcome, as well as RCTs that investigated the efficacy and safety of influenza vaccination, were included. Among 1240 references, 6 meta-analyses were included. In cohort studies of community-dwelling older people influenza vaccination was associated with a lower risk of hospitalization for heart disease and for influenza/pneumonia (strength of evidence: convincing). Evidence in lowering the risk of mortality in community-dwelling older people, of all deaths/severe respiratory diseases in high risk community-dwelling older people and of hospitalization for influenza/pneumonia in case-control studies, was highly suggestive. In RCTs, influenza vaccination, compared to placebo/no intervention, was associated to higher risk of local tenderness/sore arm and to a reduced risk of influenza like-illness. Both these associations showed moderate evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation). In conclusion, influenza vaccination in older people seems safe and effective. Further, the evidence on safety and efficacy of vaccines in this population might benefit by an extension of the follow-up period both in RCTs and in longitudinal studies, beyond the usual 6-month period, in order to be able to evaluate the impact of vaccination on long term outcomes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The early stages of the COVID-19 pandemic have focused on containing SARS-CoV-2 infection and identifying treatment strategies. While controlling this communicable disease is of utmost importance, the long-term effect on individuals with non-communicable diseases (NCD) is significant. Although certain NCDs appear to increase the severity of COVID-19 and mortality risk, SARS-CoV-2 infection in survivors with NCDs may also affect the progression of their pre-existing clinical conditions. Infection containment measures will have substantial short- and long-term consequences; social distancing and quarantine restrictions will reduce physical activity and increase other unhealthy lifestyles, thus increasing NCD risk factors and worsening clinical symptoms. Vitamin D levels might decrease and there might be a rise in mental health disorders. Many countries have made changes to routine management of NCD patients, e.g., cancelling non-urgent outpatient visits, which will have important implications for NCD management, diagnosis of new-onset NCDs, medication adherence, and NCD progression. We may have opportunities to learn from this unprecedented crisis on how to leverage healthcare technologies and improve procedures to optimize healthcare service provision. This article discusses how the COVID-19 outbreak and related infection control measures could hit the most frail individuals, worsening the condition of NCD patients, while further jeopardizing the sustainability of the healthcare systems. We suggest ways to define an integrated strategy that could involve both public institutional entities and the private sector to safeguard frail individuals and mitigate the impact of the outbreak.

No abstract available., (© Dustri-Verlag Dr. K. Feistle.)

Polydopamine (PDA) is a bioinspired fascinating polymer which is considered nowadays as a material of choice for designing drug delivery nanosystems. Indeed, PDA exhibits multiple interesting features including simple preparation protocols, biocompatibility, simple functionalization procedures, free radicals scavenging and photothermal/photoacoustic properties. However, because of its heterogeneous structure, clear procedures about PDA nanoparticles synthesis and PEGylation with well-defined and reproducible physicochemical properties such as size, shape and nanomechanics are still needed. In this work, we established tightly controlled experimental conditions to synthesize PDA nanoparticles with well-defined size and yield. This allowed us to identify the factors that affect the most these two parameters and to construct surface response plots with accurate predictive values of size and yield. The nanomechanical properties of PDA NPs exhibiting different sizes have been studied with AFM nanoindentation experiments. Our results demonstrated for the first time that the elasticity of PDA NPs was decreasing with their size. This could be explained by the higher geometric packing order of the stacked oligomeric fractions inside the core of the biggest PDA NPs. Next, in order to determine the best PEGylation experimental conditions of PDA NPs using thiol-terminated PEG that allow grafting the highest polymer density with proteins repelling properties, we have first optimized the PEGylation strategy on PDA films. By using a combination of QCM-D and AFM experiments, we could demonstrate that efficient PEGylation of PDA films could be done even at low PEG concentration but in the presence of NaCl which exerts a salting out effect on PEG chains improving thus the grafting density. Finally, we transposed these experimental conditions to PDA NPs and we could synthesize PEGylated PDA NPs exhibiting high stability in physiological conditions as revealed by FTIR and DLS experiments respectively.

A locally organized monolayer film strongly attached to a gold surface is obtained by transfer of a Langmuir-Blodgett (LB) film of octadecylamine (ODA) or alcohol (ODOH) onto a Au surface and simultaneous oxidative electrografting of this film still in contact with the aqueous subphase. As opposed to LB films, these films resist ultrasonication; and unlike electrografted films, they are organized monolayers by construction. They are characterized by AFM (atomic force microscopy), water contact angle, ellipsometry, XPS (X-ray photoelectron spectroscopy), IRRAS (infrared reflection absorption spectroscopy), and GIXD (grazing incidence X-ray diffraction).

Vaccine-preventable diseases represent a considerable burden on world health, and can have long-lasting consequences in those infected, especially in older adults, who can suffer functional decline, disability, and death. Vaccine uptake across the life course is desirable, but often suboptimal. A number of factors have been identified as contributors to low vaccine coverage, including sociodemographic characteristics, logistic factors such as ease of access and convenience, cultural attitudes including health literacy, and vaccine hesitancy. Strategies to improve vaccine uptake can target all the components underpinning low coverage, and include technology and communication-based strategies, physician-centered approaches, targeting healthcare workers for influenza vaccination, system-based factors, improved vaccine efficacy, and above all, political will and leadership., (© 2020 S. Karger AG, Basel.)

As populations age globally, the health of older adults is looming larger on the agendas of public health bodies. In particular, the priority is to ensure that older adults remain healthy, independent, and engaged in their communities. In other words, ensuring that increasing life spans are matched by increasing "health spans," meaning years spent in good health. Chronic conditions such as cancer or respiratory and cardiovascular diseases account for the bulk of the disease burden in older adults, and the consensus is that these can best be tackled by effective primary prevention. However, given the diverse nature of older populations, whose prior health experiences can be complicated by multi-morbidity and poly-pharmacy, effective primary prevention can be challenging. One approach that is gaining momentum is what is called "precision" or P4 medicine. The acronym stands for "predictive, personalized, preventive, participatory" medicine, and is based on the premise that preventing disease is better than treating it. However, effective prevention requires the ability to predict disease risk for a given patient, the tailoring of treatment to their circumstances, and their consent for or participation in the offered treatment. A P4 approach may seem counter-intuitive, given that vaccination is generally considered a public health intervention. However, in this article, we discuss the application of P4 medicine as a complement to planning the vaccination of older individuals, with a special focus on the important role that vaccine-preventable infections play in the burden of non-communicable disease., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background: Despite the existence of efficacious vaccines, the burden of vaccine-preventable diseases remains high and the potential health benefits of paediatric, adolescent and adult vaccination are not being achieved due to suboptimal vaccine coverage rates. Based on emerging evidence that pharmacy-based vaccine interventions are feasible and effective, the European Interdisciplinary Council for Ageing (EICA) brought together stakeholders from the medical and pharmacy professions, the pharmaceutical industry, patient/ageing organisations and health authorities to consider the potential for pharmacy-based interventions to increase vaccine uptake. We report here the proceedings of this 3-day meeting held in March 2018 in San Servolo island, Venice, Italy, focussing firstly on examples from countries that have introduced pharmacy-based vaccination programmes, and secondly, listing the barriers and solutions proposed by the discussion groups., Conclusions: A range of barriers to vaccine uptake have been identified, affecting all target groups, and in various countries and healthcare settings. Ease of accessibility is a potentially modifiable determinant in vaccine uptake, and thus, improving the diversity of settings where vaccines can be provided to adults, for example by enabling community pharmacists to vaccinate, may increase the number of available opportunities for vaccination.

The positive gerontological approach to aging has resulted in successive terminologies to describe the process of aging, including successful aging, active aging, healthy aging, or healthy and active aging, amongst others. Each definition proposed by geriatricians, psychologists, sociologists or public health specialists has been based on specific aspects of aging that are most important to the authors' discipline, explaining the current difficulty in determining which is the best set of criteria to determine "good aging". Two successive analyses of the measurements used in longitudinal studies from 1989 to 2018 testify to this heterogeneity in the types of questions proposed to evaluate the quality of the individual aging process. To confront this complexity, new and integrated indices have successively been proposed to quantify and qualify the survival period of aging individuals. The present paper aims to describe and compare the value of the "healthy aging index", the "modified healthy aging index", the "healthy aging score" and the "selfie aging test". Attempts to date to identify the best individual measurement of "aging well" have been interesting, and certainly show promise, but their limitations to specific populations call for more concerted effort from the scientific community to obtain worldwide validation. Another option would be to identify the best self-assessment questionnaire and include it in a mobile device, enabling longer term personal follow-up of aging functions. There is a clear lack of data of this type at present, and an urgent need to obtain such information, to enable early and targeted interventions.

The development of elongated nanoparticles for drug delivery is of growing interest in recent years, due to longer blood circulation and improved efficacy compared to spherical counterparts. Squalenoyl-doxorubicin (SQ-Dox) conjugate was previously shown to form elongated nanoparticles with improved therapeutic efficacy and decreased toxicity compared to free doxorubicin. By using experimental and computational techniques, we demonstrate here that the specific physical properties of SQ-Dox, which include stacking and electrostatic interactions of doxorubicin as well as hydrophobic interactions of squalene, are involved in the formation of nanoassemblies with diverse elongated structures. We show that SQ-Dox bioconjugate concentration, ionic strength, and anion nature can be used to modulate the shape and stiffness of SQ-Dox nanoparticles. As those parameters are involved in nanoparticle behavior in biological media, these findings could bring interesting opportunities for drug delivery and serve as an example for the design of original nanodrugs with stacking properties tuned for particular clinical purposes.

Almost six decades after the first proposals to define and evaluate the quality of individual aging, the first indexes for assessing the aging process at the societal level have appeared. Moreover, in five years, three different scores for measuring societal aging have been developed and tested in different areas. The Global Age Watch Index focused on 96 countries from around the world, while the Active Ageing index is limited to the European Union countries and the Ageing Society Index targets Organization for Economic Co-operation and Development countries. This paper analyzed and compared the results of these three indexes. The rankings vary little at the bottom end of the scale, with the same countries consistently ranked among the lowest scores (for example, Poland ranked last among the European countries in the three indexes). The same is true at the top of the rankings, with Sweden, the Netherlands, and Ireland consistently among the high-scoring countries. However, the three indices tend to differently rank the countries in the middle. The United States, for example, is ranked ninth in the Global Age Watch 2015 and third in the Ageing Societal Index 2018. In cases in which the results are not consistent, it is difficult for politicians and policymakers to adequately identify needs and orient the policy to promote active and healthy aging. There is clearly a compelling need for wide-scale debate to reach a consensus on a comprehensive score or index at the societal level., Competing Interests: The researcher claims no conflicts of interest., (Copyright © 2019 by The Korean Geriatric Society.)

Squalene-adenosine (SQAd) nanoparticles (NPs) were found to display promising pharmacological activity similar to many other nanomedicines, but their long-term stability was still limited, and their preparation required specific know-how and material. These drawbacks represented important restrictions for their potential use in the clinic. Freeze-drying nanoparticles is commonly presented as a solution to allow colloidal stability, but this process needs to be adapted to each nanoformulation. Hence, we aimed at developing a specific protocol for freeze-drying SQAd NPs while preserving their structural features. NPs were lyophilised, resuspended and analysed by dynamic light scattering, atomic force microscopy and small-angle scattering. Among four different cryoprotectants, trehalose was found to be the most efficient in preserving NPs physico-chemical characteristics. Interestingly, we identified residual ethanol in NP suspensions as a key parameter which could severely affect the freeze-drying outcome, leading to NPs aggregation. Long-term stability was also assessed. No significant change in size distribution or zeta potential could be detected after three-month storage at 4 °C. Finally, freeze-dried NPs innocuity was checked in vitro on cultured hepatocytes and in vivo on mice. In conclusion, optimisation of freeze-drying conditions resulted in safe lyophilised SQAd NPs that can be easily stored, shipped and simply reconstituted into an injectable form.

The analysis of the ageing trajectory clearly demonstrates the constant involvement of functional ability in daily life, from its development in youth, to its preservation through midlife into very old age. While maintaining function appears to be largely related to persistent regular exercise, the risk factors for functional decline are extremely diverse, ranging from a decrease or discontinuation of physical activity, to nutritional/metabolic disturbances, chronic diseases and unfavourable socio-demographic and socio-economic contexts. Prevention of functional decline is a major public health challenge, both for individuals and for society as a whole, and needs to be urgently addressed. Engaging citizens to be conscious of their responsibility for, and role in their own ageing process is equally as important as reinforcing the involvement of society in promoting healthy ageing through enhanced basic and health education, promotion of a healthy diet, long term practice of moderate physical activity, and the continual battle against deleterious life habits and behaviours. The success of these combined actions would be quite simply demonstrated by a change from the current pandemics of morbidity, to the compression of disability, which is expected by all., Competing Interests: The author has no conflict of interest., (Copyright: © 2019 Hylonome Publications.)

If the mycelium of Aspergillus fumigatus is very short-lived in the laboratory, conidia can survive for years. This survival capacity and extreme resistance to environmental insults is a major biological characteristic of this fungal species. Moreover, conidia, which easily reach the host alveola, are the infective propagules. Earlier studies have shown the role of some molecules of the outer conidial layer in protecting the fungus against the host defense. The outer layer of the conidial cell wall, directly in contact with the host cells, consists of α-(1,3)-glucan, melanin, and proteinaceous rodlets. This study is focused on the global importance of this outer layer. Single and multiple mutants without one to three major components of the outer layer were constructed and studied. The results showed that the absence of the target molecules resulting from multiple gene deletions led to unexpected phenotypes without any logical additivity. Unexpected compensatory cell wall surface modifications were indeed observed, such as the synthesis of the mycelial virulence factor galactosaminogalactan, the increase in chitin and glycoprotein concentration or particular changes in permeability. However, sensitivity of the multiple mutants to killing by phagocytic host cells confirmed the major importance of melanin in protecting conidia., (© 2018 John Wiley & Sons Ltd.)

Herpes zoster (HZ) is a painful cutaneous rash with vesicular lesions, lasting up to 3 weeks, and caused by reactivation of the latent varicella zoster virus (VZV). It may be associated with complications, the most feared being post-herpetic neuralgia. Effective vaccines are available to prevent HZ, but uptake remains low. We report here the conclusions of an expert focus group convened by the European Interdisciplinary Council on Ageing (EICA). The group discussed how existing recommendations regarding HZ vaccination could be better implemented, and how compliance and coverage with HZ vaccination could be enhanced. This report proposes strategies to increase awareness of HZ and its vaccine, enhance vaccine uptake, and educate regarding the role of prevention, including immunization, as a means to "age well". A key strategy that could rapidly and easily be implemented at low cost is co-administration of HZ vaccine with other vaccines scheduled in the target age group. The scientific evidence surrounding the safety and efficacy of co-administration is discussed. Other strategies, such as active calls, publicity campaigns and national vaccine registries are also outlined. There is a compelling need for a full consensus document that carries weight across all the healthcare professions involved in vaccination, to issue simple and basic recommendations for all healthcare providers.

In specific conditions, co-incubation of polymer nanoparticles and phospholipid vesicles leads to the formation of lipid bilayer coated nanoparticles usable as biocompatible drug delivery systems for co-encapsulation of two drugs. In this work, we focused on the preparation and characterization of liponanoparticles obtained by co-incubation of poly(d,l, lactic acid) (PDLLA) and neutral (POPC) or cationic (POPC/DOTAP) liposomes. The comparison of the behavior of the various studied vesicles co-incubated with nanoparticles highlighted the role of electrostatic interactions. Although the bilayer adsorbed at the surface of polymer nanoparticles was not visible by cryoTEM, zeta-potential measurements and fluorescence confocal microscopy showed evidence of the formation of hybrid nanoparticles in the presence of cationic vesicles. Using silicon dioxide and Langmuir-Schaefer transferred polymer layer-coated surfaces, a thorough analysis of the process of formation of a phospholipid bilayer at the surface of a PDLLA film was performed by combining QCM-D and AFM experiments, taking into account the nature and properties of the support, and the concentration and charge of the lipids. Contrarily to POPC vesicles, cationic ones formed a bilayer on the PDLLA layer in water, but their fast rupture on the soft material did not allow complete nanoparticle surface coverage. This work demonstrates the role of charges and polymer mechanical stiffness in the mechanism and kinetics of formation of PDLLA liponanoparticles in pure water.

Objectives: Healthy ageing (HA) is a key concept and highly desirable phenomenon in every ageing and already old societies. The aim of our study was to evaluate the influence of socio-economic conditions as well as life-style and other health-related factors on the WHO definition of HA., Design, Setting, Participants: The study used cross-sectional data of the PolSenior Project - nationwide research evaluating different aspects of ageing in Poland - which included 4'653 respondents aged 65 years and over., Measurements: Data were collected by trained interviewers in respondents' homes. Three definitions of HA including or not the participants' chronic conditions were analyzed., Results: The prevalence of HA appeared as high as 17.6% if none or 1 chronic disease was present and 42.8% if no information about chronic diseases was taken into account. The association between known health predictors (age, marital status, education, income) and HA was observed. Moreover, HA appeared in relation with indicators of physical functioning and lifestyle. There was a strong concordance between HA and the fair self-rated health (OR = 1.87; 1.99, and 2.74 for the 1st, 2nd and 3rd definitions, respectively) and opposite relation with self-reported need for help (OR = 0.15; 0.15; and 0.13, respectively)., Conclusions: The HA definition based on no functional activity limitations, no cognitive impairment, no depressive symptoms, no more than one disease and being socially active seems to be a useful approach of HA., Competing Interests: None declared.

Amphiphilic triblock (Atri) copolymers made of perfluorinated alkyl chain linked to hydrocarbon chain and methoxy-poly(ethylene glycol) of three different molecular weights were synthesized. In vitro evaluation demonstrated that these new compounds were noncytotoxic. Characterization and interaction of each triblock copolymer with a branched polyamine myristoyl lipid (2-{3[bis-(3-amino-propyl)-amino]-propylamino}- N-ditetradecyl carbamoyl methyl-acetamide, DMAPAP) were studied by the Langmuir film method and thermal analysis. The triblock copolymer/cationic lipids (1:10, w/w) were mixed with perfluorobutane gas to form microbubbles (MBs). The latter were characterized by optical microscopy to get the microbubble size and concentration by densimetry to determine the amount of encapsulated gas and by ultrasound to assess oscillation properties. Atri with the lowest and intermediate weights were shown to interact with the cationic lipid DMAPAP and stabilize the Langmuir film. In that case, monodisperse microbubbles ranging from 2.3 ± 0.1 to 2.8 ± 0.1 μm were obtained. The proportion of encapsulated gas within the MB shell increased up to 3 times after the incorporation of the copolymer with the lowest and intermediate weights. Moreover, the acoustic response of the microbubbles was maintained in the presence of the copolymers.

The outer membrane (OM) of Gram-negative bacteria is a complex and asymmetric bilayer that antimicrobial peptides must disrupt in order to provoke the cell lysis. The inner and external leaflets of the OM are mainly composed of phospholipids (PL), and lipopolysaccharide (LPS), respectively. Supported lipid bilayers are interesting model systems to mimic the lipid asymmetric scaffold of the OM and determine the quantitative and mechanistic effect of antimicrobial agents, using complementary physicochemical techniques. We report the formation of asymmetric PL/LPS bilayers using the Langmuir-Blodgett/Langmuir-Schaefer technique on two different surfaces (sapphire and mica) with synthetic phospholipids constituting the inner leaflet and bacteria-extracted mutant LPS making up the outer one. The combination of neutron reflectometry and atomic force microscopy techniques allowed the examination of the asymmetric scaffold structure along the normal to the interface and its surface morphology in buffer conditions. Our results allow discrimination of two structurally related peptides, one neutral and inactive, and the other cationic and active. The active cationic plasticin PTCDA1-KF disrupts the asymmetric OM at relevant concentrations through a carpeting scenario characterized by a dramatic removal of lipid molecules from the surface.

Malnutrition is common in Asia, especially among people who are critically ill and/or older. Study results from China, Japan, and Taiwan show that malnutrition or risk of malnutrition is found in up to 30% of communitydwelling people and as much as 50% of patients admitted to hospitals-with prevalence even higher among those older than 70 years. In Asia, malnutrition takes substantial tolls on health, physical function, and wellbeing of people affected, and it adds huge financial burdens to healthcare systems. Attention to nutrition, including protein intake, can help prevent or delay disease- and age-related disabilities and can speed recovery from illness or surgery. Despite compelling evidence and professional guidelines on appropriate nutrition care in hospital and community settings, patients' malnutrition is often overlooked and under-treated in Asian healthcare, as it is worldwide. Since the problem of malnutrition continues to grow as many Asian populations become increasingly "gray", it is important to take action now. A medical education (feedM.E.) Global Study Group developed a strategy to facilitate best-practice hospital nutrition care: screen-intervene-supervene. As members of a newly formed feedM.E. Northeast Asia Study Group, we endorse this care strategy, guiding clinicians to screen each patient's nutritional status upon hospital admission or at initiation of care, intervene promptly when nutrition care is needed, and supervene or follow-up routinely with adjustment and reinforcement of nutrition care plans, including post-discharge. To encourage best-practice nutrition in Asian patient care settings, our paper includes a simple, stepwise Nutrition Care Pathway (NCP) in multiple languages.

The overlap between one innovative paradigm (P4 medicine: predictive, personalized, participatory and preventive) and another (a new definition of "Healthy ageing") is fertile ground for new technologies; a new mobile application (app) that could broaden our scientific knowledge of the ageing process and help us to better analyse the impact of possible interventions in slowing the ageing decline. A novel mobile application is here presented as a game including questions and tests will allow in 10 minutes the assessment of the following domains: robustness, flexibility (lower muscle strength), balance, mental and memory complaints, semantic memory and visual retention. This game is completed by specific measurements, which could allow establishing precise information on functional and cognitive abilities. A global evaluation precedes advice and different types of exercises. The repetition of the tests and measures will allow a long follow up of the individual performances which could be shared (on specific request) with family members and general practitioners., Competing Interests: No conflict of interest.

The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).

Gram-negative bacteria possess a unique and complex cell envelope, composed of an inner and outer membrane separated by an intermediate cell wall-containing periplasm. This tripartite structure acts intrinsically as a significant biological barrier, often limiting the permeation of anti-infectives, and so preventing such drugs from reaching their target. Furthermore, identification of the specific permeation-limiting envelope component proves difficult in the case of many anti-infectives, due to the challenges associated with isolation of individual cell envelope structures in bacterial culture. The development of an in vitro permeation model of the Gram-negative inner membrane, prepared by repeated coating of physiologically-relevant phospholipids on Transwell ® filter inserts, is therefore reported, as a first step in the development of an overall cell envelope model. Characterization and permeability investigations of model compounds as well as anti-infectives confirmed the suitability of the model for quantitative and kinetically-resolved permeability assessment, and additionally confirmed the importance of employing bacteria-specific base materials for more accurate mimicking of the inner membrane lipid composition - both advantages compared to the majority of existing in vitro approaches. Additional incorporation of further elements of the Gram-negative bacterial cell envelope could ultimately facilitate model application as a screening tool in anti-infective drug discovery or formulation development., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The majority of old people suffer from various clinical conditions that affect health, functioning and quality of life. This research is a part of a cross-sectional, nationwide PolSenior Study that provides a comprehensive assessment of eight geriatric impairments and their co-occurrence in a representative sample (3471 participant aged 65-104 years, mean age 78.3 years) of the old adults living in the community in Poland. The participants were recruited randomly from all administrative regions of Poland by a three-stage, proportional, stratified-by-age group selection process. Eight geriatric conditions were assessed: falls, incontinences, cognitive impairment, mood disorders, vision and hearing impairments, malnutrition, and functional dependence. We showed that the most common deficits causing disability were vision and hearing impairments, and mood disorders, with more than two thirds of the participants presented at least one geriatric deficit. We showed that presence any of the analyzed conditions significantly increased the risk for co-occurrence of other examined weaknesses. The highest prevalence odds ratios were for functional dependence and, respectively: malnutrition (8.61, 95%CI:4.70-15.80), incontinences (8.0, 95%CI:5.93-10.70), and cognitive impairment (7.22; 95%CI:5.91-8.83). We concluded that the majority of the old people living in the community present various clinical conditions that prompt disability., Competing Interests: The authors declare that they have no competing interests. Disclaimers: All authors declared that the views expressed in the submitted article are his or her own and not an official position of the institution or funder.

Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority.' Numerous longitudinal studies and meta-analyses were conducted to analyze the risk and protective factors for dementia. Among the 93 identified risk factors, seven major modifiable ones should be considered: low education, sedentary lifestyle, midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression. Three other important modifiable risk factors should also be added to this list: midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney disease. After their identification, numerous authors attempted to establish dementia risk scores; however, the proposed values were not convincing. Identifying the possible interventions, able to either postpone or delay dementia has been an important challenge. Observational studies focused on a single life-style intervention increased the global optimism concerning these possibilities. However, a recent extensive literature review of the randomized control trials (RCTs) conducted before 2014 yielded negative results. The first results of RCTs of multimodal interventions (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and Prediva) brought more optimism. Lastly, interventions targeting compounds of beta amyloid started in 2012 and no results have yet been published., Competing Interests: No potential conflict of interest relevant to this article was reported.

Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.

Rapid population aging has become a major challenge in the industrialized world and progressive aging is a key reason for making improvement in vaccination a cornerstone of public health strategy. An increase in age-related disorders and conditions is likely to be seen in the near future, and these are risk factors for the occurrence of a number of vaccine-preventable diseases. An improvement in infectious diseases prevention specifically aimed at adults and the elderly can therefore also decrease the burden of these chronic conditions by reducing morbidity, disability, hospital admissions, health costs, mortality rates and, perhaps most importantly, by improving the quality of life. Among adults, it is necessary to identify groups at increased risk of vaccine-preventable diseases and highlight the epidemiological impact and benefits of vaccinations using an evidence-based approach. This document provides clinical practice guidance on immunization for adults in order to provide recommendations for decision makers and healthcare workers in Europe. Although immunization is considered one of the most impactful and cost-effective public health measures that can be undertaken, vaccination coverage rates among adults are largely lower than the stated goal of ≥ 95% among adults, and stronger efforts are needed to increase coverage in this population. Active surveillance of adult vaccine-preventable diseases, determining the effectiveness of the vaccines approved for marketing in the last 5 y, the efficacy and safety of vaccines in immunocompromised patients, as well as in pregnant women, represent the priorities for future research.

Purpose: To identify and prioritize potential topics to be addressed in the development of European multidisciplinary guidelines on the management of chronic kidney disease stage 3b-5 in older patients., Methods: We composed a list of 47 potential guideline topics by reviewing the literature, consulting online 461 nephrologists and 107 geriatricians, and obtaining expert input. A multidisciplinary panel of twelve experts then prioritized the topics during a face-to-face consensus meeting, following a nominal group technique structure with two voting rounds. Topics were rated on a 9-point scale ranging from 1 ('not at all important') to 9 ('critically important')., Results: The highest rating (median; range) was assigned to 'Screening and referral' (8.5; 2.0). Eight topics shared the second highest rating with a median priority score of 8.0 (2.0) and included 'Starting dialysis or not' and 'Accurate assessment of renal function.' 'Targets for and treatment of diabetes' received the lowest rating with (3.0; 6.0)., Conclusions: This joint initiative of the European Renal Association-European Dialysis Transplant Association (ERA-EDTA) and the European Union Geriatric Medicine Society (EUGMS) prioritized the development of guidance on interdisciplinary referral of older patients with chronic kidney disease stage 3b-5. Future guidance will therefore focus on identifying prognostic scores to predict death and progression to end-stage renal disease, as well as accurate tests for assessment of renal function in older kidney patients. This will contribute to more informed treatment decision making in this growing patient population.

Although populations around the world are rapidly ageing, evidence that increasing longevity is being accompanied by an extended period of good health is scarce. A coherent and focused public health response that spans multiple sectors and stakeholders is urgently needed. To guide this global response, WHO has released the first World report on ageing and health, reviewing current knowledge and gaps and providing a public health framework for action. The report is built around a redefinition of healthy ageing that centres on the notion of functional ability: the combination of the intrinsic capacity of the individual, relevant environmental characteristics, and the interactions between the individual and these characteristics. This Health Policy highlights key findings and recommendations from the report., (Copyright © 2016 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

The absolute and relative increases in the number of older persons are evident worldwide, from the most developed countries to the lowest-income regions. Multimorbidity and need for social support increase with age. Age-related conditions and, in particular, disabilities are a significant burden for the person, his or her family, and public health care systems. To guarantee the sustainability of public health systems and improve the quality of care provided, it is becoming urgent to act to prevent and delay the disabling cascade. Current evidence shows that too large a proportion of community-dwelling older people present risk factors for major health-related events and unmet clinical needs. In this scenario, the "frailty syndrome" is a condition of special interest. Frailty is a status of extreme vulnerability to endogenous and exogenous stressors exposing the individual to a higher risk of negative health-related outcomes. Frailty may represent a transition phase between successful aging and disability, and a condition to target for restoring robustness in the individual at risk. Given its syndromic nature, targeting frailty requires a comprehensive approach. The identification of frailty as a target for implementing preventive interventions against age-related conditions is pivotal. Every effort should be made by health care authorities to maximize efforts in this field, balancing priorities, needs, and resources. Raising awareness about frailty and age-related conditions in the population is important for effective prevention, and should lead to the promotion of lifelong healthy behaviors and lifestyle., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: There is a variation in dialysis withdrawal rates, but reasons for this variation across European countries are largely unknown. We therefore surveyed nephrologists' perceptions of factors concerning dialysis withdrawal and palliative care and explored relationships between these perceptions and reports of whether withdrawal actually occurred in practice., Methods: We developed a 33-item electronic survey, disseminated via an email blast to all European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) members. In our data analyses, we distinguished those respondents who reported occurrence from those reporting no dialysis withdrawal in their unit. With multilevel logistic regression, we investigated the association between respondents' characteristics and perceptions and whether they reported occurrence of dialysis withdrawal or not., Results: Five hundred and twenty-eight nephrologists from 45 countries completed the questionnaire; 42% reported occurrence of withdrawal in their unit in the past year, and 56% perceived that stopping life-prolonging treatment in terminally ill patients was allowed. Few respondents reported presence in their unit of protocols on withdrawal decision making (7%) or palliative care (10%) or the common involvement of a geriatrician in withdrawal decisions (10%). The majority stated that palliative care had not been part of their core curriculum (74%) and that they had not recently attended continuous medical education sessions on this topic (73%). Respondents from Eastern and Southern Europe had a 42 and 40% lower probability, respectively, of reporting withdrawal compared with those from North European countries. Working in a public centre [odds ratio (OR), 2.41; 95% confidence interval (CI), 1.36-4.25] and respondents' perception that stopping life-prolonging treatment in terminally ill patients was allowed (OR, 1.96; 95% CI, 1.23-3.12), that withdrawal decisions were commonly shared between doctor and patient (OR, 1.97; 95% CI, 1.26-3.08) and that palliative care was reimbursed (OR, 1.81; 95% CI, 1.16-2.83) increased the odds of reporting occurrence of withdrawal., Conclusion: Reports of dialysis withdrawal occurrence varied between European countries. Occurrence reports were more likely if respondents worked in a public centre, if stopping life-prolonging treatments was perceived as allowed, if withdrawal decisions were considered shared between doctors and patients and if reimbursement of palliative care was believed to be in place. There is room for improvement regarding protocols on withdrawal and palliative care processes and regarding nephrologists' training and education on end-of-life care., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Bacterial resistance to antibiotics has become today a major public health issue. In the development of new anti-infectious therapies, antimicrobial peptides appear as promising candidates. However, their mechanisms of action against bacterial membranes are still poorly understood. We describe for the first time the interaction and penetration of plasticins into lipid monolayers and bilayers modeling the two leaflets of the asymmetrical outer membrane of Gram-negative bacteria. The lipid composition of these monolayers mimics that of each leaflet: mixtures of LPS Re 595 mutant and wild type S-form from Salmonella enterica for the external leaflet, and SOPE/SOPG/cardiolipin (80/15/5) for the inner one. The analysis of the interfacial behavior of native (PTCDA1) and modified (PTCDA1-KF) antimicrobial plasticins showed that PTCDA1-KF exhibited better surface properties than its unmodified counterpart. Both peptides could penetrate into the model monolayers at concentrations higher than 0.1 μM. The penetration was particularly enhanced for PTCDA1-KF into the mixed LPS monolayer, due to attractive electrostatic interactions. Grazing X-ray diffraction and atomic force microscopy studies revealed the changes in LPS monolayers organization upon peptide insertion. The interaction of plasticins with liposomes was also monitored by light scattering and circular dichroism techniques. Only the cationic plasticin achieved full disaggregation and structuration in α helices, whereas the native one remained aggregated and unstructured. The main steps of the penetration mechanism of the two plasticins into lipid models of the external leaflet of the outer membrane of Gram-negative bacteria have been established.

Compared with intravenous (i.v.) chemotherapy, oral administration is convenient, requires fewer healthcare resources, is generally preferred by patients, and may be appropriate in older people with breast, colorectal and lung cancers. The effects of organ dysfunction on drug metabolism and drug interactions in patients with multiple comorbidities must be considered but are not specific to oral chemotherapy. Single-agent oral chemotherapy with capecitabine or vinorelbine is active in older patients with advanced or metastatic breast cancer. Choice of treatment is based mainly on different safety profiles. In the adjuvant treatment of colorectal cancer (CRC), single-agent oral capecitabine is an effective alternative to i.v. fluorouracil (5-FU) regimens. In metastatic CRC, oral, single-agent capecitabine has recently shown encouraging median overall survival in combination with bevacizumab. In non-small cell lung cancer, fit older patients, like their younger counterparts, benefit from platinum-based doublets, with carboplatin preferred to cisplatin. Single agent vinorelbine is an option for those less suited to combination chemotherapy, and oral may be an alternative to i.v. administration. For elderly cancer patients in general, metronomic chemotherapy combines good tolerability with acceptable activity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Health is a multi-dimensional concept, capturing how people feel and function. The broad concept of Active and Healthy Ageing was proposed by the World Health Organisation (WHO) as the process of optimizing opportunities for health to enhance quality of life as people age. It applies to both individuals and population groups. A universal Active and Healthy Ageing definition is not available and it may differ depending on the purpose of the definition and/or the questions raised. While the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has had a major impact, a definition of Active and Healthy Ageing is urgently needed. A meeting was organised in Montpellier, France, October 20-21, 2014 as the annual conference of the EIP on AHA Reference Site MACVIA-LR (Contre les Maladies Chroniques pour un Vieillissement Actif en Languedoc Roussillon) to propose an operational definition of Active and Healthy Ageing including tools that may be used for this. The current paper describes the rationale and the process by which the aims of the meeting will be reached.

This article first reports the spontaneous course of frailty conditions, and then focuses on randomized, controlled frailty interventions (such as physical exercise, nutrition, combined exercise plus nutrition, and multifactorial interventions) or metaanalysis in community-dwelling older adults or volunteers published in 2012, 2013, and 2014. The main take-home messages that emerge from recent literature are summarized., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Herpes zoster (HZ) is primarily a disease of nerve tissue but the acute and longer-term manifestations require multidisciplinary knowledge and involvement in their management. Complications may be dermatological (e.g. secondary bacterial infection), neurological (e.g. long-term pain, segmental paresis, stroke), ophthalmological (e.g. keratitis, iridocyclitis, secondary glaucoma) or visceral (e.g. pneumonia, hepatitis). The age-related increased incidence of HZ and its complications is thought to be a result of the decline in cell-mediated immunity (immunosenescence), higher incidence of comorbidities with age and social-environmental changes. Individuals who are immunocompromised as a result of disease or therapy are also at increased risk, independent of age. HZ and its complications (particularly postherpetic neuralgia) create a significant burden for the patient, carers, healthcare systems and employers. Prevention and treatment of HZ complications remain a therapeutic challenge despite recent advances. This is an overview of the multidisciplinary implications and management of HZ in which the potential contribution of vaccination to reducing the incidence HZ and its complications are also discussed.