The influence of optimal dietary protein intake for muscle metabolism across the lifespan

Research has demonstrated a deterioration of skeletal muscle mass and function with increasing age (termed ‘sarcopenia’), and protein nutrition, in particular amount and source of protein, has been highlighted as a key factor regulating its progression. This thesis endeavours to explore the role of protein dose and source on muscle metabolism across the lifespan; from younger adults to frail older adults in care homes. Chapter 2 of this thesis explores the causes of protein-energy malnutrition in the residential care setting and evaluates the interventional literature targeting this. A review of the literature establishes that oral nutritional supplementation and protein-fortified foods are most commonly used to increase daily protein intake in care home residents. However, the effectiveness of these on musculoskeletal health outcomes and their compliance rates are unclear and conflicting due to the complexity in carrying out interventional work in this setting. Chapter 3 of this thesis investigates the role of habitual dietary protein intake on physiological muscle parameters in healthy older adults, with results suggesting that there are no differences between the habitual protein intakes of these two populations. However, whole-body lean mass and knee extensor strength were significantly higher in younger adults, suggesting that in recreationally active, healthy older adults, other factors aside from habitual protein intake are playing a role in regulation of muscle metabolism. To further explore this, Chapter 4 aims to develop a human serum ex vivo C2C12 co-culture model to explore the use of fasted vs. fed serum to investigate muscle responsiveness to feeding, with results demonstrating negligible differences between serum conditions. Further optimisation of this model is needed, with no clear protocol for AA starvation period, serum treatment concentration, nor media glucose content yet identified. The final data chapter of this thesis explores the amino acid (AA) kinetics in young and older adults following ingestion of a vegan-blend and whey protein, and highlights a lower circulating concentration of several AAs, including leucine, following consumption of a vegan-blend protein in comparison to a whey protein, with little effect of age. Further investigation confirmed the muscle protein synthesis (MPS) response of C2C12 myotubes to AA treatment mimicking vegan and whey protein compositions. However, when ‘preconditioning’ C2C12 myotubes with young and older adult fasted serum prior to AA treatment, there is negligible age nor protein source differences in the myotube MPS response

Prevalence of multisensory hallucinations in people at risk of transition to psychosis

Hallucinations can occur in single or multiple sensory modalities. Greater attention has been paid to single sensory experiences with a comparative neglect of hallucinations that occur across two or more sensory modalities (multisensory hallucinations). This study explored how common these experiences were in people at risk of transition to psychosis (n=105) and considered whether a greater number of hallucinatory experiences increased delusional ideation and reduced functioning, both of which are associated with a greater risk of transition to psychosis. Participants reported a range of unusual sensory experiences, with two or three being common. However, when a strict definition of hallucinations was applied, in which the experience has the quality of a real perception and in which the person believes them to be real experiences, then multisensory experiences were rare and when reported, single sensory hallucinations in the auditory domain were most common. The number of unusual sensory experiences or hallucinations was not significantly associated with greater delusional ideation or poorer functioning. Theoretical and clinical implications are discussed

Impacts of extreme climatic events on the energetics of long-lived vertebrates: the case of the greater flamingo facing cold spells in the Camargue.

International audienceMost studies analyzing the effects of global warming on wild populations focus on gradual temperature changes, yet it is also important to understand the impact of extreme climatic events. Here we studied the effect of two cold spells (January 1985 and February 2012) on the energetics of greater flamingos (Phoenicopterus roseus) in the Camargue (southern France). To understand the cause of observed flamingo mass mortalities, we first assessed the energy stores of flamingos found dead in February 2012, and compared them with those found in other bird species exposed to cold spells and/or fasting. Second, we evaluated the monthly energy requirements of flamingos across 1980-2012 using the mechanistic model Niche Mapper™. Our results show that the body lipids of flamingos found dead in 2012 corresponded to 2.6±0.3% of total body mass, which is close to results found in woodcocks (Scolopax rusticola) that died from starvation during a cold spell (1.7±0.1%), and much lower than in woodcocks which were fed throughout this same cold spell (13.0±2%). Further, Niche Mapper™ predicted that flamingo energy requirements were highest (+6-7%) during the 1985 and 2012 cold spells compared with 'normal' winters. This increase was primarily driven by cold air temperatures. Overall, our findings strongly suggest that flamingos starved to death during both cold spells. This study demonstrates the relevance of using mechanistic energetics modelling and body condition analyses to understand and predict the impact of extreme climatic events on animal energy balance and winter survival probabilities

Overcoming Protein-Energy Malnutrition in Older Adults in the Residential Care Setting: A Narrative Review of Causes and Interventions.

Malnutrition, in particular protein-energy malnutrition, is a highly prevalent condition in older adults, and is associated with low muscle mass and function, and increased prevalence of physical frailty. Malnutrition is often exacerbated in the residential care setting due to factors including lack of dentition and appetite, and increased prevalence of dementia and dysphagia. This review aims to provide an overview of the available literature in older adults in the residential care setting regarding the following: links between sarcopenia, frailty, and malnutrition (in particular, protein-energy malnutrition (PEM)), recognition and diagnosis of malnutrition, factors contributing to PEM, and the effectiveness of different forms of protein supplementation (in particular, oral nutritional supplementation (ONS) and protein-fortified foods (PFF)) to target PEM. This review found a lack of consensus on effective malnutrition diagnostic tools and lack of universal requirement for malnutrition screening in the residential care setting, making identifying and treating malnutrition in this population a challenge. When assessing the use of protein supplementation in the residential care setting, the two primary forms of supplementation were ONS and PFF. There is evidence that ONS and PFF increase protein and energy intakes in residential care setting, yet compliance with supplementation and their impact on functional status is unclear and conflicting. Further research comparing the use of ONS and PFF is needed to fully determine feasibility and efficacy of protein supplementation in the residential care setting

Determining the Influence of Habitual Dietary Protein Intake on Physiological Muscle Parameters in Youth and Older Age.

Protein ingestion is a potent stimulator of skeletal muscle protein synthesis (MPS). However, older adults demonstrate resistance to anabolic stimuli. Some evidence has demonstrated that a larger acute protein dose is required in older compared to younger adults to elicit the same synthetic response, suggesting that older adults should be consuming higher habitual dietary protein to optimise muscle mass. However, limited research has explored dietary habits in different age groups or the relationship between habitual dietary intake and mechanistic physiological parameters associated with muscle mass and function. This work investigated the effect of habitual dietary intake in young ( = 10, 25.9 (3.2y)) and older ( = 16, 70.2 (3.2y)) community-dwelling adults (16:10 male: female) on physiological muscle parameters. Dietary intake was assessed using four-day diet diaries. Post-absorptive MPS and MPS responses to feeding (4.25x basal metabolic rate; 16% protein) were determined in muscle biopsies of the via stable isotope tracer ([1, 2C]-leucine) infusions with mass-spectrometric analyses. Body composition was measured by dual-energy x-ray absorptiometry. Whole body strength was assessed via 1-repetition maximum assessments. No significant differences in habitual dietary intake (protein, fat, carbohydrate and leucine as g.kgWBLM.day) were observed between age groups. Whole-body lean mass (61.8 ± 9.9 vs. 49.8 ± 11.9 kg, = 0.01) and knee-extensor strength (87.7 ± 28.3 vs. 56.8 ± 16.4 kg, = 0.002) were significantly higher in young adults. Habitual protein intake (g.kg.day) was not associated with whole-body lean mass, upper-leg lean mass, whole-body strength, knee-extensor strength, basal MPS or fed-state MPS across both age groups. These findings suggest that differences in muscle mass and strength parameters between youth and older age are not explained by differences in habitual dietary protein intake. Further research with a larger sample size is needed to fully explore these relationships and inform on interventions to mitigate sarcopenia development

High dose benzodiazepine dependence: Description of 29 patients treated with flumazenil infusion and stabilised with clonazepam

The withdrawal syndrome from benzodiazepine (BZD) can be severe and in some cases may impede cessation of the use of the drug. We present here a case series of benzodiazepine detoxification by flumazenil infusion, stabilised with clonazepam. Patients were treated with flumazenil 1.35. mg/day for a median of 7. days. Self-reported physical withdrawal symptoms were recorded daily. In addition to flumazenil, antidepressants were given before treatment commenced and clonazepam was administered nightly with both being continued after discharge. Twenty-nine patients were treated. No patients dropped out from the treatment programme. Nine patients (31%) required a temporary reduction/cessation of the infusion. The linear trend in the reduction of the daily withdrawal scores in the overall study population was significant. The linear trends were also significant in the group of patients for whom a temporary reduction/suspension of the flumazenil was required. Six months after treatment, 15 patients (53%) were abstinent from clonazepam and other BZDs. For five (21%) the BZD dependence were reinstated. More than two-thirds of the subjects tolerated the procedure well and about half had a good long term response. Slow flumazenil infusion appears to merit consideration as a possible future treatment. Suggestions for future research are examined. © 2012 Elsevier Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Bibliometric Assessment of European and Sub-Saharan African Research Output on Poverty-Related and Neglected Infectious Diseases from 2003 to 2011.

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a partnership of European and sub-Saharan African countries that aims to accelerate the development of medical interventions against poverty-related diseases (PRDs). A bibliometric analysis was conducted to 1) measure research output from European and African researchers on PRDs, 2) describe collaboration patterns, and 3) assess the citation impact of clinical research funded by EDCTP.Disease-specific research publications were identified in Thomson Reuters Web of Science using search terms in titles, abstracts and keywords. Publication data, including citation counts, were extracted for 2003-2011. Analyses including output, share of global papers, normalised citation impact (NCI), and geographical distribution are presented. Data are presented as five-year moving averages. European EDCTP member countries accounted for ~33% of global research output in PRDs and sub-Saharan African countries for ~10% (2007-2011). Both regions contributed more to the global research output in malaria (43.4% and 22.2%, respectively). The overall number of PRD papers from sub-Saharan Africa increased markedly (>47%) since 2003, particularly for HIV/AIDS (102%) and tuberculosis (TB) (81%), and principally involving Southern and East Africa. For 2007-2011, European and sub-Saharan African research collaboration on PRDs was highly cited compared with the world average (NCI in brackets): HIV/AIDS 1.62 (NCI: 1.16), TB 2.11 (NCI: 1.06), malaria 1.81 (NCI: 1.22), and neglected infectious diseases 1.34 (NCI: 0.97). The NCI of EDCTP-funded papers for 2003-2011 was exceptionally high for HIV/AIDS (3.24), TB (4.08) and HIV/TB co-infection (5.10) compared with global research benchmarks (1.14, 1.05 and 1.35, respectively).The volume and citation impact of papers from sub-Saharan Africa has increased since 2003, as has collaborative research between Europe and sub-Saharan Africa. >90% of publications from EDCTP-funded research were published in high-impact journals and are highly cited. These findings corroborate the benefit of collaborative research on PRDs

Progress in promoting data sharing in public health emergencies

In February 2016, the World Health Organization (WHO) declared the Zika virus-related cluster of microcephaly cases and other neurological disorders reported in Brazil, a Public Health Emergency of International Concern (PHEIC).1 Following the declaration, over 30 global health bodies issued a joint statement committing to data sharing to ensure that the global response to the Zika virus and future emergencies, could be informed by the best and most current evidence.2 The statement represented a concerted effort by those involved to address past failures of timely access to relevant data. It also highlighted the lack of a clear path to implementation for data sharing during public health emergencies. In March 2016, the Global Research Collaboration for Infectious Disease Preparedness (GloPID-R) established a data-sharing working group which has been working in coalition with other stakeholders including WHO, scientists, nongovernmental organizations, journals and other agencies. This group is working to identify barriers to data sharing in public health emergencies that should be addressed to better prepare for any future epidemic. We review the progress since the joint statement was made, outline the key challenges related to data sharing and summarize the group’s activities to date