Hypoxia Inducible transcription Factors (HIFs) are principally regulated by the 2-oxoglutarate and Iron(II) prolyl hydroxylase (PHD) enzymes, which hydroxylate the HIFα subunit, facilitating its ...proteasome-mediated degradation. Observations that HIFα hydroxylation can be impaired even when oxygen is sufficient emphasise the importance of understanding the complex nature of PHD regulation. Here, we use an unbiased genome-wide genetic screen in near-haploid human cells to uncover cellular processes that regulate HIF1α. We identify that genetic disruption of the Vacuolar H+ ATPase (V-ATPase), the key proton pump for endo-lysosomal acidification, and two previously uncharacterised V-ATPase assembly factors, TMEM199 and CCDC115, stabilise HIF1α in aerobic conditions. Rather than preventing the lysosomal degradation of HIF1α, disrupting the V-ATPase results in intracellular iron depletion, thereby impairing PHD activity and leading to HIF activation. Iron supplementation directly restores PHD catalytic activity following V-ATPase inhibition, revealing important links between the V-ATPase, iron metabolism and HIFs.
Age-related swallowing changes are well-researched in deglutology, usually distinguishing those over 60 years as older aged. World-wide, older adults are healthier and forecast to live longer: many ...over 85 years. It is necessary for clinicians to understand healthy swallowing changes in this ‘oldest old’ in order to appropriately manage swallowing complaints in older patients. This systematic review collated and critically appraised studies investigating swallowing changes in adults over 85 years using instrumental assessment. Criteria for inclusion were healthy subjects over 85 years. Exclusion criteria included studies focused on anatomy and oral processing. Studies published until December 2018 were retrieved from BIOSIS, CINAHL, Embase, Medline, and Scopus, totaling 2125 articles. During data screening, 64% of studies investigating age-related swallowing changes were excluded, as the oldest old were not recruited. After PRISMA screening, 44 articles met criteria. These were further reviewed for data extraction, bias and quality. Main quantitative age-related changes in swallowing included increases in delay in swallow onset, bolus transit times, duration of UES opening, pressure above the UES and UES relaxation pressure, and reduction in pressure at the UES. Few studies detected increased residue or airway compromise in the form of aspiration. Results were not easily comparable due to differences in age ranges, methods for deeming participants ‘healthy’, measures used to define swallowing physiology, and swallowing tasks. Age-related swallowing changes are identified that do not compromise safety. The oldest old are underrepresented in normative deglutition research. It is essential future studies plan accordingly to recruit those over 85 years.
Early identification and intervention has shown better health outcomes for children with dysphagia. Instrumental swallowing assessments are vital and have been a focus of dysphagia research in the ...last two decades. This systematic review explores published quantitative instrumental measures of swallowing in children. Five subject-related databases were searched to identify original scientific articles published in English, using instrumental quantitative measures of swallowing to study swallowing/feeding mechanism in children since 1998. Two thousand two hundred and two articles were found from the initial database search and 36 were included in the final qualitative synthesis following PRISMA guidelines. Selected studies showed great diversity in target population, phase/s of swallowing studied, instrumentation used (
n
= 10) and quantitative measures reported (
n
= 144). Videofluoroscopy and manometry have been studied most repeatedly. With less frequency, a variety of other instruments has been used to describe suck-swallow patterns and swallowing-related respiration. High-resolution manometry shows the greatest increase in publications with validated, reliable quantitative measures of pharyngeal and oesophageal pressures and timing. More recently, quantification of videofluoroscopy analysis has been a focus.
Conclusion
: A diverse range of quantitative measures of swallowing is available for children in the literature. However, further reliability and validity testing is needed. Opportunities for clinical application of these quantitative manometric and videofluoroscopic measures are restricted by limited normative comparisons and vast variability in published measures.
What is known?
• Instrumental swallowing assessments are reliable and accurate in diagnosing swallowing difficulties in children
.
• However
,
subjective interpretation of observational findings often questions the optimal use of instrumentation
.
What is new?
• High
-
resolution manometry has shown promising progress with the development of quantitative objective swallow measures for children
.
While attempts to quantify video-fluoroscopic measures have been increased in the recent past
.
• A vast variety of instruments has been used to obtain quantitative and
/
or objective swallow measures of children
,
yet clinical application is still in progress
.
Lee Silverman Voice Treatment (LSVT LOUD®) is an effective therapy for phonation in Parkinson's Disease (PD) but little is known about any additional spread of effects to swallowing and cough ...function. This pilot study examined the effect of LSVT LOUD on pharyngeal swallowing parameters and reflexive cough strength.
Twenty participants (14 men, 6 women; mean 68years, SD3.5) with PD referred for LSVT LOUD with complaints of voice deterioration were recruited. Mean duration of PD was 6yrs., SD 3. Self-reported Eating Assessment Tool-10 scores ranging from 0 to 25 (normal<3). Prior to LSVT LOUD, 1-week post- and 6-months post-treatment, participants undertook a videofluoroscopic study of swallowing and aerodynamic measures of involuntary cough.
All participants completed the LSVT LOUD programme; 3 participants were lost to follow-up at 6-months. All participants made significant gains in average sound pressure level (dB SPL). Aspiration was not observed. Pharyngeal residue (p<0.05) and pharyngeal area at rest reduced (p<0.01) while maximal opening of pharyngoesophageal segment (PES) (p<0.05) and PES opening duration (p<0.05) significantly increased. There was a significant improvement in involuntary cough peak expiratory flow rate and peak expiratory flow rise time. All changes were maintained at 6-months.
LSVT LOUD demonstrates additional spread effects on pharyngoesophageal deglutitive function and involuntary cough effectiveness in people with mild PD referred with voice complaints. Consequently, LSVT LOUD has potential to provide additional benefits for swallowing safety and efficiency in this patient group.
•LSVT LOUD® is a non-invasive programme to enhance Parkinson's disease-related hypophonia.•This study demonstrates additional spread effects of LSVT LOUD® on swallowing and cough function.•Following LSVT LOUD®, swallowing videofluoroscopic physiology parameters significantly improved.•Swallowing improvements were sustained six months after LSVT LOUD®.•Following LSVT LOUD®, quantitative expiratory airflow parameters significantly improved.
Texture-modified diets (TMDs) play an important role in ensuring safety for those with dysphagia but come with risks to nutrition and quality of life. The use of TMDs has been addressed with the ...increasing prevalence of dysphagia in previous decades. However, there is limited literature that investigates the nutrition perspectives of TMD consumers. This review summarises the nutrition outcomes of adults consuming TMDs and thickened fluids (TFs) and identifies the limitations of TMD and TF productions. A systematic database search following PICO criteria was conducted using Cochrane Central (via Ovid), MEDLINE, CINAHL, EMBASE, and Scopus databases. Nutrition intake, meal consumption, adequacy, and meal composition were identified as relevant outcomes. 35 studies were included for analysis. Consumption of TMDs demonstrated a poorer intake compared to regular diets, in particular significant in energy and calcium. Meta-analysis of mean differences showed favourable effects of shaped TMDs on both energy (-273.8 kJ/d; 95%CI: -419.1 to -128.6,
= 0.0002) and protein (-12.4 g/d; 95%CI: -17.9 to -6.8,
< 0.0001) intake compared to traditional cook-fresh TMDs. Nutrition intake was compromised in TMD consumers. Optimisation of nutrition intake was achievable through enrichment and adjusting meal texture and consistency. However, the heterogeneity of studies and the missing verification of the consistencies lead to difficulty in drawing conclusions regarding particular texture or intervention.
As a result of the high prevalence of dysphagia in aged care facilities, demand for pureed diets is increasing. One of the biggest challenges for pureed diets is the reduced nutritional density due ...to the cooking process, such as when blending or softening with liquid. This study aimed to investigate the impact of innovative energy and protein-enriched meat puree on the nutrition intake and nutritional status of aged care residents requiring pureed diets.
This is a single-blinded randomised controlled trial conducted in two aged care facilities using a crossover design. Twenty-two residents aged 83.2 ± 7.3 years participated in a 12-week study. Participants were blocked randomised into two groups and received a 6-week of either control (unaltered freshly made pureed diets by facilities) or intervention diet, followed by a 2-week washout and then 6-week of alternative treatment. During the intervention, freshly made meat pureed portions were swapped to hydrolysed meat, which contained 144 -392 kcal and 5.6-6.8 g more energy and protein per 100 g. Nutrition intake was collected using a validated visual estimation method over 24 h on two non-consecutive days during the control and intervention phases. A two-tailed t-test was used to compare the significance.
The intervention diet significantly increased energy (147 ± 285 kcal, p = .02), protein (4 ± 7 g, p = .04), and fat (3 ± 8 g, p = .07) intake in comparison to the control diet. Nutritional status was improved by the end of the intervention as evidenced by a higher nutritional assessment score using Mini-Nutritional Assessment - Short Form (9.1 ± 1.8) and a weight gain of 1.3 ± 1.7 g, p = .04. No significant differences were found in body composition using bioelectrical impedance analysis, calf circumference and mid-upper arm circumference. Though handgrip strength did not differ at the end of control and intervention, significance was found between the changes in control and intervention period. Plasma branched-chain amino acid increased significantly with hydrolysed meat consumption.
As a dietary enrichment, hydrolysed meat is a promising intervention for pureed diet consumers in aged care facilities, improving residents' dietary intake and reducing malnutrition risk. Future larger multicentre studies with longer intervention periods are required to confirm the effectiveness and residents' acceptance.
Australian New Zealand Clinical Trials Registry (ACTRN12622000888763).
Oral nutritional supplements (ONS) are high-energy and protein-rich nutrition drinks that are commonly prescribed to individuals with compromised nutritional status. Aged care residents requiring ...texture-modified diets are exposed to poor oral intake and malnutrition. This study aimed to investigate the dietary intake and nutritional status of residents consuming texture-modified diets with and without ONS. This multicentre cross-sectional study included 85 residents consuming texture-modified diets (86.0 ± 8.7 y; n = 46 requiring ONS and n = 39 without ONS). A one-day dietary record was completed using a validated visual plate waste estimation method. To determine the adequacy, nutrition intake was then calculated using FoodWorks (Xyris Ltd., Brisbane, Australia) and compared to the recommended dietary intake for Australia and New Zealand. The Mini-Nutritional Assessment Short Form was collected to assess nutritional status. Residents receiving ONS had significantly higher energy, protein, carbohydrates and fat intake than those who did not consume ONS (p < 0.05). No significant differences were found in saturated fat, fibre or sodium intake. With the administration of ONS, residents were able to meet their protein requirement but fell short of their energy and carbohydrates requirements. Both groups had inadequate fibre intake and a high saturated fat intake. A total of 48% of the residents were at risk of malnutrition and 38% were malnourished. Aged care residents requiring texture-modified diets are at high risk of malnutrition as a result of inadequate dietary intake. Administration of ONS may be an effective strategy to optimise nutrition intake.
Facial palsy is a frequent and debilitating sequela of stroke and brain injury, causing functional and aesthetic deficits as well as significant adverse effects on quality of life and well-being. ...Current literature reports many cases of acquired facial palsy that do not recover spontaneously, and more information is needed regarding the efficacy of physical therapies used in this population.
A systematic search of eight electronic databases was performed from database inception to December 2018. Gray literature searches were then performed to identify additional articles. Studies were included if they addressed physical rehabilitation interventions for adults with acquired facial palsy. Reasons for exclusion were documented. Independent data extraction, quality assessment, and risk of bias assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Following abstract screening, a total of 13 full-text articles were identified for independent screening by two reviewers. This included four randomized control trials, two non-randomized control trials, one cohort study, and six prospective case series studies. Twelve out of the 13 included studies reported on facial palsy as a sequela of stroke. A total of 539 participants received intervention for facial palsy across the 13 included studies. Therapy design, length and frequency of intervention varied across the studies, and a wide range of outcome measures were used. Improvement on various outcome measures was reported across all 13 studies. The quality of the evidence was low overall, and most studies were found to have high risk of bias.
All the studies in this review report improvement of facial movement or function following application of various methods of physical rehabilitation for facial palsy. Methodological limitations and heterogeneity of design affect the strength of the evidence and prevent reliable comparison between intervention methods. Strong evidence supporting physical rehabilitation was not found; well-designed rigorous research is required.
Objectives:
Establishing the range of normal esophageal bolus transit times (ETT) is valuable when distinguishing pathology from normal variance, especially in elderly patients, and has not been ...documented for paste or pill. The aim of this study was to measure esophageal transit of liquid, paste, and pill during upright videofluoroscopy.
Methods:
One hundred eighteen healthy adults (mean age 54; range 20-98 years; SD = 21.40) with no complaints of dysphagia completed a videofluoroscopy with esophageal visualization including 20 ml liquid barium, 5 ml paste, and pill.
Results:
Mean ETTs were: 20 ml fluid, 10.7 seconds (SD = 13.6, median = 5.76, IQR = 4.33, range, 2.0-60.0); pill, 25.3 seconds (SD = 24.0, median = 12.70, IQR = 49.81, range, 1.0-60.0); paste, 28.6 seconds (SD = 23.31, median = 17.47, IQR = 53, range, 4.0-60.0). Age was significantly associated with increasing 20 ml fluid ETT (P < .001) but not pill (P = .58) or paste ETT (P = .12). Fluid ETT over 10 seconds occurred in 10% of participants between 20 and 59 years, in comparison to 35% over 60 years (P < .001).
Conclusions:
These normative values provide a standardized protocol and guidance in interpretation when completing esophageal visualization as part of videofluoroscopy. While measuring fluid ETT may support referral for further specialist investigations, slower paste and pill ETT may be normal findings. Age-related slowing in fluid ETT was seen in healthy adults. Further investigation of ETT is needed in both normal and dysphagic subjects.
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