A quantitative comparison of plantar soft tissue strainability distribution and homogeneity between ulcerated and non-ulcerated patients using ultrasound strain elastography.

The primary objective of this study was to develop a method that allows accurate quantification of plantar soft tissue stiffness distribution and homogeneity. The secondary aim of this study was to investigate if the differences in soft tissue stiffness distribution and homogeneity can be detected between ulcerated and non-ulcerated foot. Novel measures of individual pixel stiffness, named as quantitative strainability (QS) and relative strainability (RS) were developed. Strain Elastography data obtained from 39 (nine with active diabetic foot ulcers) patients with diabetic neuropathy. The patients with active diabetic foot ulcer had wound in parts of the foot other than the first metatarsal head and the heel where the elastography measures were conducted. RS was used to measure changes and gradients in the stiffness distribution of plantar soft tissues in participants with and without active diabetic foot ulcer. The plantar soft tissue homogeneity in superior-inferior direction in the left forefoot was found to be significantly (p < 0.05) higher in ulcerated group compared to non-ulcerated group. The assessment of homogeneity showed potentials to further explain the nature of the change in tissue that can increase internal stress. This can have implications in assessing the vulnerability to plantar soft tissue damage and ulceration in diabetes.

Phytoconstituents as Lead Compounds for Anti-Dengue Drug Discovery.

Dengue is an arthropod-borne viral disease common in subtropical and tropical regions. The widespread use of traditional medicines in these regions for dengue fever (DF) has encouraged researchers to explore the therapeutic effect of herbs and their phytochemicals in dengue infection. Phytochemicals such as quercetin, baicalein, luteolin, oxindole alkaloids, celastrol and geraniin have shown significant inhibition of dengue virus in vitro. Many phytoconstituents have better selectivity index supporting their safety profile for future development. However, in vivo studies supporting therapeutic potency for these active phytoconstituents are limited. There is a need for studies translating anti-dengue profile of active phytoconstituents to find successful anti-dengue compounds.

Formulation and evaluation of rutin-loaded solid lipid nanoparticles for the treatment of brain tumor.

The primary requirement for curing cancer is the delivery of essential drug load at the cancer microenvironment with therapeutic efficacy. Considering this, the present study aims to formulate "Rutin"-encapsulated solid lipid nanoparticles (SLNs) for effective brain delivery across the blood-brain barrier (BBB). Rutin-loaded SLNs were fabricated by oil-in-water microemulsion technique and were characterized for their physicochemical properties. The in vivo biodistribution study of rutin-loaded SLNs was studied using Rattus norvegicus rats. Subsequently, in silico molecular docking and dynamic calculations were performed to examine the binding affinity as well as stability of rutin at the active site of target protein "epidermal growth factor receptor (EGFR)." Formulated rutin-loaded SLNs were predominantly spherical in shape with an average particle diameter of 100 nm. Additionally, the biocompatibility and stability have been proved in vitro. The presence and biodistribution of rutin in vivo after 54 h of injection were observed as 15.23 ± 0.32% in the brain, 8.68 ± 0.63% in the heart, 4.78 ± 0.28% in the kidney, 5.04 ± 0.37% in the liver, 0.92 ± 0.04% in the lung, and 11.52 ± 0.65% in the spleen, respectively. Molecular docking results revealed the higher binding energy of - 150.973 kJ/mol of rutin with EGFR. Molecular dynamic simulation studies demonstrated that rutin with EGFR receptor complex was highly stable at 30 ns. The observed results exemplified that the formulated rutin-loaded SLNs were stable in circulation for a period up to 5 days. Thus, rutin-encapsulated SLN formulations can be used as a promising vector to target tumors across BBB. Graphical abstract.

Reliability and validity of an enhanced paper grip test; A simple clinical test for assessing lower limb strength.

BACKGROUND: The paper-grip-test (PGT) involves pulling a small card from underneath the participant's foot while asking them to grip with their hallux. The PGT is shown to be effective in detecting foot muscle-weakening but its outcome is operator-dependent. To overcome this limitation, an enhanced PGT (EPGT) is proposed that replaces the pass/fail outcome of the PGT with a continuous measurement of the pulling force that is needed to remove the card (EPGT-force). RESEARCH QUESTION: Is the EPGT-force an accurate, reliable and clinically applicable measurement of strength? METHODS: Reliability and clinical applicability were examined in two ways. Firstly, two examiners measured EPGT-force for twenty healthy volunteers in a test/retest set-up. EPGT force was measured using a dynamometer, the hallux grip force was measured using a pressure mat. The clinical applicability of the EPGT was tested in ten people with diabetes. Postural sway was also measured. RESULTS: Interclass correlation coefficients (ICC) revealed excellent inter-rater reliability (ICC > 0.75). Intra-rater reliability was excellent for the first examiner (ICC = 0.795) and good for the second (ICC = 0.703). Linear regression analysis indicated that hallux grip force accounted (on average) for 83 %±4 % of the variability in EPGT force. This strong relationship between EPGT force and hallux grip force remained when the test was performed in a clinical setting with the latter accounting for 88 % in EPGT force variability. Spearman rank order correlation showed that people with diabetes with a higher difference in EPGT force between limbs swayed more. SIGNIFICANCE: EPGT force is a reliable and accurate measurement of hallux grip force. Hallux grip force was previously found to be strongly correlated to the strength of all muscle groups of the foot and ankle and to the ability to maintain balance. The proposed EPGT could be used to monitor muscle weakness in clinics for better falls-risk assessment.

The relationship between hallux grip force and balance in people with diabetes.

BACKGROUND: Diabetes accelerates the decline in muscle strength in older people and substantially increases the risk for fall and injury. Weakening of lower extremity muscles, in particular, is a strong predictor for falls, but currently there is no established method for its assessment in clinics. The paper grip test (PGT) offers a qualitative assessment of hallux plantar flexor strength and its usefulness for predicting falls has been demonstrated in non-diabetic populations. RESEARCH QUESTION: The aim of this study is to test whether the PGT can be used for a quantitative assessment of lower-extremity strength and to investigate its relationship with isometric muscle strength and balance in people with diabetes and peripheral neuropathy. METHODS: Isometric muscle strength of all muscle groups of the foot-ankle was assessed using a dynamometer in sixty-nine people with diabetes and neuropathy. Postural sway and the gripping force exerted by the participants during the PGT was measured for the same participants using a plantar pressure assessment system. These measurements were repeated in regular intervals for 18 months in a longitudinal observational cohort study. RESULTS: Cross-sectional analysis of baseline data showed that people who failed the PGT swayed more. Analysis of longitudinal data showed that increasing hallux grip force is significantly associated with reduced postural sway. No significant association was found between dynamometry-based measurements of strength and postural sway. Hallux grip force was significantly correlated to the strength of all muscle groups of the foot-ankle complex. SIGNIFICANCE: These results indicate that hallux grip force can assess the strength of the foot-ankle muscles and could potentially be used to identify people at risk of falling. This sets the basis for the development of new screening protocols to assess weakening of the muscles of the foot-ankle and to enhance risk assessment for falls in people with diabetes and peripheral neuropathy.

Hallux plantar flexor strength in people with diabetic neuropathy: Validation of a simple clinical test.

AIM: To validate the paper grip test for assessing plantar flexion strength of the hallux. METHODS: Plantar flexor strength for 69 people with diabetic neuropathy was assessed: (a) using the paper grip test while simultaneously a plantar pressure platform quantified the force under the hallux, and (b) using a hand-held dynamometer. Following testing, participants were divided into groups: (1) passed vs. failed paper grip test (2) males vs. females. Statistical analyses determined if differences were evident between the groups and assessed the relationship between the paper grip test and the hand-held dynamometer. The discrimination ability, sensitivity, specificity, and reproducibility of the paper grip test was established. RESULTS: Participants who passed the paper grip test demonstrated greater grip force at the hallux than those who failed, and they also exhibited greater isometric maximum force during the hand-held dynamometry test (p ≤ 0.05). Grip force for males was significantly higher than for females. A moderate positive correlation between the paper grip test and the hand-held dynamometer was evident. CONCLUSIONS: In the population examined the paper grip test was found to be a valid clinical tool; it offers a non-invasive, inexpensive, and quick method to assess plantar flexion strength of the hallux.

Complementary Role of Herbal Medicine and Exercise in Cardiovascular Disease Prevention and Management: A Review of Evidence.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. Herbal medicine and exercise interventions have individually been shown to be effective in the prevention and management of CVD. However, the complementary roles of herbal medicine and exercise interventions for CVD prevention and management have not been adequately reported. OBJECTIVE: 1. Identify studies analysing complementary roles of herbal medicine and exercise intervention in CVD prevention and management, 2. Identify herbs and exercise strategies that have been reported to exhibit complementary roles in CVD prevention and management, and 3. Summarize evidence of complementary roles of herbal medicine and exercise interventions for CVD prevention and management. METHOD: PubMed, CINAHL and Web of Science were searched with a customised search strategy in May 2015. Two reviewers screened the search results for inclusion using pre-specified criteria. Data were extracted from full text of selected abstracts in a predetermined template by two reviewers and verified by the third reviewer when needed. RESULTS: A total of 35 titles were identified for full texts review after screening 827 abstracts. Data were extracted from 23 titles, representing 12 human studies and six animal studies. This review identified effects of 14 different herbs and 10 exercise strategies on over 18 CVD risk factors and markers. Complementary roles of herbal medicine and exercise were reported from five studies. CONCLUSION: Evidence of complementary role of herbal medicine and exercise is emerging from animal studies. More robust clinical studies on proven risk factors are needed before they can be recommended for clinical practice.

Differences in the mechanical characteristics of plantar soft tissue between ulcerated and non-ulcerated foot.

AIMS: The purpose of this study was to investigate the differences in mechanical properties of the plantar soft tissue between the ulcerated and non-ulcerated feet in patients with diabetic neuropathy. METHODS: Thirty nine patients who met the inclusion criteria participated in this study. Ten out of 39 participants had an active ulcer at a site other than the plantar heel and the first metatarsal head. Real time ultrasound elastography was performed to measure the soft tissue thickness and stiffness of the heel pad and sub-metatarsal fat pad. To account for the qualitative nature of conventional real time elastography, relative tissue stiffness was assessed against that of a standardised ultrasound standoff material. RESULTS: The results indicated that the ulcerated group had a significantly lower heel pad relative stiffness (t (37)=2.559, P=0.015, η2=0.150) in the left foot. CONCLUSIONS: The observed difference in the stiffness of the heel pad between the ulcerated and non-ulcerated feet indicates a possible link between tissue mechanics and ulceration. Further analysis of the data proposed in this study provided a quantitative assessment of plantar fat pad deformability which can contribute to understanding the role of tissue biomechanics in ulceration.

Assessment of lower leg muscle force distribution during isometric ankle dorsi and plantar flexion in patients with diabetes: a preliminary study.

AIM: The aim of this study was to evaluate the differences in ankle muscle strength using hand-held dynamometry and to assess difference in the isometric muscle force distribution between the people with diabetes and control participants. METHODS: The maximal muscle strength of ankle plantarflexion, dorsiflexion, eversion, inversion, lesser toes flexors and extensors, hallux flexors, and extensors was assessed in 20 people with diabetes and 20 healthy participants using hand-held dynamometry. The maximal isometric ankle plantarflexion and dorsiflexion were imported to OpenSim software to calculate 12 individual muscle (8 plantarflexors and 4 dorsiflexors) forces acting on ankle joint. RESULTS: A significant reduction in ankle strength for all measured actions and a significant decrease in muscle force for each of the 12 muscles during dorsi and plantar flexion were observed. Furthermore, the ratios of agonist to antagonist muscle force for 6 of the muscles were significantly different between the control group and the group with diabetes. CONCLUSIONS: It is likely that the muscles for which the agonist/antagonist muscle force ratio was significantly different for the healthy people and the people with diabetes could be more affected by diabetes.

The relationship between the mechanical properties of heel-pad and common clinical measures associated with foot ulcers in patients with diabetes.

AIM: The present study aims at investigating the correlation between the mechanical properties of the heel-pad of people with type-2 diabetes and the clinical parameters used to monitor their health and ulceration risk. METHODS: A new device for the in-vivo testing of plantar soft tissues was built and pilot-tested. This device consists of an ultrasound probe connected in series with a dynamometer. Loading is applied manually using a ball-screw actuator. A total of 35 volunteers with type-2 diabetes were recruited and the thickness, stiffness of their heel-pads as well as the energy absorbed during loading were assessed. The participants with diabetes also underwent blood tests and measurements of Ankle Brachial Index and Vibration Perception Threshold. RESULTS: Pearson correlation analysis revealed strong correlations between triglycerides and heel-pad stiffness (r=0.675, N=27, p<0.001) and between triglycerides and energy (r=-0.598, N=27, p=0.002). A correlation of medium strength was found between Fasting Blood Sugar (FBS) and stiffness (r=0.408, N=29, p=0.043). CONCLUSIONS: People with type-2 diabetes and high levels of triglycerides and FBS are more likely to have stiffer heel-pads. Increased stiffness could limit the tissues' ability to evenly distribute loads making them more vulnerable to trauma and ulceration.