Can probiotics, prebiotics and synbiotics improve functional outcomes for older people: a systematic review.

PURPOSE: Research evaluating the effect of probiotics, prebiotics and synbiotics (PPS) on laboratory markers of health (such as immunomodulatory and microbiota changes) is growing but it is unclear whether these markers translate to improved functional outcomes in the older population. This systematic review evaluates the effect of PPS on functional outcomes in older people. METHODS: We conducted a systematic review of the effect of PPS in older adults on functional outcomes (physical strength, frailty, mood and cognition, mortality and receipt of care). Four electronic databases were searched for studies published since year 2000. RESULTS: Eighteen studies (including 15 RCTs) were identified. One of five studies evaluating physical function reported benefit (improved grip strength). Two analyses of one prebiotic RCT assessed frailty by different methods with mixed results. Four studies evaluated mood with no benefit reported. Six studies evaluated cognition: four reported cognitive improvement in participants with pre-existing cognitive impairment receiving probiotics. Seven studies reported mortality as a secondary outcome with a trend to reduction in only one. Five studies reported length of hospital stay but only two peri-operative studies reported shorter stays. CONCLUSION: There is limited evidence that probiotics may improve cognition in older people with pre-existing cognitive impairment but no clear evidence of benefit of PPS on physical function, frailty, mood, length of hospitalisation and mortality. Larger studies with more homogenous interventions, accounting for confounding factors, such as diet, co-morbidities and medications, are required. There is currently inadequate evidence to recommend PPS use to older people in general. PROSPERO REGISTRATION NUMBER: PROSPERO registration number is CRD42020173417. Date of PROSPERO registration: 01/05/20.

The inferomedial femoral neck is compromised by age but not disease: Fracture toughness and the multifactorial mechanisms comprising reference point microindentation.

The influence of ageing on the fracture mechanics of cortical bone tissue is well documented, though little is known about if and how related material properties are further affected in two of the most prominent musculoskeletal diseases, osteoporosis and osteoarthritis (OA). The femoral neck, in close proximity to the most pertinent osteoporotic fracture site and near the hip joint affected by osteoarthritis, is a site of particular interest for investigation. We have recently shown that Reference Point micro-Indentation (RPI) detects differences between cortical bone from the femoral neck of healthy, osteoporotic fractured and osteoarthritic hip replacement patients. RPI is a new technique with potential for in vivo bone quality assessment. However, interpretation of RPI results is limited because the specific changes in bone properties with pathology are not well understood and, further, because it is not conclusive what properties are being assessed by RPI. Here, we investigate whether the differences previously detected between healthy and diseased cortical bone from the femoral neck might reflect changes in fracture toughness. Together with this, we investigate which additional properties are reflected in RPI measures. RPI (using the Biodent device) and fracture toughness tests were conducted on samples from the inferomedial neck of bone resected from donors with: OA (41 samples from 15 donors), osteoporosis (48 samples from 14 donors) and non age-matched cadaveric controls (37 samples from 10 donoros) with no history of bone disease. Further, a subset of indented samples were imaged using micro-computed tomography (3 osteoporotic and 4 control samples each from different donors) as well as fluorescence microscopy in combination with serial sectioning after basic fuchsin staining (7 osteoporotic and 5 control samples from 5 osteoporotic and 5 control donors). In this study, the bulk indentation and fracture resistance properties of the inferomedial femoral neck in osteoporotic fracture, severe OA and control bone were comparable (p > 0.05 for fracture properties and <10% difference for indentation) but fracture toughness reduced with advancing age (7.0% per decade, r = -0.36, p = 0.029). Further, RPI properties (in particular, the indentation distance increase, IDI) showed partial correlation with fracture toughness (r = -0.40, p = 0.023) or derived elastic modulus (r = -0.40, p = 0.023). Multimodal indent imaging revealed evidence of toughening mechanisms (i.e. crack deflection, bridging and microcracking), elastoplastic response (in terms of the non-conical imprint shape and presence of pile-up) and correlation of RPI with damage extent (up to r = 0.79, p = 0.034) and indent size (up to r = 0.82, p < 0.001). Therefore, crack resistance, deformation resistance and, additionally, micro-structure (porosity: r = 0.93, p = 0.002 as well as pore proximity: r = -0.55, p = 0.027 for correlation with IDI) are all contributory to RPI. Consequently, it becomes clear that RPI measures represent a multitude of properties, various aspects of bone quality, but are not necessarily strongly correlated to a single mechanical property. In addition, osteoporosis or osteoarthritis do not seem to further influence fracture toughness of the inferomedial femoral neck beyond natural ageing. Since bone is highly heterogeneous, whether this finding can be extended to the whole femoral neck or whether it also holds true for other femoral neck quadrants or other material properties remains to be shown.

Investigation of In Vivo skin stiffness anisotropy in breast cancer related lymphoedema.

There is a limited range of suitable measurement techniques for detecting and assessing breast cancer related lymphoedema (BCRL). This study investigated the suitability of using skin stiffness measurements, with a particular focus on the variation in stiffness with measurement direction (known as anisotropy). In addition to comparing affected tissue with the unaffected tissue on the corresponding site on the opposite limb, volunteers without BCRL were tested to establish the normal variability in stiffness anisotropy between these two corresponding regions of skin on each opposite limb. Multi-directional stiffness was measured with an Extensometer, within the higher stiffness region that skin typically displays at high applied strains, using a previously established protocol developed by the authors. Healthy volunteers showed no significant difference in anisotropy between regions of skin on opposite limbs (mean decrease of 4.7 +/-2.5% between non-dominant and dominant arms), whereas BCRL sufferers showed a significant difference between limbs (mean decrease of 51.0+/-16.3% between unaffected and affected arms). A large difference in anisotropy was apparent even for those with recent onset of the condition, indicating that the technique may have potential to be useful for early detection. This difference also appeared to increase with duration since onset. Therefore, measurement of stiffness anisotropy has potential value for the clinical assessment and diagnosis of skin conditions such as BCRL. The promising results justify a larger study with a larger number of participants.

Variability in reference point microindentation and recommendations for testing cortical bone: location, thickness and orientation heterogeneity.

Reference Point Indentation (RPI) has been proposed as a new clinical tool to aid the diagnosis of Osteoporosis. This study has examined the performance of the tool within entire femurs to improve the understanding of the mechanical properties of bone and also to guide future RPI testing to optimize repeatability of results obtained using the technique. Human, bovine, porcine and rat femurs were indented along three longitudinal axes: anterior and posterior: medial and lateral as well as around the circumference of the femoral head and neck. Cortical and subchondral bone thickness was measured using CT and radiography. The study shows that in some samples, bone is too thin to support the high loads applied with the technique and in these cases, RPI values are highly influenced by thickness. The technique will be useful in the mid-shaft region where cortical thickness is greatest, providing previously established guidelines are followed to optimize measurement repeatability, including performing multiple measurements per sample and investigating multiple samples. The study has also provided evidence that RPI values vary significantly with test site, hence mechanical properties should not be inferred from RPI findings alone away from the test site, even within the same bone. In conclusion, RPI appears to be a useful tool for scientific investigation; however further work is required to examine the feasibility of using RPI for assessing differences between healthy and diseased bone in a clinical setting.

Variability in reference point microindentation and recommendations for testing cortical bone: maximum load, sample orientation, mode of use, sample preparation and measurement spacing.

Reference Point Indentation (RPI) is a novel microindentation tool that has emerging clinical potential for the assessment of fracture risk as well as use as a laboratory tool for straight-forward mechanical characterisation of bone. Despite increasing use of the tool, little research is available to advise the set-up of testing protocols or optimisation of testing parameters. Here we consider five such parameters: maximum load, sample orientation, mode of use, sample preparation and measurement spacing, to investigate how they affect the Indentation Distance Increase (IDI), the most published measurement parameter associated with the RPI device. The RPI tool was applied to bovine bone; indenting in the proximal midshaft of five femora and human bone; indenting five femoral heads and five femoral neck samples. Based on the findings of these studies we recommend the following as the best practice. (1) Repeat measurements should be utilised to reduce the coefficient of variation (e.g. 8-15 repeats to achieve a 5-10% error, however the 3-5 measurements used here gives a 15-20% error). (2) IDI is dependent on maximum load (r=0.45 on the periosteal surface and r=0.94 on the machined surface, p<0.05), mode of use (i.e. comparing the device held freehand compared to fixed in its stand, p=0.04) and surface preparation (p=0.004) so these should be kept consistent throughout testing. Though sample orientation appears to have minimal influence on IDI (p>0.05), care should also be taken in combining measurements from different orientations. (3) The coefficient of variation is higher (p=0.04) when holding the device freehand, so it should ideally be kept supported in its stand. (4) Removing the periosteum (p=0.04) and machining the surface of the bone (p=0.08) reduces the coefficient of variation, so should be performed where practical. (5) There is a hyperbolic relationship between thickness and IDI (p<0.001) with a sample thickness 10 fold greater than the maximum indentation depth recommended, to ensure a representative measurement. (6) Measurement spacing does not appear to influence the IDI (p>0.05), so it can be as low as 500 µm. By following these recommendations, RPI users can minimise the potential confounding effects associated with the variables investigated here and reduce the coefficient of variation, hence achieving more consistent testing. This optimisation of the technique enhances both the clinical and laboratory potential of the tool.

New strategies for the synthesis of biologically important tetrapyrroles. The "B,C + D + A" approach to linear tetrapyrroles.

Linear tetrapyrroles related to phytochrome (1) were prepared in enantiospecific fashion by a new strategy beginning with ring-B,C synthons of type 19 (bis-iododipyrrins). Rings A and D were elaborated by Pd(0)-mediated coupling of 19a with the appropriate alkyne acid or amide derivatives 9 and 20, followed by intramolecular cyclization (method C: BC + D + A --> ABCD).

Humanism: is its evaluation captured in commonly used performance measures?

BACKGROUND: There is an increased awareness of the importance of humanistic behavior and its education in the medical school curriculum. Relatively little is known about correlations between humanism and other performance measures. PURPOSES: To determine the correlation between humanism and other commonly used performance measures, and to determine if more humanistic students perform better, the same, or worse than less humanistic students. METHODS: During the Family Medicine clerkship, standardized patients (SPs) used the Physician Humanism Scale to assess 428 students for humanism. Clinical preceptors, SPs, written assignments, and a national knowledge examination also assessed student performance. The humanism scores were correlated with the SP and non-SP performance measures. RESULTS: Humanism scores were significantly and positively correlated to all of the performance measures, but the correlation coefficients were low, ranging from .12 to .31. Students in the lowest quartile for humanism consistently scored lower for all of the performance measures, including both local and national exams (two-tailed significance < .018). Students with very low humanism scores still passed other performance evaluations. CONCLUSIONS: The correlation between humanism and other performance measures is quite low, indicating that a separate measure for humanism provides different and additional information that current performance measures do not include. More humanistic students perform better than their less humanistic peers, but current performance measures do not identify students with the lowest scores on humanistic behavior. This study supports the inclusion of humanism as an additional, independent performance measure.

Extracted image analysis: a technique for deciphering mediated portrayals.

A technique for analyzing print media that we have developed as a consequence of our interest in the portrayal of women in menstrual product advertising is reported. The technique, which we call extracted image analysis, involves a unique application of grounded theory and the concomitant heuristic use of the concept of ideal type (Weber, 1958). It provides a means of heuristically conceptualizing the answer to a variant of the "What is going on here?" question asked in analysis of print communication, that is, "Who is being portrayed/addressed here?" Extracted image analysis involves the use of grounded theory to develop ideal typologies. Because the technique re-constructs the ideal types embedded in a communication, it possesses considerable potential as a means of identifying the profiles of members of identifiable groups held by the producers of the directed messages. In addition, the analysis of such portrayals over time would be particularly well suited to extracted image analysis. A number of other possible applications are also suggested.

The extended curse: being a woman every day.

Inductive analysis of the portrayal of menstruating women in contemporary menstrual product advertisements revealed a profound shift in the meaning of feminine hygiene over the last few decades. The phrase sanitary protection has been replaced by a more euphemistic phrase, feminine hygiene, to refer to menstrual management products. What first appeared to be mere euphemistic substitution, on further analysis, was revealed to involve considerably more than semantics. In the case of panty liners, it was found that the marketing of these specialized products involves the invocation of negative definitions of femaleness and a concomitant subscription to altered definitions of femininity. These altered meanings, conveyed in recent menstrual product advertisements, have serious implications for contemporary women's self-images.