Is manipulative therapy more effective than sham manipulation in adults?: A systematic review and meta-analysis

Background: Manipulative therapy is widely used in the treatment of spinal disorders. Manipulative techniques are under debate because of the possibility of adverse events. To date, the efficacy of manipulations compared to sham manipulations is unclear. The purpose of the study is: to assess the efficacy of manipulative therapy compared to sham in adults with a variety of complaints.Study design: Systematic review and meta-analysis.Methods: Bibliographic databases (PubMed, EMBASE, CINAHL, PEDro, Central) along with a hand search of selected bibliographies were searched from inception up to April 2012.Two reviewers independently selected randomized clinical trials (RCTs) that evaluated manipulative therapy compared to sham manipulative therapy in adults, assessed risk of bias and extracted data concerning participants, intervention, kind of sham, outcome measures, duration of follow-up, profession, data on efficacy and adverse events. Pooled (standardized) mean differences or risk differences were calculated were possible using a random effects model. The primary outcomes were pain, disability, and perceived recovery. The overall quality of the body of evidence was evaluated using GRADE.Results: In total 965 references were screened for eligibility and 19 RCTs (n = 1080) met the selection criteria. Eight studies were considered of low risk of bias. There is moderate level of evidence that manipulative therapy has a significant effect in adults on pain relief immediately after treatment (standardized mean difference [SMD] - 0.68, 95% confidence interval (-1.06 to -0.31). There is low level of evidence that manipulative therapy has a significant effect in adults on pain relief (SMD - 0.37, -0.69 to -0.04) at short- term follow-up. In patients with musculoskeletal disorders, we found moderate level of evidence for pain relief (SMD - 0.73, -1.21 to -0.25) immediate after treatment and low level of evidence for pain relief (SMD - 0.52, -0.87 to -0.17) at short term-follow-up. We found very low level of evidence that manipulative therapy has no statistically significant effect on disability and perceived (asthma) recovery. Sensitivity analyses did not change the main findings. No serious adverse events were reported in the manipulative therapy or sham group.Conclusions: Manipulative therapy has a clinical relevant effect on pain, but not on disability or perceived (asthma) recovery. Clinicians can refer patients for manipulative therapy to reduce pain

Are cereal bars significantly healthier and more natural than chocolate bars? A preliminary assessment in the German market

The main aim of the current study was to examine and compare the nutritional quality and degree of naturalness of chocolate and cereal bars. Our analysis relied on a dataset (n = 100) of the most consumed chocolate and cereal bars in Germany in 2019. The Nutri-Score and the Food Naturalness Index were calculated to measure nutritional quality and naturalness of the bars, respectively. Cereal bars were nutritionally better and slightly more natural, but had longer ingredient lists, as compared to chocolate bars. Nutritional quality and food naturalness were only weakly correlated, which suggests that they are two distinct food characteristics. Despite increased criticism regarding the effects of ultra-processed foods on health, our results suggest that not all ultra-processed foods are necessarily unhealthy. Although there is plenty of room for improvement in the formulation of cereal bars, they have the potential to be a healthier and more natural alternative to chocolate bars

The effect of chewing on oral glucoraphanin hydrolysis in raw and steamed broccoli

Chewing disrupts broccoli cells, and myrosinase can effectively hydrolyze the glucosinolate glucoraphanin into the biological active sulforaphane. The influence of chewing time and steaming time on glucoraphanin hydrolysis as well as sulforaphane and sulforaphane nitrile formation in broccoli was studied. To study the effect of chewing time on differently steamed broccoli, broccoli was chewed for 11 s, 22 s, 30 s and 40 s by volunteers. To determine the effect of steaming time, raw and steamed broccoli samples were chewed for 22 s. Glucoraphanin, sulforaphane and sulforaphane nitrile were analyzed in all samples. Longer chewing times of raw, 0.5-min and 1-min steamed broccoli, which contained active myrosinase, lead to a higher hydrolysis. The highest hydrolysis rate of glucoraphanin was found in 0.5-min steamed broccoli (38%) and 2-min steamed samples which contained the highest sulforaphane concentration. This could lead to a recommendation to steam broccoli for a short time before consumption

The effect of chewing on oral glucoraphanin hydrolysis in raw and steamed broccoli

Chewing disrupts broccoli cells, and myrosinase can effectively hydrolyze the glucosinolate glucoraphanin into the biological active sulforaphane. The influence of chewing time and steaming time on glucoraphanin hydrolysis as well as sulforaphane and sulforaphane nitrile formation in broccoli was studied. To study the effect of chewing time on differently steamed broccoli, broccoli was chewed for 11 s, 22 s, 30 s and 40 s by volunteers. To determine the effect of steaming time, raw and steamed broccoli samples were chewed for 22 s. Glucoraphanin, sulforaphane and sulforaphane nitrile were analyzed in all samples. Longer chewing times of raw, 0.5-min and 1-min steamed broccoli, which contained active myrosinase, lead to a higher hydrolysis. The highest hydrolysis rate of glucoraphanin was found in 0.5-min steamed broccoli (38%) and 2-min steamed samples which contained the highest sulforaphane concentration. This could lead to a recommendation to steam broccoli for a short time before consumption

Expression profile of proteins involved in scar formation in the healing process of full-thickness excisional wounds in the porcine model

Scar formation in deep dermal wounds is associated with excessive collagen deposition and contraction. Increased collagen synthesis and decreased collagen degradation are the mechanisms through which this form of fibrosis can occur. Another factor might be a different kind of collagen cross-linking seen in fibrotic skin diseases. This type of cross-linking is dependent on the enzyme lysyl hydroxylase-2b. In this study, we examined the expression profile of the potential key players in scar formation in time in healing of acute wounds. Collagen types I and III, lysyl hydroxylase-2b, α-smooth muscle actin, transforming growth factor βs, and the matrix metalloproteinases and their inhibitor mRNA levels were determined. All genes examined show distinct expression patterns over time. The expression of lysyl hydroxylase-2b peaks at day 7, and precedes collagen types I and III expression. Eight weeks after wounding, the scars showed an increased level of lysyl hydroxylase-2b-mediated collagen cross-linking. This study shows that the fibrosis-specific type of cross-linking of collagen seen in human hypertrophic scarring also plays a role in this animal model of wound healing. Moreover, the expression of the putative gene responsible for this type of cross-linking, the lysyl hydroxylase-2b, is elevated during wound healing

Culture of keratinocytes for transplantation without the need of feeder layer cells

Patients with large burn wounds have a limited amount of healthy donor skin. An alternative for the autologous skin graft is transplantation with autologous keratinocytes. Conventionally, the keratinocytes are cultured with mouse feeder layer cells in medium containing fetal calf serum (FCS) to obtain sufficient numbers of cells. These xenobiotic materials can be a potential risk for the patient. The aim of the present study was to investigate if keratinocytes could be expanded in culture without the need of a feeder layer and FCS. Keratinocytes were cultured on tissue culture plastic with or without collagen type IV coating in medium containing Ultroser G (serum substitute) and keratinocyte growth factor (KGF). An in vitro skin equivalent model was used to examine the capacity of these cells to form an epidermis. Keratinocytes in different passages (P2, P4, and P6) and freshly isolated cells were studied. Keratinocytes grown on collagen type IV were able to form an epidermis at higher passage numbers than cells grown in the absence of collagen type IV (P4 and P2, respectively). In both cases the reconstructed epidermis showed an increased expression of Ki-67, SKALP, involucrin, and keratin 17 compared to normal skin. Only 50,000 keratinocytes grown on collagen type IV in P4 were needed to form 1 cm2 epidermis, whereas 150,000 of freshly isolated keratinocytes were necessary. Using this culture technique sufficient numbers of keratinocytes, isolated from 1 cm2 skin, were obtained to cover 400 cm2 of wound surface in 2 weeks. The results show that keratinocytes can be cultured without the need of a fibroblast feeder layer and FCS and that these cells are still able to create a fully differentiated epidermis. This culture technique can be a valuable tool for the treatment of burn wounds and further development of tissue engineered skin

Upside-down transfer of porcine keratinocytes from a porous, synthetic dressing to experimental full-thickness wounds

Currently, the use of cultured epithelial autografts as an alternative to split-thickness skin autografts for coverage of full-thickness wounds is limited due to fragility of the sheet and variability in the outcome of healing. This could be circumvented by the transfer of proliferating keratinocytes, instead of differentiated sheets, to the wound bed and the "in vivo" regeneration of epidermis. The aim of this study was to achieve re-epithelialization on experimental full-thickness wounds in the pig using a porous, synthetic carrier seeded with proliferating keratinocytes. Porcine keratinocytes were isolated by enzymatic digestion and cultured in Optimem® basal medium with mitogens. In a full-thickness wound model, carriers with different seeding densities were transplanted upside down onto the wound bed. Keratinocytes were labeled using a fluorescent red membrane marker, PKH-26GL. Transfer of keratinocytes and re-epithelialization were recorded macroscopically and histologically. On day 4 after transplantation, transfer of fluorescently labeled keratinocytes was shown by their presence in the granulation tissue. An immature epidermis, as well as epithelial cords and islands, formed as early as day 8. At day 12 a stratified epidermis and wound closure were established and epithelial cysts were formed by differentiation of epithelial islands. Wounds treated with seeding densities as low as 50,000 cells/cm2 showed wound closure within 12 days, whereas wounds treated with 10,000 cells/cm2 or the nonseeded (acellular) carriers did not show complete re-epithelialization before day 17 after treatment. This study showed that porcine keratinocytes, transplanted "upside down" in experimental full-thickness wounds using a synthetic carrier, continued to proliferate and started to differentiate, enabling the formation of a new epidermis in a time frame of 12 days

Differential expression of CRABP-II in fibroblasts derived from dermis and subcutaneous fat

We have shown previously that fibroblasts derived from fat or dermal tissue differ in their functional properties, such as proliferation rate and contractile properties. To study these differences further, two-dimensional electrophoresis (2D PAGE) was performed on proteins isolated from cultured subcutaneous fat and dermal fibroblasts. The 2D gels were screened for proteins that were differentially expressed in all donors (n=5). Five protein spots were subjected to further analysis by mass spectrometry. Two proteins could be identified: brain acid soluble protein 1 (BASP1) and cellular retinoic acid binding protein-II (CRABP-II). CRABP-II is of interest in terms of re-epithelialisation and was clearly expressed in dermal fibroblasts but not in fat fibroblasts. Real time PCR was performed to confirm the 2D data on CRABP-II. The CRABP-II mRNA level was significantly increased in dermal tissue and cultured dermal fibroblasts compared to fat tissue and cultured fat-derived fibroblasts, respectively. The mode of action of CRABP-II in skin is to mediate retinoic acid activity. Retinoic acid is known to inhibit migration and to stimulate differentiation of keratinocytes. The expression of CRABP-II by dermal fibroblasts implicates a role for these fibroblasts in wound re-epithelialisation, in contrast to subcutaneous fat-derived fibroblasts