Massage-like stroking boosts the immune system in mice

Recent clinical evidence suggests that the therapeutic effect of massage involves the immune system and that this can be exploited as an adjunct therapy together with standard drug-based approaches. In this study, we investigated the mechanisms behind these effects exploring the immunomodulatory function of stroking as a surrogate of massage-like therapy in mice. C57/BL6 mice were stroked daily for 8 days either with a soft brush or directly with a gloved hand and then analysed for differences in their immune repertoire compared to control non-stroked mice. Our results show that hand-but not brush-stroked mice demonstrated a significant increase in thymic and splenic T cell number (p lt 0.05; p lt 0.01). These effects were not associated with significant changes in CD4/CD8 lineage commitment or activation profile. The boosting effects on T cell repertoire of massage-like therapy were associated with a decreased noradrenergic innervation of lymphoid organs and counteracted the immunosuppressive effect of hydrocortisone in vivo. Together our results in mice support the hypothesis that massage-like therapies might be of therapeutic value in the treatment of immunodeficiencies and related disorders and suggest a reduction of the inhibitory noradrenergic tone in lymphoid organs as one of the possible explanations for their immunomodulatory function

Application of holistic liquid chromatography-high resolution mass spectrometry based urinary metabolomics for prostate cancer detection and biomarker discovery

Human exhibit wide variations in their metabolic profiles because of differences in genetic factors, diet and lifestyle. Therefore in order to detect metabolic differences between individuals robust analytical methods are required. A protocol was produced based on the use of Liquid Chromatography- High Resolution Mass Spectrometry (LC-HRMS) in combination with orthogonal Hydrophilic Interaction (HILIC) and Reversed Phase (RP) liquid chromatography methods for the analysis of the urinary metabolome, which was then evaluated as a diagnostic tool for prostate cancer (a common but highly heterogeneous condition). The LC-HRMS method was found to be robust and exhibited excellent repeatability for retention times (0.9. In addition, using the receiver operator characteristics (ROC) test, the area under curve (AUC) for the combination of the four best characterised biomarker compounds was 0.896. The four biomarker compounds were also found to differ significantly (

Ovine Fetal Thymus Response to Lipopolysaccharide-Induced Chorioamnionitis and Antenatal Corticosteroids

RATIONALE: Chorioamnionitis is associated with preterm delivery and involution of the fetal thymus. Women at risk of preterm delivery receive antenatal corticosteroids which accelerate fetal lung maturation and improve neonatal outcome. However, the effects of antenatal corticosteroids on the fetal thymus in the settings of chorioamnionitis are largely unknown. We hypothesized that intra-amniotic exposure to lipopolysaccharide (LPS) causes involution of the fetal thymus resulting in persistent effects on thymic structure and cell populations. We also hypothesized that antenatal corticosteroids may modulate the effects of LPS on thymic development. METHODS: Time-mated ewes with singleton fetuses received an intra-amniotic injection of LPS 7 or 14 days before preterm delivery at 120 days gestational age (term = 150 days). LPS and corticosteroid treatment groups received intra-amniotic LPS either preceding or following maternal intra-muscular betamethasone. Gestation matched controls received intra-amniotic and maternal intra-muscular saline. The fetal intra-thoracic thymus was evaluated. RESULTS: Intra-amniotic LPS decreased the cortico-medullary (C/M) ratio of the thymus and increased Toll-like receptor (TLR) 4 mRNA and CD3 expression indicating involution and activation of the fetal thymus. Increased TLR4 and CD3 expression persisted for 14 days but Foxp3 expression decreased suggesting a change in regulatory T-cells. Sonic hedgehog and bone morphogenetic protein 4 mRNA, which are negative regulators of T-cell development, decreased in response to intra-amniotic LPS. Betamethasone treatment before LPS exposure attenuated some of the LPS-induced thymic responses but increased cleaved caspase-3 expression and decreased the C/M ratio. Betamethasone treatment after LPS exposure did not prevent the LPS-induced thymic changes. CONCLUSION: Intra-amniotic exposure to LPS activated the fetal thymus which was accompanied by structural changes. Treatment with antenatal corticosteroids before LPS partially attenuated the LPS-induced effects but increased apoptosis in the fetal thymus. Corticosteroid administration after the inflammatory stimulus did not inhibit the LPS effects on the fetal thymus

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

Background: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. Methods: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. Findings: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. Interpretation: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. Funding: The UK National Institute for Health Research Health Technology Assessment Programme

Treatment of post-operative infections following proximal femoral fractures: our institutional experience.

Proximal femoral fractures (PFFs) are a major health concern in the elderly population. Improvements made in implants and surgical techniques resulted in faster rehabilitation and shorter length of hospital stay. Despite this, the reduced physiological reserve, associated co-morbidities and polypharmacy intake of the elderly population put them at high risk of postoperative complications particularly of infectious origin. Out of 10061 patients with proximal femoral fractures 105 (1.05%) developed surgical site infection; 76 (72%) infections occurred in patients who had sustained intracapsular (IC) fractures with the remaining 29 (28%) infections occurring in patients with extracapsular (EC) neck of femur fractures. The median number of additional surgical debridements was 2 (range 1-7). MRSA was isolated in 49 (47%) of the cases; 38 patients (36%) ultimately underwent a Girdlestone's excisional arthroplasty. Mortality at 30 days and 3 months was 10% and 31%, respectively. It was noted that post-operative hip infection predisposed to a prolonged length of stay in the acute unit and subsequently to a more dependent destination after discharge

Treatment of post-operative infections following proximal femoral fractures: our institutional experience.

Proximal femoral fractures (PFFs) are a major health concern in the elderly population. Improvements made in implants and surgical techniques resulted in faster rehabilitation and shorter length of hospital stay. Despite this, the reduced physiological reserve, associated co-morbidities and polypharmacy intake of the elderly population put them at high risk of postoperative complications particularly of infectious origin. Out of 10061 patients with proximal femoral fractures 105 (1.05%) developed surgical site infection; 76 (72%) infections occurred in patients who had sustained intracapsular (IC) fractures with the remaining 29 (28%) infections occurring in patients with extracapsular (EC) neck of femur fractures. The median number of additional surgical debridements was 2 (range 1-7). MRSA was isolated in 49 (47%) of the cases; 38 patients (36%) ultimately underwent a Girdlestone's excisional arthroplasty. Mortality at 30 days and 3 months was 10% and 31%, respectively. It was noted that post-operative hip infection predisposed to a prolonged length of stay in the acute unit and subsequently to a more dependent destination after discharge

Identification of isoflavone derivatives as effective anticryptosporidial agents in vitro and in vivo.

We report the preparation and antiparasitic activity in vitro and in vivo of a series of isoflavone derivatives related to genistein. These analogues retain the 5,7-dihydroxyisoflavone core of genistein: direct genistein analogues (2-H isoflavones), 2-carboethoxy isoflavones, and the precursor deoxybenzoins were all evaluated. Excellent in vitro activity against Cryptosporidium parvum was observed for both classes of isoflavones in cell cultures, and the lead compound 19, RM6427, shows high in vivo efficacy against an experimental infection

Long-term results of semiclosed endarterectomy of the superficial femoral artery and the outcome of failed reconstructions

PURPOSE: The optimal method of treatment of superficial femoral artery occlusive disease has yet to be established. Therapeutic options include percutaneous transluminal angioplasty for short lesions and reversed or in situ autologous saphenous vein bypass for long lesions. Currently, staged revascularization with polytetrafluoroethylene as an initial conduit and autologous vein for secondary procedures is suggested. An alternative to these procedures is endarterectomy of the occluded superficial femoral artery, followed by a femoropopliteal bypass in cases of endarterectomy failure. Our results with this procedure are reviewed in this article. METHODS: From 1980 until 1990, 259 endarterectomies of the superficial femoral artery were attempted, 231 of which were successfully performed in 197 patients (145 men and 52 women), with an average age of 64 years (range 40 to 82 years). The indication for successfully performed endarterectomy was claudication in 186 patients (80%), rest pain in 21 (9%), and gangrene in 24 (11%). The postoperative mortality rate was 0.8% with a complication rate of 10%. RESULTS: Eighty-two failures occurred during follow-up, of which 33 were treated with peripheral bypass. Five additional bypasses were performed because of occlusions distal from the endarterectomized segment. The 5-year primary overall patency rate of successfully performed endarterectomy was 71% (SE 3.6). The 5-year overall secondary bypass patency rate was 61% (SE 11.3). The combined endarterectomy and bypass patency rate (tertiary patency) was 79% (SE 3.3) after 5 years and 45% (SE 7.6) after 10 years. The overall amputation rate was 5.6% and the amputation rate was 1.6% in patients treated for claudication. CONCLUSIONS: The combination of endarterectomy and peripheral bypass provides a valuable alternative to the current treatment of superficial femoral artery occlusive diseas