Diel investments in metabolite production and consumption in a model microbial system

Organic carbon transfer between surface ocean photosynthetic and heterotrophic microbes is a central but poorly understood process in the global carbon cycle. In a model community in which diatom extracellular release of organic molecules sustained growth of a co-cultured bacterium, we determined quantitative changes in the diatom endometabolome and the bacterial uptake transcriptome over two diel cycles. Of the nuclear magnetic resonance (NMR) peaks in the diatom endometabolites, 38% had diel patterns with noon or mid-afternoon maxima; the remaining either increased (36%) or decreased (26%) through time. Of the genes in the bacterial uptake transcriptome, 94% had a diel pattern with a noon maximum; the remaining decreased over time (6%). Eight diatom endometabolites identified with high confidence were matched to the bacterial genes mediating their utilization. Modeling of these coupled inventories with only diffusion-based phytoplankton extracellular release could not reproduce all the patterns. Addition of active release mechanisms for physiological balance and bacterial recognition significantly improved model performance. Estimates of phytoplankton extracellular release range from only a few percent to nearly half of annual net primary production. Improved understanding of the factors that influence metabolite release and consumption by surface ocean microbes will better constrain this globally significant carbon flux.

An Experimental Study to determine the Impact of Active Release Technique, Core Strengthening on Pain, Muscle Stiffness, Hardness and Quality of Life on Non- Specific Low Back Pain

Introduction: Active Release Technique (ART), works by releasing adhesions and repairing the integrity of soft tissue, thereby extending and restoring functional flexibility entirely. Core stabilization workout (CSE) aims to treat back pain by boosting your muscular strength and stamina, strengthening muscle motor patterns to relieve low-back pain. Aim: Aim of the study was to evaluate impact of active release technique and core strengthening on pain, mobility and quality of life on non-specific low-back pain. Study Design: Simple random convenient sampling, envelope method Place and Duration: A study of 40 people with non-specific low back pain and aging between 18 and 25 years was conducted at Musculoskeletal OPD, Ravi Nair Physiotherapy College, DMIMS(DU), Sawangi (Meghe), and Wardha in the duration of one year. Procedure: In this experimental investigation, the influence of active released and impacting non-specific low back pain on suffering, muscular soreness, hardness, strength, ODI, and quality of life was determined. Both groups received hot fomentation and core strengthening, but only the ART group was actively released. The findings have been obtained from NPRS to algometer, durometer, press biofeedback, ODI, and EQ-5D-5L in pre-treatment, post-treatment, and after four weeks of data to analysed impacts. Results: in this study both the groups showed reduction in pain, muscle tenderness, muscle hardness as well as increase in core strength and quality of life. When compared ART group shows significant improvement with p value of 0.001. Conclusion: In this study we find that the pain threshold, muscular hardness, muscle tenderness, deficiency and quality of life of both groups improved. The ART group was proven to be more effective than the Hpk group when the two groups were compared. In the two groups, the core strength did not change greatly, perhaps after four weeks, from pre- treatment to post- treatment to 4 weeks after.

Comparison between the Immediate Effects of Instrument Assisted Soft Tissue Mobilization and Active Release Technique in Individuals Wearing High Heels

Background: Wearing high heels regularly places muscle-tendon units (MTUs) in a shortened position. In this condition the length of the calf MTU (gastrocnemius-soleus) is reduced by the continuous ankle plantar flexion cause by the heel lift imposed by the high heels, which leads to concomitant inflexibility of these muscles. Tightness of these muscles inturns leads to formation of trigger points within the muscles. Instrument-assisted soft tissue mobilization (IASTM) is an approach to soft tissue manipulation that uses concave and convex stainless steel instruments to release scar tissue, break soft tissue adhesions, and remove fascial restrictions. Active Release Techniques, or ART, is a soft tissue treatment method that focuses on relieving tissue tension via the removal of fibrosis/adhesion that develops in tissue that is overloaded with repetitive use. Objective: To compare the immediate effect of Instrument Assisted Soft Tissue Mobilization and Active Release Technique for gastrosoleus muscle in individuals wearing high heels using VAS and active dorsiflexion using universal goniometer. Method: 30 subjects were selected as per inclusion and exclusion criteria and were randomly allocated into two groups of 15 each. Group A received Instrument Assisted soft tissue mobilization and Group B received Active Release Technique for Gastro-soleus muscle. Pre and Post intervention Dorsiflexion range of motion and VAS scores were analysed. Result: The statistical analyses showed that there is signification increase in dorsiflexion range of motion and significant reduction in pain in both the groups. (p<0.0001). However, inter group analysis showed that Group A is much more effective in improving the range of motion and reducing pain scores. Conclusion: The present study concluded that Instrument Assisted Soft Tissue Mobilization is a better intervention for the release of trigger points as it shows greater increase in ankle dorsiflexion range of motion and a significant pain reduction when compared to Active Release Technique. Key words: Instrument Assisted Soft Tissue Mobilization(IASTM), Active Release Technique(ART), Range of Motion, pain, High Heels, Calf Muscles.

COMPREHENSIVE REHABILITATION OF A PATIENT WITH UPPER CROSSED SYNDROME

Background: In upper cross syndrome (UCS), weaker neck flexors, anterior and middle serratus and lower trapezius along with rhomboids usually develop, and stiffness of the levator scapulae, pectoralis major as well as upper trapezius are biomechanically adapted. Muscle imbalance is the primary cause for the upper cross syndrome between the tonic and phasic muscles. Individuals with upper cross syndrome may also exhibit any of the following issues text neck syndrome, round upper back, reduced thoracic spine mobility, winged scapulae. Active Release Technique (ART) helps to reduce discomfort and improve the range of movement. Also, Active Release Technique (ART) is a manual procedure which is also being used for other soft tissue rehabilitation as well as for the management of the scar tissues. UCS and neck pain is common with uncomfortable job postures as well as in stress and anxiety, due to which muscle dysfunction starts which can further followed by altered posture around the neck. Active Release Technique was also used earlier for muscle dysfunction and for scar tissue mobilization. Changes in musculature structure may exhibit chronic headaches among the patients of upper cross syndrome also unbalanced soft tissue near the neck may create barriers for the head’s range of motion (ROM). Patients complaints were pain, decreased job efficiency for which he was later diagnosed as a case of upper cross syndrome. The patient showed great co-operation during the treatment and now the patient is able to perform his job-related tasks without discomfort

ACTIVE RELEASE TECHNIQUE AND ITS IMPACT ON NON-SPECIFIC LOW BACK PAIN

Non-specific low back pain (NLBP) or "simple backache" is characterized as an LBP not due to any identifiable disease such as nerve root pain and severe spinal pathologies such as infection, tumour, osteoporosis, rheumatoid arthritis, fracture or inflammation. Myofascial Trigger Points in skeletal muscles, identified with a hypersensitive palpable nodule or "knot" in the middle of the muscle belly, are described as hyperirritable. Active Release Technique (ART) is a non- invasive soft tissue restoration procedure that includes reducing the scar tissue that would induce discomfort, stiffness, muscle weakness and unusual pain like mechanical dysfunction of the myofascial and soft tissue. A 23 years old inert, after assisting in a lot surgery started with a low back pain which increased gradually. Activities like bending forward as well as backward, standing for long time, and unsupported sitting for long time which relieved on rest. She took paracetamol as the pain started, which relived her pain. In this case report, a 23 years old intern, who had non-specific low back pain was successfully rehabilitated and was able to resume her activities withing a few days which was followed for a month which was painless as well. ART proved helpful along with hot fomentation and core strengthening exercises to reduce her pain. In this case report, a 23 years old intern, who had non-specific low back pain was successfully rehabilitated and was able to resume her activities withing a few days which was followed for a month which was painless as well. ART proved helpful along with hot fomentation and core strengthening exercises to reduce her pain.

Modified-Active Release Therapy in Patients with Scapulocostal Syndrome and Masticatory Myofascial Pain: A Stratified-Randomized Controlled Trial

Modified-active release therapy (mART) was developed to treat patients experiencing upper quarter pain. The objective of the study was to determine the effectiveness of the mART in treating pain, promoting function, and measuring emotions in patients with scapulocostal syndrome (SCS) and masticatory myofascial pain (MMP). A stratified-randomized controlled trial was employed in 38 participants separated into two groups. All participants underwent the same series visual analog scale (VAS), pressure pain threshold (PPT), mouth opening (MO), maximum mouth opening (MMO), craniovertebral angle (CV-angle), and pain catastrophizing scale Thai version (PCS-Thai-version) at the baseline. The mART group underwent the mART program three times a week for 4 weeks with a hot pack and an educational briefing while the control group received only a hot pack and the educational briefing. After treatment, both groups showed significant improvement (p < 0.05) in all parameters except MO, MMO, and CV-angle. When comparing outcomes between the groups, the mART group showed a statistically significant greater number of improvements than did the control group. In conclusion, the mART program can improve pain experienced by patients with SCS and MMP and it can be used as an adjuvant technique with conservative treatment.

The Depolarization-Evoked, Ca2+-Dependent Release of Exosomes From Mouse Cortical Nerve Endings: New Insights Into Synaptic Transmission

Whether exosomes can be actively released from presynaptic nerve terminals is a matter of debate. To address the point, mouse cortical synaptosomes were incubated under basal and depolarizing (25 mM KCl-enriched medium) conditions, and extracellular vesicles were isolated from the synaptosomal supernatants to be characterized by dynamic light scattering, transmission electron microscopy, Western blot, and flow cytometry analyses. The structural and biochemical analysis unveiled that supernatants contain vesicles that have the size and the shape of exosomes, which were immunopositive for the exosomal markers TSG101, flotillin-1, CD63, and CD9. The marker content increased upon the exposure of nerve terminals to the high-KCl stimulus, consistent with an active release of the exosomes from the depolarized synaptosomes. High KCl-induced depolarization elicits the Ca2+-dependent exocytosis of glutamate. Interestingly, the depolarization-evoked release of exosomes from cortical synaptosomes also occurred in a Ca2+-dependent fashion, since the TSG101, CD63, and CD9 contents in the exosomal fraction isolated from supernatants of depolarized synaptosomes were significantly reduced when omitting external Ca2+ ions. Differently, (±)-baclofen (10 µM), which significantly reduced the glutamate exocytosis, did not affect the amount of exosomal markers, suggesting that the GABAB-mediated mechanism does not control the exosome release. Our findings suggest that the exposure of synaptosomes to a depolarizing stimulus elicits a presynaptic release of exosomes that occurs in a Ca2+-dependent fashion. The insensitivity to the presynaptic GABAB receptors, however, leaves open the question on whether the release of exosomes could be a druggable target for new therapeutic intervention for the cure of synaptopathies.

Muscle energy technique versus active release technique on motor functions in patients with carpal tunnel syndrome

Introduction Carpal tunnel syndrome is the most common median nerve neuropathy, accounting for 90% of all neuropathies, with prevalence in the general UK adult population ranging from 7–16% and bilateral symptoms reported in more than 50% of all cases. The pathophysiological mechanisms involved in the median nerve compression and traction are thought to be complex. This study compared the effectiveness of muscle energy technique and active release technique in patients with carpal tunnel syndrome. Methods This study involved a total of 30 male and female patients with carpal tunnel syndrome, aged between 30 and 50 years. The patients were randomly assigned to two equal groups, group A and group B. Group A received muscle energy technique, and group B received active release technique. Results Independent one-tailed t-tests revealed that the intragroup comparisons showed statistically significant increases in pinch grip strength and motor nerve conduction velocity of the median nerve post-treatment in group A (P=0.001 and 0.0001 respectively), while in group B, there were statistically significant increases in pinch grip strength and motor nerve conduction velocity post-treatment (P=0.037 and 0.043 respectively). The intergroup comparisons showed statistically significant differences in favour of group A. Conclusions Because there was little significant difference between the two groups, this study concluded that both treatment techniques were effective in increasing median motor nerve conduction and hand grip strength. However, muscle energy technique increased motor nerve conduction velocity and pinch grip muscle strength more than active release technique.

POS0419 ABERRANT SPLICEOSOME AND ALTERED EXPRESSION OF IFN-RESPONSE RELATED GENES ARE HALLMARKS OF MONOCYTES FROM LUPUS PATIENTS WITH RENAL DISEASE

Background:To date, novel mechanisms such as the involvement of splicing machinery components in lupus nephropathy and its interplay with the transcriptome in innate immune cells have not been evaluated.Objectives:1- To identify altered transcriptomic signatures associated with the immune response of monocytes from SLE patients and its association with clinical features. 2- To evaluate the role of the spliceosome linked to the transcriptomic profile of SLE monocytes. 3- To analyze mechanistically the impact of anti-dsDNA antibodies (Ab) and the modulation of the spliceosome in the SLE monocytes activity.Methods:Sixty SLE patients and forty healthy donors (HD) were included in the study. Infiltration rate of myeloid cells and its association with clinical features were analyzed in kidney biopsies by Immunohistochemistry. In parallel, circulating monocytes were purified from peripheral blood by immune-magnetic selection. The expression of a set of 770 genes related to autoimmune/inflammatory diseases was evaluated using NanoString Technologies. The levels of the main 45 components of the splicing machinery were further analyzed in these samples using a microfluidic qPCR array (Fluidigm). An extensive clinical/serological evaluation was also performed, comprising disease activity, renal involvement parameters, autoAb profile, and the systemic inflammatory status (27-plex Assay). Finally, in vitro studies involving anti-dsDNA-IgG Ab treatment and over/down-expression of splicing machinery components were carried out to analyze their effects in the monocyte activity.Results:Infiltration of CD68 expressing cells was confirmed in kidney biopsies and associated with parameters of kidney failure (C3/C4, chronic index), highlighting the key role of the myeloid compartment in lupus nephropathy. Gene expression profiling recognized 156 genes differentially expressed in SLE monocytes compared with HDs, including 87 genes up-regulated and 69 down-regulated. Functional analysis showed that most dysregulated genes were associated with the IFN response (i.e. IFIT1, IFI44, IFI44L, RSAD2). In parallel, the altered expression of 27 spliceosome components was demonstrated in SLE monocytes compared with HD, including 3 up-regulated and 24 down-regulated. Correlation studies demonstrated that the aberrant expression of splicing machinery components was linked to the altered interferon signature and the plasma inflammatory profile. This aberrant profile at molecular level was associated with the disease activity status, anti-dsDNA positivity and C3/C4 levels. Interestingly, SLE patients with renal disease displayed a simultaneous alteration of both, the IFN and the spliceosome signatures in monocytes, along with an enlarged pro-inflammatory profile in plasma. Logistic regression models that integrated the concomitant alteration of some splicing machinery components and IFNs genes identified lupus nephritis patients with high accuracy. Mechanistic studies showed that in vitro treatment of monocytes from HDs with anti-dsDNA promoted a concomitant deregulation of the IFN signature and the expression of several spliceosome components (i.e. PTB, RBM17, RNU6ATAC). Finally, the over/down-expression of selected spliceosome components (PTB and RBM17) in monocytes from SLE patients reduced the active release of inflammatory cytokines and their adhesion capacity.Conclusion:1) Monocytes from SLE patients with renal involvement exhibit a remarkable alteration of genes associated with the IFN response, further linked with the aberrant expression of several splicing machinery components. 2) Anti-dsDNA promoted the dysregulation in monocytes of both the IFN and spliceosome signatures, along with an active release of pro-inflammatory mediators. 3) The modulation of key splicing components in monocytes from SLE patients reduce their pro-inflammatory status and migration capacity. Ongoing studies may provide novel biomarkers and therapeutic tools to treat lupus nephropathy.Acknowledgements:Funded by ISCIII, PI18/00837 and RIER RD16/0012/0015 co-funded with FEDERDisclosure of Interests:None declared