Mechanobiological oscillators control lymph flow

The ability of cells to sense and respond to physical forces has been recognized for decades, but researchers are only beginning to appreciate the fundamental importance of mechanical signals in biology. At the larger scale, there has been increased interest in the collective organization of cells and their ability to produce complex, “emergent” behaviors. Often, these complex behaviors result in tissue-level control mechanisms that manifest as biological oscillators, such as observed in fireflies, heartbeats, and circadian rhythms. In many cases, these complex, collective behaviors are controlled—at least in part—by physical forces imposed on the tissue or created by the cells. Here, we use mathematical simulations to show that two complementary mechanobiological oscillators are sufficient to control fluid transport in the lymphatic system: Ca²⁺-mediated contractions can be triggered by vessel stretch, whereas nitric oxide produced in response to the resulting fluid shear stress causes the lymphatic vessel to relax locally. Our model predicts that the Ca²⁺ and NO levels alternate spatiotemporally, establishing complementary feedback loops, and that the resulting phasic contractions drive lymph flow. We show that this mechanism is self-regulating and robust over a range of fluid pressure environments, allowing the lymphatic vessels to provide pumping when needed but remain open when flow can be driven by tissue pressure or gravity. Our simulations accurately reproduce the responses to pressure challenges and signaling pathway manipulations observed experimentally, providing an integrated conceptual framework for lymphatic function.Flow of fluid within the lymphatic system is central to many aspects of physiology, including fluid homeostasis and immune function, and poor lymphatic drainage results in significant morbidity in millions of patients each year (1). Although it is known that various mechanical and chemical perturbations can affect lymphatic pumping, there are still no pharmacological therapies for lymphatic pathologies. A fundamental understanding of how various signals coordinate lymphatic vessel function is a necessary first step toward development of treatments to restore fluid balance and enhance immunosurveillance.The lymphatic system consists of fluid-absorbing initial lymphatic vessels that converge to collecting lymphatic vessels, which transport lymph through lymph nodes and back to the blood circulation (2). The collecting lymphatic vessels actively transport fluid via contractions of their muscle-invested walls. Unidirectional flow is achieved by intraluminal valves that limit back flow. Unfortunately, lymphatic pumping is not always operational, and this can lead to lymphedema and immune dysfunction (3, 4).Much is known about the mechanisms responsible for the contractions of the vessel wall. As in blood vessels, the muscle cells that line lymphatic vessels respond to changes in Ca²⁺ concentration. Membrane depolarization results in an influx of Ca²⁺ to initiate the contractions, and this process can be modulated by neurotransmitters (5) or inflammatory mediators, which generally alter the frequency and amplitude of lymphatic pumping (4, 6). Many studies have also reported that physical distension, either by applying isometric stretch or by pressurizing the vessel can affect the phasic contractions (7–10). Interestingly, endothelial (11) and smooth muscle cells (12) have stretch-activated ion channels that can initiate Ca²⁺ mobilization in response to mechanical stresses. Thus, stretch may constitute an important trigger for the contraction phase of a pumping cycle.There are also complementary mechanisms for tempering the Ca²⁺-dependent contractions. The most notable is nitric oxide (NO), a vasodilator that acts at multiple points in the Ca²⁺-contraction pathway to modulate Ca²⁺ release and uptake, as well as the enzymes responsible for force production (13). Blocking or enhancing NO activity can dramatically affect pumping behavior (4, 14–17). Furthermore, lymphatic endothelial cells produce NO in response to fluid flow (16, 18, 19). Importantly, NO dynamics are faster than observed pumping frequencies, so flow-induced NO production is another potential mechanosignal involved in lymphatic regulation (20).     

Vocational Rehabilitation in Spinal Cord Injury: What Vocational Service Activities Are Associated with Employment Program Outcome?

Background:

Designing effective vocational programs for persons with spinal cord injury (SCI) is essential for improving return to work outcome following injury. The relationship between specific vocational services and positive employment outcome has not been empirically studied.

Objective:

To examine the association of specific vocational service activities as predictors of employment.

Method:

Secondary analysis of a randomized, controlled trial of evidence-based supported employment (EBSE) with 12-month follow-up data among 81 Veteran participants with SCI.

Results:

Primary activities recorded were vocational counseling (23.9%) and vocational case management (23.8%). As expected, job development and employment supports were the most time-consuming activities per appointment. Though the amount of time spent in weekly appointments did not differ by employment outcome, participants obtaining competitive employment averaged significantly more individual activities per appointment. Further, for these participants, job development or placement and employment follow-along or supports were more likely to occur and vocational counseling was less likely to occur. Community-based employment services, including job development or placement and employment follow-along or supports as part of a supported employment model, were associated with competitive employment outcomes. Office-based vocational counseling services, which are common to general models of vocational rehabilitation, were associated with a lack of employment.

Conclusions:

Vocational services that actively engage Veterans with SCI in job seeking and acquisition and that provide on-the-job support are more likely to lead to employment than general vocational counseling that involves only job preparation.     

The causes, prevention, and clinical management of broken endodontic rotary files

Complications can occur during many dental procedures. The prepared clinician responds by either correcting the problem during treatment, or, ideally, preventing the problem from occurring in the first place. In endodontic treatment separated rotary Ni-Ti files are a common procedural problem. Through understanding that the main causes of file breakage are cyclic fatigue and torsional stress, a dentist can best prevent this occurrence by using hand files before rotary files, creating a straight-line (glide path) access into a canal, and preflaring the coronal portion before using rotary files in the apical third of the canal. In addition, using an up and down motion with the electric slow-speed handpiece (not allowing the file to bind within the canal) will significantly reduce the incidence of file breakage. If a file does break, successful removal primarily depends on the location of the file in the canal rather than the specific technique employed for removal. A case does not necessarily fail if the separated file cannot be removed. The prognosis when file separation occurs can still be favorable, especially if care was taken to reduce the critical concentration of canal debris with hand instrumentation and chemical irrigation prior to rotary file insertion. In addition, the introduction of a new CS file design will help the dentist increase the chance of removing the file in the event of breakage.     

Recalibration improves inter-examiner reliability of TMD examination

OBJECTIVE: The purpose of this study was to assess whether recalibration of examiners would improve the reliability of gathering clinical findings and related diagnoses of temporomandibular disorders (TMD) in accordance with the Research Diagnostic Criteria for TMD (RDC/TMD). MATERIAL AND METHODS: Two clinicians independently examined a total of 48 symptomatic and asymptomatic subjects according to the RDC/TMD on two occasions: examination 1 (E1). Aarhus, Denmark (n=24; 18 female, ages 18-59 years); examination 2 (E2). Malm?, Sweden (n=24; 18 female, ages 18-86 years). The clinicians were calibrated in the use of the RDC/TMD Axis-I examination on the day before E1. Six months later, they were recalibrated on the day before E2. Intra-class correlation coefficients (ICCs) were used to examine the inter-examiner reliability of the two clinicians on the two occasions (E1, E2). RESULTS: The intra-class correlation coefficients of vertical range of jaw motion differed little between E1 and E2. At E2, all other examination components consistently improved in reliability relative to E1. Similar improvements were seen for the frequently occurring RDC/TMD clinical diagnoses: Ia. Myofascial pain [ICC = 0.83 (E1) and 1.00 (E2)], IIa. Disk displacement with reduction [ICC = 0.26 (E1) and 0.64 (E2)], and IIIa. Arthralgia [ICC = 0.16 (E1) and 0.73 (E2)]. CONCLUSION: Recalibration considerably improved inter-examiner reliability for assessing RDC/TMD clinical variables and diagnoses, which are critically dependent on reliable assessment of clinical signs; improvement was most marked when initial inter-examiner reliability was low. Final inter-examiner reliabilities after recalibration were all associated with acceptable to excellent levels.     

An in vitro comparison of the intraradicular dentin bond strength of Resilon and gutta-percha

The purpose of this study was to compare the micropush-out bond strength of Resilon to that of gutta-percha. Extracted human anterior teeth were used for evaluation. The crowns were removed and the root canals were instrumented with Gates Glidden drills and 0.06 Profile rotary files. Instrumentation was performed with 5.25% sodium hypochlorite irrigation and a final rinse of 17% EDTA. The teeth were randomly divided into two groups. Gutta-percha group: obturation with gutta-percha and Kerr Pulp Canal Sealer EWT. Resilon group: obturation with Resilon points, Epiphany Primer, and Root Canal Sealant. The teeth were cut perpendicular to their long axis to obtain a series of 1.0 mm thick disks (n = 15 per group). Micropush-out bond strengths to root canal dentin were measured. The results show that the mean bond strength to root canal dentin was significantly higher (p < 0.05) in the Resilon/Epiphany group as compared to the gutta-percha/Kerr Pulp Canal Sealer EWT group.