In vitro wound healing activity of 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde (HDNC) and other isolates of Aegle marmelos L.: Enhances keratinocytes motility via Wnt/β-catenin and RAS-ERK pathways

Wound healing is a complex process in which injured skin and tissues repaired by interaction of a complex cascade of cellular events that generates resurfacing, reconstitution and restoration of the tensile strength of injured skin. It follows β-catenin, extracellular signal regulated kinase (ERK) and Akt signaling pathways. Aegle marmelos L., generally known as bael is found to act as anti-inflammatory, antioxidant and anti-ulcer agent. Furthermore, studies have demonstrated that this Indian traditional medicinal plant, A. marmelos flower extract (AMF) was used for wound injury. Henceforth, the current study was investigated to ascertain the effect of its active constituents in vitro wound healing with mechanism involve in migration of cells and activation of β-catenin in keratinocytes, inhibition of PGE₂ in macrophages and production of collagen in fibroblasts. We have taken full thickness wound of rats and applied AMF for 2 weeks. Cutaneous wound healing activity was performed using HaCaT keratinocytes, Hs68 dermal fibroblasts and RAW264.7 macrophages to determine cell viability, nitric oxide production, collagen expression, cell migration and β-catenin activation. Results shows that AMF treated rats demonstrated reduced wound size and epithelisation was improved, involved in keratinocytes migration by regulation of Akt signaling, beta-catenin and extracellular signal-regulated kinase (ERK) pathways. AMF and its active constituent’s increased mRNA expression, inhibited nitric oxide, PGE₂ release, mRNA expression of mediators in RAW 264.7 macrophages and enhances the motility of HaCaT keratinocytes in vitro wound healing of rats.     

How Much Is Postacute Care Use Affected by Its Availability?

OBJECTIVE: To assess the relative impact of clinical factors versus nonclinical factors-such as postacute care (PAC) supply-in determining whether patients receive care from skilled nursing facilities (SNFs) or inpatient rehabilitation facilities (IRFs) after discharge from acute care. DATA SOURCES AND STUDY SETTING: Medicare acute hospital, IRF, and SNF claims provided data on PAC choices; predictors of site of PAC chosen were generated from Medicare claims, provider of services, enrollment file, and Area Resource File data. STUDY DESIGN: We used multinomial logit models to predict PAC use by elderly patients after hospitalizations for stroke, hip fractures, or lower extremity joint replacements. DATA COLLECTION/EXTRACTION METHODS: A file was constructed linking acute and postacute utilization data for all medicare patients hospitalized in 1999. PRINCIPAL FINDINGS: PAC availability is a more powerful predictor of PAC use than the clinical characteristics in many of our models. The effects of distance to providers and supply of providers are particularly clear in the choice between IRF and SNF care. The farther away the nearest IRF is, and the closer the nearest SNF is, the less likely a patient is to go to an IRF. Similarly, the fewer IRFs, and the more SNFs, there are in the patient's area the less likely the patient is to go to an IRF. In addition, if the hospital from which the patient is discharged has a related IRF or a related SNF the patient is more likely to go there. CONCLUSIONS: We find that the availability of PAC is a major determinant of whether patients use such care and which type of PAC facility they use. Further research is needed in order to evaluate whether these findings indicate that a greater supply of PAC leads to both higher use of institutional care and better outcomes-or whether it leads to unwarranted expenditures of resources and delays in returning patients to their homes.     

A Framework for the Next Generation of Risk Science

Objectives: In 2011, the U.S. Environmental Protection Agency initiated the NexGen project to develop a new paradigm for the next generation of risk science.Methods: The NexGen framework was built on three cornerstones: the availability of new data on toxicity pathways made possible by fundamental advances in basic biology and toxicological science, the incorporation of a population health perspective that recognizes that most adverse health outcomes involve multiple determinants, and a renewed focus on new risk assessment methodologies designed to better inform risk management decision making.Results: The NexGen framework has three phases. Phase I (objectives) focuses on problem formulation and scoping, taking into account the risk context and the range of available risk management decision-making options. Phase II (risk assessment) seeks to identify critical toxicity pathway perturbations using new toxicity testing tools and technologies, and to better characterize risks and uncertainties using advanced risk assessment methodologies. Phase III (risk management) involves the development of evidence-based population health risk management strategies of a regulatory, economic, advisory, community-based, or technological nature, using sound principles of risk management decision making.Conclusions: Analysis of a series of case study prototypes indicated that many aspects of the NexGen framework are already beginning to be adopted in practice.Citation: Krewski D, Westphal M, Andersen ME, Paoli GM, Chiu WA, Al-Zoughool M, Croteau MC, Burgoon LD, Cote I. 2014. A framework for the next generation of risk science. Environ Health Perspect 122:796–805; http://dx.doi.org/10.1289/ehp.1307260     

Peer Reviewed: From Program to Policy: Expanding the Role of Community Coalitions

Background

Diabetes mortality at the United States–Mexico border is twice the national average. Type 2 diabetes mellitus is increasingly diagnosed among children and adolescents. Fragmented services and scarce resources further restrict access to health care. Increased awareness of the incidence of disease and poor health outcomes became a catalyst for creating community-based coalitions and partnerships with the University of Arizona that focused on diabetes.

Context

Five partnerships between the communities and the University of Arizona were formed to address these health issues. They began with health promotion as their goal and were challenged to add policy and environmental change to their objectives. Understanding the meaning of policy in the community context is the first step in the transition from program to policy. Policy participation brings different groups together, strengthening ties and building trust among community members and community organizations.

Methods

Data on progress and outcomes were collected from multiple sources. We used the Centers for Disease Control and Prevention''s Racial and Ethnic Approaches to Community Health (REACH) 2010 Community Change Model as the capacity-building and analytic framework for supporting and documenting the transition of coalitions from program to policy.

Consequences

Over 5 years, the coalitions made the transition, in varying degrees, from a programmatic focus to a policy planning and advocacy focus. The coalitions raised community awareness, built community capacity, encouraged a process of "change in change agents," and advocated for community environmental and policy shifts to improve health behaviors.

Interpretation

The five coalitions made environmental and policy impacts by engaging in policy advocacy. These outcomes indicate the successful, if not consistently sustained, transition from program to policy. Whether and how these "changes in change agents" are transferable to the larger community over the long term remains to be seen.     

A comparative study of reducing the extracellular potassium concentration in red blood cells by washing and by reduction of additive solution

BACKGROUND: Extracellular potassium concentration (K(+)) increases in the supernatant of whole and packed red blood cell units (pRBCs) with duration of refrigerated storage in citrate-phosphate-dextrose-adenine (CPDA-1) and additive solution (AS). Studies have shown that to avoid hyperkalemia, washed pRBCs are preferred if relatively fresh pRBCs are not available. To determine whether a simpler procedure, AS reduction, results in lowering of K(+) in pRBCs comparable to that achieved by washing, the K(+) levels by both methods were compared. STUDY DESIGN AND METHODS: Pre- and post-K(+) levels were measured in 6 washed and 11 AS-reduced pRBC units. Each unit was weighed, hematocrit was determined, K(+) was measured, and total K(+) was calculated. Washed units were 3 to 21 and AS-reduced units were 4 to 30 days old. Statistical analysis was performed with a t test. RESULTS: There was no significant difference (p > 0.35) in the initial K(+) between the two groups (mean +/- SD, 36.95 +/- 13.16 mEq/L before washing and 39.78 +/- 19.94 mEq/L before AS reduction). Washing and AS reduction both led to a significant decrease in K(+) levels (2.15 +/- 0.10 mEq/L after washing and 4.41 +/- 3.04 mEq/L after AS reduction, each p < 0.0005). Washing, however, was significantly better than AS reduction in reducing K(+) in stored pRBCs (p < 0.05). CONCLUSIONS: Washing pRBCs results in very low levels of K(+). AS reduction also significantly reduces K(+) levels. Selection of the method of K(+) reduction will depend on the stringency of K(+) reduction needed, the time constraints, and the availability of facilities and staff for washing.     

Upper Limb Neural Tension and Seated Slump Tests: The False Positive Rate among Healthy Young Adults without Cervical or Lumbar Symptoms

This study examined the false positive rate of the upper limb neural tension test (ULNTT) and seated slump test (SST) among healthy young adults with no history of cervical, lumbar, or peripheral symptoms. Eighty-four subjects (27 men and 57 women) with a mean age of 22.9 years participated in the investigation. All participants completed a screening questionnaire designed to exclude subjects with a history of cervical or lumbar spine pain or injury, or upper or lower extremity neurological symptoms. The ULNTT and the SST were performed on the left upper and lower extremity of each participant. Of the 84 participants tested, 73 (86.9%) were found to have a positive ULNTT at some point in the available range of elbow extension. Twenty-eight (33.3%) of the 84 subjects had a positive SST at some point in the available range of knee extension. The mean knee extension angle for those subjects with a positive SST was 15.1° with a 95% confidence interval (CI) of 12.3 and 19.7°. The mean elbow extension angle for those with a positive ULNTT was 49.4° with a 95% CI of 44.8 and 54.0°. The number of positive tests for both the ULNTT and the SST was found to be high in this sample of asymptomatic healthy young adults. Based on the results of this investigation, the authors suggest that the current criteria for determining a positive test for both the ULNTT and the SST should be examined using the proposed range of motion cut-off scores.Key Words: Neural Tension Testing, Neurodynamics, Radiculopathy, Test ValidityPhysical therapists and other healthcare providers use neural tension tests (neurodynamic tests) as part of the clinical examination to help differentiate the underlying pathoanatomic structures^1–7. The most common neural tension tests include the straight leg raise test (SLR), the seated slump test (SST), and the upper limb neural tension test (ULNTT)^1–7. The advancement of neural tension testing, particularly the SST and ULNTT, is credited to Butler^1,2, Elvey³, Shacklock^6,7, and Maitland^5,8,9. Today, neural tension testing has become a ubiquitous part of the orthopedic physical therapy examination. Despite numerous publications and the common use of these tests, there is relatively little scientific evidence available to support the diagnostic accuracy of these tests⁶.Several investigations have shown that a combination of specific body movements can create tension and gliding of neural tissues within the confines of the musculoskeletal system^10,11. If a nerve or nerve root becomes inflamed or damaged by chemical mediators, macroscopic or microscopic trauma, or entrapment, normal functional movements can produce or exacerbate neural mediated signs or symptoms^1,3,11–13. Chronic repetitive compression or traction can result in both intraneural and extraneural pathology^1,12. Nerve injury of this type is often manifested by sensory changes such as paresthesias and neurological signs such as motor weakness; and altered deep tendon reflexes can result from prolonged neural insult^11–13. Therefore, neural tension testing that places mechanical tension on the nervous system has the potential to serve as a useful clinical test to help differentiate between neural and non-neural anatomic structures^1,4,6,12.There are three common upper limb tension tests that assess neural tissues originating from the C5 to T1 nerve roots^1,4. The most commonly used ULNTT has been defined as (ULNTT 1) and is thought to emphasize tension on the median nerve^1,2,6,14. This test consists of a combination of scapular depression, shoulder abduction and external rotation, elbow extension, forearm supination, wrist and finger extension, and cervical lateral flexion first away from the tested extremity and then toward the tested extremity^1,2. Although the literature is not consistent, the ULNTT is often considered positive when there is a production of neural-mediated symptoms during elbow extension, and reduction of symptoms or an increase in elbow extension when the cervical spine is laterally flexed toward the involved extremity^1,2. This last maneuver is referred to as structural differentiation and is used to differentiate a neurodynamic response from a musculoskeletal response⁶.Shacklock⁶ stated that a musculoskeletal response (symptoms, range of motion, or resistance to movement) remains constant during differentiation, while a neurodynamic response is present when the symptoms, range of motion, or resistance to movement changes during structural differentiation. According to Shacklock, an overt abnormal neurodynamic response requires positive structural differentiation and reproduction of the patient''s symptoms⁶.Sandmark and Nisell¹⁵ determined that the ULNTT 1 has a sensitivity of 0.77 and a specificity of 0.94 in a sample of patients with neck pain. The intra-tester reliability of the ULNTT 1 in asymptomatic subjects has been reported to be 0.98^16,17. Hines et al¹⁸ reported poor inter-tester reliability when assessing resistance to movement rather than patient response based on structural differentiation.The SST is thought to examine the sensitivity of neural structures including meningeal tissues, nerve roots, and the sciatic and tibial nerves^4,5. The SST involves the patient sitting on the edge of the examination plinth in a slumped or slouched position (flexion of the thoracic and lumbar spine and a posterior pelvic tilt), flexion of the cervical spine with gentle manual overpressure, and passive extension of the subject''s knee, while the ankle is dorsiflexed. This sequence is referred to as ST1 by Butler¹. A positive test again requires structural differentiation by noting a change in symptoms, range of motion, or resistance when the cervical spine is extended and that reproduces the patient''s symptoms⁶.In a study examining patients with suspected herniated nucleus pulposus, Stankovic et al¹⁹ found the diagnostic sensitivity of the SST to be 0.83 and the specificity to be 0.55. Additionally, a study performed by Gabbe et al²⁰ found the intra-rater reliability using ICC_(3,1) as 0.95 and 0.80, while the inter-rater reliability was found as 0.92 using ICC_(2,1). Philip and Lew²¹ found strong agreement among physical therapists (Kappa = 0.89) when defining a positive test as reduction of symptoms and increased knee ROM upon cervical extension.As stated previously, several modifications have been proposed for both the SST and the ULNTT; thus, there is not a universally accepted procedure for either test^1,5. One suggested modification is to have proximal or distal initiation of the testing sequence⁶. In the distal-initiated SST, the subject''s ankle is dorsiflexed first for pretension of the sciatic and tibial nerves. In the proximal-initiated test, the subject is asked to flex the cervical spine first for pretension of the dura. A second alteration of the SST is to have the subject axially rotate the thoracic spine²². The order in which the test is performed is believed to influence the direction of neural glide but it may also affect symptom reproduction⁶.Clinical observation and experience teaching neural tension testing for many years led the present investigators to observe that many asymptomatic subjects without frank cervical, lumbar, or peripheral symptoms present with neural-mediated symptoms and positive structural differentiation when full-range testing of the SST and ULNTT is performed. Thus, clinical observation indicated that there might be an unusually high false positive rate among these tests when performing full-range testing of the elbow (ULNTT) and the knee (SST). Shacklock⁶ referred to the production of neural-mediated symptoms among asymptomatic subjects as a normal positive test and suggested reproduction of the patient''s symptoms should be an integral part of the diagnostic criteria. It should be noted that reproduction of symptoms is impossible in asymptomatic subjects (no pathology); therefore, this criteria cannot be used when examining the rate of false positive tests. Therefore, the purpose of this investigation was to determine the false positive rate of the SST and ULNTT in otherwise healthy young adults without cervical, lumbar, or peripheral symptoms and to identify possible cut-off scores based on knee (SST) and elbow (ULNTT) range of motion.