Elevated L-lactate Promotes Major Cellular Pathologies Associated with Neurodegenerative Diseases

Dear Editor,Small,short-chain fatty acids(SCFAs)(acetic acid,propionic acid,and butyric acid:conjugate bases,acetate,propionate,and butyrate)as well as the alpha-hydroxy acid,L-lactic acid(conjugate base,L-lactate)are important energy substrates and signaling molecules in the central nervous system(CNS)[1,2].L-lactic acid is produced by glycolysis[3]and gut microbes[4]and is released in large quantities during exercise[5].     

Influence of muscle strength to weight ratio on functional task performance

Existing models of muscle deconditioning such as bed rest are expensive and time-consuming. We propose a new model utilizing a weighted suit to manipulate muscle strength, power, or endurance relative to body weight. The aims of the study were to determine as to which muscle measures best predict functional task performance and to determine muscle performance thresholds below which task performance is impaired. Twenty subjects performed seven occupational astronaut tasks (supine and upright seat egress and walk, rise from fall, hatch opening, ladder climb, object carry, and construction board activity), while wearing a suit weighted with 0–120 % of body weight. Models of the relationship between muscle function/body weight and task completion time were developed using fractional polynomial regression and verified with pre- and post-flight astronaut performance data. Spline regression was used to identify muscle function thresholds for each task. Upright seat egress and walk was the most difficult task according to the spline regression analysis thresholds. Thresholds normalized to body weight were 17.8 N/kg for leg press isometric force, 17.6 W/kg for leg press power, 78.8 J/kg for leg press work, 5.9 N/kg isometric knee extension and 1.9 Nm/kg isokinetic knee extension torque. Leg press maximal isometric force/body weight was the most reliable measure for modeling performance of ambulatory tasks. Laboratory-based manipulation of relative strength has promise as an analog for spaceflight-induced loss of muscle function. Muscle performance values normalized to body weight can be used to predict occupational task performance and to establish relevant strength thresholds.     

What Risk Factors Are Associated With Musculoskeletal Injury in US Army Rangers? A Prospective Prognostic Study

Background

Musculoskeletal injury is the most common reason that soldiers are medically not ready to deploy. Understanding intrinsic risk factors that may place an elite soldier at risk of musculoskeletal injury may be beneficial in preventing musculoskeletal injury and maintaining operational military readiness. Findings from this population may also be useful as hypothesis-generating work for particular civilian settings such as law enforcement officers (SWAT teams), firefighters (smoke jumpers), or others in physically demanding professions.

Questions/purposes

The purposes of this study were (1) to examine whether using baseline measures of self-report and physical performance can identify musculoskeletal injury risk; and (2) to determine whether a combination of predictors would enhance the accuracy for determining future musculoskeletal injury risk in US Army Rangers.

Methods

Our study was a planned secondary analysis from a prospective cohort examining how baseline factors predict musculoskeletal injury. Baseline predictors associated with musculoskeletal injury were collected using surveys and physical performance measures. Survey data included demographic variables, injury history, and biopsychosocial questions. Physical performance measures included ankle dorsiflexion, Functional Movement Screen, lower and upper quarter Y-balance test, hop testing, pain provocation, and the Army Physical Fitness Test (consisting of a 2-mile run and 2 minutes of sit-ups and push-ups). A total of 320 Rangers were invited to enroll and 211 participated (66%). Occurrence of musculoskeletal injury was tracked for 1 year using monthly injury surveillance surveys, medical record reviews, and a query of the Department of Defense healthcare utilization database. Injury surveillance data were available on 100% of the subjects. Receiver operator characteristic curves and accuracy statistics were calculated to identify predictors of interest. A logistic regression equation was then calculated to find the most pertinent set of predictors. Of the 188 Rangers (age, 23.3 ± 3.7 years; body mass index, 26.0 ± 2.4 kg/m²) remaining in the cohort, 85 (45.2%) sustained a musculoskeletal injury of interest.

Results

Smoking, prior surgery, recurrent prior musculoskeletal injury, limited-duty days in the prior year for musculoskeletal injury, asymmetrical ankle dorsiflexion, pain with Functional Movement Screen clearing tests, and decreased performance on the 2-mile run and 2-minute sit-up test were associated with increased injury risk. Presenting with one or fewer predictors resulted in a sensitivity of 0.90 (95% confidence interval [CI], 0.83–0.95), and having three or more predictors resulted in a specificity of 0.98 (95% CI, 0.93–0.99). The combined factors that contribute to the final multivariable logistic regression equation yielded an odds ratio of 4.3 (95% CI, 2.0–9.2), relative risk of 1.9 (95% CI, 1.4–2.6), and an area under the curve of 0.64.

Conclusions

Multiple factors (musculoskeletal injury history, smoking, pain provocation, movement tests, and lower scores on physical performance measures) were associated with individuals at risk for musculoskeletal injury. The summation of the number of risk factors produced a highly sensitive (one or less factor) and specific (three or more factors) model that could potentially be used to effectively identify and intervene in those persons with elevated risk for musculoskeletal injury. Future research should establish if screening and intervening can improve musculoskeletal health and if our findings among US Army Rangers translate to other occupations or athletes.

Level of Evidence

Level II, prognostic study.     

The Effect of Granulocyte-colony Stimulating Factor on Rotator Cuff Healing After Injury and Repair

Background

The failure rate of tendon-bone healing after repair of rotator cuff tears remains high. A variety of biologic- and cell-based therapies aimed at improving rotator cuff healing have been investigated, and stem cell-based techniques have become increasingly more common. However, most studies have focused on the implantation of exogenous cells, which introduces higher risk and cost. We aimed to improve rotator cuff healing by inducing endogenous stem cell mobilization with systemic administration of granulocyte-colony stimulating factor (G-CSF).

Questions/purposes

We asked: (1) Does G-CSF administration increase local cellularity after acute rotator cuff repair? (2) Is there histologic evidence that G-CSF improved organization at the healing enthesis? (3) Does G-CSF administration improve biomechanical properties of the healing supraspinatus tendon-bone complex? (4) Are there micro-MRI-based observations indicating G-CSF-augmented tendon-bone healing?

Methods

After creation of full-thickness supraspinatus tendon defects with immediate repair, 52 rats were randomized to control or G-CSF-treated groups. G-CSF was administered for 5 days after repair and rats were euthanized at 12 or 19 postoperative days. Shoulders were subjected to micro-MR imaging, stress relaxation, and load-to-failure as well as blinded histologic and histomorphometric analyses.

Results

G-CSF-treated animals had significantly higher cellularity composite scores at 12 and 19 days compared with both control (12 days: 7.40 ± 1.14 [confidence interval {CI}, 5.98–8.81] versus 4.50 ± 0.57 [CI, 3.58–5.41], p = 0.038; 19 days: 8.00 ± 1.00 [CI, 6.75–9.24] versus 5.40 ± 0.89 [CI, 4.28–6.51], p = 0.023) and normal animals (12 days: p = 0.029; 19 days: p = 0.019). There was no significant difference between G-CSF-treated animals or control animals in ultimate stress (MPa) and strain, modulus (MPa), or yield stress (MPa) and strain at either 12 days (p = 1.000, p = 0.104, p = 1.000, p = 0.909, and p = 0.483, respectively) or 19 days (p = 0.999, p = 0.964, p = 1.000, p = 0.988, and p = 0.904, respectively). There was no difference in MRI score between G-CSF and control animals at either 12 days (2.7 ± 1.8 [CI, 1.08–4.24] versus 2.3 ± 1.8 [CI, 0.49–4.17], p = 0.623) or 19 days (2.5 ± 1.4 [CI, 1.05–3.94] versus 2.3 ± 1.5 [CI, 0.75–3.91], p = 0.737). G-CSF-treated animals exhibited significantly lower relative bone volume compared with normal animals in the entire humeral head (24.89 ± 3.80 [CI, 20.17–29.60) versus 32.50 ± 2.38 [CI, 29.99–35.01], p = 0.009) and at the supraspinatus insertion (25.67 ± 5.33 [CI, 19.04–32.29] versus 33.36 ± 1.69 [CI, 31.58–35.14], p = 0.027) at 12 days. Further analysis did not reveal any additional significant relationships with respect to regional bone volume or trabecular thickness between groups and time points (p > 0.05).

Clinical Relevance

Postoperative stem cell mobilization agents may be an effective way to enhance rotator cuff repair. Future studies regarding the kinetics of mobilization, the homing capacity of mobilized cells to injured tissues, and the ability of homing cells to participate in regenerative pathways are necessary.