Elevated Pure Tone Thresholds Are Associated with Altered Microstructure in Cortical Areas Related to Auditory Processing and Attentional Allocation.

BACKGROUND: Hearing loss is associated with cognitive decline and increased risk for Alzheimer's disease, but the basis of this association is not understood. OBJECTIVE: To determine whether hearing impairment is associated with advanced brain aging or altered microstructure in areas involved with auditory and cognitive processing. METHODS: 130 participants, (mean 76.4±7.3 years; 65% women) of the Rancho Bernardo Study of Healthy Aging had a screening audiogram in 2003-2005 and brain magnetic resonance imaging in 2014-2016. Hearing ability was defined as the average pure tone threshold (PTA) at 500, 1000, 2000, and 4000 Hz in the better-hearing ear. Brain-predicted age difference (Brain-pad) was calculated as the difference between brain-predicted age based on a validated structural imaging biomarker of brain age, and chronological age. Regional diffusion metrics in temporal and frontal cortex regions were obtained from diffusion-weighted MRIs. Linear regression analyses adjusted for age, gender, education, and health-related measures. RESULTS: PTAs were not associated with brain-PAD (ß= 0.09; 95% CI: -0.084 to 0.243; p = 0.34). PTAs were associated with reduced restricted diffusion and increased free water diffusion primarily in right hemisphere temporal and frontal areas (restricted diffusion: ßs = -0.21 to -0.30; 95% CIs from -0.48 to -0.02; ps < 0.03; free water: ßs = 0.18 to 0.26; 95% CIs 0.01 to 0.438; ps < 0.04). CONCLUSIONS: Hearing impairment is not associated with advanced brain aging but is associated with differences in brain regions involved with auditory processing and attentional control. It is thus possible that increased dementia risk associated with hearing impairment arises, in part, from compensatory brain changes that may decrease resilience.

Changes in diet and physical activity resulting from the Strong Hearts, Healthy Communities randomized cardiovascular disease risk reduction multilevel intervention trial.

BACKGROUND: Women living in rural areas face unique challenges in achieving a heart-healthy lifestyle that are related to multiple levels of the social-ecological framework. The purpose of this study was to evaluate changes in diet and physical activity, which are secondary outcomes of a community-based, multilevel cardiovascular disease risk reduction intervention designed for women in rural communities. METHODS: Strong Hearts, Healthy Communities was a six-month, community-randomized trial conducted in 16 rural towns in Montana and New York, USA. Sedentary women aged 40 and older with overweight and obesity were recruited. Intervention participants (eight towns) attended twice weekly exercise and nutrition classes for 24 weeks (48 total). Individual-level components included aerobic exercise, progressive strength training, and healthy eating practices; a civic engagement component was designed to address social and built environment factors to support healthy lifestyles. The control group (eight towns) attended didactic healthy lifestyle classes monthly (six total). Dietary and physical activity data were collected at baseline and post-intervention. Dietary data were collected using automated self-administered 24-h dietary recalls, and physical activity data were collected by accelerometry and self-report. Data were analyzed using multilevel linear regression models with town as a random effect. RESULTS: At baseline, both groups fell short of meeting many recommendations for cardiovascular health. Compared to the control group, the intervention group realized significant improvements in intake of fruit and vegetables combined (difference: 0.6 cup equivalents per day, 95% CI 0.1 to 1.1, p = .026) and in vegetables alone (difference: 0.3 cup equivalents per day, 95% CI 0.1 to 0.6, p = .016). For physical activity, there were no statistically significant between-group differences based on accelerometry. By self-report, the intervention group experienced a greater increase in walking MET minutes per week (difference: 113.5 MET-minutes per week, 95% CI 12.8 to 214.2, p = .027). CONCLUSIONS: Between-group differences in dietary and physical activity behaviors measured in this study were minimal. Future studies should consider how to bolster behavioral outcomes in rural settings and may also continue to explore the value of components designed to enact social and environmental change. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02499731. Registered 16 July 2015.

Skin pretreatment with microneedles prior to pilocarpine iontophoresis increases sweat production.

Collection of sweat via pilocarpine iontophoresis is commonly used to diagnose cystic fibrosis (CF), with thousands of tests performed each day. The main source of resistance to the passage of pilocarpine ions to the sweat glands is the electrical resistance of the stratum corneum. It was hypothesized that pretreating the skin with 0·5 mm-long microneedles would significantly decrease this resistance, thus increasing pilocarpine's permeation into the skin. Improved permeation should result in significantly reduced time to sweat initiation, time to collection of a clinically meaningful amount of sweat, and increased total amount of sweat produced in 15 min. Subjects (n = 12) had two 5 cm(2) areas on the forearm measured, marked and randomized to experimental (microneedles + iontophoresis) or control (iontophoresis alone). Microneedle pretreatment was conducted using a 35-needle microneedle stamp in a manner that 20 applications completely covered the 5 cm(2) treatment area. This was repeated five times for a total of 100 applications. Both experimental and control sites were placed under iontophoresis (1·5 mA) for 5 min. Microneedle pretreatment significantly decreased mean skin resistance (260 ± 27 kΩ versus 160 ± 19 kΩ, P = 0·006), while significantly increasing mean sweat rate (0·76 ± 0·35 versus 0·54 ± 0·19 µl cm(2) min(-1) , P = 0·007). No significant difference was found concerning pain (P = 0·059), number of active sweat glands (P = 0·627) or the osmolality of the collected sweat (P = 0·636). The results of this study suggest that microneedle pretreatment prior to pilocarpine iontophoresis significantly increases sweat production. Such results have the potential to improve the methodology currently used to diagnose cystic fibrosis and, more broadly, to administer drugs via the skin.

Tibiofemoral and patellofemoral kinematics after reconstruction of an isolated posterior cruciate ligament injury: in vivo analysis during lunge.

BACKGROUND: The actual in vivo tibiofemoral and patellofemoral kinematics of the posterior cruciate ligament (PCL)-reconstructed knee joint are unknown. HYPOTHESIS: Current single-bundle PCL reconstruction is unable to correct the abnormal tibiofemoral and patellofemoral kinematics caused by rupture of the ligament. STUDY DESIGN: Controlled laboratory study/case series; Level of evidence, 4. METHODS: Seven patients with an isolated PCL injury in 1 knee and the contralateral side intact were included in the study. Magnetic resonance and dual fluoroscopic imaging techniques were used to compare the tibiofemoral and patellofemoral kinematics between the intact contralateral (control group), PCL-deficient, and PCL-reconstructed knee during physiologic loading with a single-legged lunge. Data were collected preoperatively and 2 years after single-bundle reconstruction. RESULTS: The PCL reconstruction reduced the abnormal posterior tibial translation in PCL-deficient knees to levels not significantly different from those of the intact knee. Posterior cruciate ligament deficiency resulted in an increased lateral tibial translation between 75 degrees and 120 degrees of flexion, and reconstruction was unable to restore these values to normal. No differences were detected among the groups in varus-valgus and internal-external rotation. The PCL reconstruction reduced the increased patellar flexion of PCL-deficient knees between 90 degrees and 120 degrees of knee flexion and the lateral shift at 120 degrees . The abnormal patellar rotation and tilt seen in PCL deficiency at flexion angles of 75 degrees and greater persisted after reconstruction. CONCLUSION: Single-bundle PCL reconstruction was successful in restoring normal anteroposterior translation of the tibia, as well as the patellar flexion and shift. However, single-bundle PCL reconstruction was unable to achieve the same success in mediolateral translation of the tibia or in the patellar rotation and tilt. CLINICAL RELEVANCE: The persistent abnormal mediolateral translation of the tibia, as well as decreased patellar rotation and tilt, provide a possible explanation for the development of cartilage degeneration after reconstruction of an isolated PCL injury.

Biomechanical evaluation of subscapularis repair used during shoulder arthroplasty.

Dysfunction of the subscapularis after total shoulder replacement has become concerning and may represent poor tendon healing after surgical repair. The objectives of this study were to evaluate the restoration of subscapularis footprint anatomy and failure strength for subscapularis repair via transosseous tunnels and a second anatomic repair via combined transosseous tunnels and direct tendon-to-tendon repair. Six matched pairs of fresh-frozen human cadaveric shoulders were used, with one shoulder from each pair randomly assigned to a transosseous repair and the contralateral shoulder assigned to a combined transosseous tunnel and direct tendon-to-tendon repair. The repair footprint was digitized. Cyclic loading to the tendon repair was performed followed by a constant ramp displacement to complete failure. The transosseous tunnel repair insertional footprint area (228.6 mm2) was significantly less than that of the native footprint (697.3 mm2), and the footprint centroid moved 9.1 mm medially (P = .0001) and 5.5 mm superiorly (P = .003). The combined repair required a statistically significantly greater number of cycles (P = .028) to reach a 5-mm gap (205.7 +/- 65.1) than did the isolated transosseous tunnel technique (76.4 +/- 34.2). A similar greater number of cycles was observed for the 10-mm gap (P = .01) for combined repair (307.5 +/- 82.4) compared with isolated transosseous repair (166.2 +/- 85.8). This study has shown that transosseous tunnel repair alters subscapularis insertional anatomy, resulting in weaker strength of fixation and less contact area when compared with combined transosseous tunnel and direct tendon-to-tendon repair.

A clinical composite score accurately detects meniscal pathology.

PURPOSE: Five common tests were used to diagnose meniscal tears when used as a composite score. We evaluated how effectively the composite examination, when performed in the presence of an anterior cruciate ligament (ACL) injury or degenerative joint disease (DJD), determined the presence of meniscal tears. METHODS: Data were collected prospectively on all patients at our clinic with a primary knee complaint. Independent variables included the presence or absence of the following: (1) a history of "catching" or "locking" as reported by the patient, (2) pain with forced hyperextension, (3) pain with maximum flexion, (4) pain or an audible click with McMurray's maneuver, and (5) joint line tenderness to palpation. Comprehensive patient demographic data were collected including ligamentous examinations and other intra-articular pathologies found at arthroscopy. Composite examination findings were correlated with the presence or absence of meniscal pathology. RESULTS: We evaluated 635 knees in 576 patients for historical and physical findings. Of the knees, 209 underwent arthroscopic surgery and 426 did not. Chi(2) Analysis showed a significant relation between the number of positive diagnostic tests and the presence of meniscal tears (P = .001). Five positive findings on composite examination yielded a positive predictive value of 92.3%. Positive predictive values remained greater than 75% with composite scores of at least 3 in the absence of ACL and DJD pathologies. The presence of an ACL injury decreased the positive predictive value of 5 composite findings to 67%, whereas the presence of DJD increased predictability to 100%. CONCLUSIONS: When all 5 symptoms and signs were positive, there was a 92.3% positive predictive value of finding a meniscal tear. Although positive predictive values decreased with a concomitant ACL injury and increased with DJD, there was a higher rate of false-positive findings (ACL) and false-negative findings (DJD). LEVEL OF EVIDENCE: Level II, development of diagnostic criteria with consecutive patients and gold standard.

Localization and characterization of polysialic acid-containing N-linked glycans from bovine NCAM.

The neural cell adhesion molecule (NCAM) plays important roles during development, plasticity, and regeneration in the adult nervous system. Its function is strongly influenced by attachment of the unusual alpha 2-8-linked polysialic acid (PSA). Here we analyzed the N-glycosylation pattern of polysialylated NCAM from brains of newborn calves. Purified PSA-NCAM glycoprotein was digested with trypsin, and PSA-glycopeptides were separated by immunoaffinity chromatography. For determining the N-glycosylation sites, PNGase F-treated glycopeptides were analyzed by Edman degradation and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). They were found to be exclusively linked to the fifth (Asn 439) and sixth (Asn 468) N-glycosylation sites in the fifth immunoglobulin-like domain of NCAM. The chain length of PSA consisted of at least 30 sialic acid residues, as shown by anion exchange chromatography. For analysis of the core structures, endoneuraminidase N-treated PSA-NCAM was separated by SDS-PAGE and digested with PNGase F. The core structures of polysialylated glycans were characterized by MALDI-MS combined with exoglycosidase digestions and chromatographic fractionation. They include hybrid, di-, tri-, and small amounts of tetraantennary carbohydrates, which were all fucosylated at the innermost N-acetylglucosamine. For the triantennary glycans, the "2,6" arm was preferred in polysialylated structures. High levels of sulfated groups were found on polysialylated structures and to a lower extent also on nonpolysialylated glycans. In addition, high-mannose-type glycans could be detected on PSA-NCAM glycoforms ranging from (GlcNAc)(2)(Man)(5) up to (GlcNAc)(2)(Man)(9). In conclusion, we observed a structural variability and high regional selectivity for the PSA-glycans attached to the NCAM molecule that are most likely influencing its biological functions.