MicroRNA-34a Negatively Regulates Efferocytosis by Tissue Macrophages in Part via SIRT1.

Apoptotic cell (AC) clearance (efferocytosis) is an evolutionarily conserved process essential for immune health, particularly to maintain self-tolerance. Despite identification of many recognition receptors and intracellular signaling components of efferocytosis, its negative regulation remains incompletely understood and has not previously been known to involve microRNAs (miRs). In this article, we show that miR-34a (gene ID 407040), well recognized as a p53-dependent tumor suppressor, mediates coordinated negative regulation of efferocytosis by resident murine and human tissue macrophages (Mø). The miR-34a expression varied greatly between Mø from different tissues, correlating inversely with their capacity for AC uptake. Transient or genetic knockdown of miR-34a increased efferocytosis, whereas miR-34a overexpression decreased efferocytosis, without altering recognition of live, necrotic, or Ig-opsonized cells. The inhibitory effect of miR-34a was mediated both by reduced expression of Axl, a receptor tyrosine kinase known to recognize AC, and of the deacetylase silent information regulator T1, which had not previously been linked to efferocytosis by tissue Mø. Exposure to AC downregulated Mø miR-34a expression, resulting in a positive feedback loop that increased subsequent capacity to engulf AC. These findings demonstrate that miR-34a both specifically regulates and is regulated by efferocytosis. Given the ability of efferocytosis to polarize ingesting Mø uniquely and to reduce their host-defense functions, dynamic negative regulation by miR-34a provides one means of fine-tuning Mø behavior toward AC in specific tissue environments with differing potentials for microbial exposure.

GDF-15 plasma levels in chronic obstructive pulmonary disease are associated with subclinical coronary artery disease.

BACKGROUND: Growth differentiation factor-15 (GDF-15), a cytokine associated with cardiovascular mortality, increases during chronic obstructive pulmonary disease (COPD) exacerbations, but any role in stable COPD is unknown. We tested associations between GDF-15 and subclinical coronary atherosclerosis, assessed by coronary artery calcium (CAC) score, in COPD subjects free of clinical cardiovascular disease (CVD). METHODS: Cross-sectional analysis of COPD participants (GOLD stages 2-4) in the COPDGene cohort without CVD at enrollment, using baseline CAC (from non-EKG-gated chest computed tomography) and plasma GDF-15 (by custom ELISA). We used multinomial logistic modeling of GDF-15 associations with CAC, adjusting for demographics, baseline risk (calculated using the HEART: Personal Heart Early Assessment Risk Tool (Budoff et al. 114:1761-1791, 2006) score), smoking history, measures of airflow obstruction, emphysema and airway disease severity. RESULTS: Among 694 participants with COPD (47% women, mean age 63.6 years) mean GDF-15 was 1,304 pg/mL, and mean CAC score was 198. Relative to the lower GDF-15 tertile, higher tertiles showed bivariate association with increasing CAC score (mid tertile odds ratio [OR] 1.80, 95% confidence interval [CI] 1.29, 2.51; higher tertile OR 2.86, CI 2.04, 4.02). This association was maintained after additionally adjusting for baseline CVD risk, for co-morbidities and descriptors of COPD severity and impact, markers of cardiac stress (N-terminal pro-B-type natriuretic peptide, troponin T) and of inflammation (Interleukin-6), and in subgroup analysis excluding men, diabetics, current smokers or those with limited ambulation. CONCLUSIONS: In ever-smokers with COPD free of clinical CVD, GDF-15 contributes independently to subclinical coronary atherosclerosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00608764 . Registered 28 January 2008.

Biomechanical stability of intramedullary technique for fixation of joint depressed calcaneus fracture.

BACKGROUND: Internal fixation of the os calcis is often complicated by prolonged soft tissue management and posterior facet disruption. An ideal calcaneal construct would include minimal hardware prominence, sturdy posterior facet fixation and nominal soft tissue disruption. The purpose of this study was to develop such a construct and provide a biomechanical analysis comparing our technique to a standard internal fixation technique. METHODS AND MATERIALS: Twenty fresh-frozen cadaver calcanei were used to create a reproducible Sanders type-IIB calcaneal fracture pattern. One calcaneus of each pair was randomly selected to be fixed using our compressive headless screw technique. The contralateral matched calcaneus was fixed with a nonlocking calcaneal plate in a traditional fashion. Each calcaneus was cyclically loaded at a frequency of 1 Hz for 4000 cycles using an increasing force from 250 N to 1000 N. An Optotrak motion capturing system was used to detect relative motion of the three fracture fragments at eight different points along the fracture lines. Horizontal separation and vertical displacement at the fracture lines was recorded, as well as relative rotation at the primary fracture line. RESULTS: When the data were averaged, there was more horizontal displacement at the primary fracture line of the plate and screw construct compared to the headless screw construct. The headless screw construct also had less vertical displacement at the primary fracture line at every load. On average those fractures fixed with the headless screw technique had less rotation than those fixed with the side plate technique. CONCLUSION: A new headless screw technique for calcaneus fracture fixation was shown to provide stability as good as, or better than, a standard side plating technique under the axial loading conditions of our model. Although further testing is needed, the stability of the proposed technique is similar to that typically provided by intramedullary fixation. CLINICAL RELEVANCE: This fixation technique provides a biomechanically stable construct with the potential for a minimally invasive approach and improved post-operative soft tissue healing.

Temporal patterns of microbial community structure in the Mid-Atlantic Bight.

Although open ocean time-series sites have been areas of microbial research for years, relatively little is known about the population dynamics of bacterioplankton communities in the coastal ocean on kilometer spatial and seasonal temporal scales. To gain a better understanding of microbial community variability, monthly samples of bacterial biomass were collected in 1995-1996 along a 34-km transect near the Long-Term Ecosystem Observatory (LEO-15) off the New Jersey coast. Surface and bottom sampling was performed at seven stations along a transect line with depths ranging from 1 to 35 m (n=178). Microbial populations were fingerprinted using ribosomal 16S rRNA genes and terminal restriction fragment length polymorphism analysis. Results from cluster analysis revealed distinct temporal patterns among the bacterioplankton communities in the Mid-Atlantic Bight rather than grouping by sample location or depth. Principal components analysis models supported the temporal patterns. In addition, partial least squares regression modeling could not discern a significant correlation from traditional oceanographic physical and phytoplankton nutrient parameters on overall bacterial community variability patterns at LEO-15. These results suggest factors not traditionally measured during oceanographic studies are structuring coastal microbial communities.

Brief dialectical behavior therapy (DBT-B) for suicidal behavior and non-suicidal self injury.

The purpose of this study is to evaluate the effectiveness of a shorter course of Dialectical Behavior Therapy (DBT) in enhancing treatment retention and reducing: urges to engage in non-suicidal self injury (NSSI), NSSI, suicide ideation, and subjective distress in borderline personality disorder (BPD). Twenty patients with BPD received a six-month course of Dialectical Behavior Therapy (DBT-B). DBT-B was delivered in the standard manner except for the shortened duration from one-year minimum to six months. All variables were measured at baseline, and at six months. Data were analyzed using paired t-tests. Treatment retention rate was 95%. Significant reductions were found in NSSI urges, NSSI, suicide ideation, subjective distress, depression, and hopelessness between baseline and six months. These results support the use of DBT-B in a six-month format when NSSI and suicidal behavior and ideation are the targeted behaviors. Target behaviors were reduced significantly and retention was extremely high in comparison to other interventions for this population. A large scale randomized controlled trial investigating its efficacy is warranted to determine if the results can be replicated and if improvement can be sustained.

Acute colonic pseudo-obstruction (Ogilvie syndrome) after arthroplasty in the lower extremity.

BACKGROUND: Acute colonic pseudo-obstruction, also known as Ogilvie syndrome, is an uncommon postoperative complication of total hip and total knee arthroplasty that is characterized by massive colonic dilatation and the potential for substantial morbidity and mortality. METHODS: We conducted a retrospective case-control study of 1170 total hip and knee arthroplasties performed by one surgeon from 1995 to 2002, and identified eighteen patients with Ogilvie syndrome. Radiographs and medical records were analyzed for risk factors and treatment effectiveness. RESULTS: Eleven (1.6%) of 708 patients who had a total hip arthroplasty and seven (1.5%) of 462 patients who had a total knee arthroplasty had Ogilvie syndrome develop postoperatively. Seventeen of these patients had preoperative conditions and/or had received medications identified as risk factors for Ogilvie syndrome. The use of patient-controlled analgesia was associated with an earlier development of symptoms. Colonic decompression was performed in seven patients and was associated with a significantly shorter hospital stay (p = 0.019). CONCLUSIONS: Acute colonic pseudo-obstruction was equally prevalent after total hip and total knee arthroplasties. Most patients who had Ogilvie syndrome had risk factors that could be identified preoperatively. Knowledge of these risk factors can enable the physician to anticipate which patients may have Ogilvie syndrome develop and, therefore, to be vigilant for its development and judicious in the use of patient-controlled analgesia. We also found that decompressive colonoscopy reduced the risk of perforation and decreased the length of hospitalization for the patients in whom Ogilvie syndrome developed.

Preventive Effects of Eccentric Training on Acute Hamstring Muscle Injury in Professional Baseball.

BACKGROUND: Hamstring injuries are the second most common injury causing missed days in professional baseball field players. Recent studies have shown the preventive benefit of eccentric conditioning on the hamstring muscle group in injury prevention. Specifically, Nordic-type exercises have been shown to decrease the incidence of acute hamstring injuries in professional athletes. PURPOSE: This was a prospective study performed in coordination with a single Major League Baseball (MLB) organization (major and minor league teams) that targeted the effects of Nordic exercises on the incidence of acute hamstring injuries in the professional-level baseball player. STUDY DESIGN: Prospective cohort study; Level of evidence, 2. METHODS: The daily workouts of 283 professional baseball players throughout all levels of a single MLB organization were prospectively recorded. The intervention group participated in the Nordic exercise program and was compared with a randomly selected control group of professional athletes within the organization not participating in the exercise program. The incidence of hamstring injuries in both groups was compared, and the total number of days missed due to injury was compared with the 2 previous seasons. RESULTS: There were 10 hamstring injuries that occurred during the 2012 season among the 283 professional athletes that required removal from play. There were no injuries that occurred in the intervention group (n = 65, 0.00%; P = .0381). The number needed to treat (NNT) to prevent 1 hamstring injury was 11.3. The average repetitions per week of the injured group were assessed at multiple time points (2, 4, 6, and total weeks) prior to injury. There were significantly fewer repetitions per week performed in the injured group at all time points compared with overall average repetitions per week in the noninjured group (P = .0459, .0127, .0164, and .0299, respectively). After beginning the Nordic exercise program, there were 136 total days missed due to a hamstring injury during the 2012 season. This number was less than the 2011 season (273 days missed) and the 2010 season (309 days missed). CONCLUSION: Study results indicate the initiation of Nordic hamstring exercises may decrease the incidence of acute hamstring injuries and potentially decrease the total number of days missed due to injury in professional baseball players. CLINICAL RELEVANCE: The financial and competitive interest in professional baseball players is of large importance to the player, team, and fans. Prevention of injuries is as important to all parties involved as the treatment and rehabilitation following an injury. This prospective study shows the initiation of a simple, free exercise can reduce the incidence of hamstring injury in the professional-level baseball player.

Ammonia-oxidizing bacterial community composition in estuarine and oceanic environments assessed using a functional gene microarray.

The relationship between environmental factors and functional gene diversity of ammonia-oxidizing bacteria (AOB) was investigated across a transect from the freshwater portions of the Chesapeake Bay and Choptank River out into the Sargasso Sea. Oligonucleotide probes (70-bp) designed to represent the diversity of ammonia monooxygenase (amoA) genes from Chesapeake Bay clone libraries and cultivated AOB were used to construct a glass slide microarray. Hybridization patterns among the probes in 14 samples along the transect showed clear variations in amoA community composition. Probes representing uncultivated members of the Nitrosospira-like AOB dominated the probe signal, especially in the more marine samples. Of the cultivated species, only Nitrosospira briensis was detected at appreciable levels. Discrimination analysis of hybridization signals detected two guilds. Guild 1 was dominated by the marine Nitrosospira-like probe signal, and Guild 2's largest contribution was from upper bay (freshwater) sediment probes. Principal components analysis showed that Guild 1 was positively correlated with salinity, temperature and chlorophyll a concentration, while Guild 2 was positively correlated with concentrations of oxygen, dissolved organic carbon, and particulate nitrogen and carbon, suggesting that different amoA sequences represent organisms that occupy different ecological niches within the estuarine/marine environment. The trend from most diversity of AOB in the upper estuary towards dominance of a single type in the polyhaline region of the Bay is consistent with the declining importance of AOB with increasing salinity, and with the idea that AO-Archaea are the more important ammonia oxidizers in the ocean.

Large visuospatial sex difference in line judgment: possible role of attentional factors.

This article describes a large sex difference on a new, group-administered visuospatial task, the Judgment of Line Angle and Position (JLAP) test, and investigates the role of attentional factors in the difference. On the JLAP, adapted from a neuropsychological task (Benton et al., 1983), participants evaluate spatial attributes of lines. Study 1: College males (N = 48) outperformed females (N = 80), resulting in a large effect for sex (d = 0.85). Errors were more common on oblique (vs horizontal or vertical) lines, especially for females. Study 2: Task attributes were manipulated (N = 33 males and 36 females) to study the role of attentional factors. Findings suggest that males are more likely than females to normally attend to and be aided by geometrical reference cues.