LINKS Training and Unit Support for Mental Health: a Group-randomized Effectiveness Trial.

The LINKS curriculum, adapted from Britt et al. (2018a), was designed to improve unit climate, knowledge, and attitudes about mental health treatment seeking in military personnel. The present study extends this research by examining implementation options, comparing the effectiveness of LINKS to an active control condition with training delivered by non-experts and comparing modules that varied in training length. Eight Army platoons were randomly assigned to one of four conditions: (1) 1-h Active Control, (2) 2-h Active Control, (3) 1-h LINKS, or (4) 2-h LINKS. Two platoons were assigned to each condition. Surveys were administered at pre-training (T1), post-training (T2), and 3 months later (T3). Eighty-four participants completed all study phases. Regardless of training content, participants receiving the 2-h modules reported greater training acceptability than those receiving the 1-h modules. At T3, participants in the LINKS conditions reported more mental health knowledge than participants in the Active Control conditions. Sustained effects were also observed on a number of treatment barriers and facilitators, with the LINKS conditions generally leading to better outcomes. At T3, 2-h LINKS condition participants reported receiving more mental health treatment relative to the other conditions. Findings suggest that LINKS can be effectively delivered by non-expert trainers, is a viable intervention for targeting mental health treatment-seeking, and is optimally packaged in a 2-h module. The training might benefit from additional leadership training efforts.

Optimizing Performance and Mental Skills With Mindfulness-Based Attention Training: Two Field Studies With Operational Units.

INTRODUCTION: Mental skills such as focusing attention and managing emotions are essential for optimal performance in high-stress occupations. Studies with military samples have demonstrated that mindfulness training (MT) led to improved computer-based cognitive performance. MATERIALS AND METHODS: To examine the impact of MT on operational performance, mental skills, and psychological health, a short-form program, Mindfulness-Based Attention Training (MBAT), was delivered to active duty soldiers as part of two randomized trials. Participants in study 1 (n = 121) and study 2 (n = 77) were randomized to one of three conditions: MT with proctored practice, MT with unproctored practice, or a waitlist control. Weekly 2-hour MBAT sessions were offered to participants in both MT conditions for 4 weeks. Beyond these sessions, participants also engaged in mindfulness practice that was proctored (within the occupational context) or unproctored (left up to the individual) for four subsequent weeks. RESULTS: Overall, the frequency of mindfulness practice was generally associated with better performance and improvements in mental skills. In study 1, those who practiced 3 or more days per week performed better on marksmanship under physical stress and reported fewer attentional lapses, less emotion regulation difficulties, greater mental toughness, and higher self-reported mindfulness compared to those who did not practice. In study 2, the frequency of mindfulness practice was associated with fewer attentional lapses and emotion regulation difficulties. CONCLUSIONS: Consistent with prior findings, results suggest that regular engagement in MT practice may help to optimize operational performance and improve mental skills in military cohorts.

Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass.

Krox20/EGR2, one of the 4 early growth response genes, is a highly conserved transcription factor implicated in hindbrain development, peripheral nerve myelination, tumor suppression, and monocyte/macrophage cell fate determination. Here, we established a novel role for Krox20 in postnatal skeletal metabolism. Microcomputed tomographic analysis of 4- and 8-week-old mice revealed a low bone mass phenotype (LBM) in both the distal femur and the vertebra of Krox20(+/-) mice. This was attributable to accelerated bone resorption as demonstrated in vivo by increased osteoclast number and serum C-terminal telopeptides, a marker for collagen degradation. Krox20 haploinsufficiency did not reduce bone formation in vivo, nor did it compromise osteoblast differentiation in vitro. In contrast, growth and differentiation were significantly stimulated in preosteoclast cultures derived from Krox20(+/-) splenocytes, suggesting that the LBM is attributable to Krox20 haploinsufficiency in the monocytic lineage. Furthermore, Krox20 silencing in preosteoclasts increased cFms expression and response to macrophage colony-stimulating factor, leading to a cell-autonomous stimulation of cell-cycle progression. Our data indicate that the antimitogenic role of Krox20 in preosteoclasts is the predominant mechanism underlying the LBM phenotype of Krox20-deficient mice. Stimulation of Krox20 expression in preosteoclasts may present a viable therapeutic strategy for high-turnover osteoporosis.

Renoprotective effects of a selective estrogen receptor modulator, raloxifene, in an animal model of diabetic nephropathy.

BACKGROUND/AIMS: Our previous studies have shown that supplementation with 17beta-estradiol (E2) from the onset of diabetes attenuates diabetic nephropathy. However, E2 is accompanied by feminizing effects as well as adverse side effects on other organs. The current study examined the renoprotective effects of a selective estrogen receptor modulator, raloxifene (RAL), in an experimental model of diabetic nephropathy. RAL activates estrogen receptors and estrogen-receptor-mediated cellular events without the side effects of E2. METHODS: The study was performed in Sprague-Dawley nondiabetic (ND), streptozotocin-induced diabetic (D) and streptozotocin-induced D + RAL rats (n = 6/group). RESULTS: After 12 weeks of treatment, D was associated with increased urine albumin excretion (ND: 4.2 +/- 0.4; D: 41.3 +/- 9.0 mg/day), glomerulosclerosis [glomerulosclerotic index; ND: 0.26 +/- 0.04; D: 1.86 +/- 0.80 arbitrary units (AU)], tubulointerstitial fibrosis (tubulointerstitial fibrosis index; ND: 0.37 +/- 0.05; D: 2.12 +/- 0.50 AU), increased collagen type I [ND: 1.31 +/- 0.07; D: 4.65 +/- 0.09 relative optical density (ROD)], collagen type IV (ND: 0.64 +/- 0.03; D: 1.37 +/- 0.11 ROD) and transforming growth factor beta (TGF-beta) protein expression (ND: 0.65 +/- 0.08; D: 1.25 +/- 0.10 ROD), increased density of CD68-positive cells (ND: 1.37 +/- 3.02; D: 29.2 +/- 1.74 cells/mm2) and increased plasma levels of interleukin-6 (ND: 14.8 +/- 5.0; D: 51.3 +/- 14.0 pg/ml). Treatment with RAL partially or fully attenuated these processes (urine albumin excretion: 21.0 +/- 5.0 mg/day; glomerulosclerotic index: 0.40 +/- 0.06 AU; tubulointerstitial fibrosis index: 0.20 +/- 0.04 AU; collagen type I: 2.55 +/- 0.49 ROD; collagen type IV: 0.70 +/- 0.09 ROD; TGF-beta: 0.91 +/- 0.08 ROD; CD68: 6.03 +/- 2.38 cells/mm2; interleukin-6: 31.2 +/- 5.0 pg/ml). CONCLUSIONS: Our data indicate that treatment with RAL attenuates albuminuria and renal structural changes associated with diabetes.

Increased Incidence and Severity of Postoperative Radiographic Hallux Valgus Interphalangeus With Surgical Correction of Hallux Valgus.

BACKGROUND: A previous study has shown an increased radiographic prevalence and severity of hallux valgus interphalangeus (HVIP) after surgical correction of hallux valgus (HV) due to correction of pronation deformity. The purpose of this study was to evaluate the change in pre- and postoperative HVIP deformity with correction of HV with multiple radiographic parameters. METHODS: A retrospective chart review identified all bunion surgeries performed at a single center from July 1, 2009, to September 30, 2012. Exclusion criteria included prior bony surgery to the first ray, inadequate films, nonadult bunion, Akin osteotomy, or surgical treatment other than bunion correction. Pre- and postoperative films were reviewed for 2 HV angular measurements and 5 HVIP measurements, which were compared. The angles measured were hallux valgus angle (HVA), first intermetatarsal angle (IMA), hallux interphalangeus angle (HIA), distal metatarsal articular angle (DMAA), proximal phalangeal articular angle (PPAA), proximal to distal phalangeal articular angle (PDPAA), and total distal deformity (TDD). Prevalence of HVIP was analyzed in pre- and postoperative radiographs. A 1-sided Student t test was used to compare continuous data, and a chi-square test was used to compare categorical data. Ninety-two feet in 82 patients were eligible. RESULTS: The average preoperative HV improved with surgery. Preoperative HVA improved from 27 to 11 degrees (P < .001). Preoperative IMA improved from 13.6 to 6.1 degrees (P < .001). HVIP worsened after surgery. Preoperative HIA increased from 7.2 to 13.2 degrees (P < .001). DMAA worsened from 7.3 to 9.2 degrees (P = .001). PPAA worsened from 3.2 to 6.2 degrees. PDPAA worsened from 6.7 to 8.2 degrees (P < .001). The TDD increased from 14.6 to 17.9 degrees (P < .001). The prevalence of HVIP pre- and postoperatively as defined by HIA increased from 26% to 79% (P < .001) and by PPAA from 12% to 46% (P < .001). CONCLUSION: Initial assessment of preoperative radiographs underestimated HVIP. Postoperative correction of the deformity revealed HVIP that was not obvious preoperatively. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner.

We investigated the role of Lef1, one of the four transcription factors that transmit Wnt signaling to the genome, in the regulation of bone mass. Microcomputed tomographic analysis of 13- and 17-week-old mice revealed significantly reduced trabecular bone mass in Lef1(+/-) females compared to littermate wild-type females. This was attributable to decreased osteoblast activity and bone formation as indicated by histomorphometric analysis of bone remodeling. In contrast to females, bone mass was unaffected by Lef1 haploinsufficiency in males. Similarly, females were substantially more responsive than males to haploinsufficiency in Gsk3beta, a negative regulator of the Wnt pathway, displaying in this case a high bone mass phenotype. Lef1 haploinsufficiency also led to low bone mass in males lacking functional androgen receptor (AR) (tfm mutants). The protective skeletal effect of AR against Wnt-related low bone mass is not necessarily a result of direct interaction between the AR and Wnt signaling pathways, because Lef1(+/-) female mice had normal bone mass at the age of 34 weeks. Thus, our results indicate an age- and gender-dependent role for Lef1 in regulating bone formation and bone mass in vivo. The resistance to Lef1 haploinsufficiency in males with active AR and in old females could be due to the reduced bone turnover in these mice.

17beta-Estradiol attenuates diabetic kidney disease by regulating extracellular matrix and transforming growth factor-beta protein expression and signaling.

We previously showed that supplementation with 17beta-estradiol (E2) from the onset of diabetes attenuates the development of diabetic renal disease. The aim of the present study was to examine whether E2 can also attenuate the disease process once it has developed. The present study was performed in nondiabetic and streptozotocin-induced diabetic Sprague-Dawley rats. E2 supplementation began after 9 wk of diabetes and continued for 8 wk. Diabetes was associated with an increase in urine albumin excretion, glomerulosclerosis, tubulointerstitial fibrosis, renal cortical collagen type I and IV, laminin, plasminogen activator inhibitor-1, tissue inhibitors of metalloproteinase-1 and -2, transforming growth factor (TGF)-beta, TGF-beta receptor type I and II, Smad2/3, phosphorylated Smad2/3, and Smad4 protein expression, and CD68-positive cell abundance. Decreases in matrix metalloproteinase (MMP)-2 protein expression and activity and decreases in Smad6 and Smad7 protein expression were also associated with diabetes. E2 supplementation completely or partially attenuated all these changes, except Smad4 and fibronectin, on which E2 supplementation had no effect. These data suggest that E2 attenuates the progression of diabetic renal disease once it has developed by regulating extracellular matrix, TGF-beta, and expression of its downstream regulatory proteins. These findings support the notion that sex hormones in general, and E2 in particular, are important regulators of renal function and may be novel targets for the treatment and prevention of diabetic renal disease.