Tailoring of magnetism & electron transport of manganate thin films by controlling the Mn-O-Mn bond angles via strain engineering.

Strain engineering beyond substrate limitation of colossal magnetoresistant thin (La0.6Pr0.4)0.7Ca0.3MnO3 (LPCMO) films on LaAlO3-buffered SrTiO3 (LAO/STO) substrates has been demonstrated using metalorganic aerosol deposition technique. By growing partially relaxed 7-27 nm thick heteroepitaxial LAO buffer layers on STO a perfect lattice matching to the LPCMO has been achieved. As a result, strain-free heteroepitaxial 10-20 nm thick LPCMO/LAO/STO films with bulk-like ferromagnetic metallic ground state were obtained. Without buffer the coherently strained thin LPCMO/STO and LPCMO/LAO films were insulating and weakly magnetic. The reason for the optimized magnetotransport in strain-free LPCMO films was found to be a large octahedral Mn-O-Mn bond angle φOOR ~ 166-168° as compared to the significantly smaller one of φOOR ~ 152-156° determined for the tensile (LPCMO/STO) and compressively (LPCMO/LAO) strained films.

Three-Month Complication Rate of Ultrasound-Guided Soft Tissue Surgical Procedures Across Six Sports Medicine Clinics.

OBJECTIVES: To 1) determine the types and frequency of complications within 3 months following ultrasound-guided surgical procedures, and 2) identify any patient demographics, co-morbidities, or procedural characteristics that were associated with an increased risk of complications. METHODS: A retrospective chart review was performed at six Sports Medicine clinics across the United States. The Clavien-Dindo classification was used to categorize procedural complications on a 5-point scale from 1, representing any deviation in post-procedure care without requiring pharmacological or invasive treatment to 5, representing death. Generalized Estimating Equations for binomial outcomes with a logit link were used to estimate the overall and procedure-specific 3-month complication rates. RESULTS: Among 1902 patients, 8.1% (n = 154) had diabetes and 6.3% (n = 119) were current smokers. The analysis included 2,369 procedures, which were performed in either the upper extremity (44.1%, n = 1045) or lower extremity (55.2%, n = 1308) regions. The most common procedure was ultrasound-guided tenotomy (69.9%, n = 1655). Additional procedures included, trigger finger release (13.1%, n = 310), tendon scraping (8.0%, n = 189), carpal tunnel release (5.4%, n = 128), soft tissue release (2.1%, n = 50), and compartment fasciotomy (1.6%, n = 37). Overall, there was a complication rate of 1.2% (n = 29 complications; 95% CI: 0.8-1.7%). Individual procedures had complication rates that ranged from 0 to 2.7%. There were 13 Grade I complications in 13 patients, 12 Grade II complications in 10 patients, 4 Grade III complications in 4 patients, and 0 Grade IV or V complications. No associations between complication risk and any patient demographics (age, sex, BMI), co-morbidities (diabetes, smoker), or procedure characteristics (type, region) were identified. CONCLUSION: This retrospective review provides an evidence-based estimate supporting the low level of risk associated with ultrasound-guided surgical procedures for patients from a variety of geographical settings who are seeking care at private and academic-affiliated clinics.

Enhanced Susceptibility of ADAP-Deficient Mice to Listeria monocytogenes Infection Is Associated With an Altered Phagocyte Phenotype and Function.

The adhesion and degranulation-promoting adaptor protein (ADAP) serves as a multifunctional scaffold and is involved in the formation of immune signaling complexes. To date, only limited data exist regarding the role of ADAP in pathogen-specific immunity during in vivo infection, and its contribution in phagocyte-mediated antibacterial immunity remains elusive. Here, we show that mice lacking ADAP (ADAPko) are highly susceptible to the infection with the intracellular pathogen Listeria monocytogenes (Lm) by showing enhanced immunopathology in infected tissues together with increased morbidity, mortality, and excessive infiltration of neutrophils and monocytes. Despite high phagocyte numbers in the spleen and liver, ADAPko mice only inefficiently controlled pathogen growth, hinting at a functional impairment of infection-primed phagocytes in the ADAP-deficient host. Flow cytometric analysis of hallmark pro-inflammatory mediators and unbiased whole genome transcriptional profiling of neutrophils and inflammatory monocytes uncovered broad molecular alterations in the inflammatory program in both phagocyte subsets following their activation in the ADAP-deficient host. Strikingly, ex vivo phagocytosis assay revealed impaired phagocytic capacity of neutrophils derived from Lm-infected ADAPko mice. Together, our data suggest that an alternative priming of phagocytes in ADAP-deficient mice during Lm infection induces marked alterations in the inflammatory profile of neutrophils and inflammatory monocytes that contribute to enhanced immunopathology while limiting their capacity to eliminate the pathogen and to prevent the fatal outcome of the infection.

Robustly High Hippocampal BDNF levels under Acute Stress in Mice Lacking the Full-length p75 Neurotrophin Receptor.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) exerts its effects on neural plasticity via 2 distinct receptor types, the tyrosine kinase TrkB and the p75 neurotrophin receptor (p75NTR). The latter can promote inflammation and cell death while TrkB is critically involved in plasticity and memory, particularly in the hippocampus. Acute and chronic stress have been associated with suppression of hippocampal BDNF expression and impaired hippocampal plasticity. We hypothesized that p75NTR might be involved in the hippocampal stress response, in particular in stress-induced BDNF suppression, which might be accompanied by increased neuroinflammation. METHOD: We assessed hippocampal BDNF protein concentrations in wild-type mice compared that in mice lacking the long form of the p75NTR (p75NTRExIII-/-) with or without prior exposure to a 1-hour restraint stress challenge. Hippocampal BDNF concentrations were measured using an optimized ELISA. Furthermore, whole-brain mRNA expression of pro-inflammatory interleukin-6 (Il6) was assessed with RT-PCR. RESULTS: Deletion of full-length p75NTR was associated with higher hippocampal BDNF protein concentration in the stress condition, suggesting persistently high hippocampal BDNF levels in p75NTR-deficient mice, even under stress. Stress elicited increased whole-brain Il6 mRNA expression irrespective of genotype; however, p75NTRExIII-/- mice showed elevated baseline Il6 expression and thus a lower relative increase. CONCLUSIONS: Our results provide evidence for a role of p75NTR signaling in the regulation of hippocampal BDNF levels, particularly under stress. Furthermore, p75NTR signaling modulates baseline but not stress-related Il6 gene expression in mice. Our findings implicate p75NTR signaling as a potential pathomechanism in BDNF-dependent modulation of risk for neuropsychiatric disorders.

Quantifying the roles of space and stochasticity in computer simulations for cell biology and cellular biochemistry.

Most of the fascinating phenomena studied in cell biology emerge from interactions among highly organized multimolecular structures embedded into complex and frequently dynamic cellular morphologies. For the exploration of such systems, computer simulation has proved to be an invaluable tool, and many researchers in this field have developed sophisticated computational models for application to specific cell biological questions. However, it is often difficult to reconcile conflicting computational results that use different approaches to describe the same phenomenon. To address this issue systematically, we have defined a series of computational test cases ranging from very simple to moderately complex, varying key features of dimensionality, reaction type, reaction speed, crowding, and cell size. We then quantified how explicit spatial and/or stochastic implementations alter outcomes, even when all methods use the same reaction network, rates, and concentrations. For simple cases, we generally find minor differences in solutions of the same problem. However, we observe increasing discordance as the effects of localization, dimensionality reduction, and irreversible enzymatic reactions are combined. We discuss the strengths and limitations of commonly used computational approaches for exploring cell biological questions and provide a framework for decision making by researchers developing new models. As computational power and speed continue to increase at a remarkable rate, the dream of a fully comprehensive computational model of a living cell may be drawing closer to reality, but our analysis demonstrates that it will be crucial to evaluate the accuracy of such models critically and systematically.

Membrane estrogen receptor α is essential for estrogen signaling in the male skeleton.

The importance of estrogen receptor α (ERα) for the regulation of bone mass in males is well established. ERα mediates estrogenic effects both via nuclear and membrane-initiated ERα (mERα) signaling. The role of mERα signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERα signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ERα to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (µCT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mERα is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.

Increased bone mass in a mouse model with low fat mass.

Mice with impaired acute inflammatory responses within adipose tissue display reduced diet-induced fat mass gain associated with glucose intolerance and systemic inflammation. Therefore, acute adipose tissue inflammation is needed for a healthy expansion of adipose tissue. Because inflammatory disorders are associated with bone loss, we hypothesized that impaired acute adipose tissue inflammation leading to increased systemic inflammation results in a lower bone mass. To test this hypothesis, we used mice overexpressing an adenoviral protein complex, the receptor internalization and degradation (RID) complex that inhibits proinflammatory signaling, under the control of the aP2 promotor (RID tg mice), resulting in suppressed inflammatory signaling in adipocytes. As expected, RID tg mice had lower high-fat diet-induced weight and fat mass gain and higher systemic inflammation than littermate wild-type control mice. Contrary to our hypothesis, RID tg mice had increased bone mass in long bones and vertebrae, affecting trabecular and cortical parameters, as well as improved humeral biomechanical properties. We did not find any differences in bone formation or resorption parameters as determined by histology or enzyme immunoassay. However, bone marrow adiposity, often negatively associated with bone mass, was decreased in male RID tg mice as determined by histological analysis of tibia. In conclusion, mice with reduced fat mass due to impaired adipose tissue inflammation have increased bone mass.

ERα expression in T lymphocytes is dispensable for estrogenic effects in bone.

Estrogen treatment has positive effects on the skeleton, and we have shown that estrogen receptor alpha (ERα) expression in cells of hematopoietic origin contributes to a normal estrogen treatment response in bone tissue. T lymphocytes are implicated in the estrogenic regulation of bone mass, but it is not known whether T lymphocytes are direct estrogen target cells. Therefore, the aim of this study was to determine the importance of ERα expression in T lymphocytes for the estrogenic regulation of the skeleton using female mice lacking ERα expression specifically in T lymphocytes (Lck-ERα-/-) and ERαflox/flox littermate (control) mice. Deletion of ERα expression in T lymphocytes did not affect bone mineral density (BMD) in sham-operated Lck-ERα-/- compared to control mice, and ovariectomy (ovx) resulted in a similar decrease in BMD in control and Lck-ERα-/- mice compared to sham-operated mice. Furthermore, estrogen treatment of ovx Lck-ERα-/- led to an increased BMD that was indistinguishable from the increase seen after estrogen treatment of ovx control mice. Detailed analysis of both the appendicular (femur) and axial (vertebrae) skeleton showed that both trabecular and cortical bone parameters responded to a similar extent regardless of the presence of ERα in T lymphocytes. In conclusion, ERα expression in T lymphocytes is dispensable for normal estrogenic regulation of bone mass in female mice.

Minimally Invasive Ultrasound-Guided Carpal Tunnel Release: Preliminary Clinical Results.

Ultrasound-guided carpal tunnel release was performed on 14 patients (18 wrists) using dynamic expansion of the transverse safe zone. Our patient population included able-bodied patients and those with impairments. The first 8 cases (12 wrists) underwent the procedure in an operating room, the remainder in an outpatient setting. No complications occurred, and all patients were able to immediately resume use of their hands without therapy. Improvements in the Quick Form of the Disabilities of the Arm, Shoulder, and Hand Index and Boston Carpal Tunnel Questionnaire at 3 months were comparable to results reported with mini-open and endoscopic release. Our results show that ultrasound-guided carpal tunnel release can be safely and effectively performed in an outpatient setting.

Sonographic Changes After Ultrasound-Guided Release of the Transverse Carpal Ligament: A Case Report.

Carpal tunnel syndrome is the most common entrapment neuropathy, resulting in 500,000 carpal tunnel release (CTR) surgeries and a total cost of more than 2 billion dollars annually in the United States. Although initially performed via a large (3-5 cm) palmar incision, CTR techniques have continually evolved to reduce incision size, recovery times, postoperative pain, and improve cosmesis and clinical outcomes. More recently, multiple authors have reported excellent results after ultrasound-guided carpal tunnel release (USCTR) using a variety of techniques, and one prospective randomized trial reported faster recovery after USCTR compared with traditional mini-open CTR. However, there is a paucity of data with respect to changes in the median nerve after USCTR. This case report presents the functional outcomes and pre- and postprocedure ultrasound images of a patient after USCTR with 3-month follow-up. LEVEL OF EVIDENCE: V.

Behavior of Neutrophil Granulocytes during Toxoplasma gondii Infection in the Central Nervous System.

Cerebral toxoplasmosis is characterized by activation of brain resident cells and recruitment of specific immune cell subsets from the periphery to the central nervous system (CNS). Our studies revealed that the rapidly invaded Ly6G+ neutrophil granulocytes are an early non-lymphoid source of interferon-gamma (IFN-γ), the cytokine known to be the major mediator of host resistance to Toxoplasma gondii (T. gondii). Upon selective depletion of Ly6G+ neutrophils, we detected reduced IFN-γ production and increased parasite burden in the CNS. Ablation of Ly6G+ cells resulted in diminished recruitment of Ly6Chi monocytes into the CNS, indicating a pronounced interplay. Additionally, we identified infiltrated Ly6G+ neutrophils to be a heterogeneous population. The Ly6G+CD62-LhiCXCR4+ subset released cathelicidin-related antimicrobial peptide (CRAMP), which can promote monocyte dynamics. On the other hand, the Ly6G+CD62-LloCXCR4+ subset produced IFN-γ to establish early inflammatory response. Collectively, our findings revealed that the recruited Ly6G+CXCR4+ neutrophil granulocytes display a heterogeneity in the CNS with a repertoire of effector functions crucial in parasite control and immune regulation upon experimental cerebral toxoplasmosis.

Pilot study of intraoperative ultrasound-guided instrument placement in nerve transection surgery for peripheral nerve pain syndromes.

Surgical transection of sensory nerves in the treatment of intractable neuropathic pain is a commonly performed procedure. At times these cases can be particularly challenging when encountering obese patients, when targeting deeper nerves or those with a variable branching pattern, or in the case of repeat operations. In this case series, the authors describe their experience with ultrasound-guided surgical instrument placement during transection of a saphenous nerve in the region of prior vascular surgery in 1 patient and in the lateral femoral cutaneous nerve in 2 obese patients. The authors also describe this novel technique and provide pilot data that suggests ultrasound-assisted surgery may allow for complex cases to be completed in an expedited fashion through smaller incisions.

Greater Trochanteric Pain Syndrome: Percutaneous Tendon Fenestration Versus Platelet-Rich Plasma Injection for Treatment of Gluteal Tendinosis.

OBJECTIVES: The purpose of this study was to compare ultrasound-guided percutaneous tendon fenestration to platelet-rich plasma (PRP) injection for treatment of greater trochanteric pain syndrome. METHODS: After Institutional Review Board approval was obtained, patients with symptoms of greater trochanteric pain syndrome and ultrasound findings of gluteal tendinosis or a partial tear (<50% depth) were blinded and treated with ultrasound-guided fenestration or autologous PRP injection of the abnormal tendon. Pain scores were recorded at baseline, week 1, and week 2 after treatment. Retrospective clinic record review assessed patient symptoms. RESULTS: The study group consisted of 30 patients (24 female), of whom 50% were treated with fenestration and 50% were treated with PRP. The gluteus medius was treated in 73% and 67% in the fenestration and PRP groups, respectively. Tendinosis was present in all patients. In the fenestration group, mean pain scores were 32.4 at baseline, 16.8 at time point 1, and 15.2 at time point 2. In the PRP group, mean pain scores were 31.4 at baseline, 25.5 at time point 1, and 19.4 at time point 2. Retrospective follow-up showed significant pain score improvement from baseline to time points 1 and 2 (P< .0001) but no difference between treatment groups (P= .1623). There was 71% and 79% improvement at 92 days (mean) in the fenestration and PRP groups, respectively, with no significant difference between the treatments (P >.99). CONCLUSIONS: Our study shows that both ultrasound-guided tendon fenestration and PRP injection are effective for treatment of gluteal tendinosis, showing symptom improvement in both treatment groups.

The role of membrane ERα signaling in bone and other major estrogen responsive tissues.

Estrogen receptor α (ERα) signaling leads to cellular responses in several tissues and in addition to nuclear ERα-mediated effects, membrane ERα (mERα) signaling may be of importance. To elucidate the significance, in vivo, of mERα signaling in multiple estrogen-responsive tissues, we have used female mice lacking the ability to localize ERα to the membrane due to a point mutation in the palmitoylation site (C451A), so called Nuclear-Only-ER (NOER) mice. Interestingly, the role of mERα signaling for the estrogen response was highly tissue-dependent, with trabecular bone in the axial skeleton being strongly dependent (>80% reduction in estrogen response in NOER mice), cortical and trabecular bone in long bones, as well as uterus and thymus being partly dependent (40-70% reduction in estrogen response in NOER mice) and effects on liver weight and total body fat mass being essentially independent of mERα (<35% reduction in estrogen response in NOER mice). In conclusion, mERα signaling is important for the estrogenic response in female mice in a tissue-dependent manner. Increased knowledge regarding membrane initiated ERα actions may provide means to develop new selective estrogen receptor modulators with improved profiles.

Ultrasound-Guided Foot and Ankle Procedures.

This article reviews commonly performed injections about the foot and ankle region. Although not exhaustive in its description of available techniques, general approaches to these procedures are applicable to any injection about the foot and ankle. As much as possible, the procedures described are based on commonly used or published techniques. An in-depth knowledge of the regional anatomy and understanding of different approaches when performing ultrasonography-guided procedures allows clinicians to adapt to any clinical scenario.

The running athlete: stress fractures, osteitis pubis, and snapping hips.

CONTEXT: Pelvic stress fractures, osteitis pubis, and snapping hip syndrome account for a portion of the overuse injuries that can occur in the running athlete. EVIDENCE ACQUISITION: PUBMED SEARCHES WERE PERFORMED FOR EACH ENTITY USING THE FOLLOWING KEYWORDS: snapping hip syndrome, coxa sultans, pelvic stress fracture, and osteitis pubis from 2008 to 2013. Topic reviews, case reports, case series, and randomized trials were included for review. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Collectively, 188 articles were identified. Of these, 58 were included in this review. CONCLUSION: Based on the available evidence, the majority of these overuse injuries can be managed non-operatively. Primary treatment should include removal from offending activity, normalizing regional muscle strength/length imbalances and nutritional deficiencies, and mitigating training errors through proper education of the athlete and training staff. STRENGTH OF RECOMMENDATION TAXONOMY: C.

Posterior interosseus nerve palsy resulting from inflammatory myofibroblastic pseudotumor: case presentation.

Local compression by a mass lesion is a potential cause of posterior interosseous nerve (PIN) palsy. Reported cases of PIN pathology do not include inflammatory myofibroblastic pseudotumor. We report the case of a 44-year-old woman with a 3-month history of progressive weakness of the left finger extensors. Sonographic imaging identified a mass compressing the PIN, and histologic examination of the specimen revealed an inflammatory myofibroblastic pseudotumor. Complete resection of the mass while sparing the nerve was possible, and the patient has regained functional use of the left hand. The differential diagnosis of PIN palsy should include inflammatory myofibroblastic pseudotumor.