Intravenous ibandronate in men with osteoporosis: An open pilot study over 2 years

In the treatment of osteoporosis, the tolerance of oral bisphosphonates is often low. The high potency of ibandronate allows iv bolus injections that can be repeated every 2 to 3 months. However, the best dose and time interval of the treatment with iv ibandronate is still debated. Efficacy of 2-mg ibandronate injected every 3 months was tested in men with osteoporosis over 2 yr, in a prospective, open study. Fourteen men with primary osteoporosis, mean age 57±12 yr (range: 40-73), received 2-mg ibandronate iv every 3 months over 2 yr. All got 1 g/day calcium and 880 UI/day vitamin D for 2 yr. Bone mineral density (BMD) increased after 2 yr by 6.7±1.5% (mean change±SEM) at lumbar spine (p<0.001), by 3.2±08% at trochanter (p<0.001) and by 1.4±1.1% at femoral neck (ns). Serum ß-crosslaps and osteocalcin decreased significantly by 30-45 and 30%, respectively, during the 2 yr of treatment. Serum calcium increased from the lower to the middle tertile of the normal range during the 2 yr of the study. The observed decrease of bone remodelling and the increase of BMD are of the same magnitude as those described with oral bisphosphonates. The increase of plasma calcium confirms the positive effect of the supplementation with calcium and vitamin D. These results suggest that 3 months are a good interval between two doses of iv ibandronate, when 2 mg are give

MyD88‐dependent production of IL‐17F is modulated by the anaphylatoxin C5a via the Akt signaling pathway

The interleukin‐17 (IL‐17) family of cytokines plays important roles in innate immune defenses against bacterial and fungal pathogens. While much is known about IL‐17A, much less information is available about the IL‐17F isoform. Here, we investigated gene expression and release of IL‐17F and its regulation by the complement system. IL‐17F was produced in mouse peritoneal elicited macrophages after TLR4 activation by LPS, peaking after 12 h. This effect was completely dependent on the presence of the adaptor protein MyD88. The copresence of the complement activation product, C5a (EC50=10 nM), amplified IL‐17F production via the receptor C5aR. In vitro signaling studies indicated that LPS or C5a, or the combination, caused phosphorylation of Akt occurring at threonine 308 but not at serine 473. Treatment of macrophages with pharmacologic inhibitors of PI3K‐Akt greatly reduced production of IL‐17F as well as mRNA for IL‐17F. In endotoxemia, C5a levels peaked at 6 h, while IL‐17F levels peaked between 6‐12 h. Full in vivo production of IL‐17F during endotoxemia required C5a. A similar result was found in the cecal ligation and puncture sepsis model. These data suggest that maximal production of IL‐17F requires complement activation and presence of C5a.—Bosmann, M., Patel, V. R., Russkamp, N. F., Pache, F., Zetoune, F. S., Sarma, J. V., Ward, P. A. MyD88‐dependent production of IL‐17F is modulated by the anaphylatoxin C5a via the Akt signaling pathway. FASEB J. 25, 4222–4232 (2011). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154335/1/fsb2fj11191205.pd

Stereoselective chromium- and molybdenum-mediated transformations of arenes

Tricarbonylchromium-mediated dearomatization provides a rapid access to substituted cyclohexadienes. Efficient asymmetric routes to planar chiral arene complexes and to substituted cyclohexadienes have been developed. The article sums up the main features of this chemistry. Highly enantiomerically enriched ortho-substituted benzaldehyde complexes are accessible via asymmetric lithiation followed by trapping with electrophiles. In different solvents, the trimethylsilyl complex exhibits [alpha] values ranging from −174 to +108 for the same enantiomer. Details of two asymmetric syntheses of natural products are given: the alkaloid lasubine I starting from a highly enantiomerically enriched planar chiral arene complex and the marine furanosesquiterpene acetoxytubipofuran. The latter is assembled via asymmetric dearomatization of a benzaldehyde imine complex. Other key steps include an Eschenmoser-Claisen rearrangement and a regio- and diastereoselective Pd-catalyzed allylic substitution. The final section deals with labile arene metal complexes. For the first time, dearomatization reactions mediated by the Mo(CO)3 group have been realized. The reactions show strong analogies to the Cr(CO)3-mediated reactions, but exhibit also marked differences: the arene-Mo bond is stronger, but more labile, and the sequential double additions show different selectivities compared to the chromium analog

Risk factors for lateral meniscus posterior root tears in the anterior cruciate ligament injured knee: an epidemiological analysis of 3956 patients from the SANTI database

Background: Lateral meniscal posterior root tears (LMPRT) result in loss of hoop forces and significant increases in tibiofemoral contact pressures. Pre-operative imaging lacks reliability and therefore holding an appropriate index of suspicion, based on the epidemiology and risk factors for LMPRT, may reduce the rate of missed diagnoses. Hypothesis/Purpose: The primary objectives of this study were to evaluate the incidence and risk factors for lateral meniscus root lesions in a large series of patients undergoing anterior cruciate ligament (ACL) reconstruction. Study Design: Case series. Methods: All patients who underwent primary or revision ACL reconstruction, between January 2011 to April 2018 were considered for study eligibility. From this overall population, all patients who underwent repair of a lateral meniscus posterior root tear (LMPRT) were identified. The epidemiology of LMPRT was defined by the incidence within the study population, stratified by key demographic parameters. Potentially important risk factors for the presence of LMPRT were evaluated in multivariate logistic regression analysis. Results: 3956 patients undergoing ACL reconstruction were included in the study. A LMPRT was identified and repaired in 262 patients (6.6%). Multivariate analyses demonstrated that significant risk factors for LMPRT included a contact sports injury mechanism (7.8% incidence with contact sports mechanism vs 4.5% with non-contact mechanism 4.5%; OR = 1.69, IC95% 1.266 - 2.285; P <.001) and the presence of a medial meniscal tear (7.9% incidence with medial meniscal tear vs 5.8% in those without; OR = 1.532, IC95% 1.185 - 1.979; P <.001). Although the incidence of LMPRT in male patients (7.3%) was higher than females (4.8%) this was not significant in multivariate analysis (P = 0.270). Patient age, revision ACL reconstruction and a pre-operative side to side laxity difference of ≥ 6mm were not found to be significant risk factors for LMPRT. Conclusion: The incidence of LMPRT was 6.6% in a large series of patients undergoing ACL reconstruction. Participation in contact sports and the presence of a concomitant medial meniscal tear were demonstrated to be important independent risk factors. Their presence should raise the index of suspicion of this injury pattern

Feasibility of a prehabilitation program before major abdominal surgery: a pilot prospective study.

To assess the feasibility of a prehabilitation program and its effects on physical performance and outcomes after major abdominal surgery. In this prospective pilot study, patients underwent prehabilitation involving three training sessions per week for 3 weeks preoperatively. The feasibility of delivering the intervention was assessed based on recruitment and adherence to the program. Its impacts on fitness (oxygen uptake (VO &lt;sub&gt;2&lt;/sub&gt; )) and physical performance (Timed Up and Go Test, 6-Minute Walk Test) were evaluated. From May 2017 to January 2020, 980 patients were identified and 44 (4.5%) were invited to participate. The main obstacles to patient recruitment were insufficient time (&lt;3 weeks) prior to scheduled surgery (n = 276, 28%) and screening failure (n = 312, 32%). Of the 44 patients, 24 (55%) declined to participate, and 20 (23%) were included. Of these, six (30%) were not adherent to the program. Among the remaining 14 patients, VO &lt;sub&gt;2&lt;/sub&gt; at ventilatory threshold significantly increased from 9.7 to 10.9 mL/min/kg. No significant difference in physical performance was observed before and after prehabilitation. Although prehabilitation seemed to have positive effects on exercise capacity, logistic and patient-related difficulties were encountered. The program is not feasible in its current form for all-comers

BARD1 mediates TGF-β signaling in pulmonary fibrosis

Background Idiopathic pulmonary fibrosis (IPF) is a rapid progressive fibro-proliferative disorder with poor prognosis similar to lung cancer. The pathogenesis of IPF is uncertain, but loss of epithelial cells and fibroblast proliferation are thought to be central processes. Previous reports have shown that BARD1 expression is upregulated in response to hypoxia and associated with TGF-β signaling, both recognized factors driving lung fibrosis. Differentially spliced BARD1 isoforms, in particular BARD1β, are oncogenic drivers of proliferation in cancers of various origins. We therefore hypothesized that BARD1 and/or its isoforms might play a role in lung fibrosis. Methods We investigated BARD1 expression as a function of TGF-β in cultured cells, in mice with experimentally induced lung fibrosis, and in lung biopsies from pulmonary fibrosis patients. Results FL BARD1 and BARD1β were upregulated in response to TGF-β in epithelial cells and fibroblasts in vitro and in vivo. Protein and mRNA expression studies showed very low expression in healthy lung tissues, but upregulated expression of full length (FL) BARD1 and BARD1β in fibrotic tissues. Conclusion Our data suggest that FL BARD1 and BARD1β might be mediators of pleiotropic effects of TGF-β. In particular BARD1β might be a driver of proliferation and of pulmonary fibrosis pathogenesis and progression and represent a target for treatment

MRI phase changes in multiple sclerosis vs neuromyelitis optica lesions at 7T

OBJECTIVE: To characterize paramagnetic MRI phase signal abnormalities in neuromyelitis optica spectrum disorder (NMOSD) vs multiple sclerosis (MS) lesions in a cross-sectional study. METHODS: Ten patients with NMOSD and 10 patients with relapsing-remitting MS underwent 7-tesla brain MRI including supratentorial T2*-weighted imaging and supratentorial susceptibility weighted imaging. Next, we analyzed intra- and perilesional paramagnetic phase changes on susceptibility weighted imaging filtered magnetic resonance phase images. RESULTS: We frequently observed paramagnetic rim-like (75 of 232 lesions, 32%) or nodular (32 of 232 lesions, 14%) phase changes in MS lesions, but only rarely in NMOSD lesions (rim-like phase changes: 2 of 112 lesions, 2%, p < 0.001; nodular phase changes: 2 of 112 lesions, 2%, p < 0.001). CONCLUSIONS: Rim-like or nodular paramagnetic MRI phase changes are characteristic for MS lesions and not frequently detectable in NMOSD. Future prospective studies should ask whether these imaging findings can be used as a biomarker to distinguish between NMOSD- and MS-related brain lesions

A dimensionally continued Poisson summation formula

We generalize the standard Poisson summation formula for lattices so that it operates on the level of theta series, allowing us to introduce noninteger dimension parameters (using the dimensionally continued Fourier transform). When combined with one of the proofs of the Jacobi imaginary transformation of theta functions that does not use the Poisson summation formula, our proof of this generalized Poisson summation formula also provides a new proof of the standard Poisson summation formula for dimensions greater than 2 (with appropriate hypotheses on the function being summed). In general, our methods work to establish the (Voronoi) summation formulae associated with functions satisfying (modular) transformations of the Jacobi imaginary type by means of a density argument (as opposed to the usual Mellin transform approach). In particular, we construct a family of generalized theta series from Jacobi theta functions from which these summation formulae can be obtained. This family contains several families of modular forms, but is significantly more general than any of them. Our result also relaxes several of the hypotheses in the standard statements of these summation formulae. The density result we prove for Gaussians in the Schwartz space may be of independent interest.Comment: 12 pages, version accepted by JFAA, with various additions and improvement

Neuromyelitis optica does not impact periventricular venous density versus healthy controls: a 7.0 Tesla MRI clinical study

Objective: To quantify the periventricular venous density in neuromyelitis optica spectrum disease (NMOSD) in comparison to that in patients with multiple sclerosis (MS) and healthy control subjects. Materials and methods: Sixteen patients with NMOSD, 16 patients with MS and 16 healthy control subjects underwent 7.0-Tesla (7T) MRI. The imaging protocol included T2*-weighted (T2*w) fast low angle-shot (FLASH) and fluid-attenuated inversion recovery (FLAIR) sequences. The periventricular venous area (PVA) was manually determined by a blinded investigator in order to estimate the periventricular venous density in a region of interest-based approach. Results: No significant differences in periventricular venous density indicated by PVA were detectable in NMOSD versus healthy controls (p = 0.226). In contrast, PVA was significantly reduced in MS patients compared to healthy controls (p = 0.013). Conclusion: Unlike patients with MS, those suffering from NMOSD did not show reduced venous visibility. This finding may underscore primary and secondary pathophysiological differences between these two distinct diseases of the central nervous system

On the Second Law of thermodynamics and the piston problem

The piston problem is investigated in the case where the length of the cylinder is infinite (on both sides) and the ratio $m/M$ is a very small parameter, where $m$ is the mass of one particle of the gaz and $M$ is the mass of the piston. Introducing initial conditions such that the stochastic motion of the piston remains in the average at the origin (no drift), it is shown that the time evolution of the fluids, analytically derived from Liouville equation, agrees with the Second Law of thermodynamics. We thus have a non equilibrium microscopical model whose evolution can be explicitly shown to obey the two laws of thermodynamics.Comment: 29 pages, 9 figures submitted to Journal of Statistical Physics (2003