Summary
This meta-analysis revealed that diabetic adults had a twofold greater risk of hip fractures compared with non-diabetic populations, and this association was more pronounced in type 1 ...diabetes.
Introduction
The relationship between diabetes mellitus and risk of hip fracture yielded conflicting results. We conducted a meta-analysis to investigate the association between diabetes mellitus and the risk of hip fractures based on observational studies.
Methods
We conducted a systematic literature search of PubMed and Embase databases through May 2015. We selected cohort and case–control studies providing at least age-adjusted risk ratio (RR) and corresponding 95 % confidence intervals (CI) of hip fractures among diabetic and non-diabetic subjects. Moreover, we pooled the female-to-male RR of hip fractures from studies that reported gender-specific risk estimate in a single study.
Results
Twenty-one studies involving 82,293 hip fracture events among 6,995,272 participants were identified. Diabetes mellitus was associated with an increased risk of hip fractures (RR 2.07; 95 % CI 1.83–2.33) in a random effects model. Subgroup analysis indicated that excess risk of hip fracture was more pronounced in type 1 diabetes (RR 5.76; 95 % CI 3.66–9.07) than that in type 2 diabetes (RR 1.34; 95 % CI 1.19–1.51). The pooled female-to-male RR of hip fractures was 1.09 (95 % CI 0.93–1.28).
Conclusions
Individuals with diabetes mellitus have an excessive risk of hip fractures, and this relationship is more pronounced in type 1 diabetes. The association between diabetes and hip fracture risk is similar in men and women.
Summary Objective The objectives of this study were to (1) determine the correlation between osteoarthritis (OA) and Indian hedgehog (Ihh) expression, and (2) establish the effects of Ihh on ...expression of markers of chondrocyte hypertrophy and matrix metalloprotease (MMP)-13 in human OA cartilage. Design OA cartilage and synovial fluid samples were obtained during total knee arthroplasty. Normal cartilage samples were obtained from intra-articular tumor resections, and normal synovial fluid samples were obtained from healthy volunteers and the contralateral uninjured knee of patients undergoing anterior cruciate ligament reconstruction. OA was graded using the Mankin score. Expression of Ihh in synovial fluid was determined by Western blot. Ihh, type X collagen and MMP-13 mRNA were determined by real time PCR. Protein expression of type X collagen and MMP-13 in cartilage samples was analyzed with immunohistochemistry. Chondrocyte size was measured using image analysis. Results Ihh expression was increased 2.6 fold in OA cartilage and 37% in OA synovial fluid when compared to normal control samples. Increased expression of Ihh was associated with the severity of OA and expression of markers of chondrocyte hypertrophy: type X collagen and MMP-13, and chondocyte size. Chondrocytes were more spherical with increasing severity of OA. There was a significant correlation between Mankin score and cell size ( r2 = 0.80) and Ihh intensity ( r2 = 0.89). Exogenous Ihh induced a 6.8 fold increase of type X collagen and 2.8 fold increase of MMP-13 mRNA expression in cultured chondrocytes. Conversely, knockdown of Ihh by siRNA and Hh inhibitor cyclopamine had the opposite effect. Conclusions Ihh expression correlates with OA progression and changes in chondrocyte morphology and gene expression consistent with chondrocyte hypertrophy and cartilage degradation seen in OA cartilage. Thus, Ihh may be a potential therapeutic target to prevent OA progression.
Recent studies indicate that persistent pain after tissue or nerve injury is accompanied by an enhanced net descending facilitatory drive that contributes to an amplification and spread of pain. ...Although 5-HT-containing neurons in the rostral ventromedial medulla (RVM) provide the major descending serotonergic projection to the spinal cord, it is not clear whether the neurotransmitter 5-HT itself released from RVM-spinal neurons contributes to descending pain modulation. In the present study, we determined the role of the descending 5-HT in rat nocifensive behaviors after persistent pain by selectively depleting functional phenotypes of 5-HT in RVM neurons with regional shRNA interference (RNAi) of tryptophan hydroxylase-2 (Tph-2), the rate-limiting enzyme in the synthesis of neuronal 5-HT. Compared to negative control shRNA, Tph-2 shRNA induced significantly prolonged downregulation of Tph-2 in the RVM and 5-HT in spinal dorsal horn. The 5-HT-depleted rats showed normal pain sensitivity in responses to acute noxious stimulation. However, the same RNAi treatment attenuated formalin-induced spontaneous nocifensive responses and tissue or nerve injury-induced allodynia and hyperalgesia. Furthermore, in control shRNA-treated animals, intra-RVM microinjection of brain-derived neurotrophic factor produced a reversible hyperalgesia, which was completely prevented by Tph-2 RNAi pretreatment. Descending inhibition induced by intra-RVM electrical stimulation, but not microinjection of the mu- or kappa-opioid receptor agonists in control shRNA-treated animals was eliminated in 5-HT-depleted rats. These results indicate that the descending 5-HT from the RVM is an important contributor to pain facilitation during the development of persistent pain, and may not mediate opioid-induced descending inhibition in acute pain.
AlxCrFeNi eutectic multi-component alloys were prepared to obtain excellent mechanical properties by double-phase strengthening. The X-ray diffraction results showed that the crystal structure were ...both body-centered cubic and energy-dispersive X-ray spectrometer identified that the two phases are ordered NiAl intermetallic and disordered Fe, Cr solid solution. The formation of eutectic structures was introduced by a simplified dynamic model. After mechanical tests, the alloys presented excellent compressive strength and unexpected large deformation. Due to the solid solution and fine-grain strengthening resulted by Al addition, mechanical properties of AlxCrFeNi alloys exhibited regularity in some degree. Among all alloys, Al1.3CrFeNi has the highest fracture strength and Al0.9CrFeNi has the most excellent strain. Besides, Al1.2CrFeNi alloy showed a good combination of strength and ductility.
The change in the hydrogen-trapping behavior of a TiC particle accompanying its coherent to incoherent interfacial-character transition in a 0.05C-0.20Ti-2.0Ni steel that was quenched and tempered in ...a partially protective argon atmosphere and in ultrahigh vacuum (UHV) has been studied by thermal desorption spectrometry (TDS). The results indicated that (semi)coherent TiC precipitates demonstrate distinctly different hydrogen-trapping features from that of incoherent TiC particles with respect to hydrogen capacity, interaction energy with hydrogen, locations available for hydrogen occupation, and the capability of hydrogen absorption from the environment. The broad (semi)coherent interface of the disc-shaped (semi)coherent TiC precipitate does not trap hydrogen during tempering in a partially protected argon atmosphere, but traps hydrogen during cathodic charging at room temperature. The semicoherent interface traps 1.3 atoms/nm^sup 2^ of hydrogen at the core of the misfit dislocation with short-time charging (1 hour), which is characterized by a desorption activation energy of 55.8 kJ/mol. The side interface of the (semi)coherent TiC precipitate acts like the broad interface when the precipitate is small. As the precipitate grows, the side interface gradually loses its coherency and results in a simultaneous increase in the trapping activation energy and the binding energy. An increase in the trapping activation energy, i.e., the energy barrier for trapping, makes hydrogen trapping more difficult in cathodic charging at room temperature, while an increase in the binding energy enhances the capability of hydrogen absorption from the atmosphere during heat treatment. An incoherent TiC particle is not able to trap hydrogen during cathodic charging at room temperature due to its high energy barrier for trapping, but absorbs hydrogen during heat treatment at high temperatures. The amount of hydrogen that is trapped by incoherent TiC particles depends on their volume, which strongly indicates that incoherent TiC particles trap hydrogen within them rather than at the particle/matrix interface. Octahedral carbon vacancies are supposedly the hydrogen trap sites in incoherent TiC particles. PUBLICATION ABSTRACT
C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2-ZF arrays are highly variable, indicating that most will have unique DNA binding ...motifs. However, most of the binding motifs have not been directly determined. In addition, little is known about whether or how these proteins regulate transcription. Most of the ∼700 human C2H2-ZF proteins also contain at least one KRAB, SCAN, BTB, or SET domain, suggesting that they may have common interacting partners and/or effector functions. Here, we report a multifaceted functional analysis of 131 human C2H2-ZF proteins, encompassing DNA binding sites, interacting proteins, and transcriptional response to genetic perturbation. We confirm the expected diversity in DNA binding motifs and genomic binding sites, and provide motif models for 78 previously uncharacterized C2H2-ZF proteins, most of which are unique. Surprisingly, the diversity in protein-protein interactions is nearly as high as diversity in DNA binding motifs: Most C2H2-ZF proteins interact with a unique spectrum of co-activators and co-repressors. Thus, multiparameter diversification likely underlies the evolutionary success of this large class of human proteins.
Nanomechanical resonators (NMRs), as the quantum mechanical sensing probers, have played the important roles for various high-precision quantum measurements. Differing from the previous emission ...spectral probes (i.e., the NMR modified the atomic emission), in this paper we propose an alternative approach, i.e., by probing the scattering spectra of the quantum mechanical prober coupled to the driving microwaves, to characterize the physical features of the NMR embedded in a rf-SQUID based superconducting qubit. It is shown that, from the observed specifical frequency points in the spectra, i.e., either the dips or the peaks, the vibrational features (i.e., they are classical vibration or quantum mechanical one) and the physical parameters (typically such as the vibrational frequency and displacements) of the NMR can be determined effectively. The proposal is feasible with the current technique and should be useful to design the desired NMRs for various quantum metrological applications.
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