Treatment of diaphyseal non-unions of the ulna and radius

Non-unions of the forearm often cause severe dysfunction of the forearm as they affect the interosseus membrane, elbow and wrist. Treatment of these non-unions can be challenging due to poor bone stock, broken hardware, scarring and stiffness due to long-term immobilisation. We retrospectively reviewed a large cohort of forearm non-unions treated by using a uniform surgical approach during a period of 33 years (1975-2008) in a single trauma centre. All non-unions were managed following the AO-principles of compression plate fixation and autologous bone grafting if needed. The study cohort consisted of 47 patients with 51 non-unions of the radius and/or ulna. The initial injury was a fracture of the diaphyseal radius and ulna in 22 patients, an isolated fracture of the diaphyseal ulna in 13, an isolated fracture of the diaphyseal radius in 5, a Monteggia fracture in 5, and a Galeazzi fracture-dislocation of the forearm in 2 patients. Index surgery for non-union consisted of open reduction and plate fixation in combination with a graft in 30 cases (59%), open reduction and plate fixation alone in 14 cases (27%), and only a graft in 7 cases (14%). The functional result was assessed in accordance to the system used by Anderson and colleagues. Average follow-up time was 75 months (range 12-315 months). All non-unions healed within a median of 7 months. According to the system of Anderson and colleagues, 29 patients (62%) had an excellent result, 8 (17%) had a satisfactory result, and 10 (21%) had an unsatisfactory result. Complications were seen in six patients (13%). Our results show that treatment of diaphyseal forearm non-unions using classic techniques of compression plating osteosynthesis and autologous bone grafting if needed will lead to a high union rate (100% in our series). Despite clinical and radiographic bone healing, however, a substantial subset of patients will have a less than optimal functional outcom

Requirement of Male-Specific Dosage Compensation in Drosophila Females—Implications of Early X Chromosome Gene Expression

Dosage compensation equates between the sexes the gene dose of sex chromosomes that carry substantially different gene content. In Drosophila, the single male X chromosome is hypertranscribed by approximately two-fold to effect this correction. The key genes are male lethal and appear not to be required in females, or affect their viability. Here, we show these male lethals do in fact have a role in females, and they participate in the very process which will eventually shut down their function—female determination. We find the male dosage compensation complex is required for upregulating transcription of the sex determination master switch, Sex-lethal, an X-linked gene which is specifically activated in females in response to their two X chromosomes. The levels of some X-linked genes are also affected, and some of these genes are used in the process of counting the number of X chromosomes early in development. Our data suggest that before the female state is set, the ground state is male and female X chromosome expression is elevated. Females thus utilize the male dosage compensation process to amplify the signal which determines their fate

The Hsc/Hsp70 Co-Chaperone Network Controls Antigen Aggregation and Presentation during Maturation of Professional Antigen Presenting Cells

The maturation of mouse macrophages and dendritic cells involves the transient deposition of ubiquitylated proteins in the form of dendritic cell aggresome-like induced structures (DALIS). Transient DALIS formation was used here as a paradigm to study how mammalian cells influence the formation and disassembly of protein aggregates through alterations of their proteostasis machinery. Co-chaperones that modulate the interplay of Hsc70 and Hsp70 with the ubiquitin-proteasome system (UPS) and the autophagosome-lysosome pathway emerged as key regulators of this process. The chaperone-associated ubiquitin ligase CHIP and the ubiquitin-domain protein BAG-1 are essential for DALIS formation in mouse macrophages and bone-marrow derived dendritic cells (BMDCs). CHIP also cooperates with BAG-3 and the autophagic ubiquitin adaptor p62 in the clearance of DALIS through chaperone-assisted selective autophagy (CASA). On the other hand, the co-chaperone HspBP1 inhibits the activity of CHIP and thereby attenuates antigen sequestration. Through a modulation of DALIS formation CHIP, BAG-1 and HspBP1 alter MHC class I mediated antigen presentation in mouse BMDCs. Our data show that the Hsc/Hsp70 co-chaperone network controls transient protein aggregation during maturation of professional antigen presenting cells and in this way regulates the immune response. Similar mechanisms may modulate the formation of aggresomes and aggresome-like induced structures (ALIS) in other mammalian cell types

Cerebral cortical thickness in chronic pain due to knee osteoarthritis: the effect of pain duration and pain densitization

Objective This study investigates associations between cortical thickness and pain duration, and central sensitization as markers of pain progression in painful knee osteoarthritis. Methods Whole brain cortical thickness and pressure pain thresholds were assessed in 70 participants; 40 patients with chronic painful knee osteoarthritis (age = 66.1± 8.5 years, 21 females, mean duration of pain = 8.5 years), and 30 healthy controls (age = 62.7± 7.4, 17 females). Results Cortical thickness negatively correlated with pain duration mainly in fronto-temporal areas outside of classical pain processing areas (p<0.05, age-controlled, FDR corrected). Pain sensitivity was unrelated to cortical thickness. Patients showed lower cortical thickness in the right anterior insula (p<0.001, uncorrected) with no changes surviving multiple test correction. Conclusion With increasing number of years of suffering from chronic arthritis pain we found increasing cortical thinning in extended cerebral cortical regions beyond recognised pain-processing areas. While the mechanisms of cortical thinning remain to be elucidated, we show that pain progression indexed by central sensitization does not play a major role

Convergent Evidence from Mouse and Human Studies Suggests the Involvement of Zinc Finger Protein 326 Gene in Antidepressant Treatment Response

OBJECTIVES: The forced swim test (FST) is a commonly used model to predict antidepressant efficacy. Uncovering the genetic basis of the model may unravel the mechanism of antidepressant treatment. METHODS: FVB/NJ (FVB) and C57BL/6J (B6) were first identified as the response and non-response strains to fluoxetine (a serotonin-specific reuptake inhibitor antidepressant) treatment in the mouse FST. Simple-interval (SIM) and composite-interval (CIM) mappings were applied to map the quantitative trait loci (QTLs) of the anti-immobility effect of fluoxetine in FST (FST(FLX)) in 865 male B6×FVB-F2 mice. The brain mRNA expressions of the gene with the maximum QTL-linkage signal for FST(FLX) after the FST were compared between B6 and FVB mice and also compared between fluoxetine and saline treatment. The association of the variants in the human homologue of the mouse FST(FLX)-QTL gene with major depressive disorder (MDD) and antidepressant response were investigated in 1080 human subjects (MDD/control = 582/498). RESULTS: One linkage signal for FST(FLX)-QTL was detected at an intronic SNP (rs6215396) of the mouse Zfp326 gene (maximal CIM-LOD = 9.36). The Zfp326 mRNA expression in the FVB thalamus was significantly down-regulated by fluoxetine in the FST, and the higher FVB-to-B6 Zfp326 mRNA expressions in the frontal cortex, striatum and hypothalamus diminished after fluoxetine treatment. Two coding-synonymous SNPs (rs2816881 and rs10922744) in the human homologue of Zfp326, ZNF326, were significantly associated with the 8-week antidepressant treatment response in the MDD patients (Bonferroni-corrected p = 0.004-0.028). CONCLUSIONS: The findings suggest the involvement of the Zfp326 and ZNF326 genes in antidepressant treatment response

Treatment of Infected Hip Arthroplasty

The clinical outcomes of a consecutive series of deep total joint infections treated with a prosthesis retaining protocol were reviewed. The treatment of deep periprosthetic joint infections is challenging. In recent years, two-stage exchange arthroplasty has emerged as the gold standard for successful elimination of infection. With success rates averaging 82% to 96%, this treatment method has both the highest and most consistent rate of infection eradication. Another alternative in the treatment of the deep periprosthetic infection is the single-stage exchange arthroplasty. Successful eradication of infection after single-stage exchange arthroplasty has been reported to average from 60% to 83% after total hip infections. While both the single and two-stage exchange arthroplasty are viable treatment options, they are associated with negative factors such as they are time consuming, expensive, and may entail a 6- to 12-week period with a minimally functioning extremity after prosthesis removal. This paper reports the general principles of management, the treatment of acute infection occurring in the postoperative period or later, and the treatment of chronic infection by exchange arthroplasty or resection arthroplasty

From Global to Local and Vice Versa: On the Importance of the 'Globalization' Agenda in Continental Groundwater Research and Policy-Making.

Groundwater is one of the most important environmental resources and its use continuously rises globally for industrial, agricultural, and drinking water supply purposes. Because of its importance, more knowledge about the volume of usable groundwater is necessary to satisfy the global demand. Due to the challenges in quantifying the volume of available global groundwater, studies which aim to assess its magnitude are limited in number. They are further restricted in scope and depth of analysis as, in most cases, they do not explain how the estimates of global groundwater resources have been obtained, what methods have been used to generate the figures and what levels of uncertainty exist. This article reviews the estimates of global groundwater resources. It finds that the level of uncertainty attached to existing numbers often exceeds 100 % and strives to establish the reasons for discrepancy. The outcome of this study outlines the need for a new agenda in water research with a more pronounced focus on groundwater. This new research agenda should aim at enhancing the quality and quantity of data provision on local and regional groundwater stocks and flows. This knowledge enhancement can serve as a basis to improve policy-making on groundwater resources globally. Research-informed policies will facilitate more effective groundwater management practices to ensure a more rapid progress of the global water sector towards the goal of sustainability