[The Protective Action of Hsp70 and Hydrogen Sulfide Donors in THP-1 Macrophages in the Lipopolysaccharide-Induced Inflammatory Response by Modulating Endocytosis].

Hsp70 and hydrogen sulfide donors reduce inflammatory processes in human and animal cells. The biological action mediated by Hsp70 and H2S donors (GYY4137 and sodium thiosulfate) depends on their protection kinetics from cell activation by lipopolysaccharides. However, the molecular mechanisms of action of Hsp70 and H2S are not well understood. We studied the effect of human recombinant Hsp70 and H2S donors on the formation of reactive oxygen species and tumor necrosis factor-alpha induced in human cells (THP-1) by lipopolysaccharides. Transcriptomic changes occurring in these cells after LPS administration in combination with GYY4137 pretreatment were investigated. The results we obtained showed that Hsp70 and hydrogen sulfide donors reduce inflammatory processes in cells activated by the action of LPS. Hsp70 and H2S donors differed in the kinetics of the protective action, while hydrogen sulfide donors turned out to be more effective. The role of endocytosis in the mechanisms of protection of cells by H2S and Hsp70 donors from the action of LPS was studied. It has been found that GYY4137 pretreatment of LPS-exposed cells reduces the LPS-induced induction of various pro-inflammatory genes and affects the expression of genes of various intracellular signaling pathways.

Short-term results of the uncemented triathlon total knee arthroplasty: a large cohort single-centre comparative study.

BACKGROUND: The purpose of this study is to assess the short-term survivorship of a new uncemented TKA design in a high-volume centre to evaluate the safety of this design prior to widespread adoption. METHODS: We performed a retrospective cohort study of all primary TKAs (cemented and uncemented) between May 2018 and May 2019. Primary outcome variables included aseptic revision, all-cause revision, time to revision, operative time and radiological outcomes. Predictor variables considered included age, gender, BMI, ASA, implant type (cruciate-retaining, posterior-stabilised or totally-stabilised) and the use of cemented or uncemented implants. RESULTS: There were 300 cemented TKAs and 249 uncemented TKAs (Triathlon, Stryker Inc., Mahwah, NJ) implanted. The mean follow-up for all cases was 31.6 months (minimum follow-up 2 years). Of the entire 549 implants only 4 were revised. Two of these were for infection, 1 was for patellar maltracking and 1 was for knee stiffness. All 4 revisions occurred in the cemented cohort. The aseptic revision rate in the cemented cohort was 0.7% compared to 0.0% in the uncemented cohort (p = 0.298). Operative times were significantly reduced in the uncemented cohort from 57.9 to 51.7 min (p < 0.001). There were 8/300 (2.6%) patients with RLLs in the cemented cohort and 4/249 (1.6%) patients with RLLs in the uncemented cohort (p = 0.56). CONCLUSION: The uncemented Triathlon TKA demonstrates excellent survivorship at short-term follow-up when compared to the cemented Triathlon TKA, thus eliminating any potential clinical concerns with this novel implant in the early post-operative phase.

[A Test System for Assessment of the Activity of Mutant Cas9 Variants in Saccharomyces cerevisiae].

The key component of the revolutionary Streptococcus pyogenes CRISPR/Cas genome editing technology is the multidomain protein Cas9. However, the specificity of wild type Cas9 is not sufficiently high for editing large genomes of higher eukaryotes, which limits the realization of the potential of genomic editing both in fundamental investigations and in the therapy of genetic diseases. The main way to obtain more specific variants of Cas9 is through mutagenesis followed by characterization of mutant proteins in in vitro or in vivo test systems. The in vitro and some in vivo test systems described in the literature are often labor-intensive and have scaling limitations, which makes it challenging to screen SpCas9 mutant variant libraries. In order to develop a simple method for high-throughput screening of Cas9 mutants in vivo, we characterized three test systems using CRISPR/Cas9-mediated inactivation of the reporter genes, tsPurple, ADE2, and URA3, in the Saccharomyces cerevisiae yeast as a model subject. We measured the activities of high-precision forms of Cas9, evoCas9, and HiFiCas9, and compared them with the wild-type form. ADE2 gene inactivation was found to be the most valid method for the evaluation of Cas9 activity. In the test-system developed, the sensitivity to chromatin structure was demonstrated for the high-fidelity variant of Cas9, HiFiCas9. The proposed test-system can be used for the development of new generation genome editors.

Highly cross-linked polyethylene (HXLPE) is equivalent to conventional polyethylene (CPE) in total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: The benefits of HXLPE in total knee arthroplasty (TKA) have not been as evident as total hip arthroplasty (THA). A systematic review and meta-analysis to assess the impact of highly-crosslinked polyethylene (HXLPE) on TKA outcomes compared to conventional polyethylene (CPE) is described. METHODS: All studies comparing HXLPE with CPE for primary TKA were included for analysis. The minimum dataset included revision rates, indication for revision, aseptic component loosening and follow-up time. The primary outcome variables were all-cause revision, aseptic revision, revision for loosening, radiographic component loosening, osteolysis and incidence of radiolucent lines. Secondary outcome measures included postoperative functional knee scores. A random-effects meta-analysis allowing for all missing data was performed for all primary outcome variables. RESULTS: Six studies met the inclusion criteria. In total, there were 2,234 knees (1,105 HXLPE and 1,129 CPE). The combined mean follow-up for all studies was 6 years. The aseptic revision rate in the HXLPE group was 1.02% compared to 1.97% in the CPE group. There was no difference in the rate of all-cause revision (p = 0.131), aseptic revision (p = 0.298) or revision for component loosening (p = 0.206) between the two groups. Radiographic loosening (p = 0.200), radiolucent lines (p = 0.123) and osteolysis (p = 0.604) was similar between both groups. Functional outcomes were similar between groups. CONCLUSION: The use of HXLPE in TKA yields similar results for clinical and radiographic outcomes when compared to CPE at midterm follow-up. HXLPE does not confer the same advantages to TKA as seen in THA.

[Beta Amyloid, Tau Protein, and Neuroinflammation: An Attempt to Integrate Different Hypotheses of Alzheimer's Disease Pathogenesis].

Alzheimer's disease (AD) is a neurodegenerative disease that inevitably results in dementia and death. Currently, there are no pathogenetically grounded methods for the prevention and treatment of AD, and all current treatment regimens are symptomatic and unable to significantly delay the development of dementia. The accumulation of ß-amyloid peptide (Aß), which is a spontaneous, aggregation-prone, and neurotoxic product of the processing of signaling protein APP (Amyloid Precursor Protein), in brain tissues, primarily in the hippocampus and the frontal cortex, was for a long time considered the main cause of neurodegenerative changes in AD. However, attempts to treat AD based on decreasing Aß production and aggregation did not bring significant clinical results. More and more arguments are arising in favor of the fact that the overproduction of Aß in most cases of AD is not the initial cause, but a concomitant event of pathological processes in the course of the development of sporadic AD. The concept of neuroinflammation has come to the fore, suggesting that inflammatory responses play the leading role in the initiation and development of AD, both in brain tissue and in the periphery. The hypothesis about the key role of neuroinflammation in the pathogenesis of AD opens up new opportunities in the search for ways to treat and prevent this socially significant disease.

Exogenous recombinant Hsp70 mediates neuroprotection after photothrombotic stroke.

Ischaemic stroke is an acute interruption of the blood supply to the brain, which leads to rapid irreversible damage to nerve tissue. Ischaemic stroke is accompanied by the development of neuroinflammation and neurodegeneration observed around the affected brain area. Heat shock protein 70 (Hsp70) facilitates cell survival under a variety of different stress conditions. Hsp70 may be secreted from cells and exhibits cytoprotective activity. This activity most likely occurs by decreasing the levels of several proinflammatory cytokines through interaction with a few receptors specific to the innate immune system. Herein, we demonstrated that intranasal administration of recombinant human Hsp70 shows a significant twofold decrease in the volume of local ischaemia induced by photothrombosis in the mouse prefrontal brain cortex. Our results revealed that intranasal injections of recombinant Hsp70 decreased the apoptosis level in the ischaemic penumbra, stimulated axonogenesis and increased the number of neurons producing synaptophysin. Similarly, in the isolated crayfish stretch receptor, consisting of a single sensory neuron surrounded by the glial envelope, exogenous Hsp70 significantly decreased photoinduced apoptosis and necrosis of glial cells. The obtained data enable one to consider human recombinant Hsp70 as a promising compound that could be translated from the bench into clinical therapies.

[Effects of the Hydrogen Sulfide Donor GYY4137 and HSP70 Protein on the Activation of SH-SY5Y Cells by Lipopolysaccharide].

The effects of exogenous recombinant human heat shock protein Hsp70 and hydrogen sulfide donor GYY4137 on the mechanisms of endocytosis of lipopolysaccharide (LPS) by human neuroblastoma cells SH-SY5Ywas studied. Hsp70 and GYY4137 have been shown to significantly reduce LPS-induced production of inflammatory mediators by SH-SY5Y cells, including reactive oxygen species, nitric oxide, TNFα, IL-1ß, and IL-6. Both the recombinant protein Hsp70 and the hydrogen sulfide donor GYY4137 exhibited significant protective effects; however, the combined use of these agents did not lead to a cumulative effect. It has been shown that pinocytosis, as well as clathrin-, caveolin-, tubulin- and receptor-dependent endocytosis were involved in protecting the cells by both the hydrogen sulfide donor and Hsp70 from LPS-induced production of reactive oxygen species and NO.

Genome-wide transcriptional effects of deletions of sulphur metabolism genes in Drosophila melanogaster.

In recent years, the gasotransmitter hydrogen sulphide (H2S), produced by the transsulphuration pathway, has been recognized as a biological mediator playing an important role under normal conditions and in various pathologies in both eukaryotes and prokaryotes. The transsulphuration pathway (TSP) includes the conversion of homocysteine to cysteine following the breakdown of methionine. In Drosophila melanogaster and other eukaryotes, H2S is produced by cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulphurtransferase (MST). In the experiments performed in this study, we were able to explore the CRISPR/Cas9 technique to obtain single and double deletions in homozygotes of these three major genes responsible for H2S production in Drosophila melanogaster. In most cases, the deletion of one studied gene does not result in the compensatory induction of two other genes responsible for H2S production. Transcriptomic studies demonstrated that the deletions of the above CBS and CSE genes alter genome expression to different degrees, with a more pronounced effect being exerted by deletion of the CBS gene. Furthermore, the double deletion of both CBS and CSE resulted in a cumulative effect on transcription in the resulting strains. Overall, we found that the obtained deletions affect numerous genes involved in various biological pathways. Specifically, genes involved in the oxidative reduction process, stress-response genes, housekeeping genes, and genes participating in olfactory and reproduction are among the most strongly affected. Furthermore, characteristic differences in the response to the deletions of the studied genes are apparently organ-specific and have clear-cut sex-specific characteristics. Single and double deletions of the three genes responsible for the production of H2S helped to elucidate new aspects of the biological significance of this vital physiological mediator.

[Exogenous HSP70 and Signaling Pathways Involved in the Inhibition of LPS-Induced Neurotoxicity of Neuroblastoma Cells].

Neuroinflammation plays a key role in the pathogenesis of neurodegenerative diseases. Microglial cells are the main immune cells of the central nervous system. On exposure to lipopolysaccharides (LPS, components of the cell wall of Gram-negative enterobacteria), microglia is activated to produce reactive oxygen species (ROS), cytokines, and inflammatory mediators, which may cause neuron death. Exogenous recombinant human heat shock protein 70 (HSP70) was tested for effect on the activation of human microglial and neuroblastoma cells in response to LPS from Escherichia coli. Experiments included cell cultivation separately and transferring the conditioned medium from A-172 microglial cells to SK-N-SH neuroblastoma cells to simulate the effect of microglia treated with LPS and/or HSP70. The levels of ROS, TNFα, and apoptosis in LPS-treated cells were estimated in the presence or absence of HSP70. HSP70 was found to reduce the LPS-induced ROS generation, TNFα production, apoptosis, and necrosis, in both separate cell cultures and neuroblastoma cells grown in the conditioned medium from microglial cells. Signaling pathways involving protein kinases p38MAPK, JNK, and PI3K were demonstrated to play an important role in HSP70-mediated protection of microglial and neuroblastoma cells from LPS-induced apoptosis and ROS production.

Age-dependent expression profiles of two adaptogenic systems and thermotolerance in Drosophila melanogaster.

Here, we monitored the expression of three genes (hsp70, hsp22, and hsf1) involved in heat shock response in Drosophila melanogaster in males and females of different age. Also, we investigated age- and sex-dependent expression of three major genes participating in the production of hydrogen sulfide (H2S) (cse, cbs, and mst), implicated in stress resistance and aging. In addition to the control strain, we monitored the expression of all of these genes in a cbs knockout strain (cbs-/-) generated using the CRISPR technique. The tested strains differ in the induction capacities of the studied genes. Relative to the control strain, under normal conditions, the cbs-/- strain expresses all of the studied genes more abundantly, especially hsp22. In the control strain, aging leads to a dramatic increase in hsp22 synthesis, whereas in the cbs-/- strain, hsp22 induction is not pronounced. Furthermore, in 30-day-old cbs-/- flies, the constitutive expression of hsp70 and mst is decreased. Surprisingly, in the cbs-/- strain, we detected an upregulation of hsf1 transcription in the 30-day-old females. After heat shock in the control strain, hsp70 and hsp22 induction decreased with age in males and hsp22 decreased in females, while in the cbs-/- strain, a pronounced drop in the induction capacity of both hsp genes was seen in 30-day-old males and females. However, in most cases, the expression levels of hsf1 and H2S-producing genes do not exhibit pronounced changes depending on sex, age, or heat shock. Flies of control and cbs-/- strain exhibited strong reduction in basal thermotolerance with age. Our data suggest a cross-talk between the two studied ancient and universal adaptive systems.

Long-term results of tripolar constrained total hip arthroplasty in revision hip arthroplasty: a minimum follow-up of ten years.

AIMS: We investigated the long-term performance of the Tripolar Trident acetabular component used for recurrent dislocation in revision total hip arthroplasty. We assessed: 1) rate of re-dislocation; 2) incidence of complications requiring re-operation; and 3) Western Ontario and McMaster Universities osteoarthritis index (WOMAC) pain and functional scores. PATIENTS AND METHODS: We retrospectively identified 111 patients who had 113 revision tripolar constrained liners between 1994 and 2008. All patients had undergone revision hip arthroplasty before the constrained liner was used: 13 after the first revision, 17 after the second, 38 after the third, and 45 after more than three revisions. A total of 75 hips (73 patients) were treated with Tripolar liners due to recurrent instability with abductor deficiency, In addition, six patients had associated cerebral palsy, four had poliomyelitis, two had multiple sclerosis, two had spina bifida, two had spondyloepiphyseal dysplasia, one had previous reversal of an arthrodesis, and 21 had proximal femoral replacements. The mean age of patients at time of Tripolar insertions was 72 years (53 to 89); there were 69 female patients (two bilateral) and 42 male patients. All patients were followed up for a mean of 15 years (10 to 24). Overall, 55 patients (57 hips) died between April 2011 and February 2018, at a mean of 167 months (122 to 217) following their tripolar liner implantation. We extracted demographics, implant data, rate of dislocations, and incidence of other complications. RESULTS: At ten years, the Kaplan-Meier survivorship for dislocation was 95.6% (95% confidence interval (CI) 90 to 98), with 101 patients at risk. At 20 years, the survivorship for dislocation was 90.6% (95% CI 81.0 to 95.5), with one patient at risk. Eight patients (7.2%) had a dislocation of their constrained liners. At ten years, the survival to any event was 89.4% (95% CI 82 to 93.8), with 96 patients at risk. At 20 years, the survival to any event was 82.5% (95% CI 71.9 to 89.3), with one patient at risk. Five hips (4.4%) had deep infection. Two patients (1.8%) developed dissociated constraining rings with pain but without dislocation, which required re-operation. Two patients (1.8%) had periprosthetic femoral fractures, without dislocation, that were treated by revision stems along with exchange of the well-functioning constrained liners. CONCLUSION: Constrained tripolar liners used at revision hip arthroplasty provided favourable results in the long term for treatment of recurrent dislocation and for patients at high risk of dislocation. Cite this article: Bone Joint J 2019;101-B(6 Supple B):123-126.

[The Major Human Stress Protein Hsp70 as a Factor of Protein Homeostasis and a Cytokine-Like Regulator].

Heat shock proteins (HSPs) are important factors of protein homeostasis and possess chaperone properties, providing for a folding and intracellular transport of proteins and facilitating the recovery or utilization of proteins partly denatured on exposure to various stress factors. Proteins of the Hsp70 family are the most universal molecular chaperones and interact with the greatest number of protein substrates. Several proteins of the Hsp70 family are released into the extracellular space, where they play an important role in intercellular communications and act as alarmins, or "danger signals," to modulate the immune response. The secreted Hsp70 can additionally act as an effective neuroprotector, increasing the survival of neurons in various proteinopathies, as has been demonstrated in Alzheimer's and Parkinson's disease models. In this regard, recombinant Hsp70 and inducers of endogenous Hsp70 synthesis may be considered as candidate therapeutics with immune-modulating and neuroprotective properties.Heat shock proteins (HSPs) are important factors of protein homeostasis and possess chaperone properties, providing for a folding and intracellular transport of proteins and facilitating the recovery or utilization of proteins partly denatured on exposure to various stress factors. Proteins of the Hsp70 family are the most universal molecular chaperones and interact with the greatest number of protein substrates. Several proteins of the Hsp70 family are released into the extracellular space, where they play an important role in intercellular communications and act as alarmins, or "danger signals," to modulate the immune response. The secreted Hsp70 can additionally act as an effective neuroprotector, increasing the survival of neurons in various proteinopathies, as has been demonstrated in Alzheimer's and Parkinson's disease models. In this regard, recombinant Hsp70 and inducers of endogenous Hsp70 synthesis may be considered as candidate therapeutics with immune-modulating and neuroprotective properties.

Revision for adverse local tissue reaction following metal-on-polyethylene total hip arthroplasty is associated with a high risk of early major complications.

Aims: Fretting and corrosion at the modular head/neck junction, known as trunnionosis, in total hip arthroplasty (THA) is a cause of adverse reaction to metal debris (ARMD). We describe the outcome of revision of metal-on-polyethylene (MoP) THA for ARMD due to trunnionosis with emphasis on the risk of major complications. Patients and Methods: A total of 36 patients with a MoP THA who underwent revision for ARMD due to trunnionosis were identified. Three were excluded as their revision had been to another metal head. The remaining 33 were revised to a ceramic head with a titanium sleeve. We describe the presentation, revision findings, and risk of complications in these patients. Results: The patients presented with pain, swelling, stiffness, or instability and an inflammatory mass was confirmed radiologically. Macroscopic material deposition on the trunnion was seen in all patients, associated with ARMD. Following revision, six (18.2%) dislocated, requiring further revision in four. Three (9.1%) developed a deep infection and six (18.2%) had significant persistent pain without an obvious cause. One developed a femoral artery thrombosis after excision of an iliofemoral pseudotumor, requiring a thrombectomy. Conclusion: The risk of serious complications following revision MoP THA for ARMD associated with trunnionosis is high. In the presence of extensive tissue damage, a constrained liner or dual mobility construct is recommended in these patients. Cite this article: Bone Joint J 2018;100-B:720-4.

Heat shock protein 70 from a thermotolerant Diptera species provides higher thermoresistance to Drosophila larvae than correspondent endogenous gene.

Heat shock proteins (Hsp70s) from two Diptera species that drastically differ in their heat shock response and longevity were investigated. Drosophila melanogaster is characterized by the absence of Hsp70 and other hsps under normal conditions and the dramatic induction of hsp synthesis after temperature elevation. The other Diptera species examined belongs to the Stratiomyidae family (Stratiomys singularior) and exhibits high levels of inducible Hsp70 under normal conditions coupled with a thermotolerant phenotype and much longer lifespan. To evaluate the impact of hsp70 genes on thermotolerance and longevity, we made use of a D. melanogaster strain that lacks all hsp70 genes. We introduced single copies of either S. singularior or D. melanogaster hsp70 into this strain and monitored the obtained transgenic flies in terms of thermotolerance and longevity. We developed transgenic strains containing the S. singularior hsp70 gene under control of a D. melanogaster hsp70 promoter. Although these adult flies did synthesize the corresponding mRNA after heat shock, they were not superior to the flies containing a single copy of D. melanogaster hsp70 in thermotolerance and longevity. By contrast, Stratiomyidae Hsp70 provided significantly higher thermotolerance at the larval stage in comparison with endogenous Hsp70.

[Regulation of heat shock gene expression in response to stress].

Heat shock (HS) genes, or stress genes, code for a number of proteins that collectively form the most ancient and universal stress defense system. The system determines the cell capability of adaptation to various adverse factors and performs a variety of auxiliary functions in normal physiological conditions. Common stress factors, such as higher temperatures, hypoxia, heavy metals, and others, suppress transcription and translation for the majority of genes, while HS genes are upregulated. Transcription of HS genes is controlled by transcription factors of the HS factor (HSF) family. Certain HSFs are activated on exposure to higher temperatures or other adverse factors to ensure stress-induced HS gene expression, while other HSFs are specifically activated at particular developmental stages. The regulation of the main mammalian stress-inducible factor HSF1 and Drosophila melanogaster HSF includes many components, such as a variety of early warning signals indicative of abnormal cell activity (e.g., increases in intracellular ceramide, cytosolic calcium ions, or partly denatured proteins); protein kinases, which phosphorylate HSFs at various Ser residues; acetyltransferases; and regulatory proteins, such as SUMO and HSBP1. Transcription factors other than HSFs are also involved in activating HS gene transcription; the set includes D. melanogaster GAF, mammalian Sp1 and NF-Y, and other factors. Transcription of several stress genes coding for molecular chaperones of the glucose-regulated protein (GRP) family is predominantly regulated by another stress-detecting system, which is known as the unfolded protein response (UPR) system and is activated in response to massive protein misfolding in the endoplasmic reticulum and mitochondrial matrix. A translational fine tuning of HS protein expression occurs via changing the phosphorylation status of several proteins involved in translation initiation. In addition, specific signal sequences in the 5'-UTRs of some HS protein mRNAs ensure their preferential translation in stress.

[Heat-shock protein HSP70 decreases activity of proteasomes in human neuroblastoma cells treated by amyloid-beta 1-42 with isomerized Asp7].

Experimental evidences indicate that heat-shock protein 70 (HSP70) can serve as a prospective therapeutic agent to treat Alzheimer's disease (AD). It has demonstrated a neuroprotective effect in vivo on mice models of AD. Moreover, HSP70 decreases oxidative stress in neurons induced by amyloid-ß (Aß42) and its more toxic form with isomerized Asp7 (isoAß42). The dysfunction of Ubiquitin-proteasome system (UPS) is observed in AD. UPS is responsible for the degradation of the majority of cellular proteins and plays an important role in protecting cells from oxidative stress. Here, we have shown that the incubation of human neuroblastoma cells SK-N-SH with isoAß42 increases the activity of intracellular proteasomes, which are the principal elements of the UPS. On the contrary, the proteasomal activity was decreased in isoAß42-treated cells in the presence of exogenous HSP70. These results highlight the existence of an interplay between Aß peptides, proteasomes, and HSP70.

[The evolution of heat shock genes and expression patterns of heat shock proteins in the species from temperature contrasting habitats].

Heat shock genes are the most evolutionarily ancient among the systems responsible for adaptation of organisms to a harsh environment. The encoded proteins (heat shock proteins, Hsps) represent the most important factors of adaptation to adverse environmental conditions. They serve as molecular chaperones, providing protein folding and preventing aggregation of damaged cellular proteins. Structural analysis of the heat shock genes in individuals from both phylogenetically close and very distant taxa made it possible to reveal the basic trends of the heat shock gene organization in the context of adaptation to extreme conditions. Using different model objects and nonmodel species from natural populations, it was demonstrated that modulation of the Hsps expression during adaptation to different environmental conditions could be achieved by changing the number and structural organization of heat shock genes in the genome, as well as the structure of their promoters. It was demonstrated that thermotolerant species were usually characterized by elevated levels of Hsps under normal temperature or by the increase in the synthesis of these proteins in response to heat shock. Analysis of the heat shock genes in phylogenetically distant organisms is of great interest because, on one hand, it contributes to the understanding of the molecular mechanisms of evolution of adaptogenes and, on the other hand, sheds the light on the role of different Hsps families in the development of thermotolerance and the resistance to other stress factors.

Interplay between RNA interference and heat shock response systems in Drosophila melanogaster.

The genome expression pattern is strongly modified during the heat shock response (HSR) to form an adaptive state. This may be partly achieved by modulating microRNA levels that control the expression of a great number of genes that are embedded within the gene circuitry. Here, we investigated the cross-talk between two highly conserved and universal house-keeping systems, the HSR and microRNA machinery, in Drosophila melanogaster We demonstrated that pronounced interstrain differences in the microRNA levels are alleviated after heat shock (HS) to form a uniform microRNA pattern. However, individual strains exhibit different patterns of microRNA expression during the course of recovery. Importantly, HS-regulated microRNAs may target functionally similar HS-responsive genes involved in the HSR. Despite the observed general downregulation of primary microRNA precursor expression as well as core microRNA pathway genes after HS, the levels of many mature microRNAs are upregulated. This indicates that the regulation of miRNA expression after HS occurs at transcriptional and post-transcriptional levels. It was also shown that deletion of all hsp70 genes had no significant effect on microRNA biogenesis but might influence the dynamics of microRNA expression during the HSR.

Periprosthetic fractures associated with total knee arthroplasty: an update.

Fractures around total knee arthroplasties pose a significant surgical challenge. Most can be managed with osteosynthesis and salvage of the replacement. The techniques of fixation of these fractures and revision surgery have evolved and so has the assessment of outcome. This specialty update summarises the current evidence for the classification, methods of fixation, revision surgery and outcomes of the management of periprosthetic fractures associated with total knee arthroplasty. Cite this article: Bone Joint J 2016;98-B:1489-96.

Porous tantalum uncemented acetabular components in revision total hip arthroplasty: a minimum ten-year clinical, radiological and quality of life outcome study.

AIMS: Reconstruction of the acetabulum after failed total hip arthroplasty (THA) can be a surgical challenge in the presence of severe bone loss. We report the long-term survival of a porous tantalum revision acetabular component, its radiological appearance and quality of life outcomes. PATIENTS AND METHODS: We reviewed the results of 46 patients who had undergone revision of a failed acetabular component with a Paprosky II or III bone defect and reconstruction with a hemispherical, tantalum acetabular component, supplementary screws and a cemented polyethylene liner. RESULTS: After a minimum follow-up of ten years (ten to 12), the survivorship of the porous tantalum acetabular component was 96%, with further revision of the acetabular component as the end point. The ten-year survivorship, with hip revision for any reason as the end point, was 92%. We noted excellent pain relief (mean Western Ontario and McMaster Universities Arthritis Index (WOMAC) score pain 92.6, (40 to 100)) and good functional outcomes (mean WOMAC function 90.3 (30.9 to 100), mean University of California Los Angeles activity scale 5 (2 to 10)) and generic quality of life measures (mean Short Form-12 (SF-12) physical component 48.3 (18.1 to 56.8), mean SF-12 mental component 56.7 (32.9 to 70.3)). Patient satisfaction with pain relief, function and return to recreational activities were excellent. TAKE HOME MESSAGE: Uncemented acetabular reconstruction using a tantalum acetabular component gives excellent clinical and quality of life outcomes at a minimum follow-up of ten years. Cite this article: Bone Joint J 2016;98-B:767-71.