Cost effective, reliable implantation of acetabular cups in Total Hip Arthroplasty

Previously held under moratorium from 23 November 2016 until 23 November 2021Correct positioning of the acetabular cup is critical for success within Total Hip Arthroplasty. Malpositioning of the acetabular cup contributes to many complications, all of which lead to revision surgery. Despite recognition of the importance of correct orientation, there is no consensus on what the optimum orientation of the acetabular cup should be. The suggested orientations in the literature are contradictory and comparison between studies is difficult due to variations in angle definitions, measurement systems and reference systems. These contradictions, the lack of consensus in the literature and results from studies suggest that acetabular orientation must be patient specific. Mechanical guides are the most commonly used device to assist surgeons in positioning the acetabular cup, both in cemented and uncemented arthroplasties. However, these devices have many limitations one of which is a fixed acetabular orientation which does not allow for any patient variability. Using a combination of quantitative and qualitative product design techniques, Harrison User Centred Methodology was developed. This new methodology was adopted to design and develop a device to aid surgeons with positioning the acetabular cup in total hip arthroplasty. The aim was to design a device which could be used for both cemented and uncemented hip arthroplasty. The final device design was a novel positioning guide which addressed the lack of patient variability in current mechanical guides. The device simplified the positioning and limited the movement of the introducer. Feedback from surgeons demonstrated a positive response and with further development, a willingness to try the product. Proof of concept testing was carried out to measure the accuracy of the device. An available (uncemented) introducer was used for testing which demonstrated the device can accurately position the acetabular cup. The accuracy of the developed device and current techniques was compared. The study showed less variation in the position over time using the novel device which highlights an added benefit for cemented procedures demonstrating stability as the cement cures.Correct positioning of the acetabular cup is critical for success within Total Hip Arthroplasty. Malpositioning of the acetabular cup contributes to many complications, all of which lead to revision surgery. Despite recognition of the importance of correct orientation, there is no consensus on what the optimum orientation of the acetabular cup should be. The suggested orientations in the literature are contradictory and comparison between studies is difficult due to variations in angle definitions, measurement systems and reference systems. These contradictions, the lack of consensus in the literature and results from studies suggest that acetabular orientation must be patient specific. Mechanical guides are the most commonly used device to assist surgeons in positioning the acetabular cup, both in cemented and uncemented arthroplasties. However, these devices have many limitations one of which is a fixed acetabular orientation which does not allow for any patient variability. Using a combination of quantitative and qualitative product design techniques, Harrison User Centred Methodology was developed. This new methodology was adopted to design and develop a device to aid surgeons with positioning the acetabular cup in total hip arthroplasty. The aim was to design a device which could be used for both cemented and uncemented hip arthroplasty. The final device design was a novel positioning guide which addressed the lack of patient variability in current mechanical guides. The device simplified the positioning and limited the movement of the introducer. Feedback from surgeons demonstrated a positive response and with further development, a willingness to try the product. Proof of concept testing was carried out to measure the accuracy of the device. An available (uncemented) introducer was used for testing which demonstrated the device can accurately position the acetabular cup. The accuracy of the developed device and current techniques was compared. The study showed less variation in the position over time using the novel device which highlights an added benefit for cemented procedures demonstrating stability as the cement cures

Regional differences in nutrient-induced secretion of gut serotonin

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Enterochromaffin (EC) cells located in the gastrointestinal (GI) tract provide the vast majority of serotonin (5‐HT) in the body and constitute half of all enteroendocrine cells. EC cells respond to an array of stimuli, including various ingested nutrients. Ensuing 5‐HT release from these cells plays a diverse role in regulating gut motility as well as other important responses to nutrient ingestion such as glucose absorption and fluid balance. Recent data also highlight the role of peripheral 5‐HT in various pathways related to metabolic control. Details related to the manner by which EC cells respond to ingested nutrients are scarce and as that the nutrient environment changes along the length of the gut, it is unknown whether the response of EC cells to nutrients is dependent on their GI location. The aim of the present study was to identify whether regional differences in nutrient sensing capability exist in mouse EC cells. We isolated mouse EC cells from duodenum and colon to demonstrate differential responses to sugars depending on location. Measurements of intracellular calcium concentration and 5‐HT secretion demonstrated that colonic EC cells are more sensitive to glucose, while duodenal EC cells are more sensitive to fructose and sucrose. Short‐chain fatty acids (SCFAs), which are predominantly synthesized by intestinal bacteria, have been previously associated with an increase in circulating 5‐HT; however, we find that SCFAs do not acutely stimulate EC cell 5‐HT release. Thus, we highlight that EC cell physiology is dictated by regional location within the GI tract, and identify differences in the regional responsiveness of EC cells to dietary sugars

Pressor and Sympathetic Responses to Graded Skeletal Muscle Metaboreflex Activation in Females with Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a progressive disease characterized by demyelination in the central nervous system which disproportionately impacts females. Previous studies suggest MS-related exercise intolerance may be due to abnormal control of arterial blood pressure (BP) via the skeletal muscle metaboreflex. However, few studies have been performed and equivocal results reported. Discontinuity in prior data may be due to limited perturbation of metaboreflex activation using only low and moderate intensity exercise. PURPOSE: The purpose of this investigation was to test the hypothesis that females with MS have blunted BP and sympathetic responses to graded static handgrip (HG) exercise and isolated metaboreflex activation during postexercise ischemia (PEI) compared to healthy controls. METHODS: In 7 females with relapsing-remitting MS and 9 healthy female controls beat-to-beat BP (finometer) and muscle sympathetic nerve activity (MSNA; peroneal microneurography) were recorded at rest and during two minutes of handgrip performed at 30% and 40% maximum voluntary contraction followed by two minutes of PEI to isolate the muscle metaboreflex. RESULTS: There were no differences in resting mean arterial pressure (MAP; P= 0.16) or MSNA burst frequency (P= 0.15) between MS and controls. MAP and MSNA increased during 30% HG (MS: Δ19.8 ± 9.1 mmHg vs. Con: Δ17.8 ± 5.4 mmHg; P= 0.30 and MS: Δ17 ± 12 bursts/min vs. Con: Δ18 ± 17 bursts/min; P= 0.46) and 40% HG (MS: Δ29.3 ± 8.0 mmHg vs. Con: Δ30.0 ± 6.9 mmHg; P= 0.43 and MS: Δ36 ± 16 bursts/min vs. Con: Δ40 ± 9 bursts/min; P= 0.30) with no differences between groups. Likewise, MAP and MSNA responses were also not different during PEI post 30% HG (MS: Δ15.8 ± 7.6 mmHg vs. Con: Δ15.8 ± 6.4 mmHg; P= 0.50 and MS: Δ15 ± 9 bursts/min vs. Con: Δ11 ± 7 bursts/min; P= 0.19) or PEI post 40% HG (MS: Δ25.8 ± 6.3 mmHg vs. Con: Δ22.6 ± 8.2 mmHg; P= 0.43 and MS: Δ23 ± 13 bursts/min vs. Con: Δ24 ± 7 bursts/min; P= 0.46) between MS and controls. CONCLUSION: These preliminary data suggest intact skeletal muscle metaboreflex control of arterial BP in females with MS

A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress

Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH2-terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway

The Loss of ATRX Increases Susceptibility to Pancreatic Injury and Oncogenic KRAS in Female But Not Male Mice

Female mice lacking ATRX in the pancreas have increased sensitivity to pancreatic cancer, whereas male mice without ATRX are protected. This study identifies such susceptibility in pancreatic cancer and highlights the need for sex-specific approaches in cancer treatment. BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for \u3e30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler.-thalassemia, mental-retardation, X-linked (ATRX) affects oncogenic KRAS\u27s ability to promote PDAC. ATRX affects DNA replication, repair, and gene expression and is implicated in other cancers including glioblastomas and pancreatic neuroendocrine tumors. The hypothesis was that deletion of Atrx in pancreatic acinar cells will increase susceptibility to injury and oncogenic METHODS: Mice allowing conditional loss of Atrx within pancreatic acinar cells were examined after induction of recurrent cerulein-induced pancreatitis or oncogenic KRAS (KRASG12D). Histologic, biochemical, and molecular analysis examined pancreatic pathologies up to 2 months after induction of Atrx deletion. RESULTS: Mice lacking Atrx showed more progressive damage, inflammation, and acinar-to-duct cell metaplasia in response to injury relative to wild-type mice. In combination with KRASG12D, Atrx-deficient acinar cells showed increased fibrosis, inflammation, progression to acinar-to-duct cell metaplasia, and pre-cancerous lesions relative to mice expressing only KRASG12D. This sensitivity appears only in female mice, mimicking a significant prevalence of ATRX mutations in human female PDAC patients. CONCLUSIONS: Our results indicate the absence of ATRX increases sensitivity to injury and oncogenic KRAS only in female mice. This is an instance of a sex-specific mutation that enhances oncogenic KRAS\u27s ability to promote pancreatic intraepithelial lesion formation

FAPRI Environmental Projects 2000

Since 1995, the Food and Agricultural Policy Research Institute at the University of Missouri (FAPRI) has been providing analytical support in several areas around the state as communities try to come to grips with various water quality issues thought to derive from production agriculture's two underlying facts of life. This report provides a summary of the lessons learned as the unit has looked at and worked with these communities. It also discusses the specific projects underway in the unit, again focusing on issues directly related to the interface problem.This project is a cooperative effort of the Food and Agricultural Policy Research Institute at the University of Missouri and the Natural Resource Conservation Service. The work is supported by EPA grant X997396-01, Region VII U.S. Environmental Protection Agency, under section 104 (b) (3). The Missouri Department of Agriculture appropriated funds to support the work in this report

Positive Approaches to Phosphorus Balancing in Southwest Missouri: Animal Manure Phosphorus Recycling Initiative

Document presented on July 12, 2001 at Crowder College, Neosho, MO and on November 6 & 7 at Water Quality Research in the White River Basin Conference in Springfield, MO.Opportunities exist to create value added animal waste fertilizer products that can be used in crop production, reducing import demands for phosphorus, and relocating phosphorus from areas of excess supply to areas of need for crop production. This paper focuses on opportunities to recycle poultry litter in southwest Missouri.This project is a cooperative effort of the Food and Agricultural Policy Research Institute at the University of Missouri and the Natural Resource Conservation Service. The work is supported by EPA grant X997396-01, Region VII U.S. Environmental Protection Agency, under section 104 (b)(3). The Missouri Department of Agriculture appropriated funds to support the work in this report

Activating Transcription Factor 3 Promotes Loss of the Acinar Cell Phenotype in Response to Cerulein-Induced Pancreatitis in Mice

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of \u3e30% of differentially expressed genes during the initiation of pancreatitis. Of importance, ATF3-dependent regulation of these genes was observed only upon induction of pancreatitis, with pathways involved in inflammation, acinar cell differentiation, and cell junctions being specifically targeted. Characterizing expression of transcription factors that affect acinar cell differentiation suggested that acinar cells lacking ATF3 maintain a mature cell phenotype during pancreatitis, a finding supported by maintenance of junctional proteins and polarity markers. As a result