Relative Blood Volume Profiles Hours After Loop Diuretic Administration: A Systematic Review and Meta-analysis.

Background: Plasma refill rates can be estimated by combining measurements of urine output with relative blood volume profiles. Change in plasma refill rates could guide decongestive loop diuretic therapy in acute heart failure. The objective of the study was to assess average relative blood volume profiles generated from 2 or 3 follow-up measurements obtained hours after loop diuretic administration in subjects with vs without baseline congestion. Methods: A systematic review was conducted of articles written in English, French, Spanish, and German, using MEDLINE (1964 to 2019), Cochrane Reviews (1996 to 2019), and Embase (1974 to 2019). Search terms included the following: diuretics, hemoconcentration, plasma volume, and blood volume. We included studies of adults given a loop diuretic with at least one baseline and one follow-up measurement. A single author extracted subject- or group-level blood volume measurements, aggregated them when needed, and converted them to relative changes. Results: Across all 16 studies that met the prespecified inclusion criteria, relative blood volume maximally decreased 9.2% (6.6% to 12.0%) and returned to baseline after 3 or more hours. Compared to subjects without congestion, those with congestion experienced smaller decreases in relative blood volume across all follow-up periods (P = 0.001) and returned to baseline within the final follow-up period. Conclusions: Single doses of loop diuretics produce measurable changes in relative blood volume that follow distinct profiles for subjects with vs without congestion. Measured alongside urine output, these profiles may be used to estimate plasma refill rates-potential patient-specific targets for decongestive therapy across serial diuretic doses.

Contexte: Le taux de remplissage plasmatique peut être estimé en combinant les mesures de la diurèse et les profils volémiques relatifs. Chez les personnes atteintes d'insuffisance cardiaque aiguë, une variation du taux de remplissage plasmatique pourrait guider un traitement décongestif par un diurétique de l'anse. L'étude avait pour objectif d'évaluer les profils volémiques relatifs moyens obtenus dans le cadre de deux ou trois mesures de suivi réalisées quelques heures après l'administration d'un diurétique de l'anse à des sujets présentant ou non une congestion initiale. Méthodologie: Une revue systématique d'articles rédigés en anglais, en français, en espagnol et en allemand a été effectuée au moyen des bases de données MEDLINE (1964 à 2019), Cochrane Reviews (1996 à 2019) et Embase (1974 à 2019). Les termes de recherche comprenaient : diurétiques, hémoconcentration, volume plasmatique et volume sanguin. Nous avons inclus des études portant sur des adultes ayant reçu un diurétique de l'anse chez qui au moins une mesure initiale et une mesure de suivi avaient été effectuées. Un seul auteur a recueilli des mesures du volume sanguin individuelles ou de groupe, les a regroupées, au besoin, et converties en variations relatives. Résultats: Parmi les 16 études qui répondaient aux critères d'inclusion prédéfinis, le volume sanguin relatif a diminué de 9,2 % (de 6,6 % à 12,0 %) et est revenu aux valeurs initiales après trois heures ou plus. Les sujets qui présentaient une congestion ont connu des diminutions du volume sanguin relatif inférieures à celles de ceux n'en présentant pas lors de toutes les périodes de suivi (p = 0,001); le volume sanguin relatif est revenu aux valeurs initiales durant la période finale de suivi. Conclusions: Des doses uniques de diurétique de l'anse produisent des changements mesurables du volume sanguin relatif selon des profils distincts chez les sujets présentant une congestion, comparativement à ceux n'en présentant pas. Utilisés en association avec les mesures de la diurèse, ces profils peuvent servir à estimer le taux de remplissage plasmatique, qui constitue potentiellement une cible particulière au patient qui reçoit une série de doses d'un diurétique comme traitement décongestif.

The Cost Effectiveness of Unicompartmental versus Total Knee Arthroplasty.

This study examines the potential cost savings for the health system and the community in a broadly accessible model through the increased utilization of unicompartmental knee arthroplasty (UKA) using robotic arm-assisted UKA (raUKA) versus conventional total knee arthroplasty (cTKA). We retrospectively reviewed 240 patients where the first 120 consecutive raUKA performed during this period were matched to 120 cTKAs. Clinical data from the medical records and costs for procedure for each component were collected. Bivariate analyses were performed on the data to determine if there were statistically significant differences by surgery type in clinical outcomes and financial costs. There was a significantly lower cost incurred for raUKA versus cTKA with an average saving of AU$7,179 per case. The operating time (86.0 vs. 75.9 minutes; p = 0.004) was significantly higher for raUKA, but the length of stay was significantly lower (1.8 vs. 4.8 days; p < 0.001). There was a significant difference in the use of opioids between raUKA and cTKA (125.0 morphine equivalent [ME] vs. 522.1 ME, p < 0.001). This study demonstrated that the use of raUKA rather than cTKA in suitably indicated patients may realize significant cost savings.

Kinematic alignment in total knee arthroplasty: a five-year prospective, multicentre, survivorship study.

AIMS: The mid-term results of kinematic alignment (KA) for total knee arthroplasty (TKA) using image derived instrumentation (IDI) have not been reported in detail, and questions remain regarding ligamentous stability and revisions. This paper aims to address the following: 1) what is the distribution of alignment of KA TKAs using IDI; 2) is a TKA alignment category associated with increased risk of failure or poor patient outcomes; 3) does extending limb alignment lead to changes in soft-tissue laxity; and 4) what is the five-year survivorship and outcomes of KA TKA using IDI? METHODS: A prospective, multicentre, trial enrolled 100 patients undergoing KA TKA using IDI, with follow-up to five years. Alignment measures were conducted pre- and postoperatively to assess constitutional alignment and final implant position. Patient-reported outcome measures (PROMs) of pain and function were also included. The Australian Orthopaedic Association National Joint Arthroplasty Registry was used to assess survivorship. RESULTS: The postoperative HKA distribution varied from 9° varus to 11° valgus. All PROMs showed statistical improvements at one year (p < 0.001), with further improvements at five years for Knee Osteoarthritis Outcome Score symptoms (p = 0.041) and Forgotten Joint Score (p = 0.011). Correlation analysis showed no difference (p = 0.610) between the hip-knee-ankle and joint line congruence angle at one and five years. Sub-group analysis showed no difference in PROMs for patients placed within 3° of neutral compared to those placed > 3°. There were no revisions for tibial loosening; however, there were reports of a higher incidence of poor patella tracking and patellofemoral stiffness. CONCLUSION: PROMs were not impacted by postoperative alignment category. Ligamentous stability was maintained at five years with joint line obliquity. There were no revisions for tibial loosening despite a significant portion of tibiae placed in varus; however, KA executed with IDI resulted in a higher than anticipated rate of patella complications.Cite this article: Bone Jt Open 2022;3(8):656-665.

Clinical and radiological outcomes of robotic-assisted unicompartmental knee arthroplasty: Early lessons from the first 100 consecutive knees in 85 patients.

INTRODUCTION: Robotic-assisted unicompartmental knee arthroplasty (UKA) is associated with improved component positioning and comparable short- and mid-term implant survivorship with manual UKA. This study aims to evaluate clinical and radiological outcomes following robotic-assisted UKA as well as any potential learning-curves associated with the introduction of such new technology. METHODS: Prospective study of patients undergoing robotic-assisted UKA. Outcome measures were patient-reported outcome measures (PROMs) including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Society Score (KSS) and Oxford Knee Score (OKS), complications, implant survivorship, component positioning and learning curve. RESULTS: Eighty-five patients comprising 100 knees were recruited and followed up for 21.0 ± 4.3 months. At two years, there were significant and sustained improvements in PROMs and 100% implant survivorship rate. A high degree of implant accuracy was achieved with the robotic system. A cumulative learning curve of 20 cases was noted. CONCLUSION: Robotic-assisted UKA achieves excellent implant accuracy and clinical outcomes in the short-term. Long-term follow up is needed to evaluate this relationship.

Assessing open science and citizen science in addictions and substance use research: A scoping review.

BACKGROUND: The EU promotes 'Open Science' as a public good. Complementary to its implementation is Citizen Science, which redefines the relationship between the scientific community, civic society and the individual. Open Science and Citizen Science poses challenges for the substance use and addictions research community but may provide positive opportunities for future European addiction research. This paper explores both current barriers and potential facilitators for the implementation of Open Science and Citizen Science in substance use and addictions research. METHODOLOGY: A scoping review was used to examine barriers and facilitators identified in the substance use and addiction research literature for the adoption of Open Science and Citizen Science. RESULTS: 'Technical' facilitators included the pre-registration of study protocols; publication of open-source datasets; open peer review and online tools. 'Motivational' facilitators included enhanced reputation; embracing co-creation; engaged citizenship and gamification. 'Economic' facilitators included the use of free tools and balanced remuneration of crowdworkers. 'Political' facilitators included better informed debates through the 'triple helix' approach and trust-generating transparency. 'Legal' facilitators included epidemiologically informed law enforcement; better policy surveillance and the validation of other datasets. 'Ethical' facilitators included the 'democratisation of science' and opportunities to explore new concepts of ethics in addiction research. CONCLUSION: Open Science and Citizen Science in substance use and addictions research may provide a range of benefits in relation to the democratisation of science; transparency; efficiency and the reliability/validity of data. However, its implementation raises a range of research integrity and ethical issues that need be considered. These include issues related to participant recruitment; privacy; confidentiality; security; cost and industry involvement. Progressive journal policies to support Open Science practices; a shift in researcher norms; the use of free tools and the greater availability of methodological and ethical standards are likely to increase adoption in the field.

Entanglement entropy and edge modes in topological string theory. Part I. Generalized entropy for closed strings.

Progress in identifying the bulk microstate interpretation of the Ryu-Takayanagi formula requires understanding how to define entanglement entropy in the bulk closed string theory. Unfortunately, entanglement and Hilbert space factorization remains poorly understood in string theory. As a toy model for AdS/CFT, we study the entanglement entropy of closed strings in the topological A-model in the context of Gopakumar-Vafa duality. We will present our results in two separate papers. In this work, we consider the bulk closed string theory on the resolved conifold and give a self-consistent factorization of the closed string Hilbert space using extended TQFT methods. We incorporate our factorization map into a Frobenius algebra describing the fusion and splitting of Calabi-Yau manifolds, and find string edge modes transforming under a q-deformed surface symmetry group. We define a string theory analogue of the Hartle-Hawking state and give a canonical calculation of its entanglement entropy from the reduced density matrix. Our result matches with the geometrical replica trick calculation on the resolved conifold, as well as a dual Chern-Simons theory calculation which will appear in our next paper [1]. We find a realization of the Susskind-Uglum proposal identifying the entanglement entropy of closed strings with the thermal entropy of open strings ending on entanglement branes. We also comment on the BPS microstate counting of the entanglement entropy. Finally we relate the nonlocal aspects of our factorization map to analogous phenomenon recently found in JT gravity.

The impact of functional combined anteversion on hip range of motion: a new optimal zone to reduce risk of impingement in total hip arthroplasty.

AIMS: Pelvic tilt (PT) can significantly change the functional orientation of the acetabular component and may differ markedly between patients undergoing total hip arthroplasty (THA). Patients with stiff spines who have little change in PT are considered at high risk for instability following THA. Femoral component position also contributes to the limits of impingement-free range of motion (ROM), but has been less studied. Little is known about the impact of combined anteversion on risk of impingement with changing pelvic position. METHODS: We used a virtual hip ROM (vROM) tool to investigate whether there is an ideal functional combined anteversion for reduced risk of hip impingement. We collected PT information from functional lateral radiographs (standing and sitting) and a supine CT scan, which was then input into the vROM tool. We developed a novel vROM scoring system, considering both seated flexion and standing extension manoeuvres, to quantify whether hips had limited ROM and then correlated the vROM score to component position. RESULTS: The vast majority of THA planned with standing combined anteversion between 30° to 50° and sitting combined anteversion between 45° to 65° had a vROM score > 99%, while the majority of vROM scores less than 99% were outside of this zone. The range of PT in supine, standing, and sitting positions varied widely between patients. Patients who had little change in PT from standing to sitting positions had decreased hip vROM. CONCLUSION: It has been shown previously that an individual's unique spinopelvic alignment influences functional cup anteversion. But functional combined anteversion, which also considers stem position, should be used to identify an ideal THA position for impingement-free ROM. We found a functional combined anteversion zone for THA that may be used moving forward to place total hip components. Cite this article: Bone Jt Open 2021;2(10):834-841.

The three-year survivorship of robotically assisted versus non-robotically assisted unicompartmental knee arthroplasty.

AIM: There has been a significant reduction in unicompartmental knee arthroplasty (UKA) procedures recorded in Australia. This follows several national joint registry studies documenting high UKA revision rates when compared to total knee arthroplasty (TKA). With the recent introduction of robotically assisted UKA procedures, it is hoped that outcomes improve. This study examines the cumulative revision rate of UKA procedures implanted with a newly introduced robotic system and compares the results to one of the best performing non-robotically assisted UKA prostheses, as well as all other non-robotically assisted UKA procedures. METHODS: Data from the Australian Orthopaedic Association National Joint Arthroplasty Registry (AOANJRR) for all UKA procedures performed for osteoarthritis (OA) between 2015 and 2018 were analyzed. Procedures using the Restoris MCK UKA prosthesis implanted using the Mako Robotic-Arm Assisted System were compared to non-robotically assisted Zimmer Unicompartmental High Flex Knee System (ZUK) UKA, a commonly used UKA with previously reported good outcomes and to all other non-robotically assisted UKA procedures using Cox proportional hazard ratios (HRs) and Kaplan-Meier estimates of survivorship. RESULTS: There was no difference in the rate of revision when the Mako-assisted Restoris UKA was compared to the ZUK UKA (zero to nine months: HR 1.14 (95% CI 0.71 to 1.83; p = 0.596) vs nine months and over: HR 0.66 (95% CI 0.42 to 1.02; p = 0.058)). The Mako-assisted Restoris had a significantly lower overall revision rate compared to the other types of non-robotically assisted procedures (HR 0.58 (95% confidence interval (CI) 0.42 to 0.79); p < 0.001) at three years. Revision for aseptic loosening was lower for the Mako-assisted Restoris compared to all other non-robotically assisted UKA (entire period: HR 0.34 (95% CI 0.17 to 0.65); p = 0.001), but not the ZUK prosthesis. However, revision for infection was significantly higher for the Mako-assisted Restoris compared to the two comparator groups (ZUK: entire period: HR 2.91 (95% CI 1.22 to 6.98; p = 0.016); other non-robotically assisted UKA: zero to three months: HR 5.57 (95% CI 2.17 to 14.31; p < 0.001)). CONCLUSION: This study reports comparable short-term survivorship for the Mako robotically assisted UKA compared to the ZUK UKA and improved survivorship compared to all other non-robotic UKA. These results justify the continued use and investigation of this procedure. However, the higher rate of early revision for infection for robotically assisted UKA requires further investigation. Cite this article: Bone Joint J 2020;102-B(3):319-328.

Risk factors for femoral stem breakage: an analysis of the AOANJRR results.

INTRODUCTION: Breakage of the femoral stem component of a total hip replacement is now uncommon but continues to be seen with certain stem designs and in certain patient groups. Data previously published on this topic has been limited, either gathered from a single surgeon or centre, or included only a single stem design. METHODS: We reviewed the data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), identified and analysed 143 stem breakages over a period of 16 years, covering 44 different stem designs. RESULTS: Our data confirms previously published findings that risk factors for stem breakage include patient age at implantation of under 70, male gender, as well as the use of exchangeable necks. We found no association with initial diagnosis, or type of acetabular component implanted. We did however also find, excluding exchangeable neck designs, that after 4.5 years a cemented stem had a significantly higher risk of breakage then a cementless stem. DISCUSSION: To our knowledge this is the 1st paper to suggest cemented fixation as a specific risk factor for stem breakage. The analysis of rare complications such as stem breakage is only possible through large data collection systems such as the AOANJRR. Whilst there have been recent advances in materials and manufacturing techniques, we recommend that surgeons are aware of all the specific risks when considering implant choices for individual patients.

Prenatal intermittent hypoxia sensitizes the laryngeal chemoreflex, blocks serotoninergic shortening of the reflex, and reduces 5-HT3 receptor binding in the NTS in anesthetized rat pups.

We tested the hypothesis that exposure to intermittent hypoxia (IH) during pregnancy would prolong the laryngeal chemoreflex (LCR) and diminish the capacity of serotonin (5-hydroxytryptamine; 5-HT) to terminate the LCR. Prenatal exposure to IH was associated with significant prolongation of the LCR in younger, anesthetized, postnatal day (P) rat pups age P8 to P16 compared to control, room air (RA)-exposed rat pups of the same age. Serotonin microinjected into the NTS shortened the LCR in rat pups exposed to RA during gestation, but 5-HT failed to shorten the LCR in rat pups exposed to prenatal IH. Given these observations, we tested the hypothesis that prenatal hypoxia would decrease binding to 5-HT3 receptors in the nucleus of the solitary tract (NTS) where 5-HT acts to shorten the LCR. Serotonin 3 receptor binding was reduced in younger rat pups exposed to IH compared to control, RA-exposed rat pups in the age range P8 to P12. Serotonin 3 receptor binding was similar in older animals (P18-P24) regardless of gas exposure during gestation. The failure of the 5-HT injected into the NTS to shorten the LCR was correlated with a developmental decrease in 5-HT3 receptor binding in the NTS associated with exposure to prenatal IH. In summary, prenatal IH sensitized reflex apnea and blunted processes that terminate reflex apneas in neonatal rat pups, processes that are essential to prevent death following apneas such as those seen in babies who died of SIDS.

Antioxidant Enzyme-Mimetic Activity and Neuroprotective Effects of Cerium Oxide Nanoparticles Stabilized with Various Ratios of Citric Acid and EDTA.

Cerium oxide (CeO2) nanoparticles (CeNPs) are potent antioxidants that are being explored as potential therapies for diseases in which oxidative stress plays an important pathological role. However, both beneficial and toxic effects of CeNPs have been reported, and the method of synthesis as well as physico-chemical, biological, and environmental factors can impact the ultimate biological effects of CeNPs. In the present study, we explored the effect of different ratios of citric acid (CA) and EDTA (CA/EDTA), which are used as stabilizers during synthesis of CeNPs, on the antioxidant enzyme-mimetic and biological activity of the CeNPs. We separated the CeNPs into supernatant and pellet fractions and used commercially available enzymatic assays to measure the catalase-, superoxide dismutase (SOD)-, and oxidase-mimetic activity of each fraction. We tested the effects of these CeNPs in a mouse hippocampal brain slice model of ischemia to induce oxidative stress where the fluorescence indicator SYTOX green was used to assess cell death. Our results demonstrate that CeNPs stabilized with various ratios of CA/EDTA display different enzyme-mimetic activities. CeNPs with intermediate CA/EDTA stabilization ratios demonstrated greater neuroprotection in ischemic mouse brain slices, and the neuroprotective activity resides in the pellet fraction of the CeNPs. The neuroprotective effects of CeNPs stabilized with equal proportions of CA/EDTA (50/50) were also demonstrated in two other models of ischemia/reperfusion in mice and rats. Thus, CeNPs merit further development as a neuroprotective therapy for use in diseases associated with oxidative stress in the nervous system.

Hemiarthroplasty vs Total Hip Arthroplasty for the Management of Displaced Neck of Femur Fractures: A Systematic Review and Meta-Analysis.

BACKGROUND: Displaced femoral neck fractures (DFNF) are common and can be treated with osteosynthesis, hemiarthroplasty (HA), or total hip arthroplasty (THA). There is no consensus as to which intervention is superior in managing DFNF. METHODS: Studies were identified through a systematic search of the MEDLINE database, EMBASE database, and Cochrane Controlled Trials. Included studies were randomized or controlled trials (1966 to August 2018) comparing THA with HA for the management of DFNF. (https://www.crd.york.ac.uk/PROSPERO Identifier: CRD42018110057). RESULTS: Seventeen studies were included totaling 1364 patients (660 THA and 704 HA). THA was found to be superior to HA in terms of risk of reoperation, Harris Hip Score and Quality of Life (Short Form 36). Overall, the risk of dislocation was greater in THA group than HA in the first 4 years, after which there was no difference. There was no difference between THA and HA in terms of mortality or infection. CONCLUSION: Overall, THA appears to be superior to HA. THA should be the recommended intervention for DFNF in patients with a life expectancy >4 years and in patients younger than 80 years. However, both HA and THA are reasonable interventions in patients older than 80 years and with shorter life expectancy.

Impact of Image-Derived Instrumentation on Total Knee Arthroplasty Revision Rates: An Analysis of 83,823 Procedures from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: Computer navigation and image-derived instrumentation (IDI) are technology-based methods developed to improve outcomes and potentially reduce revision total knee arthroplasty (TKA). IDI refers to the use of manufactured, patient-specific surgical jigs. Conflicting reports exist on IDI-associated improvements in outcomes. The primary aim of the current study was to compare the rates of revision among TKA cases in which components were initially implanted with use of IDI, computer navigation, or neither of these methods ("other" TKA). The secondary aim was to determine whether the outcomes of IDI differed for specific subgroups. METHODS: Data were obtained from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) for the 3 TKA groups: IDI, computer-navigated, and other TKA. The study period was from the first IDI procedure recorded by the AOANJRR (April 2010) to December 31, 2016. The analysis was restricted to primary TKA cases undertaken for osteoarthritis and involving patellar resurfacing and the use of a cross-linked polyethylene insert. Subanalyses were performed to evaluate the effects of age, sex, implantation method, IDI manufacturer, prosthetic design, and prosthesis type on the rates of revision. Kaplan-Meier estimates of survivorship described the time to first revision. Hazard ratios (HRs, Cox proportional hazards models) with adjustment for age and sex were used to compare revision rates. RESULTS: IDI was used in 5,486 primary TKA procedures. There was no significant difference among the groups in the cumulative percent revision (CPR) at 5 years: 3.3% (95% confidence interval [CI], 2.4% to 4.6%) for IDI, 2.4% (95% CI, 2.2% to 2.7%) for the computer-navigated group, and 2.5% (95% CI, 2.3% to 2.7%) for other TKA. Posterior-stabilized TKA with use of the IDI method had a significantly higher rate of revision at >3 months (HR, 1.45 [95% CI, 1.02 to 2.04]; p = 0.036), as did IDI TKA in the ≤65-year-old patient cohort (HR, 1.52 [95% CI, 1.10 to 2.09]; p = 0.010), compared with computer-navigated TKA. Patellar revision was significantly more likely in the IDI group. CONCLUSIONS: IDI TKA demonstrated no overall difference in early to mid-term revision rates compared with standard implantation methods. However, elevated rates of revision were seen with posterior-stabilized TKA, in patients ≤65 years of age, and for patellar revision, meaning that this method should be used with some caution and requires further study. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Entanglement Entropy and TT[over ¯] Deformation.

Quantum gravity in a finite region of spacetime is conjectured to be dual to a conformal field theory (CFT) deformed by the irrelevant operator TT[over ¯]. We test this conjecture with entanglement entropy, which is sensitive to ultraviolet physics on the boundary, while also probing the bulk geometry. We find that the entanglement entropy for an entangling surface consisting of two antipodal points on a sphere is finite and precisely matches the Ryu-Takayanagi formula applied to a finite region consistent with the conjecture of McGough et al. We also consider a one-parameter family of conical entropies, which are finite and verify a conjecture due to Dong. Since ultraviolet divergences are local, we conclude that the TT[over ¯] deformation acts as an ultraviolet cutoff on the entanglement entropy. Our results support the conjecture that the TT[over ¯]-deformed CFT is the holographic dual of a finite region of spacetime.

Molecular Communications Pulse-Based Jamming Model for Bacterial Biofilm Suppression.

Studies have recently shown that the bacteria survivability within biofilms is responsible for the emergence of superbugs. The combat of bacterial infections, without enhancing its resistance to antibiotics, includes the use of nanoparticles to quench the quorum sensing of these biofilm-forming bacteria. Several sequential and parallel multi-stage communication processes are involved in the formation of biofilms. In this paper, we use proteomic data from a wet lab experiment to identify the communication channels that are vital to these processes. We also identified the main proteins from each channel and propose the use of jamming signals from synthetically engineered bacteria to suppress the production of those proteins. This biocompatible technique is based on synthetic biology and enables the inhibition of biofilm formation. We analyze the communications performance of the jamming process by evaluating the path loss for a number of conditions that include different engineered bacterial population sizes, distances between the populations, and molecular signal power. Our results show that sufficient molecular pulse-based jamming signals are able to prevent the biofilm formation by creating lossy communications channels (almost -3 dB for certain scenarios). From these results, we define the main design parameters to develop a fully operational bacteria-based jamming system.

Unicompartmental Knee Arthroplasty Revision to TKA: Are Tibial Stems and Augments Associated With Improved Survivorship?

BACKGROUND: Some surgeons contend that unicompartmental knee arthroplasty (UKA) can easily be revised to a TKA when revision is called for, whereas others believe that this can be complex and technically demanding. There has been little research regarding the efficacy or rationale of using metal augmentation and tibial stem extensions when revising a UKA to a TKA. QUESTION/PURPOSES: (1) Is the use of stem extensions for the tibial component associated with increased survival when revising a UKA to a TKA? (2) Is the addition of modular augments associated with increased survival compared with stem extensions alone? (3) Is TKA design (minimally stabilized versus posterior-stabilized) or (4) tibial fixation (cemented versus cementless) associated with differences in survivorship? METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) were used to analyze implant survival after revision of a UKA to a TKA, comparing results in which tibial components were used with and without modular components. The groups analyzed were TKA without a stem extension, those in which a tibial stem extension was used, and those in which a tibial stem extension was used together with an augment. There were 4438 revisions of UKAs to TKAs available for analysis. The mean duration of followup of patients having the TKA revisions was 5 years (SD, 3.5 years). There were 2901 (65%) procedures in which a tibial stem extension was not used, 870 (20%) procedures with a tibial stem extension, and 667 (15%) with a tibial stem extension and metallic augment. Kaplan-Meier estimates of survivorship were calculated and hazard ratios (HRs) from Cox proportional hazard models, adjusting for age and sex, were used to compare the rate of revision among groups. The overall 10-year cumulative percent revision (CPR) for UKA revised to a TKA was 16%. RESULTS: At 10 years, the CPR was increased when a stem extension was not used (19%; 95% confidence interval [CI],16.5-20.7 without a stem extension compared with 13%; 95% CI, 9.2-17.0 with a stem extension; entire period HR, 1.44; 95% CI, 1.10-1.89; p = 0.007). There was no difference in the 10-year CPR when an augment was used together with a stem extension compared with a stem extension alone (HR, 1.26; 95% CI, 0.85-1.86; p = 0.251). When minimally stabilized and posterior-stabilized TKAs were compared, there was no difference in survivorship. Minimally stabilized TKA designs without stem extensions showed higher CPR compared with when stem extensions were used (HR, 1.77; 95% CI, 1.16-2.70; p = 0.007), whereas posterior-stabilized designs without stem extensions showed higher CPR only when compared with when stem extensions and augments were both used (HR, 2.16; 95% CI, 1.24-3.77; p = 0.006). Cementless fixation of the tibial component resulted in a higher CPR than when cement was used (HR, 1.36; 95% CI 1.08-1.71; p = 0.008). CONCLUSIONS: In this registry study, the risk of repeat revision after revision of a UKA to a TKA was lower when a tibial stem extension was used, but no such difference was found with respect to augments. Our study did not account for the degree of bone loss or surgeon preference when considering stems and augments. Further research to establish the degree of bone loss associated with UKA to TKA revision procedures will help clarify these findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

Activation of serotonergic neurons in the medullary caudal raphe shortens the laryngeal chemoreflex in anaesthetized neonatal rats.

NEW FINDINGS: What is the central question of this study? Does activation of serotonergic neurons in the caudal medullary raphe, some of which project to the nucleus of the solitary tract, shorten the laryngeal chemoreflex? What is the main finding and its importance? We found that serotonin originating from neurons in the caudal raphe acts through a 5-HT3 receptor located in the nucleus of the solitary tract to terminate reflex apnoea. Failure or deficiency of this arousal-related process is likely to be relevant to the pathogenesis of sudden infant death syndrome. Failure to terminate apnoea and arouse is likely to contribute to sudden infant death syndrome (SIDS). Serotonin is deficient in the brainstems of babies who have died of SIDS. We tested the hypothesis that activation of serotoninergic neurons in the caudal medullary raphe, some of which project to the nucleus of the solitary tract (NTS), would shorten the laryngeal chemoreflex (LCR). We studied anaesthetized neonatal rat pups between postnatal days 9 and 17. We injected 5-40 µl of water into the larynx to elicit the LCR and measured the duration of respiratory disruption. Microinjection of 50 nl of 100 µm AMPA into the caudal medullary raphe shortened the apnoeas (P < 0.001) and respiratory inhibition (P < 0.005) associated with the LCR. When 50 nl of 30 mm ondansetron, a 5-HT3 antagonist, was microinjected bilaterally into the NTS, AMPA microinjected into the caudal raphe no longer shortened the LCR. After bilateral microinjection of vehicle into the NTS, AMPA microinjection into the caudal raphe significantly shortened the LCR. AMPA, a glutamate receptor agonist, may activate many neurons within the caudal raphe, but blocking the 5-HT3 receptor-dependent responses in the NTS prevented the shortening of the LCR associated with AMPA microinjections into the caudal raphe. Thus, serotonin originating from neurons in the caudal raphe acts through a 5-HT3 receptor located in the NTS to terminate or shorten the LCR. Serotonin is deficient in the brainstems of babies who have died of SIDS, and deficient serotonergic termination of apnoea is likely to be relevant to the pathogenesis of SIDS.

Serotonin in the solitary tract nucleus shortens the laryngeal chemoreflex in anaesthetized neonatal rats.

What is the central question of this study? Failure to terminate apnoea and arouse is likely to contribute to sudden infant death syndrome (SIDS). Serotonin is deficient in the brainstems of babies who died of SIDS. Therefore, we tested the hypothesis that serotonin in the nucleus of the solitary tract (NTS) would shorten reflex apnoea. What is the main finding and its importance? Serotonin microinjected into the NTS shortened the apnoea and respiratory inhibition associated with the laryngeal chemoreflex. Moreover, this effect was achieved through a 5-HT3 receptor. This is a new insight that is likely to be relevant to the pathogenesis of SIDS. The laryngeal chemoreflex (LCR), an airway-protective reflex that causes apnoea and bradycardia, has long been suspected as an initiating event in the sudden infant death syndrome. Serotonin (5-HT) and 5-HT receptors may be deficient in the brainstems of babies who die of sudden infant death syndrome, and 5-HT seems to be important in terminating apnoeas directly or in causing arousals or as part of the process of autoresuscitation. We hypothesized that 5-HT in the brainstem would limit the duration of the LCR. We studied anaesthetized rat pups between 7 and 21 days of age and made microinjections into the cisterna magna or into the nucleus of the solitary tract (NTS). Focal, bilateral microinjections of 5-HT into the caudal NTS significantly shortened the LCR. The 5-HT1a receptor antagonist, WAY 100635, did not affect the LCR consistently, nor did a 5-HT2 receptor antagonist, ketanserin, alter the duration of the LCR. The 5-HT3 specific agonist, 1-(3-chlorophenyl)-biguanide, microinjected bilaterally into the caudal NTS significantly shortened the LCR. Thus, endogenous 5-HT released within the NTS may curtail the respiratory depression that is part of the LCR, and serotonergic shortening of the LCR may be attributed to activation of 5-HT3 receptors within the NTS. 5-HT3 receptors are expressed presynaptically on C fibre afferents of the superior laryngeal nerve, and serotonergic shortening of the LCR may be mediated presynaptically by enhanced activation of inhibitory interneurons within the NTS.

The Type 3 Deiodinase Is a Critical Determinant of Appropriate Thyroid Hormone Action in the Developing Testis.

Timely and appropriate levels of thyroid hormone (TH) signaling are necessary to ensure normal developmental outcomes in many tissues. Studies using pharmacological models of altered TH status have revealed an influence of these hormones on testis development and size, but little is known about the role of endogenous determinants of TH action in the developing male gonads. Using a genetic approach, we demonstrate that the type 3 deiodinase (D3), which inactivates TH and protects developing tissues from undue TH action, is a key factor. D3 is highly expressed in the developing testis, and D3-deficient (D3KO) mice exhibit thyrotoxicosis and cell proliferation arrest in the neonatal testis, resulting in an approximately 75% reduction in testis size. This is accompanied by larger seminiferous tubules, impaired spermatogenesis, and a hormonal profile indicative of primary hypogonadism. A deficiency in the TH receptor-α fully normalizes testis size and adult testis gene expression in D3KO mice, indicating that the effects of D3 deficiency are mediated through this type of receptor. Similarly, genetic deficiencies in the D2 or in the monocarboxylate transporter 8 partially rescue the abnormalities in testis size and gonadal axis gene expression featured in the D3KO mice. Our study highlights the testis as an important tissue in which determinants of TH action coordinately converge to ensure normal development and identifies D3 as a critical factor in testis development and in testicular protection from thyrotoxicosis.