Reversal of neuronal tau pathology, metabolic dysfunction, and electrophysiological defects via adiponectin pathway-dependent AMPK activation.

Changes in brain mitochondrial metabolism are coincident with functional decline; however, direct links between the two have not been established. Here, we show that mitochondrial targeting via the adiponectin receptor activator AdipoRon (AR) clears neurofibrillary tangles (NFTs) and rescues neuronal tauopathy-associated defects. AR reduced levels of phospho-tau and lowered NFT burden by a mechanism involving the energy-sensing kinase AMPK and the growth-sensing kinase GSK3b. The transcriptional response to AR included broad metabolic and functional pathways. Induction of lysosomal pathways involved activation of LC3 and p62, and restoration of neuronal outgrowth required the stress-responsive kinase JNK. Negative consequences of NFTs on mitochondrial activity, ATP production, and lipid stores were corrected. Defects in electrophysiological measures (e.g., resting potential, resistance, spiking profiles) were also corrected. These findings reveal a network linking mitochondrial function, cellular maintenance processes, and electrical aspects of neuronal function that can be targeted via adiponectin receptor activation.

Prevalence of dysphagia following posterior fossa tumour resection in children: the Alder Hey experience.

BACKGROUND: Surgery for posterior fossa tumours (PFTs) in children is associated with bulbar palsy and swallowing difficulties although this risk is not well defined in the literature and issues contributing to dysphagia following surgery are not fully understood. AIMS: This study aims to study the eating, drinking and swallowing function of children following PFT resection in a specialist paediatric neurosurgery centre. This included the frequency and duration of dysphagia, the risk of aspiration and the link between tumour type and dysphagia. MATERIALS AND METHODS: This is a retrospective review of children undergoing surgery for PFT between 2014 and 2019. Information was obtained from the patients' hospital and speech and language therapy (SLT) notes, oncology database and clinical letters. The International Dysphagia Diet Standardisation Initiative (IDDSI) Framework was used to describe food and fluid modifications. RESULTS: Seventy children had surgery to resect a posterior fossa tumour at Alder Hey from 2014 to 2019. Thirty-one children were included in the study following referral to SLT. Videofluoroscopy (VF) was undertaken at our institution in 68% (21/31) of cases. Fifty-two percent (11/21) of children aspirated or were considered at risk, and 55% (6/11) of those who aspirated showed silent aspiration. After 3 months, 43% (13/30) still required modified food and/or fluid textures, with this proportion reducing as time progressed. By tumour type, VF was performed in 5/7 medulloblastoma patients with 3/5 showing aspiration and 3/3 silently aspirating; in 8/9 patients with ependymoma with 4/8 patients aspirating with 2/4 showing silent aspiration; and 6/12 glioma patients with 4/6 aspirating with 1/4 showing silent aspiration. CONCLUSION: Swallowing difficulties, including silent aspiration, are an important complication of PFT resection. A proportion of children will need ongoing food and/or fluid modification. Further study into dysphagia following PFT resection is indicated.

Subacute necrotizing fasciitis of the posterior neck disguised as a herpes zoster infection: A case report.

Necrotizing fasciitis is a rare soft tissue infection characterized by a rapidly spreading infection of the subcutaneous tissue. Early diagnosis is important as it requires immediate and complete debridement of infected tissues and antibiotic therapy. Necrotizing fasciitis usually involves the extremities, abdomen, and groin, but rarely involves the head and neck. Necrotizing fasciitis has an aggressive course; however, in rare cases, it can present in a subacute indolent form which can be misdiagnosed as other cutaneous diseases. Our case is a unique presentation of subacute necrotizing fasciitis of the posterior neck, which was initially diagnosed as a herpes zoster infection, in a patient with undiagnosed diabetes mellitus, which was complicated with diabetic ketoacidosis and sepsis.

Evaluation of the Salmonella CANARY® Zephyr Assay for the Detection of Salmonella enterica on Environmental Surfaces: AOAC Performance Tested MethodSM 042201.

BACKGROUND: The Salmonella CANARY® Zephyr assay is designed to provide rapid and reliable detection of Salmonella enterica from various types of environmental surfaces, including stainless steel, silicone rubber, high-density polyethylene (HDPE), and glazed ceramic. The assay is using cell- and immuno-based CANARY technology and tested on Smiths Detection's Zephyr platform. OBJECTIVE: The objective of this validation study was to evaluate the Salmonella CANARY Zephyr assay for its inclusivity/exclusivity, matrix study for 4 claimed environmental surfaces, consistency/stability, and robustness. METHODS: The Salmonella CANARY Zephyr assay was compared to the U.S. Food and Drug Administration Bacteriological Analytical Manual (BAM) Chapter 5 "Salmonella" using an unpaired study design for environmental surfaces including stainless steel, silicone rubber, HDPE, and glazed ceramic (1" × 1" test area). RESULTS: For the inclusivity and exclusivity evaluation, the Salmonella CANARY Zephyr assay correctly identified 101 out of 102 target organism isolates (with one strain of S. enterica subsp. indica not detected) and excluded all 33 non-target strains that were analyzed. For the matrix study, the Salmonella CANARY Zephyr assay demonstrated no statistically significant differences between presumptive and confirmed results or between candidate and reference method results. Probability of detection analysis of the Salmonella CANARY Zephyr method on robustness and product consistency/stability (lot-to-lot) study demonstrated no statistically significant differences. CONCLUSION: The Salmonella CANARY Zephyr assay is an effective method for the detection of Salmonella enterica from various environmental surfaces including stainless steel, silicone rubber, HDPE, and glazed ceramic. HIGHLIGHT: The Salmonella CANARY Zephyr assay allows for rapid and sensitive detection of Salmonella enterica on environmental surfaces. It only takes less than 5 min to prepare the sample and 1 min for instrument running/reading.

Rhesus monkeys as a translational model for late-onset Alzheimer's disease.

Age is a major risk factor for late-onset Alzheimer's disease (AD) but seldom features in laboratory models of the disease. Furthermore, heterogeneity in size and density of AD plaques observed in individuals are not recapitulated in transgenic mouse models, presenting an incomplete picture. We show that the amyloid plaque microenvironment is not equivalent between rodent and primate species, and that differences in the impact of AD pathology on local metabolism and inflammation might explain established differences in neurodegeneration and functional decline. Using brain tissue from transgenic APP/PSEN1 mice, rhesus monkeys with age-related amyloid plaques, and human subjects with confirmed AD, we report altered energetics in the plaque microenvironment. Metabolic features included changes in mitochondrial distribution and enzymatic activity, and changes in redox cofactors NAD(P)H that were shared among species. A greater burden of lipofuscin was detected in the brains from monkeys and humans of advanced age compared to transgenic mice. Local inflammatory signatures indexed by astrogliosis and microglial activation were detected in each species; however, the inflamed zone was considerably larger for monkeys and humans. These data demonstrate the advantage of nonhuman primates in modeling the plaque microenvironment, and provide a new framework to investigate how AD pathology might contribute to functional loss.

Shock wave lithotripsy, for the treatment of kidney stones, results in changes to routine blood tests and novel biomarkers: a prospective clinical pilot-study.

BACKGROUND: The number of patients undergoing shock wave lithotripsy (SWL) for kidney stones is increasing annually, and as such the development of post-operative complications, such as haematuria and acute kidney injury (AKI) following SWL, is likely to increase. The aim of the study was to evaluate changes in routine blood and novel biomarkers following SWL, for the treatment of kidney stones. METHODS: Twelve patients undergoing SWL for solitary unilateral kidney stones were recruited. From patients (8 males and 4 females) aged between 31 and 72 years (median 43 years), venous blood samples were collected pre-operatively (baseline), at 30, 120 and 240 min post-operatively. Routine blood tests were performed using a Sysmex XE-5000, and Beckman Coulter AU5800 and AU680 analysers. NGAL, IL-18, IL-6, TNF-α, IL-10 and IL-8 concentrations were determined using commercially available ELISA kits. RESULTS: Significant (p ≤ 0.05) changes were observed in several blood parameters following SWL. NGAL concentration significantly increased, with values peaking at 30 min post-treatment (p = 0.033). Although IL-18 concentration increased, these changes were not significant (p = 0.116). IL-6 revealed a statistically significant rise from pre-operative up to 4 h post-operatively (p < 0.001), whilst TNF-α significantly increased, peaking at 30 min post-SWL (p = 0.05). There were no significant changes to IL-10 and IL-8 concentrations post-SWL (p > 0.05). CONCLUSIONS: Changes to routine blood tests and specific biomarkers, in the future, may be more useful for clinicians. In turn, identification of a panel of biomarkers could provide valuable data on "normal" physiological response after lithotripsy. Ultimately, studies could be expanded to identify or predict those patients at increased risk of developing post-operative complications, such as acute kidney injury or. These studies, however, need validating involving larger cohorts.

Identifying high-risk commercial vehicle drivers using sociodemographic characteristics.

Crash data, from the state of Kentucky, for the 2015-2016 period, show that per capita crash rates and increases in crash-related fatalities were higher than the national average. In an effort to explain why the U.S. Southeast experiences higher crash rates than other regions of the country, previous research has argued the regions unique socioeconomic conditions provide a compelling explanation. Taking this observation as a starting point, this study examines the relationship between highway safety and socioeconomic and demographic characteristics, using an extensive crash dataset from Kentucky. Its focus is single- and two-unit crashes that involve commercial motor vehicles (CMVs) and automobiles. Using binary logistic regression and the quasi-induced exposure technique to analyze data on the socioeconomic and demographic attributes of the zip codes in which drivers reside, factors are identified which can serve as indicators of crash occurrence. Variables such as income, education level, poverty level, employment, age, gender, and rurality of the driver's zip code influence the likelihood of a driver being at fault in a crash. Socioeconomic factors exert a similar influence on CMV and automobile crashes, irrespective of the number of vehicles involved. Research findings can be used to identify groups of drivers most likely to be involved in crashes and develop targeted and efficient safety programs.

Use of codes data to improve estimates of at-fault risk for elderly drivers.

The fastest-growing demographic in the United States is people aged 65 and over. Because elderly drivers may experience decline in the physical and mental faculties required for driving (which could lead to unsafe driving behaviors), it is critical to determine whether elderly drivers are more likely than younger drivers to be at fault in a crash. This study uses Kentucky crash data and linked hospital and emergency department records to evaluate whether linked data can more accurately estimate the crash propensity of elderly drivers to be at-fault in injury crashes. The Kentucky crash data is edited to conform to the General Use Model (GUM), with crash propensities for linked data compared to propensities developed using the GUM dataset alone. The quasi-induced exposure method is used to determine crash exposure. Factors such as age, gender, and crash location are explored to assess their influence on the risk of a driver being at fault in an injury crash. The overall findings are consistent with previous research - elderly drivers are more likely than younger drivers to be at fault in a crash. Linking crash with hospital and emergency department records could also establish a clearer understanding of the injury crash propensity of all age groups. Equipped with this knowledge, transportation practitioners can design more targeted and effective countermeasures and safety programs to improve the safety of all motorists.

Sleep and diurnal rest-activity rhythm disturbances in a mouse model of Alzheimer's disease.

STUDY OBJECTIVES: Accumulating evidence suggests a strong association between sleep, amyloid-beta (Aß) deposition, and Alzheimer's disease (AD). We sought to determine if (1) deficits in rest-activity rhythms and sleep are significant phenotypes in J20 AD mice, (2) metabotropic glutamate receptor 5 inhibitors (mGluR5) could rescue deficits in rest-activity rhythms and sleep, and (3) Aß levels are responsive to treatment with mGluR5 inhibitors. METHODS: Diurnal rest-activity levels were measured by actigraphy and sleep-wake patterns by electroencephalography, while animals were chronically treated with mGluR5 inhibitors. Behavioral tests were performed, and Aß levels measured in brain lysates. RESULTS: J20 mice exhibited a 4.5-h delay in the acrophase of activity levels compared to wild-type littermates and spent less time in rapid eye movement (REM) sleep during the second half of the light period. J20 mice also exhibited decreased non-rapid eye movement (NREM) delta power but increased NREM sigma power. The mGluR5 inhibitor CTEP rescued the REM sleep deficit and improved NREM delta and sigma power but did not correct rest-activity rhythms. No statistically significant differences were observed in Aß levels, rotarod performance, or the passive avoidance task following chronic mGluR5 inhibitor treatment. CONCLUSIONS: J20 mice have disruptions in rest-activity rhythms and reduced homeostatic sleep pressure (reduced NREM delta power). NREM delta power was increased following treatment with a mGluR5 inhibitor. Drug bioavailability was poor. Further work is necessary to determine if mGluR5 is a viable target for treating sleep phenotypes in AD.

Altered circadian rhythms and oscillation of clock genes and sirtuin 1 in a model of sudden unexpected death in epilepsy.

OBJECTIVES: Circadian rhythms are affected in many neurological disorders. Although sleep disturbances are known in epilepsy, data on circadian rhythm disturbances in epilepsy are sparse. Here, we examined diurnal and circadian rest-activity and sleep-wake patterns in Kcna1-null mice, which exhibit spontaneous recurrent seizures and are a model of sudden unexpected death in epilepsy. Furthermore, we sought to determine whether seizures or aberrant oscillation of core clock genes and a regulator, sirtuin 1 (Sirt1), is associated with disrupted rhythms. METHODS: We used passive infrared actigraphy to assess rest-activity patterns, electroencephalography for seizure and sleep analysis, and reverse transcription polymerase chain reaction and Western blotting to evaluate expression of clock genes and Sirt1 in Kcna1-null and wild-type mice. RESULTS: Epileptic Kcna1-null animals have disrupted diurnal and circadian rest-activity patterns, tending to exhibit prolonged circadian periods. Electroencephalographic analysis confirmed disturbances in sleep architecture, with more time spent awake and less asleep. Although all epileptic mice manifested disrupted diurnal and circadian rest-activity patterns, we found no correlation between actual seizure burden and degree of sleep disruption. However, we found attenuated oscillations of several clock genes (ie, Clock, Bmal1, Per1, and Per2) and diurnal Sirt1 mRNA in the anterior hypothalamus. SIGNIFICANCE: Attenuated oscillation of several core clock genes correlates with, and may underlie, aberrant diurnal and circadian rest-activity and sleep-wake patterns observed in Kcna1-null mice. This could contribute to late complications in epilepsy, such as sudden unexpected death in epilepsy. Sirt1 may represent a useful therapeutic target for rescuing circadian clock gene rhythmicity and sleep patterns in epilepsy.

Using Shared Decision-Making to Address Possible Overtreatment in Patients at High Risk for Hypoglycemia: The Veterans Health Administration's Choosing Wisely Hypoglycemia Safety Initiative.

IN BRIEF Successful management of patients with diabetes requires individualizing A1C and treatment goals in conjunction with identifying and managing hypoglycemia risk. This article describes the Veterans Health Administration's Choosing Wisely Hypoglycemia Safety Initiative (CW-HSI), a voluntary program that aims to reduce the occurrence of hypoglycemia through shared decision-making about deintensifying diabetes treatment in a dynamic cohort of patients identified as being at high risk for hypoglycemia and potentially overtreated. The CW-HSI incorporates education for patients and clinicians, as well as clinical decision support tools, and has shown decreases in the proportions of high-risk patients potentially overtreated and impacts on the frequency of reported hypoglycemia.

Advancement of clinical pharmacy practice through intervention capture.

PURPOSE: The methods and processes utilized to deploy the Pharmacists Achieve Results with Medications Documentation (PhARMD) Project intervention template across the largest integrated healthcare system in the United States are described. SUMMARY: The PhARMD Project team at the Department of Veterans Affairs (VA) designed, developed, and deployed a standardized template within VA's electronic health record (EHR) that allows the clinical pharmacy specialist (CPS) to efficiently document select interventions made during patient care encounters that specifically contribute to the overall care provided and patient outcomes. The template is completed by the CPSs as part of progress note documentation within the EHR. Using point-and-click functionality, a CPS selects the check boxes corresponding to specific interventions made during that patient care encounter. This improves workflow and negates the need to document interventions in a separate software system, streamlining documentation. The implementation and use of the PhARMD template at each VA facility are voluntary. From October 1, 2016, to September 30, 2017, 4,728 CPSs documented 3,805,323 interventions during 2,384,771 patient care encounters. These interventions were documented across 592,126 unique patients, with a mean of 6.4 interventions per patient during this period. Most interventions (95%) were performed by CPSs functioning as advanced practice providers and with autonomous prescriptive authority authorized under their scope of practice. CONCLUSION: The PhARMD template demonstrated that the capture of clinical pharmacy interventions and outcomes can be achieved across a large integrated healthcare system by thousands of CPSs in numerous practice settings.

Combining Ordinary Kriging with wind directions to identify sources of industrial odors in Portland, Oregon.

This study combines Ordinary Kriging, odor monitoring, and wind direction data to demonstrate how these elements can be applied to identify the source of an industrial odor. The specific case study used as an example of how to address this issue was the University Park neighborhood of Portland, Oregon (USA) where residents frequently complain about industrial odors, and suspect the main source to be a nearby Daimler Trucks North America LLC manufacturing plant. We collected 19,665 odor observations plus 105,120 wind measurements, using an automated weather station to measure winds in the area at five-minute intervals, logging continuously from December 2014 through November 2015, while we also measured odors at 19 locations, three times per day, using methods from the American Society of the International Association for Testing and Materials. Our results quantify how winds vary with season and time of day when industrial odors were observed versus when they were not observed, while also mapping spatiotemporal patterns in these odors using Ordinary Kriging. Our analyses show that industrial odors were detected most frequently to the northwest of the Daimler plant, mostly when winds blew from the southeast, suggesting Daimler's facility is a likely source for much of this odor.

Estimation and testing problems in auditory neuroscience via clustering.

The processing of auditory information in neurons is an important area in neuroscience. We consider statistical analysis for an electrophysiological experiment related to this area. The recorded synaptic current responses from the experiment are observed as clusters, where the number of clusters is related to an important characteristic of the auditory system. This number is difficult to estimate visually because the clusters are blurred by biological variability. Using singular value decomposition and a Gaussian mixture model, we develop an estimator for the number of clusters. Additionally, we provide a method for hypothesis testing and sample size determination in the two-sample problem. We illustrate our approach with both simulated and experimental data.

The influence of tibial component malalignment on bone strain in revision total knee replacement.

Revision total knee replacement is a challenging surgical procedure typically associated with significant loss of bone stock in the proximal tibia. To increase the fixation stability, extended stems are frequently used for the tibial component in revision surgery. The design of the tibial stem influences the load transfer from tibial component to the surrounding bone and is cited as a possible cause for the clinically reported pain in the location of the stem-end. This study aimed to analyse the strain distribution of a fully cemented revision tibial component with a validated finite element model. The model was developed from a scanned composite tibia (Sawbones), with an implanted, fully cemented stemmed tibial component aligned to the mechanical axis of the tibia. Loading was applied to the tibial component with mediolateral compartment load distributions of 60:40 and 80:20. Three strain gauged composite tibias with implanted tibial components of the same design using the same loading distribution were tested to obtain experimental strains at five locations in the proximal tibia. The finite element model developed was validated against strain measurements obtained in the experimental study. The strains displayed similar patterns (R(2) = 0.988) and magnitudes with those predicted from the finite element model. The displacement of the stem-end from the natural mechanical axis in the finite element model demonstrated increased strains in the stem-end region with a close proximity of the distal stem with the cortical bone. The simulation of a mediolateral compartment load of 80:20 developed peak cortical strain values on the posterior-medial side beneath the stem. This may possibly be related to the clinically reported pain at the stem-end. Furthermore, stem positioning in close proximity or contact with the posterior cortical bone is a contributory factor for an increase in distal strain.

Seizure phenotypes, periodicity, and sleep-wake pattern of seizures in Kcna-1 null mice.

This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies.

Role of out-of-hours nurse co-ordinators in a children's hospital.

In a hospital, a high proportion of working time occurs outside the traditional working day, affecting patient safety as staffing levels are at their lowest out of hours. A service evaluation audit was used to evaluate the effectiveness of a clinical out-of-hours nurse co-ordinator (COHNC) pilot role in a tertiary children's hospital. The COHNC role was trialled over a six-month period. During the pilot, the COHNC carried the junior paediatrician's 'bleep' and prioritised all phone calls and tasks. Following a patient assessment, the COHNC either performed the investigations and treatments within their scope of practice or escalated these to the appropriate multidisciplinary team member. A description of how the COHNC role has developed and its implications to nursing practice are presented in this article, along with an overview of the quantitative and qualitative data obtained during the audit.

A Pilot Study to Evaluate Haemostatic Function, following Shock Wave Lithotripsy (SWL) for the Treatment of Solitary Kidney Stones.

PURPOSE: The number of patients undergoing shock wave lithotripsy (SWL) in the UK for solitary unilateral kidney stones is increasing annually. The development of postoperative complications such as haematuria and sepsis following SWL is likely to increase. Comparing a range of biological markers with the aim of monitoring or predicting postoperative complications following SWL has not been extensively researched. The main purpose of this pilot-study was to test the hypothesis that SWL results in changes to haemostatic function. Subsequently, this pilot-study would form a sound basis to undertake future investigations involving larger cohorts. METHODS: Twelve patients undergoing SWL for solitary unilateral kidney stones were recruited. From patients (8 male and 4 females) aged between 31-72 years (median-43 years), venous blood samples were collected pre-operatively (baseline), at 30, 120 and 240 minutes postoperatively. Specific haemostatic biomarkers [platelet counts, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, von Willebrand Factor (vWF), sE-selectin and plasma viscosity (PV)] were measured. RESULTS: Platelet counts and fibrinogen concentration were significantly decreased following SWL (p = 0.027 and p = 0.014 respectively), while D-dimer and vWF levels significantly increased following SWL (p = 0.019 and p = 0.001 respectively). PT, APTT, sE-selectin and PV parameters were not significantly changed following SWL (p>0.05). CONCLUSIONS: Changes to specific biomarkers such as plasma fibrinogen and vWF suggest that these represent a more clinically relevant assessment of the extent of haemostatic involvement following SWL. Analysis of such markers, in the future, may potentially provide valuable data on "normal" response after lithotripsy, and could be expanded to identify or predict those patients at risk of coagulopathy following SWL. The validation and reliability will be assessed through the assessment of larger cohorts.

Mutation of Npr2 leads to blurred tonotopic organization of central auditory circuits in mice.

Tonotopy is a fundamental organizational feature of the auditory system. Sounds are encoded by the spatial and temporal patterns of electrical activity in spiral ganglion neurons (SGNs) and are transmitted via tonotopically ordered processes from the cochlea through the eighth nerve to the cochlear nuclei. Upon reaching the brainstem, SGN axons bifurcate in a stereotyped pattern, innervating target neurons in the anteroventral cochlear nucleus (aVCN) with one branch and in the posteroventral and dorsal cochlear nuclei (pVCN and DCN) with the other. Each branch is tonotopically organized, thereby distributing acoustic information systematically along multiple parallel pathways for processing in the brainstem. In mice with a mutation in the receptor guanylyl cyclase Npr2, this spatial organization is disrupted. Peripheral SGN processes appear normal, but central SGN processes fail to bifurcate and are disorganized as they exit the auditory nerve. Within the cochlear nuclei, the tonotopic organization of the SGN terminal arbors is blurred and the aVCN is underinnervated with a reduced convergence of SGN inputs onto target neurons. The tonotopy of circuitry within the cochlear nuclei is also degraded, as revealed by changes in the topographic mapping of tuberculoventral cell projections from DCN to VCN. Nonetheless, Npr2 mutant SGN axons are able to transmit acoustic information with normal sensitivity and timing, as revealed by auditory brainstem responses and electrophysiological recordings from VCN neurons. Although most features of signal transmission are normal, intermittent failures were observed in responses to trains of shocks, likely due to a failure in action potential conduction at branch points in Npr2 mutant afferent fibers. Our results show that Npr2 is necessary for the precise spatial organization typical of central auditory circuits, but that signals are still transmitted with normal timing, and that mutant mice can hear even with these deficits.

Strong correlation between the morphology of the proximal femur and the geometry of the distal femoral trochlea.

PURPOSE: Previous investigations suggested that the geometry of the proximal femur may be related to osteoarthritis of the tibiofemoral joint and various patellofemoral joint conditions. This study aims to investigate the correlation between proximal and distal femoral geometry. Such a correlation could aid our understanding of patient complications after total knee arthroplasty (TKA) and be of benefit for further development of kinematic approaches in TKA. METHODS: CT scans of 60 subjects (30 males, 30 females) were used to identify anatomical landmarks to calculate anatomical parameters of the femur, including the femoral neck anteversion angle, neck-shaft angle (NSA), mediolateral offset (ML-offset), condylar twist angle (CTA), trochlear sulcus angle (TSA) and medial/lateral trochlear inclination angles (MTIA/LTIA). Correlation analyses were carried out to assess the relationship between these parameters, and the effect of gender was investigated. RESULTS: The CTA, TSA and LTIA showed no correlation with any proximal parameter. The MTIA was correlated with all three proximal parameters, mostly with the NSA and ML-offset. Per 5° increase in NSA, the MTIA was 2.1° lower (p < 0.01), and for every 5 mm increase in ML-offset, there was a 2.6° increase in MTIA (p < 0.01). These results were strongest and statistically significant in females and not in males and were independent of length and weight. CONCLUSIONS: Proximal femoral geometry is distinctively linked with trochlear morphology. In order to improve knowledge on the physiological kinematics of the knee joint and to improve the concept of kinematic knee replacement, the proximal femur seems to be a factor of clinical importance. LEVEL OF EVIDENCE: III.