Quantitative spatially resolved post-mortem analysis of lithium distribution and transition metal depositions on cycled electrodes via a laser ablation-inductively coupled plasma-optical emission spectrometry method

Diminishing the loss of performance of lithium ion batteries (LIBs) is a challenge that is yet to be fulfilled. Understanding of deterioration processes and mechanisms (i.e., so-called aging) requires analytically accurate examination of aged cells. Changes in the distribution of lithium or transition metals in the LIB cells can influence their cycle and calendar life significantly. As electrochemically treated cells and especially their electrodes do not age homogeneously and the local electrochemistry (e.g. deposition patterns) is strongly dependent on surface properties, bulk analysis is not a satisfactory investigation method. Therefore, a surface sensitive method, namely laser ablation-inductively coupled plasma-optical emission spectrometry (LA-ICP-OES) is presented. LIB cells with lithium metal oxide LiNi_1/3Co_1/3Mn_1/3O₂ (NCM111) as cathode material and graphite as anode material are investigated using a 213 nm Nd:YAG laser.

An LA-ICP-OES method was developed and applied to investigate the transition metal dissolution in lithium batteries as well as lithium deposition e.g. in case of short circuits.     

Implant‐associated localized osteitis in murine femur fracture by biofilm forming Staphylococcus aureus: A novel experimental model

Staphylococcus aureus (SA) is the most common causative agent for implant‐associated osteitis. The present study characterizes a novel model of a low grade acute SA osteitis with bone defect in the femur which is stabilized by a titanium locking plate. Wild‐type Balb/c mice were osteotomized, fixed by a locking plate and infected with SA. Mice underwent debridement 7 and 14 days later and were sacrificed at Day 28. At Days 7, 14, and 28 after inoculation local and systemic cell populations and IL‐6 were analyzed. Fracture healing was quantified by radiography. The control group underwent the same procedure without infection. The bacterial load of implant‐associated osteitis with biofilm formation was quantified by counting CFU and real‐time PCR. Fracture healing determined by radiography was delayed in infected compared to non‐infected mice. Throughout the investigation period CFU and leukocyte counts, as well as IL‐6 levels were found to be significantly elevated in infected mice at the infection site but not systemically. Our murine model allows the detailed investigation of implant associated localized osteitis with biofilm producing SA and its influence on fracture healing. The model provides a tool to analyze therapeutic or prophylactic approaches to the problem of biofilm‐associated osteitis. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:2013–2020, 2013     

Osteitis pubis and adductor tendinopathy in athletes: a novel arthroscopic pubic symphysis curettage and adductor reattachment

Introduction

Various surgical treatment options have been described in athletes with degenerative osteitis pubis who fail to respond to conservative treatment modalities. Although adductor longus tendinopathy often represents an additional pain generator in chronic groin pain associated with osteitis pubis, this has not been acknowledged in the surgical literature, to our knowledge. We present the results of a novel surgical technique for combined degenerative lesions of the pubic symphysis joint and the adjacent adductor longus tendon in a series of athletes with osteitis pubis.

Methods

During 2009 and 2010, five competitive non-professional soccer players with considerable groin and pubic pain were referred to our clinic, after conservative therapy over a period of at least 12 months had failed. According to our clinical protocol for patients with groin pain, physical examination, pelvic radiographs and arthrography of the pubic symphysis to detect microlesions of the adjacent adductor longus tendons were performed. The patients diagnosed with degenerative osteitis pubis and concomitant lesion of the adductor longus origin were indicated for surgery. Surgery consisted of resection of the degenerative soft and bone tissue and subsequent reattachment with suture anchors. With regard to stability of the symphysis pubis, a two-portal arthroscopic curettage of the degenerative fibrocartilaginous disc tissue was performed. The patients were followed prospectively at medium term with assessment of general pain level (VAS score) and sport activity with pain (NIPPS score) pre- and postoperatively.

Results

All patients recovered to full activity sports after an average period of 14.4 weeks. VAS and NIPPS scores markedly improved and overall satisfaction with the postoperative result was high. One intraoperative bleeding occurred, needing revision surgery. None of the patients developed pubic instability due to pubic symphysis curettage in the sequel.

Conclusions

This novel surgical technique combines successfully stability-preserving arthroscopic pubic symphysis curettage with adductor debridement and reattachment in well-selected cases of athletes suffering from degenerative osteitis pubis and concomitant adductor pathology, being refractory to conservative treatment. Diligent preoperative evaluation of the specific pathology will lead to successful outcome.     

Pure adult-onset Spastic Paraplegia caused by a novel mutation in the KIAA0196 (SPG8) gene

SPG8 is a rare autosomal dominant hereditary spastic paraplegia (AD-HSP), with only six SPG8 families described so far. Our purpose was to screen for KIAA0196 (SPG8) mutations in AD-HSP patients and to investigate their phenotype. Extensive family investigation was performed after positive KIAA0196 mutation analysis, which was part of an on-going mutation screening effort in AD-HSP patients. A novel pathogenic KIAA0196 mutation p.(Gly696Ala) was identified in two AD-HSP patients, who subsequently were shown to belong to a single large Dutch pedigree with more than 10 affected family members. The phenotype consisted of a pure HSP with ages at onset between 20 and 60 years, distally reduced vibration sense in the legs in all, and urinary urgency in seven out of 10 patients. Frequent features were exercise- or emotion-induced increase of spasticity and gait problems and chronic nonspecific lower back and joint pains. We have identified a fourth pathogenic KIAA0196 mutation in a Dutch HSP-family, the seventh family worldwide, with a less severe clinical course than described before.     

Recovery from severe frontotemporal dysfunction at 3 years after N-methyl-d-aspartic acid (NMDA) receptor antibody encephalitis

Encephalitis associated with antibodies against N-methyl-d-aspartic acid (NMDA) receptor is characterized by severe memory deficits, decreased consciousness, epileptic seizures and movement disorders and occurs most commonly in young women. Recovery is mostly good but little is known about the disease course in patients whose treatment has been delayed severely. We present a 16-year-old girl with a 36-month follow-up. A single course of methylprednisolone attenuated some symptoms but severe and incapacitating frontotemporal syndrome remained. Second-line treatment with rituximab was initiated 12 months after the onset of symptoms. A surprising recovery occurred 18 months after treatment and 30 months after onset. Recovery in NMDA receptor antibody-associated encephalitis can be severely delayed and does not have to be linear. Whether delayed therapy contributed to recovery in this patient cannot be answered with certainty. Spontaneous recovery independent of therapy is possible, as it has been observed previously as late as 3 years after onset. Although serum antibodies disappeared with recovery in this patient, previous cases have shown serum antibodies to be unreliable markers of disease activity. Second-line treatment, especially with substances as well tolerated as rituximab, should at least be considered in NMDA receptor encephalitis with persistent neuropsychiatric syndromes after first-line therapy.     

Impaired Vestibular Function and Low Bone Mineral Density: Data from the Baltimore Longitudinal Study of Aging

Animal studies have demonstrated that experimentally induced vestibular ablation leads to a decrease in bone mineral density, through mechanisms mediated by the sympathetic nervous system. Loss of bone mineral density is a common and potentially morbid condition that occurs with aging, and we sought to investigate whether vestibular loss is associated with low bone mineral density in older adults. We evaluated this question in a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging (BLSA), a large, prospective cohort study managed by the National Institute on Aging (N = 389). Vestibular function was assessed with cervical vestibular evoked myogenic potentials (cVEMPs), a measure of saccular function. Bone mineral density was assessed using dual-energy X-ray absorptiometry (DEXA). In two-way t test analysis, we observed that individuals with reduced vestibular physiologic function had significantly lower bone mineral density. In adjusted multivariate linear regression analyses, we observed that older individuals with reduced vestibular physiologic function had significantly lower bone mineral density, specifically in weight-bearing hip and lower extremity bones. These results suggest that the vestibular system may contribute to bone homeostasis in older adults, notably of the weight-bearing hip bones at greatest risk of osteoporotic fracture. Further longitudinal analysis of vestibular function and bone mineral density in humans is needed to characterize this relationship and investigate the potential confounding effect of physical activity.     

Firing properties of GABAergic versus non-GABAergic vestibular nucleus neurons conferred by a differential balance of potassium currents

Neural circuits are composed of diverse cell types, the firing properties of which reflect their intrinsic ionic currents. GABAergic and non-GABAergic neurons in the medial vestibular nuclei, identified in GIN and YFP-16 lines of transgenic mice, respectively, exhibit different firing properties in brain slices. The intrinsic ionic currents of these cell types were investigated in acutely dissociated neurons from 3- to 4-wk-old mice, where differences in spontaneous firing and action potential parameters observed in slice preparations are preserved. Both GIN and YFP-16 neurons express a combination of four major outward currents: Ca(2+)-dependent K(+) currents (I(KCa)), 1 mM TEA-sensitive delayed rectifier K(+) currents (I(1TEA)), 10 mM TEA-sensitive delayed rectifier K(+) currents (I(10TEA)), and A-type K(+) currents (I(A)). The balance of these currents varied across cells, with GIN neurons tending to express proportionately more I(KCa) and I(A), and YFP-16 neurons tending to express proportionately more I(1TEA) and I(10TEA). Correlations in charge densities suggested that several currents were coregulated. Variations in the kinetics and density of I(1TEA) could account for differences in repolarization rates observed both within and between cell types. These data indicate that diversity in the firing properties of GABAergic and non-GABAergic vestibular nucleus neurons arises from graded differences in the balance and kinetics of ionic currents.     

Different in vitro and in vivo tools for elucidating the human metabolism of alpha‐cathinone‐derived drugs of abuse

In vitro and in vivo experiments are widely used for studying the metabolism of new psychoactive substances (NPS). The availability of such data is required for toxicological risk assessments and development of urine screening approaches. This study investigated the in vitro metabolism of the 5 pyrrolidinophenone‐derived NPS alpha‐pyrrolidinobutyrophenone (alpha‐PBP), alpha‐pyrrolidinopentiothiophenone (alpha‐PVT), alpha‐pyrrolidinohexanophenone (alpha‐PHP), alpha‐pyrrolidinoenanthophenone (alpha‐PEP, PV8), and alpha‐pyrrolidinooctanophenone (alpha‐POP, PV9). First, they were incubated with pooled human liver microsomes (pHLM) or pooled human liver S9 fraction (pS9) for identification of the main phase I and II metabolites. All substances formed hydroxy metabolites and lactams. Longer alkyl chains resulted in keto group and carboxylic acid formation. Comparing these results with published data obtained using pHLM, primary human hepatocytes (PHH), and authentic human urine samples, PHH provided the most extensive metabolism. Second, enzyme kinetic studies showed that the initial metabolic steps were formed by cytochrome P450 isoforms (CYP) CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 resulting in pyrrolidine, thiophene or alkyl hydroxy metabolites depending on the length of the alkyl chain. The kinetic parameters indicated an increasing affinity of the CYP enzymes with increase of the length of the alkyl chain. These parameters were then used to calculate the contribution of a single CYP enzyme to the in vivo hepatic clearance. CYP2C19 and CYP2D6 were mainly involved in the case of alpha‐PBP and CYP1A2, CYP2C9 and CYP2C19 in the case of alpha‐PVT, alpha‐PHP, alpha‐PEP, and alpha‐POP.