Surgical closure of spinal cerebrospinal fluid leaks improves symptoms in patients with superficial siderosis.

BACKGROUND AND PURPOSE: Spinal cerebrospinal fluid (CSF) leaks may cause a myriad of symptoms, most common being orthostatic headache. In addition, ventral spinal CSF leaks are a possible etiology of superficial siderosis (SS), a rare condition characterized by hemosiderin deposits in the central nervous system (CNS). The classical presentation of SS involves ataxia, bilateral hearing loss, and myelopathy. Unfortunately, treatment options are scarce. This study was undertaken to evaluate whether microsurgical closure of CSF leaks can prevent further clinical deterioration or improve symptoms of SS. METHODS: This cohort study was conducted using data from a prospectively maintained database in two large spontaneous intracranial hypotension (SIH) referral centers in Germany and Switzerland of patients who meet the modified International Classification of Headache Disorders, 3rd edition criteria for SIH. Patients with spinal CSF leaks were screened for the presence of idiopathic infratentorial symmetric SS of the CNS. RESULTS: Twelve patients were included. The median latency between the onset of orthostatic headaches and symptoms attributed to SS was 9.5 years. After surgical closure of the underlying spinal CSF leak, symptoms attributed to SS improved in seven patients and remained stable in three. Patients who presented within 1 year after the onset of SS symptoms improved, but those who presented in 8-12 years did not improve. We could show a significant association between patients with spinal longitudinal extrathecal collections and SS. CONCLUSIONS: Long-standing untreated ventral spinal CSF leaks can lead to SS of the CNS, and microsurgical sealing of spinal CSF leaks might stop progression and improve symptoms in patients with SS in a time-dependent manner.

Perceptions of social media harms and potential management strategies: vaping case study.

BACKGROUND: The social media landscape is now ubiquitous in people's everyday lives. It is a space where culture, politics, economics and sociological and public health discourses occur. There is mounting evidence that e-cigarette products are being promoted and advertised on social media, a media platform particularly popular with young people. Our research aimed to understand industry professionals' perceptions of social media harms and potential management strategies using vaping as a case study. METHODS: A critical realist perspective guided reflexive thematic analysis of the qualitative in depth, semi structured interviews. Data collection occurred in January and February 2023 with 13 participants working in the areas of public health, digital media, law, governance, tobacco control and advocacy. RESULTS: Two superordinate themes emerged from the data: (1) Fathoming a complex system (social media) that contained the subordinate themes of Traversing Boundaries (crossing borders, crossing sectors) and Ungovernable (global and local landscapes, vested interests, self-regulation and opacity). (2) Addressing complexity (social media)- that contained the subordinate themes of Strengthening Institutions (global to local, policy and legislation, individuals and organisations); Defanging Industry (responsibility and transparency, moderation and algorithms, complaints); and Engaging Citizens (raising awareness, framing messaging). CONCLUSIONS: There was consensus among participants that e-cigarette related social media content can be harmful and government action is urgently needed. There was an identified need for the development of government led national-level regulatory frameworks, with government led appropriate legislation; identification of an organisation or organisations with suitable levels of regulatory power and resources to monitor, enforce and penalise noncompliant social media companies; accompanied by increased community awareness raising of harmful social media content and improved digital literacy.

Quantification of cervical spinal stenosis by automated 3D MRI segmentation of spinal cord and cerebrospinal fluid space.

DESIGN: Prospective diagnostic study. OBJECTIVES: Anatomical evaluation and graduation of the severity of spinal stenosis is essential in degenerative cervical spine disease. In clinical practice, this is subjectively categorized on cervical MRI lacking an objective and reliable classification. We implemented a fully-automated quantification of spinal canal compromise through 3D T2-weighted MRI segmentation. SETTING: Medical Center - University of Freiburg, Germany. METHODS: Evaluation of 202 participants receiving 3D T2-weighted MRI of the cervical spine. Segments C2/3 to C6/7 were analyzed for spinal cord and cerebrospinal fluid space volume through a fully-automated segmentation based on a trained deep convolutional neural network. Spinal canal narrowing was characterized by relative values, across sever segments as adapted Maximal Canal Compromise (aMCC), and within the index segment as adapted Spinal Cord Occupation Ratio (aSCOR). Additionally, all segments were subjectively categorized by three observers as "no", "relative" or "absolute" stenosis. Computed scores were applied on the subjective categorization. RESULTS: 798 (79.0%) segments were subjectively categorized as "no" stenosis, 85 (8.4%) as "relative" stenosis, and 127 (12.6%) as "absolute" stenosis. The calculated scores revealed significant differences between each category (p ≤ 0.001). Youden's Index analysis of ROC curves revealed optimal cut-offs to distinguish between "no" and "relative" stenosis for aMCC = 1.18 and aSCOR = 36.9%, and between "relative" and "absolute" stenosis for aMCC = 1.54 and aSCOR = 49.3%. CONCLUSION: The presented fully-automated segmentation algorithm provides high diagnostic accuracy and objective classification of cervical spinal stenosis. The calculated cut-offs can be used for convenient radiological quantification of the severity of spinal canal compromise in clinical routine.

Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids.

Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection.

Spinal cord motion and CSF flow in the cervical spine of 70 healthy participants.

Pulsatile spinal cord and CSF velocities related to the cardiac cycle can be depicted by phase-contrast MRI. Among patients with spontaneous intracranial hypotension, we have recently described relevant differences compared with healthy controls in segment C2/C3. The method might be a promising tool to solve clinical and diagnostic ambiguities. Therefore, it is important to understand the physiological range and the effects of clinical and anatomical parameters in healthy volunteers. Within a prospective study, 3D T2 -weighted MRI for spinal canal anatomy and cardiac-gated phase-contrast MRI adapted to CSF flow and spinal cord motion for time-resolved velocity data and derivatives were performed in 70 participants (age 20-79 years) in segments C2/C3 and C5/C6. Correlations were analyzed by multiple linear regression models; p < 0.01 was required to assume a significant impact of clinical or anatomical data quantified by the regression coefficient B. Data showed that in C2/C3, the CSF and spinal cord craniocaudal velocity ranges were 4.5 ± 0.9 and 0.55 ± 0.15 cm/s; the total displacements were 1.1 ± 0.3 and 0.07 ± 0.02 cm, respectively. The craniocaudal range of the CSF flow rate was 8.6 ± 2.4 mL/s; the CSF stroke volume was 2.1 ± 0.7 mL. In C5/C5, physiological narrowing of the spinal canal caused higher CSF velocity ranges and lower stroke volume (C5/C6 B = +1.64 cm/s, p < 0.001; B = -0.4 mL, p = 0.002, respectively). Aging correlated to lower spinal cord motion (e.g., B = -0.01 cm per 10 years of aging, p < 0.001). Increased diastolic blood pressure was associated with lower spinal cord motion and CSF flow parameters (e.g., C2/C3 CSF stroke volume B = -0.3 mL per 10 mmHg, p < 0.001). Males showed higher CSF flow and spinal cord motion (e.g., CSF stroke volume B = +0.5 mL, p < 0.001; total displacement spinal cord B = +0.016 cm, p = 0.002). We therefore propose to stratify data for age and sex and to adjust for diastolic blood pressure and segmental narrowing in future clinical studies.

Recovery and long-term outcome after neurosurgical closure of spinal CSF leaks in patients with spontaneous intracranial hypotension.

INTRODUCTION: Spontaneous intracranial hypotension due to a spinal cerebrospinal fluid leak causes orthostatic headaches and impacts quality of life. Successful closure rates are often reported, whereas data on long-term outcome are still scarce. METHODS: Between April 2020 and December 2022 surgically treated patients completed the Headache Impact Test-6 prior to surgery and at 14 days, three months, six months, and 12 months postoperatively. In addition to the Headache Impact Test-6 score, we extracted data related to orthostatic symptoms. RESULTS: Eighty patients were included. Median Headache Impact Test-6 score preoperatively was 65 (IQR 61-69), indicating severe and disabling impact of headaches. At three months headache impact significantly improved to 49 (IQR 44-58) (p < 0.001) and remained stable up to 12 months (48, IQR 40-56), indicating little to no impact of headaches on quality of life. The need to lie down "always" or "very often" was reduced from 79% to 23% three months postoperatively (p < 0.001). CONCLUSIONS: Surgical closure of spinal CSF leaks significantly improves the impact of headaches in the long term. At least three months should be expected for recovery. Despite permanent closure of the CSF-leak, a quarter of patients still have relevant long-term impairment, indicating the need for further research on its cause and possible treatment.

Automated signal intensity analysis of the spinal cord for detection of degenerative cervical myelopathy - a matched-pair MRI study.

PURPOSE: Detection of T2 hyperintensities in suspected degenerative cervical myelopathy (DCM) is done subjectively in clinical practice. To gain objective quantification for dedicated treatment, signal intensity analysis of the spinal cord is purposeful. We investigated fully automated quantification of the T2 signal intensity (T2-SI) of the spinal cord using a high-resolution MRI segmentation. METHODS: Matched-pair analysis of prospective acquired cervical 3D T2-weighted sequences of 114 symptomatic patients and 88 healthy volunteers. Cervical spinal cord was segmented automatically through a trained convolutional neuronal network with subsequent T2-SI registration slice-by-slice. Received T2-SI curves were subdivided for each cervical level from C2 to C7. Additionally, all levels were subjectively classified concerning a present T2 hyperintensity. For T2-positive levels, corresponding T2-SI curves were compared to curves of age-matched volunteers at the identical level. RESULTS: Forty-nine patients showed subjective T2 hyperintensities at any level. The corresponding T2-SI curves showed higher signal variabilities reflected by standard deviation (18.51 vs. 7.47 a.u.; p < 0.001) and range (56.09 vs. 24.34 a.u.; p < 0.001) compared to matched controls. Percentage of the range from the mean absolute T2-SI per cervical level, introduced as "T2 myelopathy index" (T2-MI), was correspondingly significantly higher in T2-positive segments (23.99% vs. 10.85%; p < 0.001). ROC analysis indicated excellent differentiation for all three parameters (AUC 0.865-0.920). CONCLUSION: This fully automated T2-SI quantification of the spinal cord revealed significantly increased signal variability for DCM patients compared to healthy volunteers. This innovative procedure and the applied parameters showed sufficient diagnostic accuracy, potentially diagnosing radiological DCM more objective to optimize treatment recommendation. TRIAL REGISTRATION: DRKS00012962 (17.01.2018) and DRKS00017351 (28.05.2019).

Tobacco companies, corporate social responsibility and the use of third-party awards: a framing analysis.

OBJECTIVE: Corporate social responsibility activities, such as third-party awards, provide an opportunity for tobacco companies (TCs) to promote themselves as socially, economically and environmentally responsible organisations. This study aimed to determine how TCs are using third-party awards to frame themselves and their core activities via company-controlled communication channels. METHODS: TC-owned media coverage promoting third-party awards was identified from company-owned media channels, including websites, reports, press releases and Twitter. Using framing theory and thematic analysis, frames and broader themes were identified using a process of inductive coding. RESULTS: TC-produced media content promoting third-party awards framed the companies as socially and environmentally responsible organisations, which excel at business and are innovative and transformative. Dominant frames identified included excellent workplace culture, championing diversity and inclusion and action on the environment. CONCLUSION: TCs are capitalising on the perceived credibility and objectivity of third-party awards using these 'honours' as a promotional strategy to justify their continuing role in society and enhance their perceived legitimacy in relation to claims of ethical and responsible behaviour. The results of this study have implications for tobacco control advocacy, as continuing to allow the promotion of these awards appears to contravene or conflict with the WHO Framework Convention on Tobacco Control.

Diffusion tensor imaging in unclear intramedullary tumor-suspected lesions allows separating tumors from inflammation.

DESIGN: Prospective diagnostic study. OBJECTIVES: Primary imaging-based diagnosis of spinal cord tumor-suspected lesions is often challenging. The identification of the definite entity is crucial for dedicated treatment and therefore reduction of morbidity. The aim of this trial was to investigate specific quantitative signal patterns to differentiate unclear intramedullary tumor-suspected lesions based on diffusion tensor imaging (DTI). SETTING: Medical Center - University of Freiburg, Germany. METHODS: Forty patients with an unclear tumor-suspected lesion of the spinal cord prospectively underwent DTI. Primary diagnosis was determined by histological or clinical work-up or remained indeterminate with follow-up. DTI metrics (FA/ADC) were evaluated at the central lesion area, lesion margin, edema, and normal spinal cord and compared between different diagnostic groups (ependymomas, other spinal cord tumors, inflammations). RESULTS: Mean DTI metrics for all spinal cord tumors (n = 18) showed significantly reduced FA and increased ADC values compared to inflammatory lesions (n = 8) at the lesion margin (p < 0.001, p = 0.001) and reduced FA at the central lesion area (p < 0.001). There were no significant differences comparing the neoplastic subgroups of ependymomas (n = 10) and other spinal cord tumors (n = 8), but remaining differences for both compared to the inflammation subgroup. We found significant higher ADC (p = 0.040) and a trend to decreased FA (p = 0.081) for ependymomas compared to inflammations at the edema. CONCLUSION: Even if distinct differentiation of ependymomas from other spinal cord neoplasms was not possible based on quantitative DTI metrics, FA and ADC were feasible to separate inflammatory lesions. This may avoid unnecessary surgery in patients with unclear intramedullary tumor-suspected lesions.

Mas-related G protein-coupled receptor X2 and its activators in dermatologic allergies.

The Mas-related G protein-coupled receptor X2 (MRGPRX2) is a multiligand receptor responding to various exogenous and endogenous stimuli. Being highly expressed on skin mast cells, MRGPRX2 triggers their degranulation and release of proinflammatory mediators, and it promotes multicellular signaling cascades, such as itch induction and transmission in sensory neurons. The expression of MRGPRX2 by skin mast cells and the levels of the MRGPRX2 agonists (eg, substance P, major basic protein, eosinophil peroxidase) are upregulated in the serum and/or skin of patients with inflammatory and pruritic skin diseases, such as chronic spontaneous urticaria or atopic dermatitis. Therefore, MRGPRX2 and its agonists might be potential biomarkers for the progression of cutaneous inflammatory diseases and the response to treatment. In addition, they may represent promising targets for prevention and treatment of signs and symptoms in patients with skin diseases or drug reactions. To assess this possibility, this review explores the role and relevance of MRGPRX2 and its activators in cutaneous inflammatory disorders and chronic pruritus.

A group of cationic amphiphilic drugs activates MRGPRX2 and induces scratching behavior in mice.

BACKGROUND: Mas gene-related G protein-coupled receptors (MRGPRs) are a G protein-coupled receptor family responsive to various exogenous and endogenous agonists, playing a fundamental role in pain and itch sensation. The primate-specific family member MRGPRX2 and its murine orthologue MRGPRB2 are expressed by mast cells mediating IgE-independent signaling and pseudoallergic drug reactions. OBJECTIVES: Our aim was to increase knowledge about the function and regulation of MRGPRX2/MRGPRB2, which is of major importance in prevention of drug hypersensitivity reactions and drug-induced pruritus. METHODS: To identify novel MRGPR (ant)agonists, we screened a library of pharmacologically active compounds by utilizing a high-throughput calcium mobilization assay. The identified hit compounds were analyzed for their pseudoallergic and pruritogenic effects in mice and human. RESULTS: We found a class of commonly used drugs activating MRGPRX2 that, to a large extent, consists of antidepressants, antiallergic drugs, and antipsychotics. Three-dimensional pharmacophore modeling revealed structural similarities of the identified agonists, classifying them as cationic amphiphilic drugs. Mast cell activation was investigated by using the 3 representatively selected antidepressants clomipramine, paroxetine, and desipramine. Indeed, we were able to show a concentration-dependent activation and MRGPRX2-dependent degranulation of the human mast cell line LAD2 (Laboratory of Allergic Diseases-2). Furthermore, clomipramine, paroxetine, and desipramine were able to induce degranulation of human skin and murine peritoneal mast cells. These substances elicited dose-dependent scratching behavior following intradermal injection into C57BL/6 mice but less so in MRGPRB2-mutant mice, as well as wheal-and-flare reactions following intradermal injections in humans. CONCLUSION: Our results contribute to the characterization of structure-activity relationships and functionality of MRGPRX2 ligands and facilitate prediction of adverse reactions such as drug-induced pruritus to prevent severe drug hypersensitivity reactions.

Motivations for use, identity and the vaper subculture: a qualitative study of the experiences of Western Australian vapers.

BACKGROUND: Vaping is a relatively new practice, and therefore its symbolic meanings and social practices are yet to be fully understood, especially within Australia where the practice is strictly regulated. This study aimed to examine vapers motivations for use, reinforcing influences, and association with the vaper subculture. METHODS: Working from a constructivist epistemology and a symbolic interaction framework, in-depth interviews were conducted with a purposive sample of 37 current (89%) and former (11%) adult vapers, 70% male, mean age of 32.5. Data was analysed via thematic analysis. RESULTS: Vapers largely started vaping to quit smoking and underwent common experiences during their initiation phase. Subsequently, vapers tended to adopt one of two dominant identities, that of the 'cloud chaser' or the 'substitute', which some users moved between during different stages of their vaping career. The social and symbolic meaning of e-cigarettes and vaping varied and involved concepts of harm reduction, addiction, pleasure, stigma and community, and for some, connection to the vaper subculture. CONCLUSIONS: Understanding the complexities of vaping, and the nuanced differences of 'cloud chasers' and 'substitute' vapers may have important implications for health communication, research and policy. E-cigarette users within this sample were not a homogeneous group and differed in their motivations for use, association with the vaper subculture and relationship with the vape community. These findings provide new insights into the socialisation process and subsequent identity adoption of vapers within the unique regulatory environment of Western Australia.

Lysophosphatidic acid activates satellite glia cells and Schwann cells.

Pruritus is a common and disabling symptom in patients with hepatobiliary disorders, particularly in those with cholestatic features. Serum levels of lysophosphatidic acid (LPA) and its forming enzyme autotaxin were increased in patients suffering from hepatic pruritus, correlated with itch severity and response to treatment. Here we show that in a culture of dorsal root ganglia LPA 18:1 surprisingly activated a large fraction of satellite glia cells, and responses to LPA 18:1 correlated inversely with responses to neuronal expressed transient receptor potential channels. LPA 18:1 caused only a marginal activation of heterologously expressed TRPV1, and responses in dorsal root ganglion cultures from TRPV1-deficient mice were similar to controls. LPA 18:1 desensitized subsequent responsiveness to chloroquine and TGR5 agonist INT-777. The LPA 18:1-induced increase in cytoplasmatic calcium stems from the endoplasmatic reticulum. LPA receptor expression in dorsal root ganglia and Schwann cells, LPAR1 immunohistochemistry, and pharmacological results indicate a signaling pathway through LPA receptor 1. Peripheral rat Schwann cells, which are of glial lineage as the satellite glia cells, were also responsive to LPA 18:1. Summarizing, LPA 18:1 primarily activates rather glial cells than neurons, which may subsequently modulate neuronal responsiveness and sensory sensations such as itch and pain.

ADSCs and adipocytes are the main producers in the autotaxin-lysophosphatidic acid axis of breast cancer and healthy mammary tissue in vitro.

BACKGROUND: Breast cancer is the most common malignancy in women affecting one out of eight females throughout their lives. Autotaxin (ATX) is upregulated in breast cancer which results in increased lysophosphatidic acid (LPA) formation within the tumor. This study's aim was to identify the role of different mammary cell populations within the ATX-LPA axis. METHODS: Epithelial-cell-adhesion-molecule-positive (EpCAM) and -negative cells from breast tumors, adipose-derived stem cells (ADSCs) of tumor-adjacent and tumor-distant mammary fat were isolated and compared to healthy ADSCs, mammary epithelial cells (HMECs), and mesenchymal cells (MES) of healthy mammary tissue (n = 4 each) and further to well-established breast (cancer) cell lines. RESULTS: mRNA expression analyses revealed that ADSCs and MES largely expressed LPA receptor 1 (LPAR1) while epithelial cells mainly expressed LPAR6. LPA 18:1 activated all the cell populations and cell lines by rise in cytosolic free calcium concentrations. MES and ADSCs expressed ATX whereas epithelial cells did not. ADSCs revealed the highest expression in ATX with a significant decline after adipogenic differentiation in healthy ADSCs, whereas ATX expression increased in ADSCs from tumor patients. Breast (cancer) cell lines did not express ATX. Transmigration of MES was stimulated by LPA whereas an inhibitory effect was observed in epithelial cells with no differences between tumors and healthy cells. Triple-negative breast cancer (TNBC) cell lines were also stimulated and the transmigration partly inhibited using the LPA receptor antagonist Ki16425. CONCLUSIONS: We here show that each mammary cell population plays a different role in the ATX-LPA axis with ADSCs and adipocytes being the main source of ATX in tumor patients in our experimental setting. Inhibitors of this axis may therefore present a valuable target for pharmacological therapies.

In cervical spondylotic myelopathy spinal cord motion is focally increased at the level of stenosis: a controlled cross-sectional study.

STUDY DESIGN: Level-, age-, and gender-matched controlled cross-sectional cohort study. OBJECTIVES: To investigate alterations of spinal cord (SC) motion within cervical spondylotic myelopathy (CSM) across the cervical spinal segments and its relation to cerebrospinal fluid (CSF)-flow, anatomic conditions, and clinical parameters. SETTING: University Hospital Balgrist, Zurich, Switzerland. METHODS: Overall, 12 patients suffering from CSM at level C5 and 12 controls underwent cardiac-gated 2D phase-contrast-MRI at level C2 and C5 and standard MRI sequences. Parameters of interest: Velocity measurements of SC and CSF (area under the curve = total displacement (normalization for duration of the heart cycle), total displacement ratio (C5/C2; intraindividual normalization for confounders)), spinal canal diameters, clinical motor- and sensory scores, and performance measures. RESULTS: Interrater reliability was excellent for SC motion at both levels and for CSF flow at C2, but not reliable for CSF flow at C5. Within controls, SC motion at C2 positively correlated with SC motion at C5 (p = 0.000); this correlation diminished in patients (p = 0.860). SC total displacement ratio was significantly increased in patients (p = 0.029) and correlated with clinical impairment (p = 0.017). Morphometric measures of the extent of stenosis were not related to SC motion or clinical symptoms. CONCLUSION: The findings revealed physiological interactions of CSF flow and SC motion across the cervical spine in healthy controls while being diminished in CSM patients. Findings of focally increased SC motion at the level of stenosis were related to clinical impairment and might be promising as a diagnostic and prognostic marker in CSM. SPONSORSHIP: CRPP Neurorehab of the University of Zurich, Switzerland.

Switch to aflibercept or ranibizumab after initial treatment with bevacizumab in eyes with neovascular AMD.

BACKGROUND: To evaluate changes in central macular thickness (CMT) and visual outcome in patients with neovascular age-related macular degeneration (AMD) treated initially with bevacizumab and subsequently switched to either aflibercept or ranibizumab. METHODS: Observational clinical study was performed. We measured the structural outcome (CMT on SD-OCT; µm) and the visual outcome (best corrected visual acuity (BCVA); logMAR), as follows: before treatment (at baseline), following bevacizumab treatment (switch follow-up) and after switching from bevacizumab to aflibercept- or ranibizumab treatment (final follow-up, AG/, RG). RESULTS: From a total of 96 eyes treated with intravitreal injections of bevacizumab (10.5 ± 7.6 (mean ± SD)), 58 eyes switched to aflibercept (6.5 ± 3.9; AG) and 38 eyes switched to ranibizumab (7.1 ± 5.3; RG) (≥ 3 injections, each). In addition, these eyes were compared to 37 eyes under bevacizumab monotherapy. PRIMARY OUTCOME: In the AG, the CMT decreased slightly from 430 ± 220 µm at baseline to 419 ± 212 µm at switch follow-up (p = 0.86), but decreased significantly to 318 ± 159 µm at final follow-up, AG (p < 0.0001). In the ranibizumab group (RG), the CMT increased from 396 ± 174 µm at baseline to 499 ± 333 µm at switch follow-up (p = 0.012), but decreased significantly to 394 ± 202 µm at final follow-up, RG (p = 0.007). Secondary outcome: In the AG, the mean BCVA worsened from logMAR 0.57 ± 0.33 at baseline to 0.63 ± 0.30 at switch follow-up and improved slightly to 0.53 ± 0.71 at final follow-up, AG (p = 0.46). In the RG, mean BCVA worsened from 0.57 ± 0.28 at baseline to 0.64 ± 0.31 at switch follow-up and improved slightly to 0.60 ± 0.36 at final follow-up, RG (p = 0.64). CONCLUSION: Switching from bevacizumab to either aflibercept, or ranibizumab, has a strong anatomical effect in eyes with neovascular AMD. Nevertheless, even if the switch to aflibercept shows a minimal functional benefit over that to ranibizumab, visual prognosis remains limited.

Human CNNM2 is not a Mg(2+) transporter per se.

CNNM2 is associated with the regulation of serum Mg concentration, and when mutated, with severe familial hypomagnesemia. The function and cellular localization of CNNM2 and its isomorphs (Iso) remain controversial. The objective of this work was to examine the following: (1) the transcription-responsiveness of CNNM2 to Mg starvation, (2) the cellular localization of Iso1 and Iso2, (3) the ability of Iso1 and Iso2 to transport Mg(2+), and (4) the complex-forming ability and spectra of potential interactors of Iso1 and Iso2. The five main findings are as follows. (1) Mg-starvation induces CNNM2 overexpression that is markedly higher in JVM-13 cells (lymphoblasts) compared with Jurkat cells (T-lymphocytes). (2) Iso1 and Iso2 localize throughout various subcellular compartments in transgenic HEK293 cells overexpressing Iso1 or Iso2. (3) Iso1 and Iso2 do not transport Mg(2+) in an electrogenic or electroneutral mode in transgenic HEK293 cells overexpressing Iso1 or Iso2. (4) Both Iso1 and Iso2 form complexes of a higher molecular order. (5) The spectrum of potential interactors of Iso1 is ten times smaller than that of Iso2. We conclude that sensitivity of CNNM2 expression to extracellular Mg(2+) depletion depends on cell type. Iso1 and Iso2 exhibit a dispersed pattern of cellular distribution; thus, they are not exclusively integral to the cytoplasmic membrane. Iso1 and Iso2 are not Mg(2+) transporters per se. Both isomorphs form protein complexes, and divergent spectra of potential interactors of Iso1 and Iso2 indicate that each isomorph has a distinctive function. CNNM2 is therefore the first ever identified Mg(2+) homeostatic factor without being a Mg(2+) transporter per se.

Gendered Authorship and Demographic Research: An Analysis of 50 Years of Demography.

Demography, the official journal of the Population Association of America, has been given the highest rating among demographic journals by the Social Sciences Citation Index (SSCI). Our aim here is to investigate the development of research subfields and female authorship in Demography over the last 50 years. We find that female authorship in Demography has risen considerably since the 1980s and that currently a woman is about as likely as a man to be the sole or the first author of a paper published in the journal. However, we find some differences by subfield. Women seem to be overrepresented in the "family and household" research subfield but underrepresented in the "mortality and health" and "data and methods" categories.

Clinical features, cytology and bacterial culture results in dogs with and without cheilitis and comparison of three sampling techniques.

BACKGROUND: Cheilitis is a common presentation in dogs associated with a variety of skin diseases and often complicated by microbial infections. OBJECTIVES: To describe and compare clinical and cytological features and bacterial culture results from the lower lips of dogs with cheilitis (as compared to healthy controls), and to evaluate three cytology sampling techniques for their abilities to differentiate between the groups. ANIMALS: Fifty six dogs with cheilitis and 54 controls. METHODS: Anatomy and clinical signs of the lower lip were recorded. Cytology samples taken by tape strip, direct impression and swabs rolled over skin were scored semiquantitatively for microorganisms, inflammatory cells and keratinocytes. Cytology scores were correlated with semiquantitative bacterial culture scores. RESULTS: Pure breeds, frequency of lip folds and all cytology scores except keratinocytes were higher in dogs with cheilitis than in controls, but a substantial overlap was seen in all microorganisms between the groups. Hypersensitivity disorders were diagnosed in 40 of 56 dogs with cheilitis. The tape strip technique yielded the greatest differences between groups. Bacterial growth was reported in 100% of dogs with cheilitis and in 93% of the controls. Pathogens such as Staphylococcus pseudintermedius, Escherichia coli and Pseudomonas spp were found more frequently in dogs with cheilitis. Cytology and bacterial culture were poorly correlated. CONCLUSION: Cheilitis was associated with primary hypersensitivity disorders and the presence of a lip fold was a predisposing factor. Results of aerobic culture were similar to prior studies on pyoderma of other body sites, except for higher rates of Pseudomonas spp. isolation.

Spinal cord stimulation of the dorsal root ganglion for groin pain-a retrospective review.

BACKGROUND: Spinal cord stimulation (SCS) is a standard treatment option for chronic neuropathic pain. However, some anatomical pain distributions are known to be difficult to cover with traditional SCS-induced paresthesias and/or may also induce additional, unwanted stimulation. We present the results from a retrospective review of data from patients with groin pain of various etiologies treated using neuromodulation of the dorsal root ganglion (DRG). METHODS: Data from 29 patients with neuropathic groin pain were reviewed. Patients underwent trial therapy where specifically designed leads were implanted at the target DRGs between T12 and L4. Patients who had a successful trial (> 50% improvement) received the fully implantable neuromodulation system. Pain scores were captured on a visual analog scale (VAS) at baseline and at regular follow-up visits. RESULTS: Twenty-five patients (86.2%) received fully implantable neurostimulators, and the average follow-up period was 27.8 ± 4.3 (standard error of the mean, SEM) weeks. The average pain reduction was 71.4 ± 5.6%, and 82.6% (19/23) of patients experienced a > 50% reduction in their pain at the latest follow-up. Individual cases showed improvement with a variety of etiologies and pain distributions; a subanalysis of postherniorrhaphy cohort also showed significant improvement. CONCLUSIONS: Early findings suggest that neuromodulation of the DRG may be an effective treatment for chronic neuropathic pain conditions in the groin region. This technique offers a useful alternative for pain conditions that do not always respond optimally to traditional SCS therapy. Neuromodulation of the DRG provided excellent cross-dermatomal paresthesia coverage, even in cases with patients with discrete pain areas. The therapy can be specific, sustained, and independent of body position.