Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats

Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.Peer reviewe

Estettävissä olevat kuolemat sairaaloissa - valtakunnassa kaikki hyvin?

Sairaalassa tapahtuneiden kuolemien systemaattinen selvittely on Suomessa jäänyt liian vähälle huomiolle. Terveydenhuollon vakavimmasta haittatapahtumasta voidaan – ja pitää – ottaa opiksi

Mitä vapaaehtoiset vaaratapahtumailmoitukset kertovat?

VertaisarvioituLÄHTÖKOHDAT Yli 300 sosiaali- ja terveydenhuollon organisaatiota käyttää vapaaehtoista vaaratapahtumien HaiPro-raportointijärjestelmää. Ilmoituksia on tehty yli miljoona. MENETELMÄT Analysoimme tilastollisesti valtaosan ilmoituksista, yhteensä 847 492. TULOKSET Ilmoitusten vuotuinen määrä on kasvussa. Kolmannes koski läheltä piti -tilanteita. Potilaaseen kohdistuneet haitat olivat useimmiten korkeintaan lieviä. Yleisimmin ilmoitukset koskivat lääke- ja nestehoitoa, tapaturmia tai tiedonkulkua. Potilaille oli kerrottu haitoista lähes aina. Lääkärit ilmoittivat vain 2 % tapauksista, ja ilmoituksissa painottuivat vakavat tapahtumat. Kehittämistoimenpiteitä esitettiin harvoin. PÄÄTELMÄT Lääkärien ilmoitusaktiivisuus oli heikko. Syynä lienee huomion painottuminen lääketieteeseen ja mestari-kisällimallin mukaiseen henkilökohtaiseen ohjaukseen enemmän kuin prosesseihin. Tämä ei yleensä johda moniammatilliseen oppimiseen.Peer reviewe

Systemic hypertonic saline enhances glymphatic spinal cord delivery of lumbar intrathecal morphine

The blood-brain barrier significantly limits effective drug delivery to central nervous system (CNS) targets. The recently characterized glymphatic system offers a perivascular highway for intrathecally (i.t.) administered drugs to reach deep brain structures. Although periarterial cerebrospinal fluid (CSF) influx and concomitant brain drug delivery can be enhanced by pharmacological or hyperosmotic interventions, their effects on drug delivery to the spinal cord, an important target for many drugs, have not been addressed. Hence, we studied in rats whether enhancement of periarterial flow by systemic hypertonic solution might be utilized to enhance spinal delivery and efficacy of i.t. morphine. We also studied whether the hyperosmolar intervention affects brain or cerebrospinal fluid drug concentrations after systemic administration. Periarterial CSF influx was enhanced by intraperitoneal injection of hypertonic saline (HTS, 5.8%, 20 ml/kg, 40 mOsm/kg). The antinociceptive effects of morphine were characterized, using tail flick, hot plate and paw pressure tests. Drug concentrations in serum, tissue and microdialysis samples were determined by liquid chromatography-tandem mass spectrometry. Compared with isotonic solution, HTS increased concentrations of spinal i.t. administered morphine by 240% at the administration level (T13-L1) at 60 min and increased the antinociceptive effect of morphine in tail flick, hot plate, and paw pressure tests. HTS also independently increased hot plate and paw pressure latencies but had no effect in the tail flick test. HTS transiently increased the penetration of intravenous morphine into the lateral ventricle, but not into the hippocampus. In conclusion, acute systemic hyperosmolality is a promising intervention for enhanced spinal delivery of i.t. administered morphine. The relevance of this intervention should be expanded to other i.t. drugs and brought to clinical trials.Peer reviewe

A digital waveguide-based approach for Clavinet modeling and synthesis

The Clavinet is an electromechanical musical instrument produced in the mid-twentieth century. As is the case for other vintage instruments, it is subject to aging and requires great effort to be maintained or restored. This paper reports analyses conducted on a Hohner Clavinet D6 and proposes a computational model to faithfully reproduce the Clavinet sound in real time, from tone generation to the emulation of the electronic components. The string excitation signal model is physically inspired and represents a cheap solution in terms of both computational resources and especially memory requirements (compared, e.g., to sample playback systems). Pickups and amplifier models have been implemented which enhance the natural character of the sound with respect to previous work. A model has been implemented on a real-time software platform, Pure Data, capable of a 10-voice polyphony with low latency on an embedded device. Finally, subjective listening tests conducted using the current model are compared to previous tests showing slightly improved results

Quality of life and neck pain in nurses

Objectives: To investigate the association between neck pain and psychological stress in nurses. Material and Methods: Nurses from the Avon Orthopaedic Centre completed 2 questionnaires: the Short Form-36 (SF-36) and 1 exploring neck pain and associated psychological stress. Results: Thirty four nurses entered the study (68% response). Twelve (35.3%) had current neck pain, 13 (38.2%) reported neck pain within the past year and 9 (26.5%) had no neck pain. Subjects with current neck pain had significantly lower mental health (47.1 vs. 70.4; p = 0.002), physical health (60.8 vs. 76.8; p = 0.010) and overall SF-36 scores (56.8 vs. 74.9; p = 0.003). Five (41.7%) subjects with current neck pain and 5 (38.5%) subjects with neck pain in the previous year attributed it to psychological stress. Conclusions: Over 1/3 of nurses have symptomatic neck pain and significantly lower mental and physical health scores. Managing psychological stress may reduce neck pain, leading to improved quality of life for nurses, financial benefits for the NHS, and improved patient care

Motor dysfunction as a primary symptom predicts poor outcome : multicenter study of glioma symptoms

Background and objectives: The objectives of this study were to investigate the prognostic value of primary symptoms and leading symptoms in adult patients with diffuse infiltrating glioma and to provide a clinical perspective for evaluating survival. Methods: This study included a retrospective cohort from two tertiary university hospitals (n = 604, 2006–2013, Tampere University Hospital and Turku University Hospital) and a prospective cohort (n = 156, 2014–2018, Tampere University Hospital). Preoperative symptoms were divided into primary and leading symptoms. Results were validated with the newer WHO 2021 classification criteria. Results: The most common primary symptoms were epileptic seizure (30.8% retrospective, 28.2% prospective), cognitive disorder (13.2% retrospective, 16.0% prospective), headache (8.6% retrospective, 12.8% prospective), and motor paresis (7.0% retrospective, 7.1% prospective). Symptoms that predicted better survival were epileptic seizure and visual or other sense-affecting symptom in the retrospective cohort and epileptic seizure and headache in the prospective cohort. Predictors of poor survival were cognitive disorder, motor dysfunction, sensory symptom, tumor hemorrhage, speech disorder and dizziness in the retrospective cohort and cognitive disorder, motor dysfunction, sensory symptom, and dizziness in the prospective cohort. Motor dysfunction served as an independent predictor of survival in a multivariate model (OR = 1.636). Conclusion: Primary and leading symptoms in diffuse gliomas are associated with prognoses in retrospective and prospective settings. Motor paresis was an independent prognostic factor for poor survival in multivariate analysis for grade 2-4 diffuse gliomas, especially in glioblastomas.Peer reviewe