I.V. MIDAZOLAM AS AN INDUCTION AGENT FOR ANAESTHESIA: A STUDY IN VOLUNTEERS

The central nervous and cardiovascular effects of midazolam 0.15 mg kg−1 were studied in 20 healthy, unpremedicated volunteers (10 male and 10 female). No important side-effects were noted and the venous tolerance to midazolam was excellent. Three minutes after injection mean systolic arterial pressure decreased from 121±(SEM) 2 mm Hg to 115±(SEM) 2 mm Hg and diastolic pressure from 78±2 to 70±2 mm Hg (P <0.05), and these effects persisted for at least 20 mm. Heart rate increased from 77±4 beat mm−1 to 90±3 and 88±3 beat mm−1 1 and 3 mm after the injection (P <0.05). Anterograde amnesia (40±3 min duration) and drowsiness (lasting 128±23 mm) were observed in all subjects. Loss of the eyelash reflex and apnoea were observed more often in the male group than in the female subjects. Midazolam 0.15 mg kg−1 was not sufficient to induce anaesthesia reliably in healthy unpretnedicated volunteer

CLINICAL EVALUATION OF A SPECIFIC BENZODIAZEPINE ANTAGONIST (RO 15-1788): Studies in Elderly Patients after Regional Anaesthesia under Benzodiazepine Sedation

The efficacy, usefulness and side effects of RO 15-1788 (RO), a specific benzodiazepine (BZD) antagonist, have been evaluated. Sixty-two patients (ASA l-lll, mean age 72±9 yr) scheduled for urological surgery under regional anaesthesia and BZD sedation received placebo or RO in a randomized, double-blind fashion at the end of the procedure, folio wing sedation with midazolam. When compared with placebo, RO improved alertness and collaboration for 15 min, and suppressed anterograde amnesia for 60 min. No major side effect was noted, although five patients became anxious after administration of RO. Two cases of a paradoxical reaction to midazolam were treated successfully by R

Aeromagnetic measurements in the Cascade Range and Modoc Plateau of northern California. Report on work done from June 1, 1980-November 30, 1980

Aeromagnetic measurements made along flightlines oriented east-west and spaced at 1.6-km intervals and along lines oriented north-south and spaced at 8-km intervals, over approximately 30,000 square km of northern California, exhibit crossing errors of less than 5 nanoTeslas. The measurements show short-wavelength magnetic anomalies associated with near-surface volcanics over and east of Lassen Peak and over and north of Mt. Shasta and the Medicine Lake Highlands, longer wavelength anomalies over the Modoc Plateau, and very long wavelength anomalies over the northernmost part of the Great Valley and the easternmost metamorphic rocks of the Klamath Mountains. Anomaly patterns exhibit northwest-southeast trends over the Modoc Plateau and a marked change in character at the juncture of the plateau and the Klamath Mountain and Great Valley complexes

Asymptotic solvability of an imaginary cubic oscillator with spikes

For the PT symmetric potential of Dorey, Dunning and Tateo we show that in the large angular momentum (i.e., strongly spiked) limit the low-lying eigenstates of this popular non-Hermitian problem coincide with the shifted Hermitian harmonic oscillators calculated at the zero angular momentum. This type of an approximate Hermitization is valid in all the domain where the spectrum of energies remains real. It proves very efficient numerically. The construction is asymmetric with respect to the sign of the subdominant square-root spike, and exhibits a discontinuity at the point where the PT symmetric regularization vanishes.Comment: 20 pages and 2 figure

Heterogeneous clinical spectrum of DNAJC12-deficient hyperphenylalaninemia:From attention deficit to severe dystonia and intellectual disability

BACKGROUND: Autosomal recessive mutations in DNAJC12, encoding a cochaperone of HSP70 with hitherto unknown function, were recently described to lead to hyperphenylalaninemia, central monoamine neurotransmitter (dopamine and serotonin) deficiency, dystonia and intellectual disability in six subjects affected by homozygous variants. OBJECTIVE: Patients exhibiting hyperphenylalaninemia in whom deficiencies in hepatic phenylalanine hydroxylase and tetrahydrobiopterin cofactor metabolism had been excluded were subsequently analysed for DNAJC12 variants. METHODS: To analyse DNAJC12, genomic DNA from peripheral blood (Sanger sequencing), as well as quantitative messenger RNA (Real Time Quantitative Polymerase Chain Reaction (RT-qPCR)) and protein expression (Western blot) from primary skin fibroblasts were performed. RESULTS: We describe five additional patients from three unrelated families with homozygosity/compound heterozygosity in DNAJC12 with three novel variants: c.85delC/p.Gln29Lysfs*38, c.596G>T/p.*199Leuext*42 and c.214C>T/p.(Arg72*). In contrast to previously reported DNAJC12-deficient patients, all five cases showed a very mild neurological phenotype. In two subjects, cerebrospinal fluid and primary skin fibroblasts were analysed showing similarly low 5-hydroxyindolacetic acid and homovanillic acid concentrations but more reduced expressions of mRNA and DNAJC12 compared with previously described patients. All patients responded to tetrahydrobiopterin challenge by lowering blood phenylalanine levels. CONCLUSIONS: DNAJC12 deficiency appears to result in a more heterogeneous neurological phenotype than originally described. While early identification and institution of treatment with tetrahydrobiopterin and neurotransmitter precursors is crucial to ensure optimal neurological outcome in DNAJC12-deficient patients with a severe phenotype, optimal treatment for patients with a milder phenotype remains to be defined

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Staff training to improve participant recruitment into surgical randomised controlled trials : A feasibility study within a trial (SWAT) across four host trials simultaneously

The PROMoting THE Use of SWATs (PROMETHEUS) programme was funded by the Medical Research Council (MRC) [grant number MR/R013748/1]. The DISC host trial is funded by the Health Technology Assessment Programme (Grant Ref: 15/102/04). IntAct is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership (Grant Ref: 14/150/62). The EME Programme is funded by the MRC and NIHR, with contributions from the CSO in Scotland and Health and Care Research Wales and the HSC R&D Division, Public Health Agency in Northern Ireland. PROFHER-2 is funded by the Health Technology Assessment Programme (Grant Ref: 16/73/03). START: REACTS is funded by the NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 16/61/18. The development of the training intervention was funded by the MRC Network of Hubs for Trials Methodology Research (MR/L004933/1- R53) and supported by the MRC ConDuCT-II Hub (Collaboration and innovation for Difficult and Complex randomized controlled Trials In Invasive procedures - MR/K025643/1). The online version of the training intervention was funded by the NIHR and is hosted on the NIHR Learn platform (https://learn.nihr.ac.uk/course/view.php?id=385). It is based on the face-to face GRANULE training course funded by the Bowel Disease Research Foundation in collaboration with the University of Birmingham, University of Bristol and former MRC ConDuCT-II Hub. This work was part-funded by the Wellcome Trust [ref: 204829] through the Centre for Future Health (CFH) at the University of York. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the MRC or the Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.Peer reviewedPublisher PD

Regional differences in the quality of maternal and neonatal care during the COVID-19 pandemic in Portugal: Results from the IMAgiNE EURO study

Objective: To compare women's perspectives on the quality of maternal and newborn care (QMNC) around the time of childbirth across Nomenclature of Territorial Units for Statistics 2 (NUTS-II) regions in Portugal during the COVID-19 pandemic. Methods: Women participating in the cross-sectional IMAgiNE EURO study who gave birth in Portugal from March 1, 2020, to October 28, 2021, completed a structured questionnaire with 40 key WHO standards-based quality measures. Four domains of QMNC were assessed: (1) provision of care; (2) experience of care; (3) availability of human and physical resources; and (4) reorganizational changes due to the COVID-19 pandemic. Frequencies for each quality measure within each QMNC domain were computed overall and by region. Results: Out of 1845 participants, one-third (33.7%) had a cesarean. Examples of high-quality care included: low frequencies of lack of early breastfeeding and rooming-in (8.0% and 7.7%, respectively) and informal payment (0.7%); adequate staff professionalism (94.6%); adequate room comfort and equipment (95.2%). However, substandard practices with large heterogeneity across regions were also reported. Among women who experienced labor, the percentage of instrumental vaginal births ranged from 22.3% in the Algarve to 33.5% in Center; among these, fundal pressure ranged from 34.8% in Lisbon to 66.7% in Center. Episiotomy was performed in 39.3% of noninstrumental vaginal births with variations between 31.8% in the North to 59.8% in Center. One in four women reported inadequate breastfeeding support (26.1%, ranging from 19.4% in Algarve to 31.5% in Lisbon). One in five reported no exclusive breastfeeding at discharge (22.1%; 19.5% in Lisbon to 28.2% in Algarve). Conclusion: Urgent actions are needed to harmonize QMNC and reduce inequities across regions in Portugal. © 2022 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.Funding text 1: This work was supported by the Ministry of Health, Rome - Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste - Italy. This study was supported by Portuguese fundings through FCT - Fundação para a Ciência e a Tecnologia, IP, in the scope of the projects EPIUnit - UIDB/04750/2020, ITR - LA/P/0064/2020, and HEILab - UIDB/05380/2020, and by the European Social Fund (ESF) and FCT (SFRH/BPD/117597/2016; RC postdoctoral fellowship). We are grateful to the women who dedicated their time to complete the survey, to Associação Portuguesa pelos Direitos da Mulher na Gravidez e Parto (APDMGP) for support with survey dissemination and to nurse Louise Semião for assistance provided in back-translation of the questionnaires. Special thanks to the IMAgiNE EURO study group for their contribution to the development of this project and support for this manuscript.; Funding text 2: This work was supported by the Ministry of Health, Rome ‐ Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste ‐ Italy. This study was supported by Portuguese fundings through FCT ‐ Fundação para a Ciência e a Tecnologia, IP, in the scope of the projects EPIUnit ‐ UIDB/04750/2020, ITR ‐ LA/P/0064/2020, and HEILab ‐ UIDB/05380/2020, and by the European Social Fund (ESF) and FCT (SFRH/BPD/117597/2016; RC postdoctoral fellowship). We are grateful to the women who dedicated their time to complete the survey, to Associação Portuguesa pelos Direitos da Mulher na Gravidez e Parto (APDMGP) for support with survey dissemination and to nurse Louise Semião for assistance provided in back‐translation of the questionnaires. Special thanks to the IMAgiNE EURO study group for their contribution to the development of this project and support for this manuscript. ; Funding text 3: IMAgiNE EURO project was supported by the Ministry of Health, Rome ‐ Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste ‐ Italy. This study was supported by Fundação para a Ciência e a Tecnologia; European Social Fund (ESF) Funding informatio