Effects of diazepam on hippocampal blood flow in people at clinical high risk for psychosis.

Elevated hippocampal perfusion has been observed in people at clinical high risk for psychosis (CHR-P). Preclinical evidence suggests that hippocampal hyperactivity is central to the pathophysiology of psychosis, and that peripubertal treatment with diazepam can prevent the development of psychosis-relevant phenotypes. The present experimental medicine study examined whether diazepam can normalize hippocampal perfusion in CHR-P individuals. Using a randomized, double-blind, placebo-controlled, crossover design, 24 CHR-P individuals were assessed with magnetic resonance imaging (MRI) on two occasions, once following a single oral dose of diazepam (5 mg) and once following placebo. Regional cerebral blood flow (rCBF) was measured using 3D pseudo-continuous arterial spin labeling and sampled in native space using participant-specific hippocampus and subfield masks (CA1, subiculum, CA4/dentate gyrus). Twenty-two healthy controls (HC) were scanned using the same MRI acquisition sequence, but without administration of diazepam or placebo. Mixed-design ANCOVAs and linear mixed-effects models were used to examine the effects of group (CHR-P placebo/diazepam vs. HC) and condition (CHR-P diazepam vs. placebo) on rCBF in the hippocampus as a whole and by subfield. Under the placebo condition, CHR-P individuals (mean [±SD] age: 24.1 [±4.8] years, 15 F) showed significantly elevated rCBF compared to HC (mean [±SD] age: 26.5 [±5.1] years, 11 F) in the hippocampus (F(1,41) = 24.7, pFDR < 0.001) and across its subfields (all pFDR < 0.001). Following diazepam, rCBF in the hippocampus (and subfields, all pFDR < 0.001) was significantly reduced (t(69) = -5.1, pFDR < 0.001) and normalized to HC levels (F(1,41) = 0.4, pFDR = 0.204). In conclusion, diazepam normalized hippocampal hyperperfusion in CHR-P individuals, consistent with evidence implicating medial temporal GABAergic dysfunction in increased vulnerability for psychosis.

The prevalence of premenstrual dysphoric disorder: Systematic review and meta-analysis.

BACKGROUND: Premenstrual dysphoric disorder is characterised by symptoms confined to the premenstrual phase of the menstrual cycle. Confirmed diagnosis requires prospective monitoring of symptoms over two cycles, otherwise the diagnosis is provisional. We aimed to measure the point prevalence of premenstrual dysphoric disorder. METHODS: We searched for studies of prevalence using MEDLINE, EMBASE, PsycINFO and PubMed. For each study, the total sample size and number of cases were extracted. The prevalence across studies was calculated using random effects meta-analysis with a generalised linear mixed model. Potential sources of heterogeneity were explored by meta-regression and subgroup analyses. Pre-registration was with PROSPERO (CRD42021249249). RESULTS: 44 studies with 48 independent samples met inclusion criteria, consisting of 50,659 participants. The pooled prevalence was 3.2 % (95 % confidence intervals: 1.7 %-5.9 %) for confirmed and 7.7 % (95 % confidence intervals: 5.3 %-11.0 %) for provisional diagnosis. There was high heterogeneity across all studies (I2 = 99 %). Sources of heterogeneity identified by meta-regression were continent of sample (p < 0.0001), type of sample (community-based, university, high school) (p = 0.007), risk of bias (p = 0.009), and method of diagnosis (p = 0.017). Restricting the analysis to community-based samples using confirmed diagnosis resulted in a prevalence of 1.6 % (95 % confidence intervals: 1.0 %-2.5 %), with low heterogeneity (I2 = 26 %). LIMITATIONS: A small number of included studies used full DSM criteria in community settings. CONCLUSIONS: The point prevalence of premenstrual dysphoric disorder using confirmed diagnosis is lower compared with provisional diagnosis. Studies relying on provisional diagnosis are likely to produce artificially high prevalence rates.

3D magnetic resonance fingerprinting on a low-field 50 mT point-of-care system prototype: evaluation of muscle and lipid relaxation time mapping and comparison with standard techniques.

OBJECTIVE: To implement magnetic resonance fingerprinting (MRF) on a permanent magnet 50 mT low-field system deployable as a future point-of-care (POC) unit and explore the quality of the parameter maps. MATERIALS AND METHODS: 3D MRF was implemented on a custom-built Halbach array using a slab-selective spoiled steady-state free precession sequence with 3D Cartesian readout. Undersampled scans were acquired with different MRF flip angle patterns and reconstructed using matrix completion and matched to the simulated dictionary, taking excitation profile and coil ringing into account. MRF relaxation times were compared to that of inversion recovery (IR) and multi-echo spin echo (MESE) experiments in phantom and in vivo. Furthermore, B0 inhomogeneities were encoded in the MRF sequence using an alternating TE pattern, and the estimated map was used to correct for image distortions in the MRF images using a model-based reconstruction. RESULTS: Phantom relaxation times measured with an optimized MRF sequence for low field were in better agreement with reference techniques than for a standard MRF sequence. In vivo muscle relaxation times measured with MRF were longer than those obtained with an IR sequence (T1: 182 ± 21.5 vs 168 ± 9.89 ms) and with an MESE sequence (T2: 69.8 ± 19.7 vs 46.1 ± 9.65 ms). In vivo lipid MRF relaxation times were also longer compared with IR (T1: 165 ± 15.1 ms vs 127 ± 8.28 ms) and with MESE (T2: 160 ± 15.0 ms vs 124 ± 4.27 ms). Integrated ΔB0 estimation and correction resulted in parameter maps with reduced distortions. DISCUSSION: It is possible to measure volumetric relaxation times with MRF at 2.5 × 2.5 × 3.0 mm3 resolution in a 13 min scan time on a 50 mT permanent magnet system. The measured MRF relaxation times are longer compared to those measured with reference techniques, especially for T2. This discrepancy can potentially be addressed by hardware, reconstruction and sequence design, but long-term reproducibility needs to be further improved.

Tackling SNR at low-field: a review of hardware approaches for point-of-care systems.

OBJECTIVE: To review the major hardware components of low-field point-of-care MRI systems which affect the overall sensitivity. METHODS: Designs for the following components are reviewed and analyzed: magnet, RF coils, transmit/receive switches, preamplifiers, data acquisition system, and methods for grounding and mitigating electromagnetic interference. RESULTS: High homogeneity magnets can be produced in a variety of different designs including C- and H-shaped as well as Halbach arrays. Using Litz wire for RF coil designs enables unloaded Q values of ~ 400 to be reached, with body loss representing about 35% of the total system resistance. There are a number of different schemes to tackle issues arising from the low coil bandwidth with respect to the imaging bandwidth. Finally, the effects of good RF shielding, proper electrical grounding, and effective electromagnetic interference reduction can lead to substantial increases in image signal-to-noise ratio. DISCUSSION: There are many different magnet and RF coil designs in the literature, and to enable meaningful comparisons and optimizations to be performed it would be very helpful to determine a standardized set of sensitivity measures, irrespective of design.

Systematic review of the association between adverse life events and the onset and relapse of postpartum psychosis.

Postpartum psychosis is defined as a psychotic episode occurring within 4 to 6 weeks of childbirth. While there is robust evidence that adverse life events are associated with the onset and relapse of psychosis outside the postpartum period, the extent to which these contribute to postpartum psychosis is less clear. This systematic review examined whether adverse life events are associated with an increased likelihood of developing postpartum psychosis or subsequent relapse in women diagnosed with postpartum psychosis. The following databases were searched from inception to June 2021: MEDLINE, EMBASE, PsycInfo. Study level data were extracted including setting, number of participants, type of adverse event, and differences between groups. A modified version of the Newcastle-Ottawa Quality Assessments Scale was used to assess risk of bias. In total, 1933 records were identified, of which 17 met the inclusion criteria, comprising nine case-control studies and eight cohort studies. Most studies (16/17) examined the association between adverse life events and the onset of postpartum psychosis, with only in which the outcome was relapse of psychosis. Overall, there were 63 different measures of adversity examined (most of which were examined in a single study only) and 87 associations between these measures and postpartum psychosis tested across the studies. In terms of statistically significant associations with onset/relapse of postpartum psychosis, 15 (17%) were positive (i.e., the adverse event increased the risk of onset/relapse), 4 (5%) were negative, and 68 (78%) were not statistically significant. Our review highlights the diversity of risk factors examined in this field, with few attempts at replication, hence limiting the ability to conclude that any single risk factor is robustly associated with the onset of postpartum psychosis. Further large-scale studies, that attempt to replicate earlier studies, are urgently needed to determine whether adverse life events play a role in the onset and exacerbation of postpartum psychosis. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=260592], identifier [CRD42021260592].

Point of care assay for blood aripiprazole concentrations: development, validation and utility.

BACKGROUND: The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis. AIMS: To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole. METHOD: Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method. RESULTS: A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml). CONCLUSIONS: The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.

Research on the Damage of the Central Nervous System Lymphoma to the Nervous System.

Management of central nervous system (CNS) lymphoma requires multidisciplinary care. The disease can manifest in the context of immunocompromised states or in the context of chronic infections. Nervous system damage from this lymphoma has highly variable presentation that is dependent on the location of the tumor lesions. Damage from disease progression can lead to lasting neurologic deficits and even death. However, some lesions are a consequence of radiation-induced neurotoxicity. This review discusses the sources of and consequences of brain damage due to tumor damage and the associated effect of clinical therapies. We discuss workup, management, and treatments. These include chemotherapy and radiation techniques. We discuss potential complications and avoidance strategies. The review will serve as a user-friendly resource for clinicians.

MaRCoS, an open-source electronic control system for low-field MRI.

Every magnetic resonance imaging (MRI) device requires an electronic control system that handles pulse sequences and signal detection and processing. Here we provide details on the architecture and performance of MaRCoS, a MAgnetic Resonance COntrol System developed by an open international community of low-field MRI researchers. MaRCoS is inexpensive and can handle cycle-accurate sequences without hard length limitations, rapid bursts of events, and arbitrary waveforms. It has also been readily adapted to meet the requirements of the various academic and private institutions participating in its development. We describe the MaRCoS hardware, firmware and software that enable all of the above, including a Python-based graphical user interface for pulse sequence implementation, data processing and image reconstruction.

Intermittent selective serotonin reuptake inhibitors for premenstrual syndromes: A systematic review and meta-analysis of randomised trials.

BACKGROUND: Intermittent (luteal phase) dosing of selective serotonin reuptake inhibitors is one treatment strategy for premenstrual syndromes such as premenstrual dysphoric disorder. This avoids the risk of the antidepressant withdrawal syndrome associated with long-term continuous dosing. AIMS: To compare intermittent dosing to continuous dosing in terms of efficacy and acceptability. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, PubMed and CINAHL for randomised trials of intermittent compared with continuous dosing of selective serotonin reuptake inhibitors in premenstrual syndromes. We extracted response rates, dropout rates and changes in symptom scores. We used random effects meta-analyses to pool study-level data and calculated odds ratio for dichotomous data and standardised mean difference for continuous data. Risk of bias was assessed using the Cochrane risk-of-bias tool. The study was registered with PROSPERO (CRD42020224176). RESULTS: A total of 1841 references were identified, with eight studies being eligible for analysis, consisting of a total of 460 participants. All included studies provided response rates, six provided dropout rates and five provided symptom scores. There was no statistically significant differences between intermittent and continuous dosing in terms of response rate (odds ratio: 1.0, 95% confidence interval (CI): 0.23-4.31, I2 = 71%), dropout rate (odds ratio 1.26, 95% CI: 0.39-4.09, I2 = 33%) or symptom change (standardised mean difference: 0.04, 95% CI: -0.27 to 0.35, I2 = 39%). All studies had a moderate or high risk of bias. CONCLUSION: Since intermittent dosing avoids the potential for withdrawal symptoms, it should be considered more commonly in this patient population.

A single-coil-based method for electromagnetic interference reduction in point-of-care low field MRI systems.

One of the main challenges for point-of-care (POC) MRI systems is electromagnetic interference (EMI), since such systems are intended for use outside conventional Faraday-shielded rooms. Many methods have been proposed based on EMI detection via sensors external to the MRI system, followed by different types of signal processing to reduce artifacts in the image. Although these methods can be very effective, they do increase the complexity of the overall system, and introduce more potential failure points for systems designed for challenging environments. In this work we introduce a new method that does not require external sensors, but rather uses the "MR-silent" mode of an RF coil to detect the EMI, followed by simple subtraction from the signal from the "MR-active" mode. This method can be performed post-acquisition if there are two receive channels available, or as demonstrated here can operate with a single-channel receive detection system with the addition of a simple passive 180° power splitter/combiner into the receive chain. Proof-of-concept in vivo results show that a reduction in the standard deviation of the EMI up to âˆ¼ 97 % is possible, with average values âˆ¼ 90 %.

A case series of premenstrual disorders presenting to the UK's National Female Hormone Clinic.

AIMS AND METHOD: We aimed to describe the clinical characteristics of female patients presenting with premenstrual disorders to a tertiary service in the UK. We conducted a retrospective case-note review of referrals to the National Female Hormone Clinic from April 2014 to August 2020. Based on clinical assessment, we determined whether the patient met criteria for premenstrual dysphoric disorder or premenstrual exacerbation of an underlying psychiatric disorder. RESULTS: Of 146 patients seen in clinic for premenstrual disorders, an ICD-10 psychiatric diagnosis was made in 130 (89.0%); a minority 16 (11.0%) did not have a psychiatric diagnosis. Following assessment, 94 patients (64.4%) met criteria for premenstrual dysphoric disorder and 67 (45.6%) had exacerbation of a psychiatric disorder. CLINICAL IMPLICATIONS: Patients presenting to this specialist service had complex psychiatric comorbidity; almost half presented with exacerbation of a psychiatric disorder.

Benchmarking the performance of a low-cost magnetic resonance control system at multiple sites in the open MaRCoS community.

PURPOSE: To describe the current properties and capabilities of an open-source hardware and software package that is being developed by many sites internationally with the aim of providing an inexpensive yet flexible platform for low-cost MRI. METHODS: This article describes three different setups from 50 to 360 mT in different settings, all of which used the MaRCoS console for acquiring data, and different types of software interface (custom-built GUI or Pulseq overlay) to acquire it. RESULTS: Images are presented both from phantoms and in vivo from healthy volunteers to demonstrate the image quality that can be obtained from the MaRCoS hardware/software interfaced to different low-field magnets. CONCLUSIONS: The results presented here show that a number of different sequences commonly used in the clinic can be programmed into an open-source system relatively quickly and easily, and can produce good quality images even at this early stage of development. Both the hardware and software will continue to develop, and it is an aim of this article to encourage other groups to join this international consortium.

Serum NOX1 and Raftlin as New Potential Biomarkers of Interest in Schizophrenia: A Preliminary Study.

Introduction: There is increasing evidence that oxidative stress (OS) and neuroinflammation play a role in the neuroprogression of schizophrenia (SCZ). Promising novel candidates which have been proposed in the search for biomarkers of psychotic illness include NADPH oxidase 1,2 (NOX1,2) and raftlin. NOX1 from the NOX family is the main source of physiological reactive oxygen species (ROS) and raftlin, the main lipid raft protein, is associated with inflammatory processes. The aim of the present study was to evaluate serum NOX1 and raftlin levels in chronic stable patients with SCZ. Methods: We measured serum NOX1 and raftlin levels from 45 clinically stable patients with SCZ and 45 healthy controls (HCs) matched for age, sex, and body-mass index. The Positive and Negative Syndrome Scale was applied to the patient group to evaluate the severity of psychotic symptoms. Results: NOX1 and raftlin levels in the patients were statistically significantly higher than the HCs (NOX1 p<0.001, raftlin p<0.001). Both parameters showed very good diagnostic performance (NOX1 AUC = 0.931, raftlin AUC = 0.915). We obtained positive and significant correlations between serum levels of both biomarkers and symptom severity. Discussion: This preliminary study indicating elevations in serum NOX1 and raftlin levels in patients with SCZ supports the importance of OS and inflammatory processes in the etiopathogenesis of the illness.

Science and Hurling: A Review.

Hurling is one of the world's fastest field sports. Since the last review of science and Gaelic sports in 2008, there has been an increase in sports science provisions across elite and sub-elite cohorts, resulting in increased hurling-specific literature equating to an additional 111 research investigations into the game across all sports science disciplines. The present review aims to provide an updated analysis of the current research on the game and propose recommendations for future research. Overall, intermittent aerobic fitness remains an important physical quality during competition, with a focus on games-based training methodologies within the literature. Within the current review, we provide updated normative data on the running demands, physiological responses, and anthropometric and performance profiles of hurling players. The increased literature across the sport has led to the development of a hurling-specific simulation, that can now be utilised practically in training and research processes for hurling cohorts. Furthermore, the monitoring of internal and external training loads across training and match environments, in addition to response variables such as well-being, appears to have become more prominent, allowing practitioners to design training regimes to achieve optimal dose and response characteristics. Analysing the game from a scientific perspective can allow for more efficient preparatory practices, to meet the specific requirements of players at all age levels. Collaborative research among the various sports science disciplines, is required to identify strategies to reduce the incidence of injury and enhance performance in hurling. The current review provides updated information to coaches and practitioners regarding position-specific physical qualities, and match-play demands that can concurrently support the training process within hurling.

Development and Evaluation of a Paper-Based Microfluidic Device for Detection of Listeria monocytogenes on Food Contact and Non-Food Contact Surfaces.

Listeria monocytogenes is the third most deadly foodborne pathogen in the United States. The bacterium is found in soil and water, contaminating raw food products and the processing environment, where it can persist for an extended period. Currently, testing of food contact and non-food contact surfaces is performed using an array of sampling devices and endpoint technologies, offering various levels of sensitivity, cost, user skill, and time to detection. Paper-based microfluidic devices (µPADs) are a rapid detection platform amenable to low-cost, user-friendly, and portable diagnostics. In this study, we developed and evaluated a µPAD platform specific for the colorimetric detection of the Listeria genus following recovery from food contact and non-food contact surfaces. For detection, four colorimetric substrates specific for the detection of ß-glucosidase, two broths selective for the detection of Listeria spp., and a nonselective broth were evaluated to facilitate detection of Listeria spp. The limit of detection and time to detection were determined by using pure bacterial cultures. After 8 h enrichment, L. monocytogenes (102 Colony Forming Units (CFU)/coupon) was detected on every surface. After 18 h enrichment, L. monocytogenes (102 CFU/coupon) was detected on all surfaces with all swabbing devices. This study demonstrated the ability of the µPAD-based method to detect potentially stressed cells at low levels of environmental contamination.

In vivo T1 and T2 relaxation time maps of brain tissue, skeletal muscle, and lipid measured in healthy volunteers at 50 mT.

PURPOSE: Low-field (B0 < 0.1 T) MRI has generated much interest as a means of increased accessibility via reduced cost and improved portability compared to conventional clinical systems (B0 ≥ 1.5 Tesla). Here we measure MR relaxation times at 50 mT and compare results with commonly used models based on both in vivo and ex vivo measurements. METHODS: Using 3D turbo spin echo readouts, T1 and T2 maps of the human brain and lower leg were acquired on a custom-built 50 mT MRI scanner using inversion-recovery and multi-echo-based sequences, respectively. Image segmentation was performed based on a histogram analysis of the relaxation times. RESULTS: The average T1 times of gray matter, white matter, and cerebrospinal fluid (CSF) were 327 ± 10 ms, 275 ± 5 ms, and 3695 ± 287 ms, respectively. Corresponding values of T2 were 102 ± 6 ms, 102 ± 6 ms, and 1584 ± 124 ms. T1 times in the calf muscle were measured to be 171 ± 11 ms and were 130 ± 5 ms in subcutaneous and bone marrow lipid. Corresponding T2 times were 39 ± 2 ms in muscle and 90 ± 13 ms in lipid. CONCLUSIONS: For tissues except for CSF, the measured T1 times are much shorter than reported at higher fields and generally lie within the range of different models in the literature. As expected, T2 times are similar to those seen at typical clinical field strengths. Analysis of the relaxation maps indicates that segmentation of white and gray matter based purely on T1 or T2 will be quite challenging at low field given the relatively small difference in relaxation times.