Attenuated psychosis symptoms are related to working alliance between therapist and service user.

AIM: Many trials have demonstrated the efficacy of specific therapy modalities for individuals with attenuated psychosis symptoms (APS). Less is known regarding mechanisms behind positive outcomes, including the role of nonspecific therapeutic factors. This study explored working alliance (WA) in a clinic serving individuals with APS to see how WA changed across the course of treatment and its relation to APS. METHODS: Session level APS and WA data was available for 12 individuals of diverse racial and gender identity, (M = 48 sessions each). Multilevel models with random intercepts tested change in WA and APS over time, and cross-sectional and prospective relations. RESULTS: WA increased and APS decreased over time. Cross sectionally, WA and APS were inversely related. Prospective relations were non-significant. CONCLUSION: When symptoms increase, therapists for individuals with APS should be attentive to potential disruptions in WA, though strong WA may be a cross-sectional protective factor.

Spatial contextual recognition memory updating is modulated by dopamine release in the dorsal hippocampus from the locus coeruleus.

Detecting novelty is critical to consolidate declarative memories, such as spatial contextual recognition memory. It has been shown that stored memories, when retrieved, are susceptible to modification, incorporating new information through an updating process. Catecholamine release in the hippocampal CA1 region consolidates an object location memory (OLM). This work hypothesized that spatial contextual memory updating could be changed by decreasing catecholamine release in the hippocampal CA1 terminals from the locus coeruleus (LC). In a mouse model expressing Cre-recombinase under the control of the tyrosine hydroxylase (TH) promoter, memory updating was impaired by photoinhibition of the CA1 catecholaminergic terminals from the LC (LC-CA1) but not from the ventral tegmental area (VTA-CA1). In vivo microdialysis confirmed that the extracellular concentration of both dopamine (DA) and noradrenaline (NA) decreased after photoinhibition of the LC-CA1 terminals (but not VTA-CA1) during the OLM update session. Furthermore, DA D1/D5 and beta-adrenergic receptor antagonists disrupted behavior, but only the former impaired memory updating. Finally, photoinhibition of LC-CA1 terminals suppressed long-term potentiation (LTP) induction in Schaffer's collaterals as a plausible mechanism for memory updating. These data will help understand the underpinning mechanisms of DA in spatial contextual memory updating.

A Method for Variant Agnostic Detection of SARS-CoV-2, Rapid Monitoring of Circulating Variants, and Early Detection of Emergent Variants Such as Omicron.

The rapid emergence of SARS-CoV-2 variants raised public health questions concerning the capability of diagnostic tests to detect new strains, the efficacy of vaccines, and how to map the geographical distribution of variants to understand transmission patterns and loads on healthcare resources. Next-generation sequencing (NGS) is the primary method for detecting and tracing new variants, but it is expensive, and it can take weeks before sequence data are available in public repositories. This article describes a customizable reverse transcription PCR (RT-PCR)-based genotyping approach which is significantly less expensive, accelerates reporting, and can be implemented in any lab that performs RT-PCR. Specific single-nucleotide polymorphisms (SNPs) and indels were identified which had high positive-percent agreement (PPA) and negative-percent agreement (NPA) compared to NGS for the major genotypes that circulated through September 11, 2021. Using a 48-marker panel, testing on 1,031 retrospective SARS-CoV-2 positive samples yielded a PPA and NPA ranging from 96.3 to 100% and 99.2 to 100%, respectively, for the top 10 most prevalent World Health Organization (WHO) lineages during that time. The effect of reducing the quantity of panel markers was explored, and a 16-marker panel was determined to be nearly as effective as the 48-marker panel at lineage assignment. Responding to the emergence of Omicron, a genotyping panel was developed which distinguishes Delta and Omicron using four highly specific SNPs. The results demonstrate the utility of the condensed panel to rapidly track the growing prevalence of Omicron across the US in December 2021 and January 2022.

Adjunctive treatments for the management of septic shock - a narrative review of the current evidence.

Septic shock is a leading cause of death and morbidity worldwide. The cornerstones of management include prompt identification of sepsis, early initiation of antibiotic therapy, adequate fluid resuscitation and organ support. Over the past two decades, there have been considerable improvements in our understanding of the pathophysiology of sepsis and the host response, including regulation of inflammation, endothelial disruption and impaired immunity. This has offered opportunities for innovative adjunctive treatments such as vitamin C, corticosteroids and beta-blockers. Some of these approaches have shown promising results in early phase trials in humans, while others, such as corticosteroids, have been tested in large, international, multicentre randomised controlled trials. Contemporary guidelines make a weak recommendation for the use of corticosteroids to reduce mortality in sepsis and septic shock. Vitamin C, despite showing initial promise in observational studies, has so far not been shown to be clinically effective in randomised trials. Beta-blocker therapy may have beneficial cardiac and non-cardiac effects in septic shock, but there is currently insufficient evidence to recommend their use for this condition. The results of ongoing randomised trials are awaited. Crucial to reducing heterogeneity in the trials of new sepsis treatments will be the concept of enrichment, which refers to the purposive selection of patients with clinical and biological characteristics that are likely to be responsive to the intervention being tested.

Cardiovascular and renal outcomes following percutaneous coronary intervention in a population with renal disease: a case-control study.

BACKGROUND: Patients with renal disease are less likely to undergo percutaneous coronary intervention (PCI) due to concerns about poor outcomes. AIM: We describe outcomes following PCI in individuals with chronic kidney disease (CKD), as compared with matched controls with comparable CKD who did not undergo PCI. We also identified factors predictive of poor outcomes following PCI amongst patients with CKD. DESIGN: Retrospective observational case-control study. METHODS: Cases were individuals with CKD (stages 1-5) undergoing PCI between 2008 and 2014. Controls were age, gender and creatinine-matched individuals not requiring PCI. We compared mortality between groups using Kaplan-Meier curves and Cox regression modelling. We assessed changes in serum creatinine using Wilcoxon Rank testing. We explored the relationship between biochemical and haematological measures (baseline creatinine, calcium, phosphate, calcium-phosphate product, parathyroid hormone, white cell count, haemoglobin, platelet count, c-reactive protein and total cholesterol) and post-PCI mortality, using logistic regression. RESULTS: We identified 144 cases and 144 controls. Mortality was significantly lower amongst cases compared with controls [hazard ratio 0.46 (95% confidence intervals 0.31, 0.69)]. PCI did not result in a significant change in renal function (P=0.52). Amongst cases, serum creatinine and calcium-phosphate product were predictors of mortality following PCI. CONCLUSION: Cases undergoing PCI had lower mortality, and PCI was not associated with accelerated CKD progression. On this data, PCI should not be deferred as a treatment option in patients with CKD. Serum creatinine and calcium-phosphate product predict mortality following PCI in this cohort, and may be useful in risk-stratifying patients with CKD being considered for PCI.

Zika Virus Infects Human Fetal Brain Microglia and Induces Inflammation.

BACKGROUND: The unprecedented reemergence of Zika virus (ZIKV) has startled the world with reports of increased microcephaly in Brazil. ZIKV can infect human neural progenitors and impair brain growth. However, direct evidence of ZIKV infection in human fetal brain tissues remains elusive. METHODS: Investigations were performed with brain cell preparations obtained from 9 donors. Virus infectivity was assessed by detection of virus antigen by flow cytometry together with various hematopoietic cell surface markers. Virus replication was determined by viral RNA quantification. Cytokine levels in supernatant obtained from virus-infected fetal brain cells were measured simultaneously in microbead-based immunoassays. RESULTS: We also show that ZIKV infection was particularly evident in hematopoietic cells with microglia, the brain-resident macrophage population being one of the main targets. Infection induces high levels of proinflammatory immune mediators such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL-1ß), and monocyte chemotactic protein 1 (MCP-1). CONCLUSIONS: Our results highlight an important role for microglia and neuroinflammation during congenital ZIKV pathogenesis.

Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral.

BACKGROUND: Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears. NEW METHOD: Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate. RESULTS: Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time. CONCLUSIONS: Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined.

The effect of antenatal anaesthetic consultation on maternal decision-making, anxiety level and risk perception in obese pregnant women.

BACKGROUND: Obese parturients are recognised as high risk and an antenatal anaesthetic consultation is recommended. The potential positive and negative effects of this consultation have not been investigated. This prospective observational study aimed to determine if antenatal anaesthetic consultation affects decisional conflict, anxiety scores or risk perception in obese women planning vaginal delivery. METHODS: Eligible women had a body mass index of > or = 35 kg/m2, planning a vaginal delivery, aged > or = 18 years and able to complete a questionnaire presented in English. Before their anaesthetic consultation, women completed a written decisional conflict questionnaire, the Six-Point Short Form of the Speilberger State-Trait Anxiety Inventory and two questions regarding risk perception. All questions were repeated by telephone consultation two weeks later. Independent samples t-tests were used to detect differences between pre and post-test scores. RESULTS: Of 114 women recruited, 89 completed the protocol and were analysed. Women had a mean ±SD age of 29.4±5.2 years and body mass index of 43.6±5.6 kg/m2. Decisional conflict scores were significantly lower after the consultation (30.04 vs. 16.54, P<0.001). Anxiety scores were lower (9.41 vs. 8.49, P=0.002) but this was not clinically significant. Only 19.1% of women felt their health was at risk in pregnancy; this did not change after the consultation. Thirteen women changed their preference toward epidural analgesia (P=0.01). DISCUSSION: Our results support the current practice of referral of obese parturients for anaesthetic consultation, but demonstrate that most women remain unaware of the risks of obesity in pregnancy despite anaesthetic consultation.

Effect of an anaesthesia information video on preoperative maternal anxiety and postoperative satisfaction in elective caesarean section: a prospective randomised trial.

Video-based patient information supplementing clinician interview has been shown to reduce anxiety and improve satisfaction in patients undergoing procedures. In Queensland more than 90% of caesarean sections are performed under regional anaesthesia. We aimed to assess the effect of using an information video about neuraxial blockade in patients having regional anaesthesia for elective caesarean section. Subjects were randomised to undergo usual care (Group C), or to view a video and undergo usual care (Group V). Subjects completed the Spielberger State-Trait Anxiety Inventory preoperatively and the Maternal Satisfaction with Caesarean Section Score questionnaire postoperatively. Satisfaction with, and duration of the preoperative anaesthetic interview, were noted. One-way analysis of variance (ANOVA) and Chi-squared tests were used in statistical analysis. One-hundred and forty three subjects were randomised and 110 completed the protocol and analysis. Group C and Group V were similar in terms demographic and anaesthesia data. There was no difference in anxiety score (41.2 versus 39.8, P=0.50), maternal satisfaction score (118.5 versus 122.7, P=0.22) or interview duration (16.3 versus 15.8 min, P=0.69) between the two groups. The use of an anaesthesia information video does not reduce preoperative anxiety or increase the duration of the anaesthetic interview. Maternal satisfaction with neuraxial blockade for elective caesarean is high and not improved by an anaesthesia information video.

Anomalous intrinsic viscosity of octadecylamine-functionalised carbon nanotubes in suspension.

Single walled carbon nanotubes, SWCNTs, are used as a model cylinder of nanoscopic dimensions for testing rheological theories of how addition of cylindrical particles affects the viscosity of a suspension of such particles. Using the rate of growth of the accompanying induced linear dichroism following application of an applied electric field, the dynamics of carbon nanotube alignment is studied in suspensions of octadecylamine functionalised single walled carbon nanotubes, ODA-SWCNTs, in 1,2 dichloroethane. From such measurements the viscosity of the suspension is measured as the concentration of the suspension is varied. While working within the dilute limit the viscosity is found to increase linearly with concentration and the intrinsic viscosity of the suspension is found to be 8000. This anomalously high intrinsic viscosity is compared with the predictions of various models for a rigid cylinder and found to be incompatible with any of the current models. Some suggestions are made as to the way this ODA-SWCNT result may be eventually accommodated within other models.

Fluorescent probes for investigation of isoprenoid configuration and size discrimination by bactoprenol-utilizing enzymes.

Undecaprenyl Pyrophosphate Synthase (UPPS) is an enzyme critical to the production of complex polysaccharides in bacteria, as it produces the crucial bactoprenol scaffold on which these materials are assembled. Methods to characterize the systems associated with polysaccharide production are non-trivial, in part due to the lack of chemical tools to investigate their assembly. In this report, we develop a new fluorescent tool using UPPS to incorporate a powerful fluorescent anthranilamide moiety into bactoprenol. The activity of this analogue in polysaccharide biosynthesis is then tested with the initiating hexose-1-phosphate transferases involved in Capsular Polysaccharide A biosynthesis in the symbiont Bacteroides fragilis and the asparagine-linked glycosylation system of the pathogenic Campylobacter jejuni. In addition, it is shown that the UPPS used to make this probe is not specific for E-configured isoprenoid substrates and that elongation by UPPS is required for activity with the downstream enzymes.

Efficacy of computed tomographic scans in the evaluation of patients with esophageal foreign bodies.

OBJECTIVES: This study aimed to determine whether computed tomographic (CT) scans on which foreign body impaction cannot be detected can be relied upon to decide whether a patient requires further investigation by esophagoscopy. This information might minimize unnecessary esophagoscopy without incurring the risk of a missed impacted foreign body. METHODS: In a retrospective chart review of all patients admitted to National University Hospital, Singapore, over the period 2004 to 2011 for an ingested foreign body, case files of patients who underwent preoperative CT scanning followed by esophagoscopy were identified and reviewed. The results of the CT scan and the findings of esophagoscopy in these patients were analyzed. RESULTS: A total of 376 patients underwent rigid esophagoscopy for an ingested foreign body during this period. Of these, 119 patients had CT scans performed before the endoscopy. Based on our analysis, the sensitivity of CT scanning was 100%, and the specificity was 70.6%. The positive predictive value was 89.5%, and the negative predictive value was 100%. None of the patients who had CT scans with no detectable foreign body had complications on follow-up. CONCLUSIONS: CT scanning appeared to be sensitive and specific in investigation of patients with an ingested foreign body. It also has a high negative predictive value, which may allow it to be the only preliminary investigation in these patients. Based on these data, a prospective study with close monitoring of patients who have CT scans with no detectable foreign body can be designed to accrue more patients to answer this query.

Applying estimated glomerular filtration rate to an ageing population: are we in danger of becoming ageist?

BACKGROUND: Management of CKD is a major public health concern. The introduction of automated eGFR reporting has seen an increase in labelling of elderly patients with CKD. The prognostic significance of the CKD label in this population remains controversial. AIM: To investigate rates of specialist intervention in the over 75's to determine whether these patients may be more appropriately managed in primary care, relieving the burden of excessive outpatient visits in this population. METHODS: Retrospective review of patient notes and laboratory reports over 25 consecutive renal outpatient clinics within a single NHS trust. RESULTS: 546 patients were studied. The mean age of patient was 68.7 years (SD+/-14.9). The over 75's had more advanced renal disease compared to under 75's (mean eGFR 28.2 vs. 41.3 ml/min/1.73 m(2)), but there was no significant difference in eGFR stability between the older and younger cohort or in the overall rate of intervention (32.5% vs. 30.7% p=0.86). The over 75's had a lower mean haemoglobin (11.8 vs. 12.6, p=<0.001) necessitating greater EPO requirements (25.2% vs. 10.5%, p=<0.001). The greatest intervention was seen in the more advanced CKD patients (29% of CKD 3 vs. 55% of CKD 5), and in those with diagnoses requiring immunosuppression. CONCLUSION: Intervention to management may be predictable on the basis of specific diagnoses and advancing CKD stage but not by patient age. We can provide no evidence to suggest that elderly CKD patients are managed any differently to younger patients and in fact have a higher need for attention to and treatment of renal anaemia, validating their attendance in nephrology clinic.

Chemoenzymatic synthesis of an isoprenoid phosphate tool for the analysis of complex bacterial oligosaccharide biosynthesis.

Undecaprenyl Pyrophosphate Synthase (UPPS) is a key enzyme that catalyzes the production of bactoprenols, which act as membrane anchors for the assembly of complex bacterial oligosaccharides. One of the major hurdles in understanding the assembly of oligosaccharide assembly is a lack of chemical tools to study this process, since bactoprenols and the resulting isoprenoid-linked oligosaccharides lack handles or chromophores for use in pathway analysis. Here we describe the isolation of a new UPPS from the symbiotic microorganism Bacteroides fragilis, a key species in the human microbiome. The protein was purified to homogeneity and utilized to accept a chromophore containing farnesyl diphosphate analogue as a substrate. The analogue was utilized by the enzyme and resulted in a bactoprenyl diphosphate product with an easy to monitor tag associated with it. Furthermore, the diphosphate is shown to be readily converted to monophosphate using a common molecular biology reagent. This monophosphate product allowed for the investigation of complex oligosaccharide biosynthesis, and was used to probe the activity of glycosyltransferases involved in the well characterized Campylobacter jejuni N-linked protein glycosylation. Novel reagents similar to this will provide key tools for the study of uncharacterized oligosaccharide assemblies, and open the possibility for the development of rapid screening methodology for these biosynthetic systems.

Impact of chronic kidney disease management in primary care.

BACKGROUND: The introduction of eGFR reporting and publication of national CKD guidelines has led to major challenges in primary and secondary care, leading to an increase in the number of referrals to nephrology clinics. We have shown that introduction of a renal patient care pathway reduces nephrology referrals and enables managed discharges of CKD patients to primary care. The aim of this article is to examine the outcome of patients discharged to primary care to find out if there is an associated risk with increased discharge supported by the patient pathway. METHODS: The study was carried out within a single NHS Trust covering a population of 560,000. All patients discharged from the trust's renal outpatient clinic between June 2007 and July 2008 were identified. Patient notes and the local laboratory database systems were used to determine the source and timing of tests. RESULTS: A total of 31 new referrals and 57 regular follow-ups were discharged during this period. The median age of discharge was 67.5 years. Most subjects (60%) had CKD stage 3 at the time of discharge. A total of 23% of discharges were categorized as CKD stages 1, 2 or normal and 17% of patients had CKD stage 4. Overall, 93% had stable eGFRs prior to discharge, 77.5% of patients had blood pressure within threshold (140/90 according to UK CKD guidelines) and 97.7% of patients had haemoglobins >10 g/dl. Post-discharge 83% of patients had eGFRs recorded by their general practitioner and 92.6% of these were measured within appropriate time frames as per CKD guidelines. The majority of patients (82%) had either improved or stable eGFR post-discharge and only three patients had a significant decline in their eGFR. CONCLUSION: These data indicate that selected CKD patients can be appropriately discharged from secondary care and adequately monitored in primary care. Furthermore, we have shown that this was a safe practice for patients.

Renal quality outcomes framework and eGFR: impact on secondary care.

BACKGROUND: The prognostic significance of impaired renal function has driven the need for its early recognition and the widespread introduction of the estimated glomerular filtration rate (eGFR) reporting, and the incorporation of Chronic Kidney Disease (CKD) in the revised Quality Outcomes Framework (QOF) of the General Medical Services (GMS) contract in the UK. AIM: To characterize the effect of these changes on referral numbers and appropriateness to a nephrology service, and the impact of a newly introduced Map of Medicine(R)-based patient care pathway coupled to the systematic screening of all new referrals. METHODS: The study was carried out within a single NHS Trust covering five primary health care Local Health Boards and a population of 560,000. RESULTS: Introduction of eGFR reporting and CKD QOF domains was associated with a rapid 61% increase in new patient referral, and an increase in the mean age of the patients at referral from 63.0 +/- 18.1 to 69.1 +/- 18.5. The referrals did not correlate with the QOF reported prevalence of CKD. Systematic screening of new referrals demonstrated 36% to be either inappropriate or inadequate in terms of clinical information supplied. Introduction of the renal patient care pathway was associated with a fall in both the number of inadequate and total new referrals received. Overall 62% of all primary care practices registered with the Map of Medicine(R) and these sent a higher proportion of appropriate referrals and were less likely to generate referrals with inadequate information. The initiative also enabled managed discharges from secondary to primary care settings, freeing up outpatient capacity. CONCLUSION: The study describes the impact of the introduction eGFR reporting and revision of the GMS contract with Renal QOF, on patient referrals to a nephrology service. In addition, we provide evidence that a new management pathway has helped to regulate and proactively manage the increased demand within the current resources.

The identification of vertical velocity profiles using an inertial sensor to investigate pre-impact detection of falls.

This study investigates distinguishing falls from normal Activities of Daily Living (ADL) by thresholding of the vertical velocity of the trunk. Also presented is the design and evaluation of a wearable inertial sensor, capable of accurately measuring these vertical velocity profiles, thus providing an alternative to optical motion capture systems. Five young healthy subjects performed a number of simulated falls and normal ADL and their trunk vertical velocities were measured by both the optical motion capture system and the inertial sensor. Through vertical velocity thresholding (VVT) of the trunk, obtained from the optical motion capture system, at -1.3 m/s, falls can be distinguished from normal ADL, with 100% accuracy and with an average of 323 ms prior to trunk impact and 140 ms prior to knee impact, in this subject group. The vertical velocity profiles obtained using the inertial sensor, were then compared to those obtained using the optical motion capture system. The signals from the inertial sensor were combined to produce vertical velocity profiles using rotational mathematics and integration. Results show high mean correlation (0.941: Coefficient of Multiple Correlations) and low mean percentage error (6.74%) between the signals generated from the inertial sensor to those from the optical motion capture system. The proposed system enables vertical velocity profiles to be measured from elderly subjects in a home environment where as this has previously been impractical.