Differential pulse oximetry readings between ethnic groups and delayed transfer to intensive care units.

BACKGROUND: Pulse oximeters are widely used to monitor blood oxygen saturations, although concerns exist that they are less accurate in individuals with pigmented skin. AIMS: This study aimed to determine if patients with pigmented skin were more severely unwell at the period of transfer to intensive care units (ICUs) than individuals with White skin. METHODS: Using data from a large teaching hospital, measures of clinical severity at the time of transfer of patients with COVID-19 infection to ICUs were assessed, and how this varied by ethnic group. RESULTS: Data were available on 748 adults. Median pulse oximetry demonstrated similar oxygen saturations at the time of transfer to ICUs (Kruskal-Wallis test, P = 0.51), although median oxygen saturation measurements from arterial blood gases at this time demonstrated lower oxygen saturations in patients classified as Indian/Pakistani ethnicity (91.6%) and Black/Mixed ethnicity (93.0%), compared to those classified as a White ethnicity (94.4%, Kruskal-Wallis test, P = 0.005). There were significant differences in mean respiratory rates in these patients (P < 0.0001), ranging from 26 breaths/min in individuals with White ethnicity to 30 breaths/min for those classified as Indian/Pakistani ethnicity and 31 for those who were classified as Black/Mixed ethnicity. CONCLUSIONS: These data are consistent with the hypothesis that differential measurement error for pulse oximeter readings negatively impact on the escalation of clinical care in individuals from other than White ethnic groups. This has implications for healthcare in Africa and South-East Asia and may contribute to differences in health outcomes across ethnic groups globally.

Postmeal optogenetic inhibition of dorsal hippocampal principal neurons increases future intake in a time-dependent manner.

Research involving human participants indicates that memories of recently eaten meals limit how much is eaten during subsequent eating episodes; yet, the brain regions that mediate the inhibitory effects of ingestion-related memory on future intake are largely unknown. We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memories of personal experiences, mediate the inhibitory effects of ingestion-related memory on future intake. Our research program aimed at testing this hypothesis has been influenced in large part by our mentor James McGaugh and his research on posttraining manipulations. In the present study, we used an activity-guided optogenetic approach to test the prediction that if dHC glutamatergic neurons limit future intake through a process that requires memory consolidation, then inhibition should increase subsequent intake when given soon after the end of a meal but delayed inhibition should have no effect. Viral vectors containing CaMKIIα-eArchT3.0-eYFP and fiber optic probes were placed in the dHC of male Sprague-Dawley rats. Compared to intake on a day when no inhibition was given, postmeal inhibition of dHC glutamatergic neurons given for 10 min after the end of a saccharin meal increased the likelihood that rats would consume a second meal 90 min later and significantly increased the amount of saccharin solution consumed during that next meal when the neurons were no longer inhibited. Importantly, delayed inhibition given 80 min after the end of the saccharin meal did not affect subsequent intake of saccharin. Given that saccharin has minimal postingestive gastric consequences, these effects are not likely due to the timing of interoceptive visceral cues generated by the meal. These data show that dHC glutamatergic neural activity is necessary during the early postprandial period for limiting future intake and suggest that these neurons inhibit future intake by consolidating the memory of the preceding meal.

Serum potassium changes due to concomitant ACEI/ARB and spironolactone therapy: A systematic review and meta-analysis.

PURPOSE: To provide evidence of serum potassium changes in individuals taking angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) concomitantly with spironolactone compared to ACEI/ARB therapy alone. METHODS: PubMed, Embase, Scopus, and Web of Science were searched for studies including exposure to both spironolactone and ACEI/ARB therapy compared to ACEI/ARB therapy alone. The primary outcome was serum potassium change over time. Main effects were calculated to estimate average treatment effect using random effects models. Heterogeneity was assessed using Cochran's Q and I2. Risk of bias was assessed using the revised Cochrane risk of bias tool. RESULTS: From the total of 1,225 articles identified, 20 randomized controlled studies were included in the meta-analysis. The spironolactone plus ACEI/ARB group included 570 patients, while the ACEI/ARB group included 547 patients. Treatment with spironolactone and ACEI/ARB combination therapy compared to ACEI/ARB therapy alone increased the mean serum potassium concentration by 0.19 mEq/L (95% CI, 0.12-0.26 mEq/L), with intermediate heterogeneity across studies (Q statistic = 46.5, P = 0.004; I2 = 59). Sensitivity analyses showed that the direction and magnitude of this outcome did not change with the exclusion of individual studies, indicating a high level of reliability. Reporting risk of bias was low for 16 studies (80%), unclear for 3 studies (15%) and high for 1 study (5%). CONCLUSION: Treatment with spironolactone in combination with ACEI/ARB therapy increases the mean serum potassium concentration by less than 0.20 mEq/L compared to ACEI/ARB therapy alone. However, serum potassium and renal function must be monitored in patients starting combination therapy to avoid changes in serum potassium that could lead to hyperkalemia.

Electrostatic subframing and compressive-sensing video in transmission electron microscopy.

We present kilohertz-scale video capture rates in a transmission electron microscope, using a camera normally limited to hertz-scale acquisition. An electrostatic deflector rasters a discrete array of images over a large camera, decoupling the acquisition time per subframe from the camera readout time. Total-variation regularization allows features in overlapping subframes to be correctly placed in each frame. Moreover, the system can be operated in a compressive-sensing video mode, whereby the deflections are performed in a known pseudorandom sequence. Compressive sensing in effect performs data compression before the readout, such that the video resulting from the reconstruction can have substantially more total pixels than that were read from the camera. This allows, for example, 100 frames of video to be encoded and reconstructed using only 15 captured subframes in a single camera exposure. We demonstrate experimental tests including laser-driven melting/dewetting, sintering, and grain coarsening of nanostructured gold, with reconstructed video rates up to 10 kHz. The results exemplify the power of the technique by showing that it can be used to study the fundamentally different temporal behavior for the three different physical processes. Both sintering and coarsening exhibited self-limiting behavior, whereby the process essentially stopped even while the heating laser continued to strike the material. We attribute this to changes in laser absorption and to processes inherent to thin-film coarsening. In contrast, the dewetting proceeded at a relatively uniform rate after an initial incubation time consistent with the establishment of a steady-state temperature profile.

The role of citizen science in addressing grand challenges in food and agriculture research.

The power of citizen science to contribute to both science and society is gaining increased recognition, particularly in physics and biology. Although there is a long history of public engagement in agriculture and food science, the term 'citizen science' has rarely been applied to these efforts. Similarly, in the emerging field of citizen science, most new citizen science projects do not focus on food or agriculture. Here, we convened thought leaders from a broad range of fields related to citizen science, agriculture, and food science to highlight key opportunities for bridging these overlapping yet disconnected communities/fields and identify ways to leverage their respective strengths. Specifically, we show that (i) citizen science projects are addressing many grand challenges facing our food systems, as outlined by the United States National Institute of Food and Agriculture, as well as broader Sustainable Development Goals set by the United Nations Development Programme, (ii) there exist emerging opportunities and unique challenges for citizen science in agriculture/food research, and (iii) the greatest opportunities for the development of citizen science projects in agriculture and food science will be gained by using the existing infrastructure and tools of Extension programmes and through the engagement of urban communities. Further, we argue there is no better time to foster greater collaboration between these fields given the trend of shrinking Extension programmes, the increasing need to apply innovative solutions to address rising demands on agricultural systems, and the exponential growth of the field of citizen science.

Screening for latent tuberculous infection in people living with HIV infection in Auckland, New Zealand.

SETTING: New Zealand, which has a low incidence of tuberculosis (TB), has historically taken a risk-based approach to screening for latent tuberculous infection (LTBI) in adult people living with the human immunodeficiency virus infection (PLHIV). OBJECTIVE: To evaluate LTBI screening, treatment and outcomes in an adult PLHIV population. DESIGN: This was a retrospective clinical record review of an initial cohort of adult PLHIV attending the Auckland City Hospital HIV clinic in 2011, and a second cohort of adult PLHIV newly attending the clinic in 2014. We analysed high-risk (born in or acquiring HIV in a high TB incidence country) and low-risk patients using descriptive statistical methods. RESULTS: Of the 752 patients from the initial cohort, 416 (55%) had documentation of LTBI screening, which was positive in 74 (10%): 19/461 (4%) low-risk and 55/291 (19%) high-risk patients. LTBI treatment was received in 13 low-risk and 44 high-risk patients. Of 73 patients in the second cohort, 68 (93%) were screened. CONCLUSION: LTBI screening was incomplete in our clinic, but improved between 2011 and 2014. A significant number of patients with LTBI did not originate from a high TB incidence country.

Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells.

Wnt5a can activate Rho GTPases in chronic lymphocytic leukemia (CLL) cells by inducing the recruitment of ARHGEF2 to ROR1. Mass spectrometry on immune precipitates of Wnt5a-activated ROR1 identified 14-3-3ζ, which was confirmed by co-immunoprecipitation. The capacity of Wnt5a to induce ROR1 to complex with 14-3-3ζ could be blocked in CLL cells by treatment with cirmtuzumab, a humanized mAb targeting ROR1. Silencing 14-3-3ζ via small interfering RNA impaired the capacity of Wnt5a to: (1) induce recruitment of ARHGEF2 to ROR1, (2) enhance in vitro exchange activity of ARHGEF2 and (3) induce activation of RhoA and Rac1 in CLL cells. Furthermore, CRISPR/Cas9 deletion of 14-3-3ζ in ROR1-negative CLL cell-line MEC1, and in MEC1 cells transfected to express ROR1 (MEC1-ROR1), demonstrated that 14-3-3ζ was necessary for the growth/engraftment advantage of MEC1-ROR1 over MEC1 cells. We identified a binding motif (RSPS857SAS) in ROR1 for 14-3-3ζ. Site-directed mutagenesis of ROR1 demonstrated that serine-857 was required for the recruitment of 14-3-3ζ and ARHGEF2 to ROR1, and activation of RhoA and Rac1. Collectively, this study reveals that 14-3-3ζ plays a critical role in Wnt5a/ROR1 signaling, leading to enhanced CLL migration and proliferation.

Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells.

ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→︀A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration.

Practitioners' experiences of adolescent suicidal behaviour in peer groups.

WHAT IS KNOWN ON THE SUBJECT?: Group suicidal behaviour can be devastating for all concerned. There is an absence of research on adolescent suicidal group behaviour. The perspectives of practitioners' experiences of these groups are largely lacking from research literature. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Practitioners work regularly with suicidal behaviour in adolescent peer groups. Practitioners identify peer relationships in groups as complex, including elements that are both suicide encouraging and preventing. Practitioners identify a range of ways in which young people become involved in suicidal behaviour in groups, including indirectly through risk taking and care-seeking as well as directly suicidal or self-harming. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Assessments of young people should routinely include a focus on the qualities of peer relations, including those in the online/digital realm. Assessments and interventions need to consider the complexity of group relationships and roles, and the multiplicity of factors that can contribute to suicidal behaviour in groups. Interventions that sustain therapeutic connectedness are helpful for taking dynamic/fluctuating risks into account. ABSTRACT: Introduction Group suicidal behaviour by young people can have harmful effects; it may be increasing, influenced by online media and reported increasing self-harm rates; new knowledge and understanding to inform interventions is required. Aim To explore how practitioners experience group suicidal behaviour amongst adolescents, how they assess risks/needs, and how these insights inform understanding about these groups. Method Ten practitioners, including Mental Health Nurses, were interviewed in one multidisciplinary CAMHS, in England. Data analysis was by Thematic Analysis (Braun & Clarke 2006). Results Participants described frequently working with suicidal groups. Roles in groups include suicide encouraging and preventing. Practitioners identify risky and protective connections between young people, online and offline. Clinical tensions include living with suicidal risks, emotional and positional challenges, and getting to grips with digital media. Discussion Peer groups appear to have a larger role in adolescent suicide than recognized to date. Practitioners need to assess young people's roles in groups, their diverse motivations and to understand constantly changing digital media. Implications for practice Assessments of suicide risk for young people should routinely include focus on peer relations including the online/digital realm. Maintaining relationships with vulnerable young people facilitates managing fluctuating risks and understanding different group dynamics.

Nonmuscle myosin IIB as a therapeutic target for the prevention of relapse to methamphetamine use.

Memories associated with drug use increase vulnerability to relapse in substance use disorder (SUD), and there are no pharmacotherapies for the prevention of relapse. Previously, we reported a promising finding that storage of memories associated with methamphetamine (METH), but not memories for fear or food reward, is vulnerable to disruption by actin depolymerization in the basolateral amygdala complex (BLC). However, actin is not a viable therapeutic target because of its numerous functions throughout the body. Here we report the discovery of a viable therapeutic target, nonmuscle myosin IIB (NMIIB), a molecular motor that supports memory by directly driving synaptic actin polymerization. A single intra-BLC treatment with Blebbistatin (Blebb), a small-molecule inhibitor of class II myosin isoforms, including NMIIB, produced a long-lasting disruption of context-induced drug seeking (at least 30 days). Further, postconsolidation genetic knockdown of Myh10, the heavy chain of the most highly expressed NMII in the BLC, was sufficient to produce METH-associated memory loss. Blebb was found to be highly brain penetrant. A single systemic injection of the compound selectively disrupted the storage of METH-associated memory and reversed the accompanying increase in BLC spine density. This effect was specific to METH-associated memory, as it had no effect on an auditory fear memory. The effect was also independent of retrieval, as METH-associated memory was disrupted 24 h after a single systemic injection of Blebb delivered in the home cage. Together, these results argue for the further development of small-molecule inhibitors of NMII as potential therapeutics for the prevention of SUD relapse triggered by drug associations.

Short-course intravenous aciclovir treatment for cutaneous herpes zoster in patients with HIV infection.

There are no comparative data on the treatment duration of cutaneous herpes zoster (HZ) in patients with HIV infection. We retrospectively reviewed all 51 adult patients with HIV infection presenting with cutaneous HZ in the 15-year period 1995-2009 treated with intravenous aciclovir alone. The median CD4 count was 297 (range 10-703) cells/mm(3). There were 44 episodes of localized and seven episodes of disseminated cutaneous HZ. Patients received a median of nine (range 3-17) doses of intravenous aciclovir given at a median dose of 6.5 (range 2.9-10.8) mg/kg eight hourly. One patient (2%) relapsed early and four patients (7.8%) relapsed late with further episodes of cutaneous HZ. Seven patients (13.7%) developed postherpetic neuralgia. Three days of intravenous aciclovir is effective treatment for cutaneous HZ in patients with HIV infection.

Proteomic divergence in Arabidopsis autopolyploids and allopolyploids and their progenitors.

Autopolyploidy and allopolyploidy are common in many plants and some animals. Rapid changes in genomic composition and gene expression have been observed in both autopolyploids and allopolyploids, but the effects of polyploidy on proteomic divergence are poorly understood. Here, we report quantitative analysis of protein changes in leaves of Arabidopsis autopolyploids and allotetraploids and their progenitors using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with mass spectrometry. In more than 1000 proteins analyzed, the levels of protein divergence were relatively high (~18%) between Arabidopsis thaliana and Arabidopsis arenosa, relatively low (~6.8%) between an A. thaliana diploid and autotetraploid and intermediate (~8.3 and 8.2%) in F(1)- and F(8)-resynthesized allotetraploids relative to mid-parent values, respectively. This pattern of proteomic divergence was consistent with the previously reported gene expression data. In particular, many non-additively accumulated proteins (61-62%) in the F(1) and F(8) allotetraploids were also differentially expressed between the parents. The differentially accumulated proteins in functional categories of abiotic and biotic stresses were overrepresented between an A. thaliana autotetraploid and diploid and between two Arabidopsis species, but not significantly different between allotetraploids and their progenitors. Although the trend of changes is similar, the percentage of differentially accumulated proteins that matched previously reported differentially expressed genes was relatively low. Western blot analysis confirmed several selected proteins with isoforms the cumulative levels of which were differentially expressed. These data suggest high protein divergence between species and rapid changes in post-transcriptional regulation and translational modifications of proteins during polyploidization.

Extended-spectrum beta-lactamase (ESBL)-producing enterobacteria: factors associated with infection in the community setting, Auckland, New Zealand.

We aimed to document the epidemiology of extended-spectrum beta-lactamase (ESBL)-producing enterobacteria in the Auckland community and identify factors associated with infection using a case-control study design. ESBL-producing enterobacteria were isolated from 107 infected patients, for which demographic and clinical data were available for 98 cases (92%). Escherichia coli was the predominant organism (82%), with urine as the commonest source (97%). Compared with a control group infected with ESBL-negative enterobacteria, factors significantly associated with infection on univariate analysis were: living in a residential care home (RCH); recent admission to hospital 'M'; recent antibiotic use; older age (>75 years); presence of a urinary catheter; and a history of comorbid chronic obstructive pulmonary disease (COPD), cardiovascular disease, neurological disease or recurrent urinary tract infection. On multivariate analysis, residence in RCH and COPD remained significant associations. Pulsed-field gel electrophoresis typing of the ESBL-producing E. coli identified a common strain. We concluded that residence in RCH and a history of COPD are significant associations with ESBL-producing enterobacterial infection in the Auckland community. Several spatial clusters in RCHs and a common strain suggest point-source outbreaks. A substantial number of community cases did not live in an RCH nor had been recently hospitalised, suggesting the independent generation of ESBL-producing enterobacteria in the broader community.

Propionibacterium acnes: an under-appreciated cause of post-neurosurgical infection.

BACKGROUND: Propionibacterium acnes is increasingly recognized as a cause of post-neurosurgical infection. This review of patients with P. acnes neurosurgical infection was carried out in order to determine clinical characteristics and outcomes in relation to duration of antimicrobial treatment. METHODS: We retrospectively reviewed the charts of consecutive patients with P. acnes isolated from neurosurgical specimens from 1 January 1999 to 30 June 2005. We defined P. acnes neurosurgical infection as isolation of P. acnes alone from a sterile neurosurgical site in a patient who clinically improved following treatment with an appropriate antibiotic. RESULTS: We identified 28 patients with definite P. acnes neurosurgical infection; median age 49 years (range 23-77); 15 (54%) male. All patients had prior neurosurgical procedures: 27 (96%) post-craniotomy. The median time from surgery to presentation was 54 days (range 12-1,578). Eighteen out of 28 (64%) patients who met the definition of neurosurgical infection had Gram-positive bacilli seen in at least one surgical specimen compared with only 2/56 (4%) patients who did not meet the definition (P < 0.0001). Intravenous benzyl penicillin +/- oral penicillin VK was the most common treatment. The median duration of antibiotic treatment for intracranial infection was 29 days. Five of nine patients who had extracranial bone-flap-associated infection had