The Poison Pen: Bedside Diagnosis of Urinary Diquat

Diquat is a bipyridyl herbicide with nephrotoxic effects. This in vitro study demonstrates a colorimetric test for detection of diquat in human urine. Urine specimens using ten concentrations of diquat herbicide solution and controls for urine and glyphosate were prepared. A two-step assay (addition of bicarbonate followed by sodium dithionite) was performed, with a resulting color change of the original solution for each specimen. Color change intensity was noted immediately and after 30 min, by gross visual inspection. A green color with concentration-dependent intensity was detected in all specimens, in which concentrations of diquat solution ranged from 0.73 to 730 mg/L. This colorimetric effect disappeared after 30 min. The sodium bicarbonate/dithionite test may be useful as a qualitative bedside technique for the detection of urinary diquat in the appropriate clinical setting

Household Transmission of Rotavirus in a Community with Rotavirus Vaccination in Quininde, Ecuador

Background: We studied the transmission of rotavirus infection in households in peri-urban Ecuador in the vaccination era. Methods: Stool samples were collected from household contacts of child rotavirus cases, diarrhea controls and healthy controls following presentation of the index child to health facilities. Rotavirus infection status of contacts was determined by RT-qPCR. We examined factors associated with transmissibility (index-case characteristics) and susceptibility (householdcontact characteristics). Results: Amongst cases, diarrhea controls and healthy control household contacts, infection attack rates (iAR) were 55%, 8% and 2%, (n = 137, 130, 137) respectively. iARs were higher from index cases with vomiting, and amongst siblings. Disease ARs were higher when the index child was ,18 months and had vomiting, with household contact ,10 years and those sharing a room with the index case being more susceptible. We found no evidence of asymptomatic infections leading to disease transmission. Conclusion: Transmission rates of rotavirus are high in households with an infected child, while background infections are rare. We have identified factors associated with transmission (vomiting/young age of index case) and susceptibility (young age/sharing a room/being a sibling of the index case). Vaccination may lead to indirect benefits by averting episodes or reducing symptoms in vaccinees

Finding the Right Setting for the Right Treatment During the Acute Treatment of Individuals with Schizophrenia: A Narrative Review and Clinical Practice Guideline

Christoph U Correll,1– 4 Celso Arango,5 Andrea Fagiolini,6 Giulia Maria Giordano,7 Stefan Leucht,4,8 Gonzalo Salazar de Pablo5,9,10 1Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; 2Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/ Northwell, Hempstead, NY, USA; 3Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany; 4German Center for Mental Health (DZPG), Partner Site Berlin, Berlin, Germany; 5Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain; 6Department of Molecular Medicine, School of Medicine, University of Siena, Siena, Italy; 7Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Naples, Italy; 8Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, Germany; 9Child and Adolescent Mental Health Services (CAMHS) South London and Maudsley NHS Foundation Trust London, London, UK; 10Department of Child and Adolescent Psychiatry Institute of Psychiatry, Psychology & Neuroscience King’s College London, London, UKCorrespondence: Christoph U Correll, The Zucker Hillside Hospital, Department of Psychiatry, 75-59 263rd Street Glen Oaks, New York, NY, 11004, USA, Email [email protected]: Schizophrenia is most times a chronic and often debilitating illness associated with poor mental health outcomes. Early and effective treatment of schizophrenia in the most appropriate setting can make a significant difference in the long-term recovery. The aim of this narrative review was to provide suggestions and recommendations for effectively managing patients with schizophrenia during acute exacerbations and to enhance awareness and skills related to personalized medicine.Methods: A panel of academics and clinicians with experience in the field of psychosis met virtually on July 13th 2023 to narratively review and discuss the research evidence and their clinical experience about the most appropriate acute treatments for patients with schizophrenia. This manuscript represents a synthesis of the panel analysis and discussion.Results: First contact is very important for service users, as is finding the most adequate treatment setting. If patients present to the emergency department, which may be a traumatic setting for service users, a dedicated environment with adequate space and specialized mental health support, including personnel trained in de-escalation techniques, is recommended. A well-connected continuum of care is strongly recommended, possibly with seamless links between inpatient units, day hospital services, outpatient facilities and rehabilitation services. Ideally, this should be structured as part of a coordinated step-down service line. Treatment challenges include suboptimal response, side effects, and nonadherence, which is reduced by the use of long-acting injectable antipsychotics.Conclusion: Individual circumstances, including age, gender, and presence of hostility/aggression or self-harm, cognitive impairment and negative symptoms, comorbidities (depression, substance use disorders) or associated symptoms (anxiety, insomnia), should be considered when selecting the most appropriate treatment for the acute phase of schizophrenia. Efficacy and feasibility, as well as acceptability and tolerability of treatments, require joint consideration from the early stages of schizophrenia, thereby enhancing the possibility of improved short- and long-term outcomes.Keywords: schizophrenia, first-episode psychosis, acute setting, clinical car

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

Effect of a Community Popular Opinion Leader HIV/STI Intervention on Stigma in Urban, Coastal Peru

Evaluating interventions that reduce HIV stigma may help to craft effective stigma-reduction programs. This study evaluates the effects of a community popular opinion leader HIV/STI intervention on stigma in urban, coastal Peru. Mixed effects modeling was used to analyze data on 3,049 participants from the Peru site of the NIHM collaborative trial. Analyses looked at differences between the comparison and intervention groups on a stigma index from baseline to 12- and 24-month follow-up. Sub-analyses were conducted on heterosexual-identified men (esquineros), homosexual-identified men (homosexuales), and socially marginalized women (movidas). Compared to participants in the comparison group, intervention participants reported lower levels of stigma at 12- and 24-month follow-up. Similar results were found within esquineros and homosexuales. No significant differences were found within movidas. Findings suggest that interventions designed to normalize HIV prevention behaviors and HIV communication can reduce HIV-related stigma and change community norms

Hybrid speciation in Heliconius butterflies? A review and critique of the evidence

The evidence supporting the recent hypothesis of a homoploid hybrid origin for the butterfly species Heliconius heurippa is evaluated. Data from selective breeding experiments, mate-choice studies, and a wide variety of DNA markers are reviewed, and an alternative hypothesis for the origin of the species and its close relatives is proposed. A scenario of occasional red wing-pattern mutations in peripheral populations of Heliconius cydno with subsequent adaptive convergence towards sympatric mimicry rings involving H. melpomene and H. erato is offered as an alternative to the HHS hypothesis. Recent twists of this tale are addressed in a postscript

Mathematical Modelling of DNA Replication Reveals a Trade-off between Coherence of Origin Activation and Robustness against Rereplication

Eukaryotic genomes are duplicated from multiple replication origins exactly once per cell cycle. In Saccharomyces cerevisiae, a complex molecular network has been identified that governs the assembly of the replication machinery. Here we develop a mathematical model that links the dynamics of this network to its performance in terms of rate and coherence of origin activation events, number of activated origins, the resulting distribution of replicon sizes and robustness against DNA rereplication. To parameterize the model, we use measured protein expression data and systematically generate kinetic parameter sets by optimizing the coherence of origin firing. While randomly parameterized networks yield unrealistically slow kinetics of replication initiation, networks with optimized parameters account for the experimentally observed distribution of origin firing times. Efficient inhibition of DNA rereplication emerges as a constraint that limits the rate at which replication can be initiated. In addition to the separation between origin licensing and firing, a time delay between the activation of S phase cyclin-dependent kinase (S-Cdk) and the initiation of DNA replication is required for preventing rereplication. Our analysis suggests that distributive multisite phosphorylation of the S-Cdk targets Sld2 and Sld3 can generate both a robust time delay and contribute to switch-like, coherent activation of replication origins. The proposed catalytic function of the complex formed by Dpb11, Sld3 and Sld2 strongly enhances coherence and robustness of origin firing. The model rationalizes how experimentally observed inefficient replication from fewer origins is caused by premature activation of S-Cdk, while premature activity of the S-Cdk targets Sld2 and Sld3 results in DNA rereplication. Thus the model demonstrates how kinetic deregulation of the molecular network governing DNA replication may result in genomic instability

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur