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Hidetomo Murakami,1 Hiroo Ichikawa,2 Azusa Sugimoto,1 Akinori Futamura,1 Yuki Shimizu,2 Masayuki Sugie,2 Michael W Miller,3 Mitsuru Kawamura11Department of Neurology, Showa University School of Medicine, Tokyo, Japan; 2Department of Neurology, Showa University Fujigaoka Hospital, Yokohama, Japan; 3MD/PhD Program, University of Tokyo Postgraduate School of Medicine, Tokyo, JapanAbstract: A 49-year-old man with mitochondrial disease presented with visual allesthesia, a rare and puzzling phenomenon. He was admitted for treatment because of convulsions. After the convulsions ceased, he exhibited left homonymous hemianopsia. Brain diffusion-weighted magnetic resonance imaging (MRI) showed a high-intensity area in the right occipital lobe. Both the hemianopsia and the MRI activation in this area disappeared by day 36 of hospitalization. On the morning of day 57, right homonymous hemianopsia emerged in a singular manner. The patient perceived an illusory object (a bottle placed by the bedside) in his left visual field, while the real object was in his blind right field. This case of visual allesthesia was ­accompanied by palinopsia, ie, perseveration of the image of the bottle. Diffusion-weighted MRI showed a new, high-intensity area in the left occipital lobe. We believe the visual allesthesia resulted from transfer of cortical information obtained by blindsight between hemispheres as a result of epileptic excitation.Keywords: visual allesthesia, blindsight, palinopsia, mitochondrial disease, epilepsy

Azusa Sugimoto1, Shinichi Koyama2, Akira Midorikawa3, Akinori Futamura1, Kiichi Ishiwata4, Kenji Ishii4, Michael W Miller5, Mitsuru Kawamura11Department of Neurology, Showa University School of Medicine, Tokyo, 2Design Psychology Unit, Department of Design Science, Graduate School of Engineering, Chiba University, Chiba, 3Department of Psychology, Faculty of Letters, Chuo University, Tokyo, 4Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, 5Medical Sciences Training Programme, Faculty of Medicine, University of Tokyo, Tokyo, JapanAbstract: Prosopagnosia, the inability to recognize faces, has a history going back to Charcot and Hughlings-Jackson, but was first named by Bodamer in 1947. Its anatomical loci are still unclear. However, progressive prosopagnosia is normally linked to right dominant temporal lobe atrophy, and diagnosed as part of frontotemporal lobar degeneration. Here we report a case of prosopagnosia linked to posterior cortical atrophy. Although case reports of posterior cortical atrophy-prosopagnosia do already exist, it is normally described as an accessory symptom. The interest of our own posterior cortical atrophy patient, possibly the first such case, is that he had a rare apperceptive type of prosopagnosia unrelated to the associative, frontotemporal lobar degeneration-type.Keywords: dementia, Alzheimer's disease, frontotemporal lobar degeneration, neuropsychology

Michael W Miller1, Richard Tren21Duke Global Health Institute, Duke University, Durham, NC, USA; 2Africa Fighting Malaria, Washington, DC, USAAbstract: Millions of people rely on public-health insecticides for malaria prevention. Yet growing insecticide resistance may threaten malaria control programs through decreasing effectiveness and possibly unsustainable cost-increases. Insufficient investment by stakeholders in the search for new public-health insecticides in recent decades has left malaria control programs with limited alternatives with which to manage resistance and maintain program effectiveness. While alternative insecticides are available, short of an unforeseen, significant increase in funding, their higher cost would compel programs to reduce malaria control coverage, leading to increased mortality and morbidity. In order to limit these negative effects on cost and coverage, we propose that policymakers and malaria stakeholders consider adoption of existing policies from successful efforts to secure reduced prices and increased access to other essential health interventions.Keywords: vector control, indoor residual spraying (IRS), malaria control policy, research and development (R+D), priority review voucher (PRV), compulsory license

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

This study evaluated evidence for 2 forms of emotional abnormality in posttraumatic stress disorder (PTSD): numbing and heightened negative emotionality. Forty-nine male veterans with PTSD and 75 without the disorder rated their emotional responses to photographs that depicted scenes of Vietnam combat or were drawn from the International Affective Picture System (Lang et al., 2005). Images varied in their trauma-relatedness and affective qualities. A series of repeated measures ANOVAs revealed that Vietnam combat veterans with PTSD responded to unpleasant images with greater negative emotionality (i.e., enhanced arousal and lower valence ratings) than those without the disorder and this effect was modified by the trauma-relatedness of the image with stronger effects for trauma-related images. In contrast, the 2 groups showed equivalent patterns of responses to pleasant images. Findings raise questions about the sensitivity of the International Affective Picture System rating protocol for the assessment of PTSD-related emotional numbing. [ABSTRACT FROM AUTHOR]

This study examined the psychometric properties of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) Restructured Clinical Scales (RCSs) in individuals with posttraumatic stress disorder (PTSD) receiving clinical services at Department of Veterans Affairs medical centers. Study 1 included 1,098 men who completed the MMPI-2 and were assessed for a range of psychological disorders via structured clinical interview. Study 2 included 136 women who completed the MMPI-2 and were interviewed with the Clinician Administered Scale for PTSD. The utility of the RCSs was compared with that of the Clinical Scales (CSs) and the Keane PTSD (PK) scale. The RCSs demonstrated good psychometric properties and patterns of associations with other measures of psychopathology that corresponded to current theory regarding the structure of comorbidity. A notable advantage of the RCSs compared with the MMPI-2 CSs was their enhanced construct validity and clinical utility in the assessment of comorbid internalizing and externalizing psychopathology. The PK scale demonstrated incremental validity in the prediction of PTSD beyond that of the RCSs or CSs. [ABSTRACT FROM AUTHOR]

Previous research suggests that grocery store characteristics may be useful in evaluating community-based dietary interventions. We undertook a study to determine whether produce ratios (ratios of produce sales to total grocery sales) were a useful indicator of fruit and vegetable (F & V) consumption in a church-based, community intervention trial that promoted 5 A Day guidelines within 10 rural counties of North Carolina. Produce ratios were collected from stores identified by participants in the Black Churches United for Better Health Project. Baseline and study period data for 21 stores in intervention counties and 18 stores in nonintervention counties were compared using repeated-measures analysis of variance. Produce ratios were significantly associated with seasonality (p < 0.0001), but no differences were seen between the two groups of stores. These findings do not support data from individual telephone surveys, which showed significant differences in F & V consumption between participants in the two groups. Our inability to detect differences at the store level may have been due to 1) the incapacity of produce ratios to capture F & V purchases that were juice, frozen, or canned products; 2) shifts in procuring F & Vs from grocery stores to other sources (i.e., gleaning and produce cooperatives); 3) the modest proportion of shoppers that received the full intervention dose; and 4) a general lack of power to detect differences at the store level. Therefore, although produce ratios did not serve as a valid measure for this project, if their limitations are recognized and compensated for, they may have applicability for future investigations that monitor F & V consumption. [ABSTRACT FROM AUTHOR]

Promoter DNA methylation is a key epigenetic mark, commonly associated with gene silencing. However, we noticed that a positive association between promoter DNA methylation and expression is surprisingly common in cancer. Here, we use hit-and-run CRISPR/dCas9 epigenome editing to evaluate how deposition of DNA methylation can regulate gene expression dependent on pre-existing chromatin environment. While the predominant effect of DNA methylation in non-bivalent promoters is gene repression, we show that in bivalent promoters this often leads to gene activation. We demonstrate that gain of DNA methylation leads to reduced MTF2 binding and eviction of H3K27me3, a repressive mark that guards bivalent genes against activation. Our cancer patient data analyses reveal that in cancer, this mechanism likely leads to activation of a large group of transcription factors regulating pluripotency, apoptosis, and senescence signalling. In conclusion, our study uncovers an activating role of DNA methylation in bivalent promoters, with broad implications for cancer and development.

Background: Larval propagation and seeding of scleractinian corals for restoration is a rapidly expanding field, with demonstrated applications to assist the recovery of declining populations on reefs. The process typically involves collecting coral reproductive material, facilitating in vitro fertilization (IVF), and settling and outplanting the resulting coral offspring. Optimizing IVF can reduce gamete wastage and increase larval yields for propagation, therefore improving the efficiency of this intervention., Methods: In this study we tested three IVF conditions in four Caribbean broadcast-spawning coral species ( i.e ., Diploria labyrinthiformis , Colpophyllia natans , Pseudodiploria strigosa , Orbicella faveolata ) to determine sperm concentration, gamete age, and co-incubation time resulting in the highest fertilization success. For each species, we exposed eggs from a single dam to pooled sperm samples from three sires (1) at concentrations ranging from zero to 10 9 cell mL -1 , (2) after letting gametes age for 2 to 6 h, and (3) for a period of 15 to 120 min., Results: These experiments revealed a gamete longevity of at least 4 h and clear minimum sperm concentration thresholds (>10 5 to 10 6 cell mL -1 ) in all four species. Fertilization took place much faster than expected (≤15 min) in the three brain corals under study, whereas O. faveolata gametes required a co-incubation period of 60 to 120 min to achieve maximum IVF success., Discussion: We present these results in the context of IVF data available for other hermaphroditic broadcast-spawning scleractinians. We then provide recommendations for coral breeding practitioners to maximize larval production from gamete collections, and finally, we discuss our findings' potential implications on fertilization dynamics during natural coral spawning events., Competing Interests: The authors declare that they have no competing interests., (© 2025 Chamberland et al.)

Posttraumatic stress disorder (PTSD) is often chronic, which is costly to the individual and society. Easy-to-measure prognostic indicators can help to ensure that those with the greatest symptoms receive treatment. Inflammatory biomarkers may precede and predict depression chronicity and worsening, as well as PTSD. Yet, it is unknown if inflammatory biomarkers predict changes in symptoms among those who have already developed PTSD. Among 82 US military veterans (82 % male) diagnosed with PTSD, we measured C-reactive protein (CRP) and conducted clinical diagnostic interviews assessing PTSD and major depression at two visits, an average of five years apart. Cross-lagged models revealed that CRP at Time 1 was positively associated with PTSD symptom severity (p = 0.017), depression diagnosis (p < 0.001), depressive symptom count (p=.001), and anhedonia (p < 0.001) but not low mood (p = 0.183) at Time 2, covarying for baseline levels of these outcomes as autoregressive effects and for potential confounds. Results suggest that elevated CRP may be a risk factor for more chronic and severe PTSD symptoms, perhaps with comorbid anhedonic depression. Further exploration of CRP as a prognostic indicator of PTSD is warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1 . The rapid development of highly effective vaccines 2,3 against SARS-CoV-2 has altered the trajectory of the pandemic, and antiviral therapeutics 4 have further reduced the number of COVID-19 hospitalizations and deaths. Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that encode various structural and non-structural proteins, including those critical for viral RNA replication and evasion from innate immunity 5 . Here we report the discovery and development of a first-in-class non-covalent small-molecule inhibitor of the viral guanine-N7 methyltransferase (MTase) NSP14. High-throughput screening identified RU-0415529, which inhibited SARS-CoV-2 NSP14 by forming a unique ternary S-adenosylhomocysteine (SAH)-bound complex. Hit-to-lead optimization of RU-0415529 resulted in TDI-015051 with a dissociation constant (K d ) of 61 pM and a half-maximal effective concentration (EC 50 ) of 11 nM, inhibiting virus infection in a cell-based system. TDI-015051 also inhibited viral replication in primary small airway epithelial cells and in a transgenic mouse model of SARS CoV-2 infection with an efficacy comparable with the FDA-approved reversible covalent protease inhibitor nirmatrelvir 6 . The inhibition of viral cap methylases as an antiviral strategy is also adaptable to other pandemic viruses., Competing Interests: Competing interests: The authors declare no competing interests. The Rockefeller University filed patent application PCT/US2024/012695 titled ‘Sulfonamide-1H-pyrrole-2-carboxamide inhibitors of SARS-CoV-2 NSP14 methyltransferase and derivatives thereof’., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Snails belonging to the genus Biomphalaria serve as obligatory intermediate hosts for the trematode Schistosoma mansoni, the causative agent for the most widespread form of schistosomiasis. The simpler nervous systems of gastropod molluscs, such as Biomphalaria, provide advantageous models for investigating neural responses to infection at the cellular and network levels. The present study examined neuropeptides related to cholecystokinin (CCK), a major multifunctional regulator of central nervous system (CNS) function in mammals. A neural transcriptome generated from the CNS of Biomphalaria alexandrina included a transcript encoding two CCK-related peptides, designated Balex-CCK1 (pEGEWSYDY (SO 3 H) GLGGGRF-NH 2 ) and Balex-CCK2 (NYGDY (SO 3 H) GIGGGRF-NH 2 ). Peptide expression was examined in Biomphalaria glabrata at the mRNA level using the hybridization chain reaction (HCR) protocol and at the protein level using an antibody against Balex-CCK1. Expression was detected in 60-70 neurons distributed throughout the CNS, as well as in profuse fiber systems connecting the ganglia and projecting to the periphery. CCK-like immunoreactive (CCK li ) fibers were also observed on organs associated with the cardiorespiratory (nephridium, mantle, gill) and male reproductive systems. A comparison of mRNA and peptide localization suggested that CCK expression could be regulated at the level of translation. A potential role of these peptides in mediating responses to infection by larval schistosomes is discussed., (© 2025 Wiley Periodicals LLC.)