Erythema multiforme-like papules after COVID vaccine administration.

A unique dermatopathology incident arose after administration of the mRNA-1273 SARS-CoV-2 (Moderna) vaccine. Specifically, a transient purpuric interface dermatitis occurred 5 days post-second vaccine with the presentation of erythematous papules with erythema multiforme-type findings. A patient developed purpuric interface dermatitis with micro-vesiculation post-vaccination which ultimately resolved without sequelae.

The harms of promoting the lab leak hypothesis for SARS-CoV-2 origins without evidence.

Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence. We discuss how the resulting anti-science movement puts the research community, scientific research, and pandemic preparedness at risk.

Preliminary investigations into the use of the ancient pigments Han blue and Han purple as luminescent dusting powders for the detection of latent fingermarks.

Here we present our preliminary studies into the inorganic pigments Han blue (BaCuSi4O10) and Han purple (BaCuSi2O6) as near-infrared luminescent fingerprint dusting powders. These pigments were developed in ancient China around 800 BCE and both show luminescence in the NIR region. There remains, however, ambiguity in the literature concerning their photophysical properties. Samples of Han blue and Han purple artist's pigments were characterized by optical microscopy, infrared, ultraviolet-visible absorbance and luminescence spectroscopy. Their performance as fingerprint dusting powders, without any further treatment, on non-porous surfaces were compared to exfoliated lipophilic coated Egyptian blue and commercial fluorescent powders in a pilot study. These results demonstrate for the first time that both ancient pigments show promise as alternative dusting powders for latent fingermarks.

Short-term hyposalinity stress increases dissolved organic carbon (DOC) release by the macroalga Sargassum fallax (Ochrophyta).

Dissolved organic carbon (DOC) released by macroalgae supports coastal ocean carbon cycling and contributes to the total oceanic DOC pool. Salinity fluctuates substantially in coastal marine environments due to natural and anthropogenic factors, yet there is limited research on how salinity affects DOC release by ecologically important macroalgae. Here we determined the effect of short-term salinity changes on rates of DOC release by the habitat-forming fucalean seaweed Sargassum fallax (Ochrophyta). Lateral branches (~4 g) cut at the axes of mature individuals were incubated across a salinity gradient (4-46) for 24 h under a 12:12 light:dark cycle, and seawater was sampled for DOC at 0, 12, and 24 h. Physiological assays (tissue water content, net photosynthesis, respiration, tissue carbon, and nitrogen content) were undertaken at the end of the 24-h experiment. Dissolved organic carbon release increased with decreasing salinity while net photosynthesis decreased. Dissolved organic carbon release rates at the lowest salinity tested (4) were ~3.3 times greater in the light than in the dark, indicating two potential DOC release mechanisms: light-mediated active exudation and passive release linked to osmotic stress. Tissue water content decreased with increasing salinity. These results demonstrate that hyposalinity stress alters the osmotic status of S. fallax, reducing photosynthesis and increasing DOC release. This has important implications for understanding how salinity conditions encountered by macroalgae may affect their contribution to the coastal ocean carbon cycle.

Self-Reported Adverse Childhood Experiences and Risk for Internalizing and Externalizing Difficulties among Adolescent Custodial Grandchildren.

Despite custodial grandchildren's (CG) traumatic histories and risk for psychological difficulties, knowledge is scant regarding the frequencies, types, and consequences es of adverse childhood experiences (ACEs) they have encountered. We examined self-reported ACEs via online surveys with 342 CG (ages 12 to 18) who were recruited to participate in an RCT of a social intelligence training program. ACEs were assessed by 14 widely used items, and risk for internalizing (ID) and externalizing (ED) difficulties were measured using 80th percentile cut-offs on the Strengths and Difficulties Questionnaire. Classification and regression tree analyses included all 14 ACEs (along with CG gender and age) as predictors of ID and ED risk separately. Given possible comorbidity, analyses were run with and without the other risk type as a predictor. Less than 9% of CG self-reported no ACEs, 48.6% reported two to five ACEs, and 30.5 % reported ≥ 6. Irrespective of ED risk, bullying from peers strongly predicted ID risk. ED risk was peak among CG who also had risk for ID. Without ID risk as a predictor, ED risk was highest among CG who were emotionally abused, not lived with a substance abuser, and encountered neighborhood violence. The frequency and types of ACEs observed were alarmingly higher than those among the general population, suggesting that many CG have histories of trauma and household dysfunction. That a small number of ACEs among the 14 studied here were significant predictors of ID and ED risk challenges the widespread belief of a cumulative dose ACE effect.

Leveraging biotin-based proximity labeling to identify cellular factors governing early alphaherpesvirus infection.

Neurotropic alphaherpesviruses, including herpes simplex virus type 1 and pseudorabies virus, establish a lifelong presence within the peripheral nervous system of their mammalian hosts. Upon entering cells, two conserved tegument proteins, pUL36 and pUL37, traffic DNA-containing capsids to nuclei. These proteins support long-distance retrograde axonal transport and invasion of the nervous system in vivo. To better understand how pUL36 and pUL37 function, recombinant viral particles carrying BioID2 fused to these proteins were produced to biotinylate cellular proteins in their proximity (<10 nm) during infection. Eighty-six high-confidence host proteins were identified by mass spectrometry and subsequently targeted by CRISPR-Cas9 gene editing to assess their contributions to early infection. Proteins were identified that both supported and antagonized infection in immortalized human epithelial cells. The latter included zyxin, a protein that localizes to focal adhesions and regulates actin cytoskeletal dynamics. Zyxin knockout cells were hyper-permissive to infection and could be rescued with even modest expression of GFP-zyxin. These results provide a resource for studies of the virus-cell interface and identify zyxin as a novel deterrent to alphaherpesvirus infection.IMPORTANCENeuroinvasive alphaherpesviruses are highly prevalent with many members found across mammals [e.g., herpes simplex virus type 1 (HSV-1) in humans and pseudorabies virus in pigs]. HSV-1 causes a range of clinical manifestations from cold sores to blindness and encephalitis. There are no vaccines or curative therapies available for HSV-1. A fundamental feature of these viruses is their establishment of lifelong infection of the nervous system in their respective hosts. This outcome is possible due to a potent neuroinvasive property that is coordinated by two proteins: pUL36 and pUL37. In this study, we explore the cellular protein network in proximity to pUL36 and pUL37 during infection and examine the impact of knocking down the expression of these proteins upon infection.

The Surgical Method of Craniectomy Differentially Affects Acute Seizures, Brain Deformation and Behavior in a TBI Animal Model.

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality worldwide. Multiple injury models have been developed to study this neurological disorder. One such model is the lateral fluid-percussion injury (LFPI) rodent model. The LFPI model can be generated with different surgical procedures that could affect the injury and be reflected in neurobehavioral dysfunction and acute EEG changes. A craniectomy was performed either with a trephine hand drill or with a trephine electric drill that was centered over the left hemisphere of adult, male Sprague Dawley rats. Sham craniectomy groups were assessed by hand-drilled (ShamHMRI) and electric-drilled (ShamEMRI) to evaluate by MRI. Then, TBI was induced in separate groups (TBIH) and (TBIE) using a fluid-percussion device. Sham-injured rats (ShamH/ShamE) underwent the same surgical procedures as the TBI rats. During the same surgery session, rats were implanted with screw and microwire electrodes positioned in the neocortex and hippocampus and the EEG activity was recorded 24 hours for the first 7 days after TBI for assessing the acute EEG seizure and Gamma Event Coupling (GEC). The electric drilling craniectomy induced greater tissue damage and sensorimotor deficits compared to the hand drill. Analysis of the EEG revealed acute seizures in at least one animal from each group after the procedure. Both TBI and Sham rats from the electric drill groups had a significant greater total number of seizures than the animals that were craniectomized manually (p<0.05). Similarly, EEG functional connectivity was lower in ShamE compared to ShamH rats. These results suggest that electrical versus hand drilling craniectomies produce cortical injury in addition to the LFPI which increases the likelihood for acute post-traumatic seizures. Differences in the surgical approach could be one reason for the variability in the injury that makes it difficult to replicate results between preclinical TBI studies.

Negative urgency as a state-level process.

OBJECTIVE: Test whether global self-reports of urgency moderated the within-person associations of affect and impulsive behaviors. BACKGROUND: Negative urgency is a personality trait that is a risk factor for a range of psychopathology. Although it is assumed that global self-reports of urgency measure individual tendencies to act more impulsively in the face of negative emotions, evidence from ecological momentary assessment studies is mixed. METHOD: In this Registered Report, we used ecological momentary assessment data from a large sample of young adults (n = 496, age 18-22, 5 surveys per day for 40 days). RESULTS: All forms of momentary impulsivity were impaired in moments when people reported more intense negative emotions, but global self-reports of urgency did not explain individual differences in this association. Moreover, averaged affective states, rather than specific dimensions, affective circumplex, or appraisals, best predicted impulsive states. CONCLUSIONS: Results suggest that face-valid interpretations of global self-report of urgency are inaccurate, and it may be important to understand how some people come to understand themselves as high on urgency rather than assuming that people's self-reports of their motivations are accurate. Momentary experiences of emotions globally impact multiple weakly to moderately associated impulsive behaviors, and future research should seek to understand both when and for whom these associations are strongest.

Snapshot Sampling May Not Be Enough to Obtain Robust Estimates for Riverine Microplastic Loads.

Wastewater treatment plants (WWTPs) have been described as key contributors of microplastics (MPs) to aquatic systems, yet temporal fluctuations in MP concentrations and loads downstream are underexplored. This study investigated how different sampling frequencies (hourly, weekly, and monthly) affect MP estimates in a stream linked to a single WWTP. Utilizing fluorescence microscopy and Raman spectroscopy, considerable hourly variations in MP concentrations were discovered, while the polymer composition remained consistent. This temporal variability in MP loads was influenced by MP concentration, discharge rates, or a mix of both. These results show a high uncertainty, as relying on sparse snapshot samples combined with annual discharge data led to significant uncertainties in MP load estimates (over- and/or underestimation of emissions by 3.8 billion MPs annually at this site). Our findings stress the necessity of higher-frequency sampling for better comprehending the hydrodynamic factors influencing MP transport. This improved understanding enables a more accurate quantification of MP dynamics, crucial for downstream impact assessments. Therefore, preliminary reconnaissance campaigns are essential for designing extended, representative site-monitoring programs and ensuring more precise trend predictions on a larger scale.

Dissimilar effect of organometallic ruthenium complexes on the viability of MDR and non-MDR experimental models.

Ruthenium complexes containing triphenylphosphine diamide ligands were prepared, characterized, and tested for their biological activity against various cancer cell lines and the malaria parasite, Plasmodium falciparum. The effect of M (mono-substituted) and B (bis-substituted) complexes on the human cervical carcinoma (HeLa) cell line was investigated using the MTT assay. Five (B2, B3, B5, B6, and B13) of the 24 synthesized ruthenium complexes showed significant effects with IC50 values ranging between 0.3 and 2.3 µM. Evaluation of the potential biomolecular targets of B2 and B13 by fluorescence spectroscopy revealed relevant interactions with BSA and only a weak affinity for ctDNA. Complexes M2, B2, M13 and B13 were selected for further biological characterization. Their effect on the viability of two ovarian cancer cell lines was compared to normal cell lines, denoting their selectivity. Upon treatment of four different drug-resistant gynaecological cancer cell lines, differing in their multidrug-resistant phenotypes, the efficacy of the bis-substituted complexes was shown to be greater than their mono-substituted counterparts. The non-MDR cells are sensitive to all the tested complexes, compared to MDR cells which are less sensitive. Upon investigation of complexes M2, M13, B2, and B13 against sensitive and multidrug-resistant parasite strains of P. falciparum, the bis-substituted complexes were again shown to be the most potent, with submicromolar activity against both strains. Furthermore, the resistance indexes for the complexes were approximately equal to 1, which is at least 5-fold lower than chloroquine diphosphate, suggesting the ability of these complexes to retain their activity in resistant forms of the parasite.

The HSV-1 pUL37 protein promotes cell invasion by regulating the kinesin-1 motor.

Neurotropic alphaherpesviruses, including herpes simplex virus type 1 (HSV-1), recruit microtubule motor proteins to invade cells. The incoming viral particle traffics to nuclei in a two-step process. First, the particle uses the dynein-dynactin motor to sustain transport to the centrosome. In neurons, this step is responsible for long-distance retrograde axonal transport and is an important component of the neuroinvasive property shared by these viruses. Second, a kinesin-dependent mechanism redirects the particle from the centrosome to the nucleus. We have reported that the kinesin motor used during the second step of invasion is assimilated into nascent virions during the previous round of infection. Here, we report that the HSV-1 pUL37 tegument protein suppresses the assimilated kinesin-1 motor during retrograde axonal transport. Region 2 (R2) of pUL37 was required for suppression and functioned independently of the autoinhibitory mechanism native to kinesin-1. Furthermore, the motor domain and proximal coiled coil of kinesin-1 were sufficient for HSV-1 assimilation, pUL37 suppression, and nuclear trafficking. pUL37 localized to the centrosome, the site of assimilated kinesin-1 activation during infection, when expressed in cells in the absence of other viral proteins; however, pUL37 did not suppress kinesin-1 in this context. These results indicate that the pUL37 tegument protein spatially and temporally regulates kinesin-1 via the amino-terminal motor region in the context of the incoming viral particle.

Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures.

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs.

Essentiality of dietary cholesterol and its interactions with phospholipid in juvenile slipper lobster (Thenus australiensis).

This study was conducted to verify the essentiality of dietary cholesterol for early juvenile slipper lobster, Thenus australiensis (initial weight 4.50 ± 0.72 g, mean ± SD, CV = 0.16), and to explore the potential for interactions between dietary cholesterol and phospholipid. An 8-week experiment was conducted using six experimental feeds containing three supplemental cholesterol concentrations (0, 0.2 and 0.4% dry matter) at two supplemental phospholipid concentrations (0% and 1.0% dry matter). Dietary cholesterol concentrations of ≥ 0.2% resulted in up to threefold greater weight gain compared to 0% dietary cholesterol, but without any significant main or interactive dietary phospholipid effect. An interaction was observed for lobster survival with lowest survival (46%) recorded for combined 0% cholesterol and 0% phospholipid compared to every other treatment (71-100%). However, all surviving lobsters at 0% dietary cholesterol, regardless of dietary phospholipid level, were in poor nutritional condition. Apparent feed intake (AFI) was significantly higher at dietary cholesterol ≥ 0.2% but was lower for each corresponding dietary cholesterol level at 1% dietary phospholipid. This implied that the feed conversion ratio was improved with supplemental phospholipid. In conclusion, this study confirms the essential nature of dietary cholesterol and that dietary phospholipid can provide additional benefits.

Does Social Intelligence Training Improve Daily Well-Being and Responsiveness to Daily Negative and Positive Events in Custodial Grandmothers?

OBJECTIVES: Custodial grandparents are grandparents who raise grandchildren on a full-time basis in absence of the grandchild's birth parents. Compared to noncaregiving grandparents, custodial grandparents report poorer mental and physical health and stronger changes in daily well-being when experiencing negative and positive events. We examine whether an online social intelligence training (SIT) program improves custodial grandmothers' (CGM) daily well-being, socioemotional skills, and changes in well-being when confronted with daily negative and positive events. METHODS: Multilevel models were applied to 200 CGM who were recruited from across the United States and completed a daily survey for 14 consecutive days prior to and following participation in a randomized clinical trial. Participants were randomized into the SIT program or an attention control condition focusing on healthy living habits. The outcomes of interest were daily well-being, social connectedness, emotional awareness, and perspective-taking. RESULTS: Multilevel analyses revealed that participants who participated in the SIT program, compared to the attention control condition, exhibited stronger emotional responsiveness (i.e., improvements) to daily positive events in the outcomes of positive affect, social engagement, and perspective-taking. DISCUSSION: Our findings illustrate that SIT improves key components of daily functioning in CGM, which may serve as a pathway linking the demands of custodial grandparenting to poorer mental and physical health. Our discussion focuses on the utility and accessibility of the SIT program for helping improve outcomes for this disadvantaged population.Clinical Trials Registration Number: NCT03239977.

Trinuclear ruthenium(II) polypyridyl complexes: Evaluation as photosensitizers for enhanced cervical cancer treatment.

Trinuclear ruthenium(II) polypyridyl complexes anchored to benzimidazole-triazine / trisamine scaffolds were investigated as photosensitizers for photodynamic therapy. The trinuclear complexes were noted to produce a significant amount of singlet oxygen in both DMF and aqueous media, are photostable and show appreciable emission quantum yields (ɸem). In our experimental setting, despite the moderate phototoxic activity in the HeLa cervical cancer cell line, the phototoxic indices (PI) of the trinuclear complexes are superior relative to the PIs of a clinically approved photosensitizer, Photofrin®, and the pro-drug 5-aminolevulinic acid (PI: >7 relative to PI: >1 and PI: 4.4 for 5-aminolevulinic acid and Photofrin®, respectively). Furthermore, the ruthenium complexes were noted to show appreciable long-term cytotoxicity upon light irradiation in HeLa cells in a concentration-dependent manner. Consequently, this long-term activity of the ruthenium(II) polypyridyl complexes embodies their ability to reduce the probability of the recurrence of cervical cancer. Taken together, this presents a strong motivation for the development of polymetallic complexes as anticancer agents.

Eating disorder-related functional impairment predicts greater depressive symptoms across one semester of college.

Eating disorder (ED) behaviors and depression are associated with numerous negative outcomes, including lower quality of life and functional impairment. College women are at elevated risk for both. Prior research indicates ED behaviors, including binge eating, self-induced vomiting, and fasting, predict increases in future depressive symptoms. However, symptom heterogeneity in EDs is common, and all disordered eating, or its associated distress, cannot be captured by the endorsement of behaviors. Impairment that results from ED behaviors may be a comparable, or stronger, predictor of depressive symptoms. We sought to characterize the longitudinal relationship between ED-related functional impairment, ED behaviors, and depressive symptoms. College-aged women [N = 304; 72 % white, mean (SD) age = 18.45 (0.88)] completed an online survey in August (baseline), and then three months later in November (follow-up). Baseline ED-related functional impairment, but not baseline ED behaviors, significantly predicted depressive symptoms at follow-up, controlling for baseline depressive symptoms, negative affect, and body mass index. Findings indicate ED-related functional impairment is a risk factor for increases in depressive symptoms across one semester of college, irrespective of ED behavior engagement, weight status, and dispositional negative affect. Intervening upon ED-related functional impairment may reduce or prevent future depressive symptoms among college-aged women.

Selective Targeting of Regulated Rhabdomyosarcoma Cells by Trinuclear Ruthenium(II)-Arene Complexes.

The use of benzimidazole-based trinuclear ruthenium(II)-arene complexes (1-3) to selectively target the rare cancer rhabdomyosarcoma is reported. Preliminary cytotoxic evaluations of the ruthenium complexes in an eight-cancer cell line panel revealed enhanced, selective cytotoxicity toward rhabdomyosarcoma cells (RMS). The trinuclear complex 1 was noted to show superior short- and long-term cytotoxicity in RMS cell lines and enhanced selectivity relative to cisplatin. Remarkably, 1 inhibits the migration of metastatic RMS cells and maintains superior activity in a 3D multicellular spheroid model in comparison to that of the clinically used cisplatin. Mechanistic insights reveal that 1 effectively induces genomic DNA damage, initiates autophagy, and prompts the intrinsic and extrinsic apoptotic pathways in RMS cells. To the best of our knowledge, 1 is the first trinuclear ruthenium(II) arene complex to selectively kill RMS cells in 2D and 3D cell cultures.

Exploring the modulatory influence on the antimalarial activity of amodiaquine using scaffold hybridisation with ferrocene integration.

Amodiaquine (AQ) is a potent antimalarial drug used in combination with artesunate as part of artemisinin-based combination therapies (ACTs) for malarial treatment. Due to the rising emergence of resistant malaria parasites, some of which have been reported for ACT, the usefulness of AQ as an efficacious therapeutic drug is threatened. Employing the organometallic hybridisation approach, which has been shown to restore the antimalarial activity of chloroquine in the form of an organometallic hybrid clinical candidate ferroquine (FQ), the present study utilises this strategy to modulate the biological performance of AQ by incorporating ferrocene. Presently, we have conceptualised ferrocenyl AQ derivatives and have developed facile, practical routes for their synthesis. A tailored library of AQ derivatives was assembled and their antimalarial activity evaluated against chemosensitive (NF54) and multidrug-resistant (K1) strains of the malaria parasite, Plasmodium falciparum. The compounds generally showed enhanced or comparable activities to those of the reference clinical drugs chloroquine and AQ, against both strains, with higher selectivity for the sensitive phenotype, mostly in the double-digit nanomolar IC50 range. Moreover, representative compounds from this series show the potential to block malaria transmission by inhibiting the growth of stage II/III and V gametocytes in vitro. Preliminary mechanistic insights also revealed hemozoin inhibition as a potential mode of action.

Mononuclear η6-arene ruthenium(II) complexes with pyrazolyl-pyridazine ligands: synthesis, CT-DNA binding, reactivity towards glutathione, and cytotoxicity.

Organometallic η6-arene ruthenium(II) complexes with 3-chloro-6-(1H-pyrazol-1-yl)pyridazine (Ru1, Ru2, and Ru5) and 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine (Ru3-4) N,N' heterocyclic and η6-arene (cymene (Ru1-4) or toluene (Ru 5)) have been synthesized. The ruthenium(II) complexes have common "three-legged piano-stool" pseudo-octahedral structures known for half-sandwich complexes. Evolution of their UV-Visible absorption spectra in PBS buffer or DMSO over 24 h confirmed their good solvolysis stability. Titrations of the complexes with the calf thymus DNA (CT-DNA) were monitored using UV-Visible absorption and fluorescence spectroscopies. The complexes interact moderately with CT-DNA and their binding constants are in the order of 104 M-1. Competitive binding of the complexes to a DNA-Hoechst 33,258 depicted competitive displacement of Hoechst from DNA's minor grooves. These complexes bind to glutathione forming GSH-adducts through S coordination by replacement of a halide, with the iodo-analogues having higher binding constants than the chloro-complexes. Cyclic voltammograms of the complexes exhibited one electron-transfer quasi-reversible process. Trends in the molecular docking data of Ru1-5/DNA were similar to those for DNA binding constants. Of the five, only Ru1, Ru3 and Ru5 showed some activity (moderate) against the MCF-7 breast cancer cells with IC50 values in the range of 59.2-39.9 for which Ru5 was the most active. However, the more difficult-to-treat cell line, MDA-MB 231 cell was recalcitrant to the treatment by these complexes.