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The transmembrane protein claudin‐1 is critical for formation of the epidermal barrier structure called tight junctions (TJ) and has been shown to be important in multiple disease states. These include neonatal ichthyosis and sclerosing cholangitis syndrome, atopic dermatitis and various viral infections. To develop a model to investigate the role of claudin‐1 in different disease settings, we used CRISPR/Cas9 to generate human immortalized keratinocyte (KC) lines lacking claudin‐1 (CLDN1 KO). We then determined whether loss of claudin‐1 expression affects epidermal barrier formation/function and KC differentiation/stratification. The absence of claudin‐1 resulted in significantly reduced barrier function in both monolayer and organotypic cultures. CLDN1 KO cells demonstrated decreases in gene transcripts encoding the barrier protein filaggrin and the differentiation marker cytokeratin‐10. Marked morphological differences were also observed in CLDN1 KO organotypic cultures including diminished stratification and reduced formation of the stratum granulosum. We also detected increased proliferative KC in the basale layer of CLDN1 KO organotypic cultures. These results further support the role of claudin‐1 in epidermal barrier and suggest an additional role of this protein in appropriate stratification of the epidermis. [ABSTRACT FROM AUTHOR]

Background: Suicidal thoughts and behaviours (STB) are a common reason for presentation to emergency departments and general hospitals. A meta‐analysis of the strength of clinical risk factors for subsequent suicide might aid understanding of suicidal behaviour and help suicide prevention. Methods: We conducted a meta‐analysis of cohort and controlled studies on clinical risk factors and later suicide among people presenting to emergency departments and general hospitals with STB. Data were extracted from papers meeting inclusion criteria, published in Medline, PsycINFO, and Embase between 1 January 1960 and 10 October 2022 using papers located with the search terms ((suicide*).m_titl AND (emergency* OR accident and emergency OR casualty OR general hospital OR toxicology service).mp) or were indexed in PubMed and had titles located with the search terms (suicide* OR self‐harm OR self‐harm OR self‐injury OR self‐injury OR self‐poisoning OR self‐poisoning OR overdose OR para‐suicide OR parasuicide [title/abstract]) AND (Emergency department OR emergency room OR Casualty OR general hospital OR toxicology OR accident and emergency [all fields]). Data about the association between clinical risk factors and suicide extracted from three or more studies were included in a random‐effects meta‐analysis of the odds of later death by suicide. The study was registered in PROSPERO and conducted according to MOOSE and PRISMA guidelines. Results: Seventy‐five studies reported on 741,624 people, of which 19,649 died by suicide (2.65%). Male sex (odds ratio (OR) = 1.99) and age (OR = 2.01) were the most consistently reported risk factors. The strongest associations with subsequent death by suicide related to violent self‐harm methods at the hospital presentation, including: unspecified violent method (OR = 4.97), any violent method (OR = 4.57) and the specific violent methods of drowning (OR = 4.32), hanging (OR = 4.26), and use of firearms (OR = 10.08). Patients categorised as higher risk using suicide prediction scales or any other method that combined risk factors had moderately increased odds of suicide (OR = 2.58). Younger age, Black and Hispanic ethnicity, overdose, a diagnosis of adjustment disorder, and the absence of any psychiatric diagnosis were protective against suicide. Conclusions: Most risk factors for suicide among people who have presented with STB are not strongly associated with later suicide. The strongest risk factors relate to self‐harm methods. In the absence of clear indicators of future suicide, all people presenting with suicidality warrant a thorough assessment of their needs, and further research is needed before we can meaningfully categorise people with STB according to suicide risk. [ABSTRACT FROM AUTHOR]

Fish are common definitive and intermediate hosts for a variety of parasitic flatworms. In unstressed wild populations, parasitic infections often go unnoticed and are perceived to represent a lesser threat to fish health. In contrast, platyhelminth parasitism of captive fish often results in decreased weight gain and increased mortality which often necessitates chemotherapeutic treatment. The presence of platyhelminth parasites in fish tissues is not only unappealing but in some cases also represents a threat to human health. In veterinary medicine, one of the most commonly used agents with anti‐flatworm activity is praziquantel; yet, no praziquantel products are labeled for use in fish in the United States. Veterinarians may use praziquantel preparations approved for other vertebrate species under the Animal Medicinal Drug Use Clarification Act (AMDUCA). However, such extra‐label use should be informed by scientific evidence including efficacy and tissue residue studies. Herein, we review studies testing the efficacy of praziquantel for treatment of platyhelminthes along with an assessment of routes of administration, pharmacokinetics, and toxicity information. [ABSTRACT FROM AUTHOR]

Background: Chronic activation of macrophages/microglia plays a critical role in the onset and progression of neurological diseases, including Alzheimer's. While PET imaging could enable non‐invasive visualization and quantification of activated macrophages/microglia in vivo, most available PET tracers are nonspecific for macrophages/microglia (Lambert, 2009). To address this need, we developed [18F]OP‐801, a synthetic hydroxyl dendrimer‐based PET tracer that is selectively (>95%) taken up by reactive macrophages/microglia across the blood‐brain barrier (Alnasser, 2018). Here, we evaluated the ability of [18F]OP‐801 to detect activated macrophages/microglia in the 5XFAD murine model of Alzheimer's compared to an established neuroinflammation imaging approach (translocator protein 18 kDa [TSPO]‐PET, using [18F]GE180). Method: [18F]OP‐801 (150‐250 μCi) was injected intravenously into female 5XFAD (TG) mice (n=12) and age/sex‐matched wild types (WT, n=7) at 3.75 and 5 months old. Sensitivity of [18F]OP‐801 was compared to [18F]GE180 by assessing brain signal‐to‐background ratios. [18F]GE180 (150‐250 μCi) was administered to a subset of TG (n=5) and WT (n=4) 3.75‐months‐old mice. Static 10‐minute PET/CT images were acquired at 50‐60 minutes post‐injection for both tracers. VivoQuant brain atlas was fit to CT images and fused to PET to quantify uptake in specific brain regions. Result: In this model, macrophage/microglial activation is associated with amyloid plaque formation and can be detected using immunohistochemistry between 2‐4 months. Image quantification revealed 3‐fold higher PET signal in 3.75‐months‐old TG compared to WT mice using [18F]OP‐801, whereas [18F]GE180 signal provided no significant difference in brain regions known to contain activated microglia: cortex and hippocampus (Figure 1, Table 1). Significant differences in [18F]OP‐801 uptake were observed between 5‐months‐old TG and WT mice in cortex (p=0.005) (TG: 0.26±0.095%ID/g, WT: 0.11±0.041%ID/g), hippocampus (p=0.017) (TG: 0.18±0.065%ID/g, WT: 0.10±0.026%ID/g) and whole brain (p=0.004) (TG: 0.20±0.082%ID/g, WT: 0.10±0.039%ID/g). TG had almost 5‐fold higher [18F]OP‐801 signal compared to WT mice (Table 2). Conclusion: These results suggest that [18F]OP‐801 can detect early stage neuroinflammation with higher sensitivity than TSPO‐PET. We are currently replicating this study in a larger cohort of 5XFAD mice to correlate PET image findings with immunohistochemistry. [18F]OP‐801 is shows promise for visualizing the progression of neuroinflammation with high specificity and sensitivity, warranting further preclinical investigation. [ABSTRACT FROM AUTHOR]