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Abstract Background Cervical cancer is the second cause leading of malignancy-related death among Mexican women. The present study determined the population-based prevalence of high risk Human Papillomavirus (HR-HPV) infection and associated cofactors in female beneficiaries of the Institute of Security and Social Services for State Workers (ISSSTE) attending the Program for HPV Screening and Early Detection of Cervical Cancer and registered in the Women’s Cancer Detection System (SIDECAM). Methods In a cross-sectional study, cervical samples from 115,651 female users of the program for HPV screening and early detection of cervical cancer recruited in 23 ISSSTE care centers were analyzed for HR-HPV. Logistic regression analyses, adjusting for potential confounders, were performed to determine the association of HR-HPV infection with sexual health and behavior variables and with positivity to cervical premalignant lesions by cytology. Results The overall prevalence of HR-HPV infection among female ISSSTE beneficiaries in the 2013–2015 period was 13%. A bivariate analysis of relevant variables for HR-HPV infection showed a statistically significant association for age, number of sexual partners, use of hormonal contraceptives and smoking. A statistical association was found between infection by HR-HPV with the use of hormonal contraceptives, number of sexual partners and smoking and association of HPV 16 and other non-16/18 HR-HPV infection with number of lifetime sexual partners and tobacco use adjusted for age, history of hormonal contraception, number of sexual partners and tobacco use with the exception of exposition variable itself. Similarly, an association was found between HR-HPV infection, regardless of the virus genotype, with positivity to cervical premalignant lesions adjusted for age, number of lifetime sexual partners, history of hormonal contraception and tobacco use. Conclusions HR-HPV prevalence in female ISSSTE Women’s Cancer Program users is similar to the population-based prevalence previously reported in Mexican women without cervical alterations. The ISSSTE robust screening and early detection program, based on cytology studies and HPV co-testing, allows us to know the prevalence of HR-HPV infection among female users of the service.

A plethora of studies indicate that iron metabolism is dysregulated in Parkinson's disease (PD). The literature reveals well-documented alterations consistent with established dogma, but also intriguing paradoxical observations requiring mechanistic dissection. An important fact is the iron loading in dopaminergic neurons of the substantia nigra pars compacta (SNpc), which are the cells primarily affected in PD. Assessment of these changes reveal increased expression of proteins critical for iron uptake, namely transferrin receptor 1 and the divalent metal transporter 1 (DMT1), and decreased expression of the iron exporter, ferroportin-1 (FPN1). Consistent with this is the activation of iron regulator protein (IRP) RNA-binding activity, which is an important regulator of iron homeostasis, with its activation indicating cytosolic iron deficiency. In fact, IRPs bind to iron-responsive elements (IREs) in the 3ꞌ untranslated region (UTR) of certain mRNAs to stabilize their half-life, while binding to the 5ꞌ UTR prevents translation. Iron loading of dopaminergic neurons in PD may occur through these mechanisms, leading to increased neuronal iron and iron-mediated reactive oxygen species (ROS) generation. The “gold standard” histological marker of PD, Lewy bodies, are mainly composed of α-synuclein, the expression of which is markedly increased in PD. Of note, an atypical IRE exists in the α-synuclein 5ꞌ UTR that may explain its up-regulation by increased iron. This dysregulation could be impacted by the unique autonomous pacemaking of dopaminergic neurons of the SNpc that engages L-type Ca+2 channels, which imparts a bioenergetic energy deficit and mitochondrial redox stress. This dysfunction could then drive alterations in iron trafficking that attempt to rescue energy deficits such as the increased iron uptake to provide iron for key electron transport proteins. Considering the increased iron-loading in PD brains, therapies utilizing limited iron chelation have shown success. Greater therapeutic advancements should be possible once the exact molecular pathways of iron processing are dissected.

Purpose Though a worldwide period of uncertainty (COVID-19) has “ended”, there exists a legacy of maladaptive experiences among people with significant appearance concerns (SAC) that requires care and attention. Methods Using Giddens’ concept of ontological security, we explored how people experienced their SAC before, during and “since” COVID-19. Qualitative surveys allowed us to capture diverse perspectives from individuals transnationally, analysed with deductive reflexive thematic analysis using ontological security as our theoretical foundation. Results Themes named “More Mirror(ed) Time” and “Locked Out, Shut Down, and Shut Out” gave a contextual grounding for the embodied experiences of this group through times of social restrictions, and the theme “Redefining Relevance” explored the continued legacy of COVID-19 – and continued global uncertainties such as economic hardship and warfare – that impact the wellbeing of people with SAC. Conclusions People with SAC are still “locked out” from essential healthcare support as those providing healthcare are overworked, under-resourced and rely on efficient interactive methods such as tele-health that may be triggers for people with SAC. Care providers may consider expanding appearance concerns verbiage, look to involve trusted others in the care-seeking process, and utilize modalities beyond digital health to support people with SAC.

Ethnocentric models of disability have resulted in an ontology that rarely embraces the cultural nuances and social structures of specific countries. There have been increasing calls from scholars to expand understandings of disability beyond this hegemonic focus and develop new ways to do culturally specific and respectful inclusive work. Utilizing a novel methodological approach based on Paulo Freire's "Pedagogy of the Oppressed", we problematized past research and the current knowledge landscape of inclusive physical education (PE) in Japan. We identified that PE teachers were constantly "Grappling with Conflict" regarding their intrinsic desire to include disabled students in PE, and the cultural, institutional demands that instructed them how to teach. We drew upon numerous holistic, cultural, and Globally Eastern philosophies of thought to interpret these findings. Through reinterpreting past research, we developed a future research agenda for improving inclusive PE in Japan to support teachers and students through cultural praxis.

In its native range, Halyomorpha halys (Stål) is suppressed by parasitoids in the genus Trissolcus (Hymenoptera: Scelionidae). Trissolcus native to Utah have demonstrated low parasitism of H. halys, while adventive Trissolcus japonicus (Ashmead) have shown parasitism of up to 20%. Custom rubber septa lures containing stink bug kairomones, n-tridecane (attractant), and (E)-2-decenal (repellent), at 100%, 90%, and 80% levels of attractant (10 mg load rate), were placed adjacent to sentinel H. halys egg masses in northern Utah field trials. Egg masses were evaluated for the presence and intensity (proportion of parasitized eggs) of parasitism. Parasitism by T. japonicus and T. euschisti (Ashmead) was low; however, the 100% lure showed double the parasitism of the control and more than three times that of the 90% and 80%. Two-way choice mesocosm trials in the laboratory evaluated previous lures and a lower load rate of 5 mg—100% attractant treatment. Lures of 10 mg at 100% and 80% were more attractive to T. japonicus than the control, while 5 mg at 100% and 10 mg at 90% showed no significant attraction. Our results support a proof-of-concept of rubber septa as release devices for kairomones to attract T. japonicus and provide a baseline for future field-based studies.

Abstract Background Hypoplastic left heart syndrome (HLHS) covers a spectrum of rare congenital anomalies characterised by a non-apex forming left ventricle and stenosis/atresia of the mitral and aortic valves. Despite many studies, the causes of HLHS remain unclear and there are conflicting views regarding the role of flow, valvar or myocardial abnormalities in its pathogenesis, all of which were proposed prior to the description of the second heart field. Our aim was to re-evaluate the patterns of malformation in HLHS in relation to recognised cardiac progenitor populations, with a view to providing aetiologically useful sub-groupings for genomic studies. Results We examined 78 hearts previously classified as HLHS, with subtypes based on valve patency, and re-categorised them based on their objective ventricular phenotype. Three distinct subgroups could be identified: slit-like left ventricle (24%); miniaturised left ventricle (6%); and thickened left ventricle with endocardial fibroelastosis (EFE; 70%). Slit-like ventricles were always found in combination with aortic atresia and mitral atresia. Miniaturised left ventricles all had normally formed, though smaller aortic and mitral valves. The remaining group were found to have a range of aortic valve malformations associated with thickened left ventricular walls despite being described as either atresia or stenosis. The degree of myocardial thickening was not correlated to the degree of valvar stenosis. Lineage tracing in mice to investigate the progenitor populations that form the parts of the heart disrupted by HLHS showed that whereas Nkx2–5-Cre labelled myocardial and endothelial cells within the left and right ventricles, Mef2c-AHF-Cre, which labels second heart field-derived cells only, was largely restricted to the endocardium and myocardium of the right ventricle. However, like Nkx2–5-Cre, Mef2c-AHF-Cre lineage cells made a significant contribution to the aortic and mitral valves. In contrast, Wnt1-Cre made a major contribution only to the aortic valve. This suggests that discrete cardiac progenitors might be responsible for the patterns of defects observed in the distinct ventricular sub-groups. Conclusions Only the slit-like ventricle grouping was found to map to the current nomenclature: the combination of mitral atresia with aortic atresia. It appears that slit-like and miniature ventricles also form discrete sub-groups. Thus, reclassification of HLHS into subgroups based on ventricular phenotype, might be useful in genetic and developmental studies in investigating the aetiology of this severe malformation syndrome.

Salt-sensitive hypertension is common in glucocorticoid excess. Glucocorticoid resistance also presents with hypercortisolemia and hypertension but the relationship between salt intake and blood pressure (BP) is not well defined. GRβgeo/+ mice have global glucocorticoid receptor (GR) haploinsufficiency and increased BP. Here we examined the effect of high salt diet on BP, salt excretion and renal blood flow in GRβgeo/+mice. Basal BP was ∼10 mmHg higher in male GRβgeo/+ mice than in GR+/+ littermates. This modest increase was amplified by ∼10 mmHg following a high-salt diet in GRβgeo/+ mice. High salt reduced urinary aldosterone excretion but increased renal mineralocorticoid receptor expression in both genotypes. Corticosterone, and to a lesser extent deoxycorticosterone, excretion was increased in GRβgeo/+ mice following a high-salt challenge, consistent with enhanced 24 h production. GR+/+ mice increased fractional sodium excretion and reduced renal vascular resistance during the high salt challenge, retaining neutral sodium balance. In contrast, sodium excretion and renal vascular resistance did not adapt to high salt in GRβgeo/+ mice, resulting in transient sodium retention and sustained hypertension. With high-salt diet, Slc12a3 and Scnn1a mRNAs were higher in GRβgeo/+ than controls, and this was reflected in an exaggerated natriuretic response to thiazide and benzamil, inhibitors of NCC and ENaC, respectively. Reduction in GR expression causes salt-sensitivity and an adaptive failure of the renal vasculature and tubule, most likely reflecting sustained mineralocorticoid receptor activation. This provides a mechanistic basis to understand the hypertension associated with loss-of-function polymorphisms in GR in the context of habitually high salt intake.

Abnormalities of the arterial valve leaflets, predominantly bicuspid aortic valve, are the commonest congenital malformations. Although many studies have investigated the development of the arterial valves, it has been assumed that, as with the atrioventricular valves, endocardial to mesenchymal transition (EndMT) is the predominant mechanism. We show that arterial is distinctly different from atrioventricular valve formation. Whilst the four septal valve leaflets are dominated by NCC and EndMT-derived cells, the intercalated leaflets differentiate directly from Tnnt2-Cre+/Isl1+ progenitors in the outflow wall, via a Notch-Jag dependent mechanism. Further, when this novel group of progenitors are disrupted, development of the intercalated leaflets is disrupted, resulting in leaflet dysplasia and bicuspid valves without raphe, most commonly affecting the aortic valve. This study thus overturns the dogma that heart valves are formed principally by EndMT, identifies a new source of valve interstitial cells, and provides a novel mechanism for causation of bicuspid aortic valves without raphe.

The reactions of 3,4,9,10-perylenetetracarboxylic dianhydride with 4,4′-diamino-p-terphenyl and with 2,4,6-tris(4-aminophenyl)-1,3,5-triazine on an Au(111) surface have been followed by low-temperature UHV-STM in the range of 300 to 700 K at coverages of up to one monolayer. Well-ordered, H-bonded structures are observed even after annealing at temperatures up to 470 K, while above 550 K reaction is initiated with evidence of amic acid intermediates. At higher temperatures, full imidisation leads to a covalently linked, surface polyimide networks. There is evidence of gold reconstruction playing a role in the early stages of imidisation and signs of limited order in the final polyimide. With the diamine as precursor, 1D-interconnectivity results, while with the triamine as partner, full 2D-connectivity is possible. In contrast to the situation in the bulk, the intermediate amic acid seems to be less stable and iso-imides are common in the final networks, as witnessed by the conformation of the product and the prevalence of triangular features in the case of the polyimide formed from the triamine precursor. [ABSTRACT FROM AUTHOR]

Interest in the observation and characterization of organic isomers in astronomical environments has grown rapidly with an increase in the sensitivity of detection techniques. Accurate modeling and interpretation of these environments require experimental isomer-specific reactivity and spectroscopic measurements. Given the abundance of formaldehyde (H 2 CO) in various astrophysical objects, the properties and reactivities of its cation isomers H 2 CO •+ and HCOH •+ are of significant interest. However, for the hydroxymethylene radical cation HCOH •+ (and its isotopologue DCOH •+ ), detailed reactivity studies have been limited by the lack of suitable experimental methods to generate this isomer with high purity. Here, potential approaches to the isomer-selective generation of HCOH •+ and DCOH •+ are characterized through differential reactivity measurements. While the dissociative photoionization of cyclopropanol (c-CH 2 CH 2 CHOH) is determined to be unsuitable, the dissociation of methanol- d 3 (CD 3 OH) allows for the formation of DCOH •+ with a fractional abundance of >99% at photon energies below 14.8 eV. These results will allow future spectroscopic and reactivity measurements of HCOH •+ /DCOH •+ to be conducted, laying the groundwork for future detection and incorporation into models of the interstellar medium.

The coordination chemistry and electrochemistry of novel N -acridine thiosemicarbazones (NATs) were investigated along with their redox activity, antiproliferative efficacy, transmetalation, and dissociation properties. The ability of NAT Fe(III) complexes to inhibit detrimental oxy-myoglobin (oxy-Mb) oxidation was also examined. The NATs act as tridentate ligands with a 2:1 L/Zn(II) complex crystal structure, revealing a distorted octahedral geometry, where both ligands bind Zn(II) in a meridional conformation. The NAT Fe(III) complexes exhibited fully reversible one-electron Fe III/II couples with more positive potentials than the Fe(III) complexes of a related clinically trialed thiosemicarbazone (e.g., [Fe(DpC) 2 ] + ) due to the electron-donating capacity of acridine. Surprisingly, the NAT-Zn(II) complexes showed generally greater or similar antiproliferative activity than their ligands, Cu(II), or Fe(III) complexes. This may be explained by ( 1 ) formation of a highly lipophilic Zn(II) complex that acts as a chaperone to promote cellular uptake and ( 2 ) the capacity of the Zn(II) complex to dissociate or undergo transmetalation to the redox-active Cu(II) complex. Of the NAT-Fe(III) complexes, [Fe(AOBP) 2 ] + demonstrated a significant ( p < 0.0001) improvement in preventing oxy-Mb oxidation than the Fe(III) complex of the clinically trialed thiosemicarbazone, DpC. This article advances our understanding of NAT coordination chemistry, electrochemistry, and the intriguing biological activity of their complexes.

Background: Current acute healthcare service metrics are not meaningful for older people living with frailty. Healthcare knowledge, situational security, and physical and psychosocial function are important outcomes typically not collected. The use of patient-reported outcome measures (PROMs) could support these assessments. Existing instruments are not comprehensive as they typically consider function, while older people with frailty also value enablement (self-determination and security in health and healthcare). This study field-tested and validated a PROM for older people with frailty receiving acute care (PROM-OPAC) to measure enablement., Methods: People aged 65+ with Clinical Frailty Scale 5-8 were recruited within seventy-two hours of an emergency attendance. Iterations of the novel instrument were administered over three stages: (1) preliminary field-testing for reliability (response distribution and internal consistency) and structure (exploratory factor analysis, EFA); (2) intermediate field-testing of an improved instrument for reliability and structure; (3) final draft validation assessing reliability, structure (confirmatory factor analysis, CFA), and construct validity based on a priori hypotheses. Feasibility was appraised throughout using data completeness and response rates and times., Results: 241 people participated. Three items of a preliminary seven-item measure had poor response distribution or loading and were accordingly improved. The intermediate instrument had interpretability issues and three items required further improvement. The final eight-item draft had acceptable reliability (Cronbach's alpha: 0.71), structure (two factors for self-determination and security; RMSEA: 0.065; TLI: 0.917; CFI: 0.944), and construct validity (lower scores from respondents waiting longer and requiring admission). Feasibility was promising (response rate 39%; 98% responses complete; median completion time 11 (IQR: 12) minutes)., Conclusions: Administration of the PROM-OPAC appeared feasible and the instrument had acceptable psychometric properties. Further evaluation is required to assess generalisability., (© 2024. The Author(s).)

The gas phase reactivity of the radical cation isomers H 2 CNH˙ + (methanimine) and HCNH 2 ˙ + (aminomethylene) with propene (CH 3 CHCH 2 ) has been investigated by measuring absolute reactive cross sections and product branching ratios, under single collision conditions, as a function of collision energy (in the range ∼0.07-11.80 eV) using guided ion beam mass spectrometry coupled with VUV photoionization for selective isomer generation. Experimental results have been merged with theoretical calculations to elucidate reaction pathways and structures of products. The H 2 CNH˙ + isomer is over a factor two more reactive than HCNH 2 ˙ + . A major channel from both isomers is production of protonated methanimine CH 2 NH 2 + via hydrogen-atom transfer reaction but, while H 2 CNH˙ + additionally gives charge and proton transfer products, the HCNH 2 ˙ + isomer leads instead to protonated vinylimine CH 2 CHCHNH 2 + , produced alongside CH 3 ˙ radicals. The reactions have astrochemical implications in the build up of chemical complexity in both the interstellar medium and the hydrocarbon-rich atmospheres of planets and satellites.

Objectives: We explored the perspectives of older veterans in Gerofit, a Department of Veteran Affairs (VA) supervised clinical exercise program, to understand the factors associated with participation and how the program supported personal health goals., Methods: Twenty semistructured interviews were conducted with active and inactive Gerofit participants. We used a hybrid inductive and deductive approach to thematic analysis of transcripts, with the latter informed by the Health Action Process Approach model of behavior change., Results: Active and inactive participants differed in their perspectives about how Gerofit impacted their progress toward meeting personal health goals. Active participants noted program features (e.g., schedule, staffing) as facilitators and suggested greater self-efficacy about program participation compared to inactive participants. Both groups perceived the camaraderie with other veterans as a facilitator., Conclusions: Exercise program features, including camaraderie, are important factors that affect the ability of older veterans to participate in exercise and achieve personal health goals., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Parents exposed to psychosocial adversities often experience challenges which, combined with the needs of a new-born infant, can be difficult to manage and increase the risk of poor outcomes for both parents and infants. Psychosocial adversity can disrupt the development of parental-foetal attachment to the baby during pregnancy, which can have a negative effect on parental care and quality of interaction during the postnatal period. This intervention is based on the proposition that enhanced parental capacity to mentalise and emotionally connect to unborn children during pregnancy, and better understanding about how to manage distressing infant behaviour (i.e., persistent crying and sleep problems) will: (i) promote the development of secure parent-infant attachment; (ii) improve antenatal bonding and postnatal parenting; and, (ii) reduce parental distress., Method: This protocol is for a pilot randomised control trial evaluating a new intervention, which makes use of innovative technologies to support parents experiencing moderate psychosocial adversity (Australian New Zealand Clinical Trials Registry: ACTRN12622000287730). The New Technology for New Parents (NTNP) intervention provides support using antenatal ultrasound scans and 'virtual home visits' during the perinatal period. Quantitative outcomes include mentalising capacity, parental-foetal/infant attachment, and parental competence., Conclusion: To the best of our knowledge, no study has evaluated the combined effectiveness of two novel technologies (3D/4D ultrasound scans and virtual home visits) to support parents across the antenatal and postnatal periods. This protocol, which includes the rationale for this innovative intervention, addresses a gap in services for parents experiencing moderate psychosocial adversity.

Innovative N -acridine thiosemicarbazones (NATs) were designed along with their iron(iii), copper(ii), and zinc(ii) complexes. Lysosomal targeting was promoted by specifically incorporating the lysosomotropic Pgp substrate, acridine, into the thiosemicarbazone scaffold to maintain the tridentate N, N, S-donor system. The acridine moiety enables a significant advance in thiosemicarbazone design, since: (1) it enables tracking of the drugs by confocal microscopy using its inherent fluorescence; (2) it is lysosomotropic enabling lysosomal targeting; and (3) as acridine is a P-glycoprotein (Pgp) substrate, it facilitates lysosomal targeting, resulting in the drug overcoming Pgp-mediated resistance. These new N -acridine analogues are novel, and this is the first time that acridine has been specifically added to the thiosemicarbazone framework to achieve the three important properties above. These new agents displayed markedly greater anti-proliferative activity against resistant Pgp-expressing cells than very low Pgp-expressing cells. The anti-proliferative activity of NATs against multiple Pgp-positive cancer cell-types (colon, lung, and cervical carcinoma) was abrogated by the third generation Pgp inhibitor, Elacridar, and also Pgp siRNA that down-regulated Pgp. Confocal microscopy demonstrated that low Pgp in KB31 (-Pgp) cells resulted in acridine's proclivity for DNA intercalation promoting NAT nuclear-targeting. In contrast, high Pgp in KBV1 (+Pgp) cells led to NAT lysosomal sequestration, preventing its nuclear localisation. High Pgp expression in KBV1 (+Pgp) cells resulted in co-localization of NATs with the lysosomal marker, LysoTracker™, that was significantly ( p < 0.001) greater than the positive control, the di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) Zn(ii) complex, [Zn(DpC) 2 ]. Incorporation of acridine into the thiosemicarbazone scaffold led to Pgp-mediated transport into lysosomes to overcome Pgp-resistance., Competing Interests: The authors declare no competing conflict of interest., (This journal is © The Royal Society of Chemistry.)

We implemented isosteric replacement of sulfur to selenium in a novel thiosemicarbazone (PPTP4c4mT) to create a selenosemicarbazone (PPTP4c4mSe) that demonstrates potentiated anticancer efficacy and selectivity. Their design specifically incorporated cyclohexyl and styryl moieties to sterically inhibit the approach of their Fe(III) complexes to the oxy-myoglobin heme plane. Importantly, in contrast to the Fe(III) complexes of the clinically trialed thiosemicarbazones Triapine, COTI-2, and DpC, the Fe(III) complexes of PPTP4c4mT and PPTP4c4mSe did not induce detrimental oxy-myoglobin oxidation. Furthermore, PPTP4c4mSe demonstrated more potent antiproliferative activity than the homologous thiosemicarbazone, PPTP4c4mT, with their selectivity being superior or similar, respectively, to the clinically trialed thiosemicarbazone, COTI-2. An advantageous property of the selenosemicarbazone Zn(II) complexes relative to their thiosemicarbazone analogues was their greater transmetalation to Cu(II) complexes in lysosomes. This latter effect probably promoted their antiproliferative activity. Both ligands down-regulated multiple key receptors that display inter-receptor cooperation that leads to aggressive and resistant breast cancer.

The metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), inhibits pro-oncogenic signaling in pancreatic cancer (PC). This investigation dissected a novel mechanism induced by NDRG1 on WNT/β-catenin signaling in multiple PC cell types. NDRG1 overexpression decreased β-catenin and downregulated glycogen synthase kinase-3β (GSK-3β) protein levels and its activation. However, β-catenin phosphorylation at Ser33, Ser37, and Thr41 are classically induced by GSK-3β was significantly increased after NDRG1 overexpression, suggesting a GSK-3β-independent mechanism. Intriguingly, NDRG1 overexpression upregulated protein kinase Cα (PKCα), with PKCα silencing preventing β-catenin phosphorylation at Ser33, Ser37, and Thr41, and decreasing β-catenin expression. Further, NDRG1 and PKCα were demonstrated to associate, with PKCα stabilization occurring after NDRG1 overexpression. PKCα half-life increased from 1.5 ± 0.8 h (3) in control cells to 11.0 ± 2.5 h (3) after NDRG1 overexpression. Thus, NDRG1 overexpression leads to the association of NDRG1 with PKCα and PKCα stabilization, resulting in β-catenin phosphorylation at Ser33, Ser37, and Thr41. The association between PKCα, NDRG1, and β-catenin was identified, with the formation of a potential metabolon that promotes the latter β-catenin phosphorylation. This anti-oncogenic activity of NDRG1 was multi-modal, with the above mechanism accompanied by the downregulation of the nucleo-cytoplasmic shuttling protein, p21-activated kinase 4 (PAK4), which is involved in β-catenin nuclear translocation, inhibition of AKT phosphorylation (Ser473), and decreased β-catenin phosphorylation at Ser552 that suppresses its transcriptional activity. These mechanisms of NDRG1 activity are important to dissect to understand the marked anti-cancer efficacy of NDRG1-inducing thiosemicarbazones that upregulate PKCα and inhibit WNT signaling., Competing Interests: Conflict of 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis., Objective: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines., Methods: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts., Results: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination., Limitations: Studies regarding infection rates after vaccination are lacking., Conclusion: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases., Competing Interests: Conflicts of interest Dr Chat, Dr Ellebrecht, Ms. Kingston, and Dr Cordoro have no conflicts of interest to declare. Dr Bell is an employee of the National Psoriasis Foundation. Author Gondo is an employee of the National Psoriasis Foundation. Dr Desai has served as a research investigator, consultant, speaker, and/or advisor for AbbVie, Galderma, Foundation for Research & Education of Dermatology, Almirall, Dermavant, Ferndale Laboratories, Inc, Incyte Corporation, Gore Range Capital, AOBiome, LLC, Bristol Myers Squibb, Verrica Pharmaceuticals, UCB, Ortho Dermatologics, Scientis, EPI Health, Avita, Pfizer, Lilly, LEO, Incyte Corporation, L'Oreal USA, Inc, Beiersdorf, Inc, and Johnson and Johnson; is a board member of the National Psoriasis Foundation and Women's Derm Society; and is a stockholder for Gore Range Capital. Dr Duffin has been a consultant, advisor, or served as an investigator for AbbVie, AnaptysBio, Amgen, Bristol-Myers Squib, Celgene, CorEvitas/Corrona, Boehringer-Ingelheim, Janssen, Lilly, Novartis, Ortho Dermatologica, Pfizer, Regeneron, Sienna, Stiefel, and UCB. Dr Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen Inc, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, SunPharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Valeant, Menlo, Merck & Co, Qurient Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Advance Medical, Suncare Research, Informa, UpToDate and the National Psoriasis Foundation; is the founder and majority owner of www.DrScore.com; is a founder and part owner of Causa Research; and has stock in Sensal Health. Dr Garg is an advisor for AbbVie, Aclaris Therapeutics, Anaptys Bio, Aristea Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Incyte, InflaRx, Insmed, Janssen, Novartis, Pfizer, UCB, and Viela Biosciences; receives honoraria; and receives research grants from AbbVie, UCB and National Psoriasis Foundation. Dr Gelfand served as a consultant for Abbvie, BMS, Boehringer Ingelheim, Celldex (DSMB), FIDE (which is sponsored by multiple pharmaceutical companies) GSK, Happify, Lilly (DMC), Leo, Janssen Biologics, Neumentum, Novartis Corp, Pfizer, UCB (DSMB), Neuroderm (DSMB), Regeneron, Trevi, and Mindera Dx., receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from Boehringer Ingelheim, and Pfizer Inc; and received payment for continuing medical education work related to psoriasis that was supported indirectly pharmaceutical sponsors. Dr Gelfand is a co-patent holder of resiquimod for treatment of cutaneous T cell lymphoma. Dr Gelfand is a Deputy Editor for the Journal of Investigative Dermatology receiving honoraria from the Society for Investigative Dermatology, is Chief Medical Editor for Healio Psoriatic Disease (receiving honoraria) and is a member of the Board of Directors for the International Psoriasis Council, receiving no honoraria. Dr Gladman has served as a consultant for AbbVie, Amgen, BMS, Eli Lily, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB; and has received grants from AbbVie, Amgen, Eli Lily, Janssen, Novartis, Pfizer, and UCB. Dr Green is a research investigator, speaker, and/or consultant for AbbVie, Amgen, Arcutis, BMS, Dermavant, Lilly, MC2, SunPharma, and UCB. Dr Gudjonsson has served as an advisor for Novartis, Janssen, Almirall, Eli Lilly, Sanofi, and Boehringer Ingelheim; and has received research support from Almirall, Eli Lilly, Prometheus, BMS, and Janssen. Dr Han has served as a research investigator, consultant, and/or speaker for AbbVie, Amgen, Boehringer Ingelheim, BMS, Dermavant, Janssen, Lilly, UCB, Novartis, Leo Pharma, Regeneron, Sanofi Genzyme, Ortho Dermatologics, Bond Avillion, Pellepharm, MC2, Athenex, Celgene, Sun Pharma, and Pfizer. Dr Hawkes is an advisor and/or consultant for AbbVie, Arcutis, Boehringer Ingelheim, Janssen, LearnSkin, LEO, Lilly, Novartis, Pfizer, Regeneron-Sanofi Genzyme, and UCB; is a board member of the National Psoriasis Foundation; and has stock ownership/equity of Regeneron Pharmaceuticals. Dr Kircik is a research investigator, speaker, advisor, and/or consultant for Abbott Laboratories, Allergan, Almirall, Amgen, Arcutis, Biogen-Idec, BMS, Boehringer-Ingleheim, Breckinridge Pharma, Celgene, Centocor, Inc, Cellceutix, Cipher, Combinatrix, Connetics Corporation, Coria, Dermavant, Dermira, Dow Pharmaceutical Sciences, Inc, Dr Reddy's Lab, Eli Lilly, Galderma, Genentech, Inc, GlaxoSmithKline, PLC, Idera, Leo, Maruho, Merck, Medicis Pharmaceutical Corp., Novartis AG, Promius, PharmaDerm, Pfizer, Serono, Stiefel Laboratories, Inc, Sun Pharma, Taro, UCB, Valeant Pharmaceuticals Intl, and XenoPort. Dr Koo is a speaker and/or advisor for AbbVie, Amgen, Lilly, UCB, Ortho Dermatologics, LEO, Sun Pharma, Janssen, and Epi Pharm. Dr Langley has been an investigator, served on the scientific advisory board, and/or has provided a lecture for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Leo, Lilly, Merck, Novartis, Pfizer, and UCB. Dr Lebwohl is an employee of Mount Sinai; receives research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc; and is a consultant for Aditum Bio, Almirall, AltruBio Inc, AnaptysBio, Arcutis, Inc, Arena Pharmaceuticals, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Brickell Biotech, Boehringer-Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corevitas, Dermavant Sciences, Dr Reddy's Laboratories, Evelo Biosciences, Evommune, Inc, Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd., LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica. Dr Lewitt has received speaking and/or consulting support from AbbVie, Lilly, Janssen, Ortho Dermatologics, UCB, Galderma, Pfizer; received honoraria; and served as an advisor for AbbVie, Janssen, and Dermavant. Dr Liao has received research/grant support from AbbVie, Amgen, Janssen, Leo, Novartis, Trex Bio, Pfizer, and Regeneron. Dr Martin has served as an advisor for Bristol Meyers Squibb, DUSA/SUN, AbbVie, Ortho/Bausch Health, Galderma, Pfizer, LEO, Janssen, Horizon, UCB, Trevi, Almirall, Dermavent, Incyte, and Lilly; has served as a consultant for Bristol Meyers Squibb, DUSA/SUN, AbbVie, Ortho/Bausch Health, Galderma, Pfizer, LEO, UCB, Trevi, Almirall, Lilly, Arcutis, and Dermavant; and has received speaking support from UCB, Almirall, LEO, Incyte, Dermavant, and Bristol Meyers Squibb. Dr Orbai is a consultant and/or advisor for Janssen, Novartis, and UCB; and receives research support from AbbVie, Amgen, and Celgene. Dr Reddy has served as a consultant for Novartis, AbbVie, Janssen, and UCB; and has received grant support from Pfizer. Ms Richardson has served as an advisor for and received honoraria from Boehringer Engelheim and Lilly. Dr Ritchlin is a consultant and/or speaker for Novartis, Lilly, AbbVie, Janssen, UCB, and Pfizer. Dr Schwartzman has received speaking support from AbbVie, Janssen, Lilly, Pfizer, Novartis, and UCB; served as a consultant for Abbvie, Janssen, Lilly, Myriad, Novartis, Regeneron, Sanofi, UCB, Stelexis, Jubilant, and Teijin; is a board member of the National Psoriasis Foundation; and served as an advisor for Myriad. Dr Siegel has served as an advisor, speaker, and/or consultant for Abbvie, UCB, Lilly, Horizon, and BMS. Dr Van Voorhees has served as a research investigator and/or scientific advisor for Lilly, AbbVie, UCB, Bristol Meyers Squibb, Amgen, Boehringer Ingelheim, Novartis, and Merck. Dr Wallace serves as an investigator for Pfizer and Target RWE. Dr Weinberg is a research investigator, consultant, and/or speaker for Novartis, Lilly, Amgen, AbbVie, Sun, Janssen, and BMS. Dr Winthrop is a consultant for Pfizer, AbbVie, Union Chimique Belge (UCB), Eli Lilly & Company, Galapagos, GlaxoSmithKline (GSK), Roche, Gilead, Bristol Myers Squibb (BMS), Regeneron, Sanofi, AstraZeneca, and Novartis; and receives research funding from BMS and Pfizer. Dr Yamauchi serves as a research investigator, consultant, and speaker for Abbvie, Amgen, BMS, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, UCB. Dr Armstrong has served as a research investigator, scientific advisor, and/or speaker to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Mindera, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, and Pfizer., (Copyright © 2024. Published by Elsevier Inc.)