Discrete Metal Complexes of Two Multiply-Armed Ligands

The syntheses and metal complexes of 1,2,4,5-tetrakis(8-quinolyloxymethyl)benzene 1 and hexakis(8-quinolyloxymethyl)benzene 2 are described. X-Ray crystal structures are reported of the free ligand 1, a binuclear silver(i) and a tetranuclear copper(i) complex of 1, as well as a binuclear cobalt(ii) and trinuclear palladium(ii) and silver(i) complexes of 2. Within these discrete metal complexes the ligands are found to adopt a range of coordination modes, with considerable variation in the relative orientations of the ligand arms as a result of the flexibility imparted by the CH₂O linker units

Interaction of N solitons in the massive Thirring model and optical gap system: the Complex Toda Chain Model

Using the Karpman-Solov''ev quasiparticle approach for soliton-soliton interaction I show that the train propagation of N well separated solitons of the massive Thirring model is described by the complex Toda chain with N nodes. For the optical gap system a generalised (non-integrable) complex Toda chain is derived for description of the train propagation of well separated gap solitons. These results are in favor of the recently proposed conjecture of universality of the complex Toda chain.Comment: RevTex, 23 pages, no figures. Submitted to Physical Review

Biomarkers for disease progression identified in psoriasis patients : a pilot study

DATA AVAILABILITY STATEMENT : Data available on request from the authors.BACKGROUND : Psoriasis is an immune-mediated polygenic skin disorder. It is influenced by multiple genes as well as environmental factors including infection and trauma. Psoriasis is associated with molecular biomarkers such as HLA-C*06:02 and associated single-nucleotide variants (SNVs). Furthermore, the circulatory cytokines, interleukin (IL)-17 and IL-23 are elevated in psoriasis patients. OBJECTIVES : To investigate the incidence of biomarkers namely, HLA-C*06:02, SNV's (rs30187, rs27044, rs2248374), and IL17 and IL23 as possible diagnostic/prognostic biomarkers of value, individually or in combination in psoriasis patients. METHODS : These biomarkers, HLA-C*06:02, SNV's (rs3018, rs27044, rs2248374), and IL17 and IL23 (and their ratio) were tested in a cohort of 40 psoriasis patients attending a dermatology clinic situated in a tertiary academic hospital as well as 40 healthy controls by: HLA typing using sequence-specific primers (PCR SSP), real time PCR, and Luminex technology, respectively. RESULTS : HLA-C*06:02 was significantly elevated in our patient cohort with 53% (n = 21) of psoriasis patients expressing the HLA-C*06:02 allele versus 15% (n = 6), p = 0.001 in the healthy controls. Both IL-17 and IL-23 were significantly elevated in the psoriasis patients compared to the normal controls (p = 0.0001 and p = 0.0005, respectively). The SNV rs2248374 showed an association with both IL-17 and HLA-C*06:02 in patients with psoriasis. CONCLUSIONS : Overall, these novel findings are the first to be published for South African and African populations in the public health sector. The finding of the current study corroborates international studies. Further validation through geographic and population expansion may assist in identifying individuals at risk of disease progression in psoriasis. These biomarkers may be used as potential prognosticators which will offer the opportunity for early medical intervention to reduce the burden of disease.The National Health K- funding of South Africa.https://onlinelibrary.wiley.com/journal/27686566hj2024ImmunologySDG-03:Good heatlh and well-bein

Transforming growth factor-β1 and soluble co-inhibitory immune checkpoints as putative drivers of immune suppression in patients with basal cell carcinoma

DATA AVAILABILITY : Data are available upon reasonable request. The data generated in this study are available on request from the corresponding author.The current study compared the levels and possible associations between systemic soluble immune checkpoints (sICPs, n = 17) and a group of humoral modulators of immune suppressor cells ( n = 7) in a cohort of patients with basal cell carcinoma (BCC, n = 40) and a group of healthy control subjects ( n = 20). The seven humoral modulators of immunosuppressor cells were represented by the enzymes, arginase 1 and fibroblast activation protein (FAP), the chemokine, RANTES (CCL5) and the cytokines, interleukin-10 and transforming growth factor-β1 (TGF-β1), as well as the M2-type macrophage markers, soluble CD163 (sCD163) and sCD206. The plasma levels of six co-inhibitory sICPs, sCTLA-4, sLAG-3, sPD-1, sPD-L1, sTIM-3 and sPD-L2 were significantly elevated in the cohort of BCC patients ( p <0.001- p <0.00001), while that of sBTLA was significantly decreased ( p <0.006). Of the co-stimulatory sICPs, sCD27 and sGITR were significantly increased ( p< 0.0002 and p< 0.0538) in the cohort of BCC patients, while the others were essentially comparable with those of the control participants; of the dual active sICPs, sHVEM was significantly elevated ( p <0.00001) and TLR2 comparable with the control group. A correlation heat map revealed selective, strong associations of TGF-β1 with seven co-stimulatory ( z = 0.618468–0.768131) and four co-inhibitory ( z = 0.674040–0.808365) sICPs, as well as with sTLR2 ( z = 0.696431). Notwithstanding the association of BCC with selective elevations in the levels of a large group of co-inhibitory sICPs, our novel findings also imply the probable involvement of TGF-β1 in driving immunosuppression in this malignancy, possibly via activation of regulatory T cells. Notabhttps://www.elsevier.com/locate/tranonhj2024ImmunologySDG-03:Good heatlh and well-bein

Elevated levels of soluble CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3 and systemic inflammatory stress as potential contributors to immune suppression and generalized tumorigenesis in a cohort of South African Xeroderma pigmentosum patients

Xeroderma Pigmentosum (XP), an autosomal recessive disorder characterized by ultraviolet radiation-induced abnormalities of DNA excision and repair pathways is associated with early development of cutaneous cancers. Intracellular oxidative stress has also been proposed as a contributor to the occurrence of skin cancers. However, little is known about the possible augmentative contributions of chronic inflammation, immune suppression and oxidative stress to the pathogenesis of malignancies associated with other subtypes of XP. This has been addressed in the current study, focused on the measurement of systemic biomarkers of inflammation, immune dysfunction and oxidative damage in XP patients, consisting of XP-C, XP-D and XP-E cases, including those XP-C cases who had already developed multiple skin malignancies. The inflammatory biomarker profile measured in XP patients and healthy control subjects included the cytokines, interleukins (ILs)-2, -4, -6, -10, interferon-γ (IFN- γ) and tumor-necrosis factor-α (TNF-α), the acute phase reactant, C-reactive protein (CRP), and cotinine (as an objective indicator of smoking status). Immune suppression was detected according to the levels of five soluble inhibitory immune checkpoint proteins (CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3), as well as those of vitamin D, while oxidative stress was determined according to the circulating levels of the DNA adduct, 8-hydroxy-2-deoxyguanosine (8-OH-dG). These various biomarkers were measured in plasma using immunofluorimetric, nephelometric and ELISA procedures. Significant elevations in IL-6 (P<0.01) and TNF-α (P<0.0001), but none of the other cytokines, as well as increased levels of all five soluble inhibitory immune checkpoints (P=0.032-P=0.0001) were detected in the plasma of the XP patients. C-reactive protein and vitamin D were increased and decreased, respectively (both P<0.0001), while only one participant had an elevated level of plasma cotinine. Surprisingly, the levels of 8-OH-dG were significantly (P=0.0001) lower in the group of XP patients relative to a group of healthy control subjects. The findings of increased levels of pro-inflammatory cytokines and, in particular, those of the soluble immune checkpoints, in the setting of decreased vitamin D and moderately elevated levels of CRP in XP patients suggest a possible secondary role of ongoing, inflammatory stress and immune suppression in the pathogenesis of XP-associated malignancies.University of Pretoria.https://www.frontiersin.org/journals/oncologydm2022ImmunologyNuclear Medicin

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial

Objective: To evaluate the clinical efficacy of an established programme of occupational therapy in maintaining functional activity and reducing further health risks from inactivity in care home residents living with stroke sequelae.Design: Pragmatic, parallel group, cluster randomised controlled trial.Setting: 228 care homes (>10 beds each), both with and without the provision of nursing care, local to 11 trial administrative centres across the United Kingdom.Participants: 1042 care home residents with a history of stroke or transient ischaemic attack, including those with language and cognitive impairments, not receiving end of life care. 114 homes (n=568 residents, 64% from homes providing nursing care) were allocated to the intervention arm and 114 homes (n=474 residents, 65% from homes providing nursing care) to standard care (control arm). Participating care homes were randomised between May 2010 and March 2012.Intervention: Targeted three month programme of occupational therapy, delivered by qualified occupational therapists and assistants, involving patient centred goal setting, education of care home staff, and adaptations to the environment.Main outcome measures: Primary outcome at the participant level: scores on the Barthel index of activities of daily living at three months post-randomisation. Secondary outcome measures at the participant level: Barthel index scores at six and 12 months post-randomisation, and scores on the Rivermead mobility index, geriatric depression scale-15, and EuroQol EQ-5D-3L questionnaire, at all time points.Results: 64% of the participants were women and 93% were white, with a mean age of 82.9 years. Baseline characteristics were similar between groups for all measures, personal characteristics, and diagnostic tests. Overall, 2538 occupational therapy visits were made to 498 participants in the intervention arm (mean 5.1 visits per participant). No adverse events attributable to the intervention were recorded. 162 (11%) died before the primary outcome time point, and 313 (30%) died over the 12 months of the trial. The primary outcome measure did not differ significantly between the treatment arms. The adjusted mean difference in Barthel index score at three months was 0.19 points higher in the intervention arm (95% confidence interval −0.33 to 0.70, P=0.48). Secondary outcome measures also showed no significant differences at all time points.Conclusions: This large phase III study provided no evidence of benefit for the provision of a routine occupational therapy service, including staff training, for care home residents living with stroke related disabilities. The established three month individualised course of occupational therapy targeting stroke related disabilities did not have an impact on measures of functional activity, mobility, mood, or health related quality of life, at all observational time points. Providing and targeting ameliorative care in this clinically complex population requires alternative strategies

The EDGE2 protocol: Advancing the prioritisation of Evolutionarily Distinct and Globally Endangered species for practical conservation action

The conservation of evolutionary history has been linked to increased benefits for humanity and can be captured by phylogenetic diversity (PD). The Evolutionarily Distinct and Globally Endangered (EDGE) metric has, since 2007, been used to prioritise threatened species for practical conservation that embody large amounts of evolutionary history. While there have been important research advances since 2007, they have not been adopted in practice because of a lack of consensus in the conservation community. Here, building from an interdisciplinary workshop to update the existing EDGE approach, we present an “EDGE2” protocol that draws on a decade of research and innovation to develop an improved, consistent methodology for prioritising species conservation efforts. Key advances include methods for dealing with uncertainty and accounting for the extinction risk of closely related species. We describe EDGE2 in terms of distinct components to facilitate future revisions to its constituent parts without needing to reconsider the whole. We illustrate EDGE2 by applying it to the world’s mammals. As we approach a crossroads for global biodiversity policy, this Consensus View shows how collaboration between academic and applied conservation biologists can guide effective and practical priority-setting to conserve biodiversity

Gaussian quantum operator representation for bosons

We introduce a Gaussian quantum operator representation, using the most general possible multimode Gaussian operator basis. The representation unifies and substantially extends existing phase-space representations of density matrices for Bose systems and also includes generalized squeezed-state and thermal bases. It enables first-principles dynamical or equilibrium calculations in quantum many-body systems, with quantum uncertainties appearing as dynamical objects. Any quadratic Liouville equation for the density operator results in a purely deterministic time evolution. Any cubic or quartic master equation can be treated using stochastic methods