Effect of mono- and dinuclear thiosemicarbazone platinacycles in the proliferation of a colorectal carcinoma cell line.

Herein, we describe the synthesis and characterization of a series of thiosemicarbazone platinacycles. Their activity towards HCT116 and A2780 cancer cell lines as well as normal fibroblasts was explored and conclusions about the influence of their structures were drawn based on the results. Ligands L1-3, tetranuclear compounds [Pt(L1-3)]4, [Pt(L1-3)(PPh3)], and [Pt(L1-L3)2{Ph2P(CH2)4PPh2}], and phosphine derivatives, were deemed unpromising owing to their lack of activity. However, mono-coordinated diphosphine complexes [Pt(L1-L3)(Ph2PCH2PPh2-P)] showed high selectivity and low IC50 values, and their antiproliferative activity was further studied. The three studied derivatives 3a, 3b and 3c showed a fast internalization of HCT116 colorectal cancer cells with similar IC50 values, which induced a depolarization of mitochondrial membrane potential, with the subsequent triggering of apoptosis and autophagy in the case of 3c. In the case of compounds 3a and 3b, cell death mechanisms (extrinsic and intrinsic apoptosis, respectively) were triggered via the induction of reactive oxygen species (ROS). The three compounds were not toxic to a chicken embryo in vivo (after 48 h), and, importantly, showed an anti-angiogenic potential after exposure to the IC50 of compounds 3a, 3b and 3c.

Unusual low-temperature behavior in the half-filled band of the one-dimensional extended Hubbard model in atomic limit.

Recently, a kind of finite-temperature pseudotransition was observed in several quasi-one-dimensional models. In this work, we consider a genuine one-dimensional extended Hubbard model in the atomic limit, influenced by an external magnetic field and with the arbitrary number of particles controlled by the chemical potential. The one-dimensional extended Hubbard model in the atomic limit was initially studied in the seventies and has been investigated over the past decades, but it still surprises us today with its fascinating properties. We rigorously analyze its low-temperature behavior using the transfer matrix technique and provide accurate numerical results. Our analysis confirms that there is an anomalous behavior in the half-filled band, specifically occurring between the alternating pair (AP) and paramagnetic (PM) phases at zero temperature. Previous investigations did not deeply identify this anomalous behavior, maybe due to the numerical simplicity of the model, but from an analytical point of view this is not so easy to manipulate algebraically because one needs to solve an algebraic cubic equation. In this study, we explore this behavior and clearly distinguish the pseudotransition, which could easily be mistaken with a real phase transition. This anomalous behavior mimics features of both first- and second-order phase transitions. However, due to its nature, we cannot expect a finite-temperature phase transition in this model.

MOSCA 2.0: A bioinformatics framework for metagenomics, metatranscriptomics and metaproteomics data analysis and visualization.

The analysis of meta-omics data requires the utilization of several bioinformatics tools and proficiency in informatics. The integration of multiple meta-omics data is even more challenging, and the outputs of existing bioinformatics solutions are not always easy to interpret. Here, we present a meta-omics bioinformatics pipeline, Meta-Omics Software for Community Analysis (MOSCA), which aims to overcome these limitations. MOSCA was initially developed for analysing metagenomics (MG) and metatranscriptomics (MT) data. Now, it also performs MG and metaproteomics (MP) integrated analysis, and MG/MT analysis was upgraded with an additional iterative binning step, metabolic pathways mapping, and several improvements regarding functional annotation and data visualization. MOSCA handles raw sequencing data and mass spectra and performs pre-processing, assembly, annotation, binning and differential gene/protein expression analysis. MOSCA shows taxonomic and functional analysis in large tables, performs metabolic pathways mapping, generates Krona plots and shows gene/protein expression results in heatmaps, improving omics data visualization. MOSCA is easily run from a single command while also providing a web interface (MOSGUITO). Relevant features include an extensive set of customization options, allowing tailored analyses to suit specific research objectives, and the ability to restart the pipeline from intermediary checkpoints using alternative configurations. Two case studies showcased MOSCA results, giving a complete view of the anaerobic microbial communities from anaerobic digesters and insights on the role of specific microorganisms. MOSCA represents a pivotal advancement in meta-omics research, offering an intuitive, comprehensive, and versatile solution for researchers seeking to unravel the intricate tapestry of microbial communities.

Portuguese validation of the foot health status Questionnaire in patients with diabetic foot disease.

PURPOSE: This study aims to adapt and validate the Foot Health Status Questionnaire, developed by Bennett et al., in Portuguese patients with diabetic foot. MATERIALS AND METHODS: A cross-sectional study was conducted with 143 patients with diabetic foot. A principal component analysis with oblique rotation and a confirmatory factor analysis using structural equation modeling were performed. RESULTS: The Portuguese version of the FHSQ (FHSQ-PT) in patients with diabetic foot remains equal to the original version, although with all factors correlated with each other. All scales presented high internal consistency values (pain: ω = 0.884; function: ω = 0.890; general foot health: ω = 0.910; and footwear: ω = 0.702), except for the footwear scale, although with a minimum acceptable coefficient. The FHSQ-PT scales showed good convergent validity and good discriminant validity. The FHSQ-PT scales were also able to discriminate between male and female patients as well as between patients with an active diabetic foot ulcer from those who did not. CONCLUSIONS: The results of the validated FHSQ-PT for Portuguese patients with diabetic foot showed good psychometric properties, being a useful, objective, and small instrument that may be used in clinical practice by health professionals without consuming too much time.

Diabetic foot ulcer has been consistently reported to be associated to lower health-related quality of life, impairing the patient's everyday function.Validated comprehensive measures that assess specific dimensions related to foot health in patients with diabetic foot are needed.The Portuguese version of the Foot Health Status Questionnaire (FHSQ-PT) showed good psychometric properties.FHSQ-PT is a useful short instrument that may be used to measure foot health status in clinical practice by health professionals who provide care to patients with diabetic foot.

Relaxation intervention to improve diabetic foot ulcer healing: protocol for a pilot study with a nested qualitative study.

OBJECTIVE: A mixed-methods approach nested in a pilot three-arm randomised controlled trial (RCT) was conducted to evaluate the feasibility and acceptability of an intervention of progressive muscle relaxation with guided imagery (experimental group) compared to a neutral guided imagery placebo (active control group) and a group that did not receive any psychological intervention (passive control group). The purpose was to inform a future definitive RCT that will test its effectiveness. Qualitatively, this study examined patients and health professionals' perspectives regarding the relaxation intervention, in order to assess the acceptability and applicability of relaxation as an adjuvant therapy. METHOD: Participants must have had a diagnosis of diabetes and diabetic foot disease; one or two active hard-to-heal ulcers at the time of the assessment; and clinical levels of stress or anxiety or depression. Participants were randomised and assessed at three timepoints after the first hospital consultation for hard-to-heal diabetic foot ulcer (DFU). RESULTS: Rates of eligibility, recruitment, refusal, adherence to study protocol, participation in follow-up and dropout, and patients' satisfaction with the relaxation intervention were assessed as primary outcomes. Secondary outcomes were DFU healing; patients' DFU-related quality of life; physical and mental quality of life; perceived stress; emotional distress; adherence to DFU care; perceptions of DFU; as well as arterial systolic/diastolic pressure and heart rate. CONCLUSION: The results of this pilot study contributed to clarification and better elucidation of the benefits of relaxation techniques regarding patients' HRQoL and DFU healing. DECLARATION OF INTEREST: Funding: This study was conducted at the Psychology Research Centre (CIPsi/UM) School of Psychology, University of Minho, Portugal and supported by the Foundation for Science and Technology (FCT) through the Portuguese State Budget (UIDB/01662/2020) and by a PhD fellowship from FCT assigned to GF (SFRH/BD/131780/2017) and an FCT grant (PTDC/PSI-GER/28163/2017) assigned to MGP. The authors have no conflicts of interest to declare.

Acceptability and perceived benefits of validated pruritus assessment instruments in the dermatological office and clinic: The perspectives of patients and physicians.

BACKGROUND: Several patient-reported outcome measures (PROMs) have been developed for research to assess the multiple dimensions of chronic pruritus (CP). The acceptability and perceived benefits of their use in clinical practice remain unknown. OBJECTIVES: To assess the acceptability and perceived benefits of validated PROMs from the perspective of patients and physicians in dermatological offices and clinics. METHODS: Patients with CP due to atopic dermatitis, psoriasis, chronic prurigo or chronic urticaria were recruited at 10 dermatological offices and two dermatological clinics in Germany. Patients completed a set of validated PROMs on pruritus intensity (numerical rating scale, NRS), symptom control (itch-controlled days, ItchCD), quality of life (Dermatology Life Quality Index, DLQI; 5-pruritus life quality, 5PLQ) and general health status (EuroQol, EQ-VAS). Acceptability (relevance, difficulty of completion, length) and benefits (usefulness, feasibility) of these tools were assessed on a NRS (0-10) by patients and physicians, respectively. Data were analysed descriptively. Linear regression was used to study potential associations between age, sex, occupation, office versus clinic, change of therapy and physician-reported benefits. RESULTS: N = 523 patients (46% male, average age: 53.5 years) participated. Acceptability of PROMs by patients was high, indicated by low difficulty (Md = 0, IQR = 0-1 for all PROMs) and high relevance (Md = 8, IQR = 4-10 for all PROMs). Also, most patients (89-95%) rated length of the questionnaires as 'exactly right'. Physicians rated the NRS as the most beneficial instrument (feasibility: Md = 8, IQR = 6-10; usefulness: Md = 9, IQR = 7-10). Hierarchical linear regression revealed that only recruitment site (dermatological office vs. clinic) was significantly associated with usefulness and feasibility (higher ratings for clinical context; ßs = 0.149-0.258, ps <0.05; except feasibility for EQ5d, ß = ns). CONCLUSION: PROMs are welcomed by patients, while physicians consider instruments measuring pruritus intensity and impairment of quality of life as beneficial for the clinical routine. Widespread implementation of PROMs in daily clinical work is needed to improve care.

Effect of glycerol supplementation in early lactation on metabolic health, milking activity, and production of dairy cows in automated milking system herds.

The objective of this study was to quantify the effects of supplementing early-lactation cows with a dry pure glycerol product, delivered through the automated milking system (AMS) concentrate, in the first 21 d in milk (DIM) on metabolic markers, milking behavior, and milk production. In 5 commercial AMS dairy herds, 389 dairy cows were randomly assigned, controlling for parity, 21 d before expected calving to 1 of 2 treatments, within farm: (1) control group (CON) receiving the standard AMS pellet (n = 213) from 1 to 150 DIM, or (2) glycerol group (GLY) receiving the treatment AMS pellet (n = 176) formulated to deliver 250 as fed g/d of glycerol product from 1 to 21 DIM (mean actual = 249 g/d dry matter [DM]), then they received the standard AMS pellet from 22 to 150 DIM. Across all farms, cows were fed partial mixed rations (PMR) that were similar in ingredient and nutrient composition. One prepartum blood sample and 5 postpartum blood samples were collected from each cow to determine serum nonesterified fatty acids (NEFA), blood ß-hydroxy butyrate (BHB), and blood glucose concentrations. Cow body condition score (BCS) was recorded every 21 d from -21 to 63 DIM. Data were collected and analyzed for the treatment period (1 to 21 DIM) and a follow-up period (22 to 150 DIM). There was no detected treatment effect on serum NEFA concentrations in the first week of lactation. There was a treatment by time interaction for blood BHB and blood glucose, where GLY cows tended to have increased BHB concentrations at 5 DIM and had decreased glucose concentrations at 9 and 12 DIM. There was an interaction of BCS with treatment on the incidence of BHB ≥1.2 mmol/L, whereby over-conditioned CON cows (BCS ≥3.5) were 3.5x more likely to have a high BHB test than CON cows with normal prepartum BCS. During the treatment period GLY cows had 0.1 ± 0.05 more successful milkings/d, were delivered 0.27 ± 0.05 DM kg/d more AMS concentrate and tended to yield 0.8 ± 0.47 kg/d more milk. During the follow-up period GLY cows had 0.1 ± 0.04 more successful milkings/d, were delivered 0.18 ± 0.06 DM kg/d more AMS concentrate, and yielded 1.5 ± 0.53 kg/d more milk than CON cows. Glycerol supplementation allowed cows to maintain better BCS, as GLY cows lost less BCS from calving to 63 DIM than CON cows. Overall, the results of this study demonstrate that supplementing pure glycerol through the AMS concentrate for the first 21 DIM can reduce BCS loss in early lactation, improve milking behavior, and increase milk yield to mid lactation.

Non-conductive silicon-containing materials improve methane production by pure cultures of methanogens.

Conductive materials (CM) enhance methanogenesis, but there is no clear correlation between conductivity and faster methane production (MP) rates. We investigated if MP by pure cultures of methanogens (Methanobacterium formicicum, Methanospirillum hungatei, Methanothrix harundinacea and Methanosarcina barkeri) is affected by CM (activated carbon (AC), magnetite), and other sustainable alternatives (sand and glass beads, without conductivity, and zeolites (Zeo)). The significant impact of the materials was on M. formicicum as MP was significantly accelerated by non-CM (e.g., sand reduced the lag phase (LP) duration by 48 %), Zeo and AC (LP reduction in 71% and 75 %, respectively). Conductivity was not correlated with LP reduction. Instead, silicon content in the materials was inversely correlated with the time required for complete MP, and silicon per se stimulated M. formicicum's activity. These findings highlight the potential of using non-CM silicon-containing materials in anaerobic digesters to accelerate methanogenesis.

Spatial patterns and factors associated with the incidence of tuberculosis-diabetes in Brazil.

OBJECTIVES: The aim of this study was to analyse the spatial patterns and factors associated with the incidence of tuberculosis-diabetes (TB-DM) in Brazil, from 2001 to 2019. STUDY DESIGN: Ecological study. METHODS: Brazilian municipalities were used as the units of analysis. The local empirical Bayesian rate and the spatial autocorrelation test were calculated. Moran and Getis-Ord Gi∗ were used to identify spatial clusters, and spatially weighted regression was conducted. RESULTS: In total, 75,021 new cases of TB associated with DM were reported in Brazil during the study period. Most Brazilian municipalities had an average TB-DM incidence of 1.0-2.0/100,000 inhabitants. The regression showed that the Gini index (ß = 0.85) and family health strategy coverage (ß = -0.26) were the two indicators that had the most influence on TB-DM incidence in Brazil. CONCLUSIONS: This study identified spatial clusters of TB-DM in Brazil. The results also indicated that social inequalities played a key role in the incidence of TB.

Persistence of PFOA Pollution at a PTFE Production Site and Occurrence of Replacement PFASs in English Freshwaters Revealed by Sentinel Species, the Eurasian Otter (Lutra lutra).

Concentrations of 33 PFASs were determined in 20 Eurasian otters, sampled 2015-2019, along a transect away from a factory, which used PFOA in PTFE manufacture. Despite cessation of usage in 2012, PFOA concentrations remained high near the factory (>298 µg/kg ww <20 km from factory) and declined with increasing distance (<57 µg/kg ww >150 km away). Long-chain legacy PFASs dominated the Σ33PFAS profile, particularly PFOS, PFOA, PFDA, and PFNA. Replacement compounds, PFECHS, F-53B, PFBSA, PFBS, PFHpA, and 8:2 FTS, were detected in ≥19 otters, this being the first report of PFBSA and PFECHS in the species. Concentrations of replacement PFASs were generally lower than legacy compounds (max: 70.3 µg/kg ww and 4,640 µg/kg ww, respectively). Our study underscores the utility of otters as sentinels for evaluating mitigation success and highlights the value of continued monitoring to provide insights into the longevity of spatial associations with historic sources. Lower concentrations of replacement, than legacy, PFASs likely reflect their lower bioaccumulation potential, and more recent introduction. Continued PFAS use will inevitably lead to increased environmental and human exposure if not controlled. Further research is needed on fate, toxicity, and bioaccumulation of replacement compounds.

Dependency and frailty in the older haemodialysis patient.

BACKGROUND: Frailty among older adults undergoing hemodialysis is increasingly prevalent, significantly impacting cognitive function, mobility, and social engagement. This study focuses on the clinical profiles of very older adults in hemodialysis, particularly examining the interplay of dependency and frailty, and their influence on dialysis regimens. METHODS: In this observational, descriptive study, 107 patients aged over 75 from four outpatient centers and one hospital unit were examined over a year. Patient data encompassed sociodemographic factors, dialysis specifics, analytical outcomes, lifestyle elements, and self-reported post-treatment fatigue. Malnutrition-inflammation scale was used to measure the Nutritional status; MIS scale for malnutrition-inflammation, Barthel index for dependency, Charlson comorbidity index; FRIED scale for frailty and the SF12 quality of life measure. RESULTS: The study unveiled that a substantial number of older adults on hemodialysis faced malnutrition (55%), dependency (21%), frailty (46%), and diminished quality of life (57%). Patients with dependency were distinctively marked by higher comorbidity, severe malnutrition, enhanced frailty, nursing home residency, dependency on ambulance transportation, and significantly limited mobility, with 77% unable to walk. Notably, 56% of participants experienced considerable post-dialysis fatigue, correlating with higher comorbidity, increased dependency, and poorer quality of life. Despite varying clinical conditions, dialysis patterns were consistent across the patient cohort. CONCLUSIONS: The older adult cohort, averaging over four years on hemodialysis, exhibited high rates of comorbidity, frailty, and dependency, necessitating substantial support in transport and living arrangements. A third of these patients lacked residual urine output, yet their dialysis regimen mirrored those with preserved output. The study underscores the imperative for tailored therapeutic strategies to mitigate dependency, preserve residual renal function, and alleviate post-dialysis fatigue, ultimately enhancing the physical quality of life for these patients.

Uric acid and acute kidney injury in high-risk patients for developing acute kidney injury undergoing cardiac surgery: A prospective multicenter study.

PURPOSE: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN: Multicenter prospective international cohort study. SETTING: Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

Is prolonged luteal phase a problem in lactating Holstein cows?

In this study, the main objective was to assess if long luteal phases could have other causes than pregnancy losses. We enrolled Holstein dairy cows ≥50 d in milk (DIM) from a commercial herd in Brazil from October 2016 to August 2017. All cows received an estradiol-based synchronization protocol, and, on the day of insemination (d 0), were randomly assigned either an artificial insemination (AI) or a placebo insemination (PBO) in a 3:1 ratio. An ultrasound was used to assess the presence of a CL on d17, 24, and 31, which, combined to the information from patches for the detection of estrus, was used to determine the length of the luteal phase following AI or PBO. Pregnancy was assessed by ultrasound on d 31 and cows that were pregnant were excluded from the analyses. The length of the estrous cycles was categorized as short (<17 d), normal (17-23 d), long (24-30 d), and very long (≥31 d). We compared the proportion of cows in each category between the AI and PBO groups using a cumulative ordinal mixed model. We define prolonged luteal phase as estrous cycles ≥24 d and tested its association with potential risk factors (parity, season, DIM, uterine size and position score, milk production, body condition score, and the presence of a corpus luteum (CL) at enrollment to the synchronization protocol) using mixed logistic regression models. Results are presented as odds ratio (OR) and 95% credible intervals (BCI). Data from 876 inseminations (AI: n = 616, PBO: n = 260) was collected. Overall, 12% of estrous cycles were short, 31% were normal, 19% were long, and 38% were very long. There was no difference in the odds of being in longer estrous cycle categories for the AI compared with the PBO group (OR = 0.92, 95% BCI = 0.76-1.10). Season and presence of a CL at enrollment were associated with prolonged luteal phase. In the AI group, there was a possible effect of early pregnancy losses on the lifespan of the CL, but not the PBO group, which led us to conclude that long and very long estrous cycles were not all caused by the embryonic loss. In fact, the high prevalence of cows with an extended CL lifespan in the present study suggests this could be an under- or miss-reported characteristic of high-producing lactating Holstein cows. This finding may have important repercussions in the understanding of the CL function physiology of lactating Holstein cows.

Robotic endoscopic transforaminal lumbar interbody fusion: A single institution case series.

Background: Robotic-assisted, endoscopic transforaminal lumbar interbody fusion (RE-TLIF) is a promising, minimally invasive surgical option for degenerative lumbar spondylosis/spondylolisthesis; however, outcomes data and efficacy are limited, especially in multilevel disease. Here, we present the first reported series of patients that underwent either single or multilevel RE-TLIF. Methods: A retrospective review was performed on 23 consecutive patients who underwent a single level or multilevel RE-TLIF by a single surgeon. Variables included demographics, perioperative results, pain scores, and functional outcome scores. Results: Eighteen patients (78.3 %) underwent single level RE-TLIF and 5 patients (21.7 %) underwent multilevel RE-TLIF. The median reduction of visual analog scale (VAS) for low back pain (LBP) of all subjects was 6 (IQR = 4.5, 6.5) with no significant difference between single level and multilevel RE-TLIF (p = 0.565). The median reduction of VAS for leg pain of all subjects 7 (IQR = 6, 8) with no significant difference between single level and multilevel RE-TLIF (p = 0.702). Median blood loss was 25 cc (IQR = 25, 25) and 50 cc (IQR = 25, 100) for single and multilevel RE-TLIF, respectively (p = 0.025), whereas median length of stay was 1 (IQR = 1, 1; mean = 1.0 ± 00.18) days and 1 (IQR = 1, 2; mean = 1.4 ± 00.54) days, respectively (p = 0.042). One major complication was observed requiring reoperation for demineralized bone matrix migration resulting in an L5 radiculopathy. Conclusions: Single and multi-level RE-TLIF appears to be a safe and efficacious approach with comparable outcomes to open and other minimally invasive approaches. Additionally, we observed favorable accuracy in robot-assisted pedicle screw, endoscope, and interbody device placement.

Portuguese Caregivers of Persons With Alzheimer's Disease in the Context of the COVID-19 Pandemic: A Qualitative Study of the Grieving Process.

This study addresses the experiences of informal caregivers caring for elderly family members with Alzheimer's disease (AD) during the COVID-19 pandemic. The study includes a sample of eight informal caregivers who were evaluated through a semi-structured interview six months after the death of a loved one they cared for. A thematic content analysis was applied to the interviews and yielded two higher-order domains: (1) Experiencing the AD and the death of a family member and (2) The grieving process during the COVID-19 pandemic. The results provide valuable insights into family caregivers' experiences regarding the profound emotional impact of caregiving and grief during the COVID-19 pandemic. Caregivers maintain their identity even after loss, underscoring the enduring impact of caregiving. The identity as a caregiver impacted coping and grief responses, highlighting the need for tailored interventions.

EADV Task Force Pruritus White Paper on chronic pruritus and chronic prurigo: Current challenges and future solutions.

Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prurigo (CPG) is the most severe disease in the chronic pruritus spectrum, being associated with long-standing scratch-induced skin lesions and a therapy refractory itch-scratch-cycle. It is thus important to raise disease awareness for CP and CPG in the general public and among decision-makers in the health system. Further, there is a need to support a rational clinical framework to optimize both diagnostics and therapeutics. Currently, there is still a shortcoming regarding approved therapies and understanding CP/CPG as severe medical conditions. Therefore, the EADV Task Force Pruritus decided to publish this white paper based on several consensus meetings. The group consented on the following goals: (a) ensure that CP is recognized as a serious condition, (b) increase public awareness and understanding of CP and CPG as chronic and burdensome diseases that can greatly affect a person's quality of life, (c) clarify that in most cases CP and CPG are non-communicable and not caused by a psychiatric disease, (d) improve the support and treatment given to patients with CP to help them manage their disease and (e) publicize existing therapies including current guidelines. We aim to point to necessary improvements in access and quality of care directed to decision-makers in health policy, among payers and administrations as well as in practical care.

Co-located ecological data for exploring top- and subsoil carbon dynamics across grassland-woodland contrasts.

Soil organic carbon (SOC) is a soil health indicator and understanding dynamics changing SOC stocks will help achieving net zero goals. Here we present four datasets featuring 11,750 data points covering co-located aboveground and below-ground metrics for exploring ecosystem SOC dynamics. Five sites across England with an established land use contrast, grassland and woodland next to each other, were rigorously sampled for aboveground (n = 109), surface (n = 33 soil water release curves), topsoil, and subsoil metrics. Commonly measured soil metrics were analysed in five soil increments for 0-1 metre (n = 4550). Less commonly measured soil metrics which were assumed to change across the soil profile were measured on a subset of samples only (n = 3762). Additionally, we developed a simple method for soil organic matter fractionation using density fractionation which is part of the less common metrics. Finally, soil metrics which may impact SOC dynamics, but with less confidence as to their importance across the soil profile were only measured on topsoil (~5-15 cm = mineral soil) and subsoil (below 50 cm) samples (n = 2567).

Reactivity of Schiff base-[C,N,S] pincer palladacycles: hydrolysis renders singular trinuclear, tetranuclear, and heteropentanuclear Pd3W2 coordinated complexes.

Treatment of the Schiff base ligands a-f with Li2[PdCl4]/NaAcO in methanol under reflux gave the single nuclear palladacycles 1a-1f, with the metal atom bonded to a terdentate monoanionic [C,N,S] iminic ligand and to a chloride ligand that completes the palladium coordination sphere. Reaction of 1a-1c with silver perchlorate/triphenylphosphine in acetone at room temperature yielded the single nuclear complexes 2a-2c as the perchlorate salts, after substitution of the chloride ligand by a triphenylphosphine. However, reaction of a-c with Na2[PdCl4]/NaAcO in methanol at room temperature also gave compounds 1a-1c albeit contaminated with small amounts of the corresponding free aldehyde (mixture A). Reaction of mixture A with silver perchlorate/triphenylphosphine in acetone at room temperature gave analogously 2a-2c with some of the corresponding free aldehyde (mixture B). Attempts to purify mixtures A and B via recrystallization produced single crystals of 5 and 6 respectively: two serendipitously formed complexes, bearing thiomethyl aniline and/or acetate ligands, and void of aldehyde or iminic residue; the structures contain eight- and six-membered rings of alternating palladium and nitrogen atoms, respectively. To clarify this situation the aniline itself was reacted with palladium(II) acetate or with Na2[PdCl4]; in the latter case after recrystallization a unique behavior is revealed, giving rise to a tetranuclear complex containing a Pd4N4 ring with three differing coordination environments on the palladium atoms. Treatment of 1d with Ph2PCH2PPh2 (dppm)/AgClO4 or with Ph2PCH2(PPh2)W(CO)5/AgClO4 gave 3d, with a mono-coordinated dppm ligand, and 4d, respectively; complex 3d could not be converted into 4d by reaction with W(CO)5(THF). Recrystallization of 4d gave a still further noticeable species, complex 8: a pentanuclear trans-configured heterometallic mixed valent Pd(II)/W(0) linear complex with the palladium atoms supported by two acetate and two thiomethyl aniline bridging ligands. The complexes were fully characterized by microanalysis, IR, 1H, and 31P NMR spectroscopies, as appropriate. The X-ray single-crystal analyses for compounds 1b, 5, 6, 7 and 8 are described.

Toxicity of butylone and its enantiomers to Daphnia magna and its degradation/toxicity potential using advanced oxidation technologies.

Butylone (BTL) is a chiral synthetic cathinone available as a racemate and reported as contaminant in wastewater effluents. However, there are no studies on its impact on ecosystems and possible enantioselectivity in ecotoxicity. This work aimed to evaluate: (i) the possible ecotoxicity of BTL as racemate or its isolated (R)- and (S)- enantiomers using Daphnia magna; and (ii) the efficiency of advanced oxidation technologies (AOTs) in the removal of BTL and reduction of toxic effects caused by wastewaters. Enantiomers of BTL were obtained by liquid chromatography (LC) using a chiral semi-preparative column. Enantiomeric purity of each enantiomer was > 97 %. For toxicity assessment, a 9-day sub-chronic assay was performed with the racemate (at 0.10, 1.0 or 10 µg L-1) or each enantiomer (at 0.10 or 1.0 µg L-1). Changes in morphophysiological, behavioural, biochemical and reproductive endpoints were observed, which were dependent on the form of the substance and life stage of the organism (juvenile or adult). Removal rates of BTL in spiked wastewater (10 µg L-1) treated with different AOTs (ultraviolet, UV; ozonation, O3; and UV/O3) were similar and lower than 29 %. The 48 h D. magna acute toxicity assays demonstrated a reduction in the toxicity of the treated spiked effluents, but no differences were found amongst AOTs treatments. These results warn for the contamination and negative impact of BTL on ecosystems and highlight the need for efficient removal processes.