Metabolomic investigation of a new rat model of autosomal recessive polycystic kidney disease

Metabolomics is complementary to genomics, transcriptomics and proteomics; however, it has the capacity to reflect the activities of the organism at a functional level. Metabolomics can therefore be used as a diagnostic tool by identifying the up- or down-regulation of metabolites in the cell, tissue, plasma, serum or urine. Specifically, these are, but are not limited to, identifying biomarkers of disease, monitoring drug treatments, and monitoring surgical procedures such as organ transplant. Autosomal recessive polycystic kidney disease (ARPKD) makes up 5-8% of patients requiring kidney dialysis and/or transplantation and of these, an estimated 50% of patients progress to end-stage renal disease (ESRD) by the age of 10 years, resulting in renal and liver-related morbidity and mortality. The purpose of this research was to utilise the Lewis Polycystic Kidney (LPK) rat to investigate the ARPKD phenotype using metabolomics. Spot urine samples were collected from 7 male Lewis; 8 male LPK; and 6 female LPK rats aged 5 weeks. Metabolites were extracted from urine and derivatised for GC/MS analysis. The peak area of target components was normalised to the internal standard ribitol and then to creatinine. Principal component analysis (PCA) was used to visualise sample grouping and the loadings plot of the PCA was used to determine key metabolites attributed to the variance between sample groups. α-ketoglutarate, uric acid and allantoin were proposed as potential biomarkers for ARPKD in the 5-week old male LPK rat. The findings of this study, particularly the development of a GC/MS method to analyse Lewis and LPK rat urine, demonstrate the potential of metabolomics to further investigate ARPKD

Analysis of prehistoric brown earth paleosols under the podzol soils of Exmoor, UK

The deforestation of the upland landscapes in southwest Britain during prehistory is an established archaeological narrative, documenting human impacts on the environment and questioning the relationship of prehistoric societies to the upland landscapes they inhabited. Allied to the paleoenvironmental analyses of pollen sequences, which have provided the evidence of this change, there has been some investigation of prehistoric paleosols fossilized under principally Bronze Age archaeological monuments. These analyses identified brown earth soils that were originally associated with temperate deciduous woodland, on occasion showing evidence of human impacts such as tilling. However, the number of analyses of these paleosols has been limited. This study presents the first analysis of a series of pre‐podzol brown earth paleosols on Exmoor, UK, two of which are associated with colluvial soil erosion sediments before the formation of peat. This study indicates these paleosols are spatially extensive and have considerable potential to inform a more nuanced understanding of prehistoric human impacts on the upland environments of the early‐mid Holocene and assess human agency in driving ecosystem change

Developing consensus on the principles and key actions for collaborative working between general practices and community pharmacies: a modified eDelphi study

OBJECTIVES: To develop consensus on the principles and key actions for collaborative working in practice between general practice, community pharmacy and patients and their carers. DESIGN: Three-round modified eDelphi study, starting from an established conceptual model of collaboration between general practitioners (GPs) and community pharmacists. SETTING: Community pharmacies and general practices in England, UK. PARTICIPANTS: A panel of 123 experts: 43% from a community pharmacy background; 36% from a GP background; 13% patients, carers or patient representatives and 8% from academic or commissioner backgrounds. Panellist numbers reduced by approximately 30% in rounds 2 and 3. PRIMARY AND SECONDARY OUTCOME MEASURES: Consensus between expert panellists, defined as at least 75% agreement. RESULTS: A high level of consensus (>80%) was achieved on all components of a model of collaboration composed of Fundamental Principles of Collaboration and Key Activities for Action, supported by a series of aspirational statements and suggested practical actions. The fundamental principles and key activities are appended by contextual points. The findings indicate that collaboration in practice involves team members other than just GPs and community pharmacists and recognises that patients often want to know how each professional team is involved in their care. This study also provides insights into how collaboration between general practice and community pharmacy settings appears to have shifted during the COVID-19 pandemic, especially through opportunities for virtual collaboration and communication that can transcend the need for close geographical proximity. CONCLUSION: A consensus-based model of collaboration between general practice teams, community pharmacy teams, and patients and their carers has been developed. It is practically focused, values the patient voice and incorporates general practice and community pharmacy team members. While developed in England, the model is likely to also have applicability to other countries with similar health systems that include general practices and community pharmacies

Potential Environmental Effects of Deepwater Floating Offshore Wind Energy Facilities

Over the last few decades, the offshore wind energy industry has expanded its scope from turbines mounted on foundations driven into the seafloor and standing in less than 60 m of water, to floating turbines moored in 120 m of water, to prospecting the development of floating turbines moored in ~1,000 m of water. Since there are few prototype turbines and mooring systems of these deepwater, floating offshore wind energy facilities (OWFs) currently deployed, their effects on the marine environment are speculative. Using the available scientific literature concerning appropriate analogs, including fixed-bottom OWFs, land-based wind energy facilities, wave and tidal energy devices, and oil and gas platforms, we conducted a qualitative systematic review to estimate the potential environmental effects of deepwater, floating OWFs during operation, as well as potential mitigation measures to address some of the effects. We evaluated six categories of potential effects: changes to atmospheric and oceanic dynamics due to energy removal and modifications, electromagnetic field effects on marine species from power cables, habitat alterations to benthic and pelagic fish and invertebrate communities, underwater noise effects on marine species, structural impediments to wildlife, and changes to water quality. Our synthesis of 89 articles selected for the review suggests that many of these potential effects could be mitigated to pose a low risk to the marine environment if developers adopt appropriate mitigation strategies and best-practice protocols. This review takes the necessary first steps in summarizing the available information on the potential environmental effects of deepwater, floating OWFs and can serve as a reference document for marine scientists and engineers, the energy industry, permitting agencies and regulators of the energy industry, project developers, and concerned stakeholders such as coastal residents, conservationists, and fisheries

Autologous Blood and Platelet-Rich Plasma Injections in the Treatment of Achilles Tendinopathy: A Critically Appraised Topic

Clinical Scenario: Achilles tendinopathy is a painful condition commonly affecting the general and athletic population. It presents with localized pain, stiffness, and swelling in the midportion of the Achilles tendon. The physical stress placed on the tendon results in microtrauma, which leads to subsequent inflammation and degeneration. While it is not surprising that this condition affects the physically active, nearly one-third of Achilles tendinopathy cases occur in sedentary individuals. Etiology for this condition stems from a change in loading patterns and/or overuse of the tendon, resulting in microscopic tearing and degenerative changes. There are numerous causes contributing to the maladaptive response in these patients, such as mechanical, age-related, genetic, and vascular factors. The treatment for these patients is typically load management and eccentric strengthening of the gastrocnemius soleus complex. Unfortunately, conservative treatment can lead to surgical intervention in up to 45% of cases. A relatively new phenomenon in the treatment of this condition is the use of autologous blood injections (ABI) and platelet-rich plasma injections (PRPI). This need for a less invasive treatment fostered more investigation into ABI and PRPI to treat these nonresponsive patients. However, the evidence concerning the effectiveness of these treatments in patients with Achilles tendinopathy has not been synthesized. Focused Clinical Question: In patients with Achilles tendinopathy, how do variations of ABI and PRPI compared with a placebo and/or eccentric training affect pain and function

Assessment of surface wind datasets for estimating offshore wind energy along the Central California Coast

In the United States, Central California has gained significant interest in offshore wind energy due to its strong winds and proximity to existing grid connections. This study provides a comprehensive evaluation of near-surface wind datasets in this region, including satellite-based observations (QuikSCAT, ASCAT, and CCMP V2.0), reanalysis (NARR and MERRA), and regional atmospheric models (WRF and WIND Toolkit). This work highlights spatiotemporal variations in the performance of the respective datasets in relation to in-situ buoy measurements using error metrics over both seasonal and diurnal time scales. The two scatterometers(QuikSCAT and ASCAT) showed the best overall performance, albeit with significantly less spatial and temporal resolution relative to other datasets. These datasets only slightly outperformed the next best dataset (WIND Toolkit), which has significantly greater temporal and spatial resolution as well as estimates of winds aloft. Considering tradeoffs between spatiotemporal resolution of the underlying datasets, error metrics relative to in-situ measurements, and the availability of data aloft, the WIND Toolkit appears to be the best dataset for this region. The framework and tradeoff analysis this research developed and demonstrated to assess offshore wind datasets can be applied in other regions where offshore wind energy is being considered

Recovery in Borderline Personality Disorder (BPD): A Qualitative Study of Service Users' Perspectives

PMCID: PMC3355153This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Comparison of a Powdered, Acidified Liquid, and Non-Acidified Liquid Human Milk Fortifier on Clinical Outcomes in Premature Infants.

We previously compared infant outcomes between a powdered human milk fortifier (P-HMF) vs. acidified liquid HMF (AL-HMF). A non-acidified liquid HMF (NAL-HMF) is now commercially available. The purpose of this study is to compare growth and outcomes of premature infants receiving P-HMF, AL-HMF or NAL-HMF. An Institutional Review Board (IRB) approved retrospective chart review compared infant outcomes (born \u3c 2000 g) who received one of three HMF. Growth, enteral nutrition, laboratory and demographic data were compared. 120 infants were included (P-HMF = 46, AL-HMF = 23, NAL-HMF = 51). AL-HMF infants grew slower in g/day (median 23.66 vs. P-HMF 31.27, NAL-HMF 31.74 (p \u3c 0.05)) and in g/kg/day, median 10.59 vs. 15.37, 14.03 (p \u3c 0.0001). AL-HMF vs. NAL-HMF infants were smaller at 36 weeks gestational age (median 2046 vs. 2404 g, p \u3c 0.05). However AL-HMF infants received more daily calories (p = 0.21) and protein (p \u3c 0.0001), mean 129 cal/kg, 4.2 g protein/kg vs. P-HMF 117 cal/kg, 3.7 g protein/kg , NAL-HMF 120 cal/kg, 4.0 g protein/kg. AL-HMF infants exhibited lower carbon dioxide levels after day of life 14 and 30 (p \u3c 0.0001, p = 0.0038). Three AL-HMF infants (13%) developed necrotizing enterocolitis (NEC) vs. no infants in the remaining groups (p = 0.0056). A NAL-HMF is the most optimal choice for premature human milk-fed infants in a high acuity neonatal intensive care unit (NICU)

Evaluating associations between metabolic health, obesity and depressive symptoms : a prospective analysis of data from the English Longitudinal Study of Ageing (ELSA) with a 2-year follow-up

OBJECTIVES: Conflicting results have been reported when the associations between metabolic health, obesity and depression were examined previously. The primary aim of this study was to determine whether metabolic health or obesity are independently associated with depressive symptoms, among a representative sample of older people living in England. Independent associations between covariates and depression were also examined. DESIGN: Prospective study with a 2-year follow-up. SETTING: The English Longitudinal Study of Ageing Wave 6 (2012-2013) and Wave 7 (2014-2015). PARTICIPANTS: 6804 participants aged older than 50 years. DATA ANALYSIS: Multivariate models were used to determine whether metabolic health or obesity are independently associated with depressive symptoms at 2-year follow-up. Unadjusted and adjusted ORs with corresponding 95% CI were calculated; the adjusted ORs took account of baseline depression, gender, age, wealth, obesity and poor metabolic health. RESULTS: Before adjusting for covariates, poor metabolic health was associated with depressive symptoms at 2-year follow-up (OR 1.24; 95% CI, 1.07 to 1.44, p<0.01). After adjusting for covariates, the association was no longer statistically significant (OR 1.17; 95% CI, 0.99 to 1.38, p=0.07). Similarly, obesity was associated with depressive symptoms at 2-year follow-up before adjusting for covariates (OR 1.54; 95% CI, 1.33 to 1.79, p<0.01). However, after adjusting for covariates the association between obesity and depressive symptoms at 2-year follow-up became statistically insignificant (OR 1.19; 95% CI, 1.00 to 1.41, p=0.06). The strongest predictors for future depression were baseline depression (OR 10.59; 95% CI, 8.90 to 12.53, p<0.01) and lower wealth (OR 3.23; 95% CI, 2.44 to 4.35, p<0.01). CONCLUSION: Neither poor metabolic health nor obesity were associated with a risk of depressive symptoms at 2-year follow-up, after adjusting for covariates. As wealth inequalities continue to rise across England, the risk of depressive symptoms at 2-year follow-up is likely to be elevated in individuals living in the lower wealth quintiles

Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension

To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements. Junctional stability is dependent on actomyosin contractility within the actin ring. Here we describe a novel function for the axon guidance receptor, Neogenin, as a key component of the actin nucleation machinery governing junctional stability. Loss of Neogenin perturbs AJs and attenuates junctional tension. Neogenin promotes actin nucleation at AJs by recruiting the Wave regulatory complex (WRC) and Arp2/3. A direct interaction between the Neogenin WIRS domain and the WRC is crucial for the spatially restricted recruitment of the WRC to the junction. Thus, we provide the first example of a functional WIRS-WRC interaction in epithelia. We further show that Neogenin regulates cadherin recycling at the AJ. In summary, we identify Neogenin as a pivotal component of the AJ, where it influences both cadherin dynamics and junctional tension