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Dysregulated phosphate metabolism is a common consequence of chronic kidney disease, and is characterized by a high circulating level of fibroblast growth factor (FGF)-23, hyperparathyroidism, and hyperphosphataemia. Kidney transplantation can elicit specific alterations to phosphate metabolism that evolve over time, ranging from severe hypophosphataemia (1.50 mmol/l) and high FGF-23 levels. The majority of renal transplant recipients develop hypophosphataemia during the first 3 months after transplantation as a consequence of relatively slow adaptation of FGF-23 and parathyroid hormone levels to restored renal function, and the influence of immunosuppressive drugs. By 3-12 months after transplantation, phosphate homeostasis is at least partially restored in the majority of recipients, which is paralleled by a substantially reduced risk of cardiovascular-associated morbidity and mortality compared with the pre-transplantation setting. Many renal transplant recipients, however, exhibit persistent abnormalities in phosphate homeostasis, which is often due to multifactorial causes, and may contribute to adverse outcomes on the cardiovascular system, kidney, and bone. Dietary and pharmacologic interventions might improve phosphate homeostasis in renal transplant recipients, but additional insight into the pathophysiology of transplantation-associated abnormalities in phosphate homeostasis is needed to further optimize disease management and improve prognosis for renal transplant recipients.Protein sorting is an important mechanism for transporting proteins to their target subcellular locations after their synthesis. Mutations on genes may disrupt the well regulated protein sorting process, leading to a variety of mislocation related diseases. This paper proposes a methodology to discover such disease genes based on gene expression data and computational protein localization prediction. A kernel logistic regression based algorithm is used to successfully identify several candidate cancer genes which may cause cancers due to their mislocation within the cell. Our results also showed that compared to the gene co-expression network defined on Pearson correlation coefficients, the nonlinear Maximum Correlation Coefficients (MIC) based co-expression network give better results for subcellular localization prediction.There is significant expectation in the pharmacological community that an understanding of biased signalling will lead to the development of new drugs and a better understanding of molecular targets in the in vivo context. I think it is safe to say that Pharma is withholding judgment on the promise and potential of what they view as an interesting pharmacological curiosity. That said, beyond successes of biased ligands in clinical trials and their appearance on the market, what it is need is a clear plan and the right tools and analytical methods to characterize functional selectivity from in cellulo to in vivo. In this issue of Methods, we have put together a series of articles that help lay out a methodological and analytical framework to help get us there.

Irrigation of the cutaneous abscess cavity is often described as a standard part of incision and drainage despite no randomized, controlled studies showing benefit. Our goal is to determine whether irrigation of a cutaneous abscess during incision and drainage in the emergency department (ED) decreases the need for further intervention within 30 days compared with no irrigation.

We performed a single-center, prospective, randomized, nonblinded study of ED patients receiving an incision and drainage for cutaneous abscess, randomized to irrigation or no irrigation. Patient characteristics and postprocedure pain visual analog scale score were obtained. Thirty-day telephone follow-up was conducted with a standardized data form examining need for further intervention, which was defined as repeated incision and drainage, antibiotic change, or abscess-related hospital admission.

Of 209 enrolled patients, 187 completed follow-up. The irrigation and no-irrigation groups were similar with respect to diabetes, immunocompromise, fever, abscess size, cellulitis, and abscess location, but the irrigation group was younger (mean age 36 versus 40 years) and more often treated with packing (89% versus 75%) and outpatient antibiotics (91% versus 73%). The need for further intervention was not different in the irrigation (15%) and no-irrigation (13%) groups (difference 2%; 95% confidence interval -8% to 12%). There was no difference in pain visual analog scale scores (5.6 versus 5.7; difference 0.1; 95% confidence interval -0.7 to 0.9).

Although there were baseline differences between groups, irrigation of the abscess cavity during incision and drainage did not decrease the need for further intervention.

Although there were baseline differences between groups, irrigation of the abscess cavity during incision and drainage did not decrease the need for further intervention.

To compare the prevalence in residential aged care (RAC) of preventative and potentially inappropriate medications (PIMs) in those who died within 12 months versus those alive after 12 months.

Firstly, a cross-sectional survey of 6196 people living in RAC in Auckland. Secondly, a research physician searched electronic hospital records in one District Health Board for a sub-sample (n = 222) of these residents. Classes of medications and dates of death were obtained from the Ministry of Health databases. Those who died versus those alive at 12 months were compared.

Over half of the 6196 participants received antihypertensives and/or antiplatelet agents. Cardiovascular preventative medications were significantly more common in those who died within 12 months. Seventy percent in high-level care received psychotropics. PIMs were commonly used.

Use of preventative medications is common in RAC, especially during the last year of life. Psychotropics are very commonly used, despite being potentially inappropriate.

Use of preventative medications is common in RAC, especially during the last year of life. Psychotropics are very commonly used, despite being potentially inappropriate.Neonatal sepsis is common in neonatal intensive care units, often complicated by injury to the immature brain. Previous studies have shown that the expression of the gap junction protein connexin 43 (Cx43) in the brain decreases when stimulated by neuro-inflammatory drugs such as lipopolysaccharide (LPS). Here we showed that partial deletion of Cx43 in astrocytes resulted in weakened inflammatory responses. The up-regulation of pro-inflammatory cytokines was significantly reduced in mice with partial deletion of Cx43 in astrocytes compared with wild-type littermates after systemic LPS injection. Moreover, microglial activation was inhibited in mice with partial deletion of Cx43. These results showed that Cx43 in astrocytes plays a critical role in neuro-inflammatory responses. This work provides a potential therapeutic target for inhibiting neuro-inflammatory responses in neonatal sepsis.

Whereas vismodegib is effective in the treatment of locally advanced/metastatic basal cell carcinoma, dysgeusia and weight loss are common side effects of such treatment. The main objective of this study was to monitor the nutritional status of vismodegib-treated patients. Secondary objective was to assess the incidence of dysgeusia and the benefit of early nutritional management.

This prospective study included all patients who started vismodegib between October 2011 and May 2013 at Nantes University Hospital. Prior to July 2012, patients treated with vismodegib had not received any specific nutritional management (Historical cohort). Body weight and presence of dysgeusia were recorded monthly. Patients treated after July 2012 (Nutrition cohort) were evaluated by a physician of the Nutrition Support Unit and received dietary counseling at vismodegib initiation. A standardized nutritional management protocol was initiated in case of significant weight loss.

Forty-five patients (21 and 24 in the Nutrition and Historical cohort, respectively) were enrolled. In the Nutrition cohort, five patients (24 %) were undernourished at vismodegib initiation, and the 6-month cumulative incidence of dysgeusia was 71 %. Eight patients (38 %) and 13 patients (54 %) had a weight loss greater than 5 % in the Nutrition and Historical cohort, respectively (p = 0.3727).

The results of this pilot study suggest the benefit of early nutritional screening. The potential benefit of nutritional support in this setting warrants further investigation.

The results of this pilot study suggest the benefit of early nutritional screening. The potential benefit of nutritional support in this setting warrants further investigation.

It is unknown why some breast cancer survivors experience cancer-related cognitive impairments (CRCI) after cancer treatment, and modifiable risk factors for CRCI remain to be explicated. This mixed-method systematic review synthesizes quantitative and qualitative evidence for relationships between modifiable factors and CRCI in breast cancer survivors who receive chemotherapy as part of their treatment.

Keyword Searches of PubMed/Medline, PsychINFO, and CINAHL were performed for January 2005 through June 2015. Studies that provided data on associations between modifiable biological, behavioral, environmental, and psychosocial factors and cognition were included.

Twenty-two quantitative studies and five qualitative studies were identified after applying inclusion and exclusion criteria yielding evidence for significant relationships among modifiable biological (inflammatory cytokines), behavioral (sleep quality, physical activity), and psychosocial (stress, distress, affect) factors and CRCI.

Many womivity, stress management, and sleep quality may be appropriate targets for behavioral interventions to improve cognitive function following breast cancer chemotherapy; however, further research is necessary.A novel phytase from Ganoderma australe G24 was produced by submerged cultivation and recovery. Liquid and solid forms of phytase were developed; both types of product were formulated using different additives. Ganoderma australe G24 phytase was very stable in liquid form with NaCl and sodium acetate buffer. Solid form products were obtained by spray-drying using different polymers to encapsulate the phytase and the capsules obtained were analyzed by electron microscopy. Micrographs confirmed micro and nanoparticles formed with maltodextrin (300 nm to 7-8 µm) without the presence of agglomerates. The use of maltodextrin for solid formulation of G. australe G24 phytase is recommended, and resulted in good stability after the drying process and during storage (shelf life). Kinetic models of phytase inactivation in the microencapsulated powders over time were proposed for the different stabilizing additives. Inactivation rate constants, half-lives and D values (decimal reduction time) were obtained. Phytase encapsulated with maltodextrin remained stable after 90 days, with k 0.0019 day(-1) and a half-life (t1/2) of 367.91 days(-1).The phosphazene-phosphazane rearrangement of N3P3Cl5O(CH2)2OC(=O)CMe=CH2 (8) has been examined in detail using one and two dimensional NMR ((31)P, (1)H) spectroscopy and mass spectrometry. The mixed phosphazene-phosphazane [NPCl2]2[N((CH2)2OC(=O)CMe=CH2)P(O)Cl] (14), [NPCl2]2[NHP(O)Cl] (13) and a two ring assembly [NPCl2]2[NP(O(NPCl2)2(N((CH2)2OC(=O)CMe=CH2)P(O)] (15) have all been detected in the product mixture. The rate of the rearrangement has been measured at five temperatures by (31)P and (1)H NMR. The reaction is first order in 8 (T1/2 at 111° is 4.65 hours). learn more The activation enthalpy is positive and the activation entropy is negative. A mechanism involving competing intra and inter molecular processes which fits the product distribution and kinetic data has been proposed. Several other methyacrylphosphazenes were examined under the same thermolysis conditions. The rearrangement was observed and the rates obtained in cases where the (CH2)2 spacer unit of the methacrylate was replaced by linear and branched propyl units.

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