A comparison of renal phosphorus regulation in thermally-injured and multiple trauma patients receiving specialized nutrition support

To compare phosphorus intake and renal phosphorus regulation between thermally injured patients and multiple trauma patients, 40 consecutive critically ill patients, 20 with thermal injury and 20 with multiple trauma, who required enteral tube feeding were evaluated. Phosphorus intakes were recorded for 14 days from the initiation of tube feeding which was started 1 to 3 days post-injury. Serum for determination of phosphorus concentrations was collected at days 1, 3, 7, and 14 of the study period. A 24-hour urine collection was obtained during the first and second weeks of nutrition support for urinary phosphorus excretion, fractional excretion of phosphorus, renal threshold phosphate concentration, and phosphorus clearance. Average total daily phosphorus intake during the 14-day study for thermally injured patients and multiple trauma patients was 0.99 ± 0.26 mmol/kg/d vs 0.58 ± 0.21 mmol/kg/d, respectively, p \u3c .001. Serum phosphorus concentration on the third day of observation was significantly lower in the thermally injured group than those with multiple trauma (1.9 ± 0.8 mg/dL vs 3.0 ± 0.8 mg/dL, p ≤ .01). A trend toward hypophosphatemia in the thermally injured group persisted by the seventh day of feeding (2.7 ± 1.2 mg/dL vs 3.3 ± 0.6 mg/dL, p ≤ .04). Differences in urinary phosphorus excretion was not statistically significant between the thermally injured and multiple trauma groups (271 ± 213 mg/d vs 171 ± 181 mg/d for week 1, and 320 ± 289 mg/d vs 258 ± 184 mg/d for week 2, respectively). Urinary phosphorus clearance, fractional excretion of phosphorus, or renal threshold phosphate concentrations were also not significantly different between thermally injured and multiple trauma patients. During nutrition support, serum phosphorus concentrations are lower in thermally injured patients compared with multiple trauma patients despite receiving a significantly greater intake of phosphorus. Renal phosphorus regulation does not significantly contribute to the profound hypophosphatemia observed in thermally injured patients when compared with multiple trauma patients during nutrition support

Capacity for recovery in Bornean orangutan populations when limiting offtake and retaining forest

The analysis would not have been possible without the Specialist and High-Performance Computing systems provided by Information Services at the University of Kent.Peer reviewe

Renal phosphorus regulation in thermally-injured and multiple trauma patients receiving enteral nutrition

Abstract from the 22nd Clinical Congress of the American Society for Parenteral and Enteral Nutrition, Orlando, FL, January 18-21, 1998

Analysis of Safety from a Human Clinical Trial with Pterostilbene

Objectives. The purpose of this trial was to evaluate the safety of long-term pterostilbene administration in humans. Methodology. The trial was a prospective, randomized, double-blind placebo-controlled intervention trial enrolling patients with hypercholesterolemia (defined as a baseline total cholesterol ≥200 mg/dL and/or baseline low-density lipoprotein cholesterol ≥100 mg/dL). Eighty subjects were divided equally into one of four groups: (1) pterostilbene 125 mg twice daily, (2) pterostilbene 50 mg twice daily, (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily, and (4) matching placebo twice daily for 6–8 weeks. Safety markers included biochemical and subjective measures. Linear mixed models were used to estimate primary safety measure treatment effects. Results. The majority of patients completed the trial (91.3%). The average age was 54 years. The majority of patients were females (71%) and Caucasians (70%). There were no adverse drug reactions (ADRs) on hepatic, renal, or glucose markers based on biochemical analysis. There were no statistically significant self-reported or major ADRs. Conclusion. Pterostilbene is generally safe for use in humans up to 250 mg/day

Pterostilbene on Metabolic Parameters: A Randomized, Double-Blind, and Placebo-Controlled Trial

Introduction. The purpose of this trial was to evaluate the effect of pterostilbene on metabolic parameters. Methods. A prospective, randomized, double-blind, and placebo-controlled study that enrolled 80 patients with a total cholesterol ≥200 mg/dL and/or LDL≥100 mg/dL. Subjects were divided into four groups: (1) pterostilbene 125 mg twice daily; (2) pterostilbene 50 mg twice daily; (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily; (4) matching placebo twice daily for 6–8 weeks. Endpoints included lipids, blood pressure, and weight. Linear mixed models were used to examine and compare changes in parameters over time. Models were adjusted for age, gender, and race. Results. LDL increased with pterostilbene monotherapy (17.1 mg/dL; P=0.001) which was not seen with GE combination (P=0.47). Presence of a baseline cholesterol medication appeared to attenuate LDL effects. Both systolic (−7.8 mmHg; P<0.01) and diastolic blood pressure (−7.3 mmHg; P<0.001) were reduced with high dose pterostilbene. Patients not on cholesterol medication (n=51) exhibited minor weight loss with pterostilbene (−0.62 kg/m2; P=0.012). Conclusion. Pterostilbene increases LDL and reduces blood pressure in adults. This trial is registered with Clinicaltrials.gov NCT01267227

Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop-Dependent Cell Death in Murine Fibroblasts

As part of the International Cooperative Biodiversity Groups (ICBG) Program, we were interested in identifying biologically active unfolded protein response (UPR) inducing compounds from marine microorganisms isolated from Costa Rican biota. With this aim in mind we have now generated more than 33,000 unique prefractionated natural product extracts from marine and terrestrial organisms that have been submitted to the Center of Chemical Genomics (CCG) at the University of Michigan for high throughput screening (HTS). An effective complementary cell-based assay to identify novel modulators of UPR signaling was used for screening extracts. Active fractions were iteratively subjected to reverse-phase HPLC chromatographic analysis, and together with lobophorin A, B, E, and F (1–4), three new lobophorin congeners, designated as CR1 (5), CR2 (6), and CR3 (7) were isolated. Herein, we report that secondary assays revealed that the new lobophorins induced UPR-associated gene expression, inhibited oral squamous cell carcinoma cell growth, and led to UPR-dependent cell death in murine embryonic fibroblast (MEF) cells.International Cooperative Biodiversity Groups/[U01 TW007404]/ICBG/Estados UnidosNational Institutes of Health/[DK042394]/NIH/Estados UnidosNational Institutes of Health/[DK088227]/NIH/Estados UnidosNational Institutes of Health/[HL052173]/NIH/Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones en Productos Naturales (CIPRONA)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Químic

A horizon scan of priorities for coastal marine microbiome research

Research into the microbiomes of natural environments is changing the way ecologists and evolutionary biologists view the importance of microbes in ecosystem function. This is particularly relevant in ocean environments, where microbes constitute the majority of biomass and control most of the major biogeochemical cycles, including those that regulate the Earth's climate. Coastal marine environments provide goods and services that are imperative to human survival and well-being (e.g. fisheries, water purification), and emerging evidence indicates that these ecosystem services often depend on complex relationships between communities of microorganisms (the ‘microbiome’) and their hosts or environment – termed the ‘holobiont’. Understanding of coastal ecosystem function must therefore be framed under the holobiont concept, whereby macroorganisms and their associated microbiomes are considered as a synergistic ecological unit. Here we evaluated the current state of knowledge on coastal marine microbiome research and identified key questions within this growing research area. Although the list of questions is broad and ambitious, progress in the field is increasing exponentially, and the emergence of large, international collaborative networks and well-executed manipulative experiments are rapidly advancing the field of coastal marine microbiome research

Borrelidin Induces the Unfolded Protein Response in Oral Cancer Cells and Chop-Dependent Apoptosis

Oral squamous cell carcinoma (OSCC) is the most common cancer affecting the oral cavity, and US clinics will register about 30,000 new patients in 2015. Current treatment modalities include chemotherapy, surgery, and radiotherapy, which often result in astonishing disfigurement. Cancers of the head and neck display enhanced levels of glucose-regulated proteins and translation initiation factors associated with endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Previous work demonstrated that chemically enforced UPR could overwhelm these adaptive features and selectively kill malignant cells. The threonyl-tRNA synthetase (ThRS) inhibitor borrelidin and two congeners were discovered in a cell-based chemical genomic screen. Borrelidin increased XBP1 splicing and led to accumulation of phosphorylated eIF2α and UPR-associated genes, prior to death in panel of OSCC cells. Murine embryonic fibroblasts (MEFs) null for GCN2 and PERK were less able to accumulate UPR markers and were resistant to borrelidin. This study demonstrates that UPR induction is a feature of ThRS inhibition and adds to a growing body of literature suggesting ThRS inhibitors might selectively target cancer cells.National Institutes of Health/[DE019678]/NIH/Estados UnidosInternational Cooperative Biodiversity Groups/[U01 TW007404]/ICBG/Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones en Productos Naturales (CIPRONA)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Químic

A horizon scan of priorities for coastal marine microbiome research

Research into the microbiomes of natural environments is changing the way ecologists and evolutionary biologists view the importance of microbes in ecosystem function. This is particularly relevant in ocean environments, where microbes constitute the majority of biomass and control most of the major biogeochemical cycles, including those that regulate the Earth's climate. Coastal marine environments provide goods and services that are imperative to human survival and well-being (e.g. fisheries, water purification), and emerging evidence indicates that these ecosystem services often depend on complex relationships between communities of microorganisms (the ‘microbiome’) and their hosts or environment – termed the ‘holobiont’. Understanding of coastal ecosystem function must therefore be framed under the holobiont concept, whereby macroorganisms and their associated microbiomes are considered as a synergistic ecological unit. Here we evaluated the current state of knowledge on coastal marine microbiome research and identified key questions within this growing research area. Although the list of questions is broad and ambitious, progress in the field is increasing exponentially, and the emergence of large, international collaborative networks and well-executed manipulative experiments are rapidly advancing the field of coastal marine microbiome research