Diet changes due to urbanization in South Africa are linked to microbiome and metabolome signatures of Westernization and colorectal cancer.

Transition from traditional high-fiber to Western diets in urbanizing communities of Sub-Saharan Africa is associated with increased risk of non-communicable diseases (NCD), exemplified by colorectal cancer (CRC) risk. To investigate how urbanization gives rise to microbial patterns that may be amenable by dietary intervention, we analyzed diet intake, fecal 16 S bacteriome, virome, and metabolome in a cross-sectional study in healthy rural and urban Xhosa people (South Africa). Urban Xhosa individuals had higher intakes of energy (urban: 3,578 ± 455; rural: 2,185 ± 179 kcal/d), fat and animal protein. This was associated with lower fecal bacteriome diversity and a shift from genera favoring degradation of complex carbohydrates (e.g., Prevotella) to taxa previously shown to be associated with bile acid metabolism and CRC. Urban Xhosa individuals had higher fecal levels of deoxycholic acid, shown to be associated with higher CRC risk, but similar short-chain fatty acid concentrations compared with rural individuals. Fecal virome composition was associated with distinct gut bacterial communities across urbanization, characterized by different dominant host bacteria (urban: Bacteriodota; rural: unassigned taxa) and variable correlation with fecal metabolites and dietary nutrients. Food and skin microbiota samples showed compositional differences along the urbanization gradient. Rural-urban dietary transition in South Africa is linked to major changes in the gut microbiome and metabolome. Further studies are needed to prove cause and identify whether restoration of specific components of the traditional diet will arrest the accelerating rise in NCDs in Sub-Saharan Africa.

A taste of cell-cultured meat: a scoping review.

Cell-cultured meat (CM) is a novel meat product grown in vitro from animal cells, widely framed as equivalent to conventional meat but presented as produced in a more sustainable way. Despite its limited availability for human consumption, consumer acceptance of CM (e.g., willingness to purchase and consume) has been extensively investigated. A key but under-investigated assumption of these studies is that CM's sensory qualities are comparable to conventional, equivalent meat products. Therefore, the current review aims to clarify what is actually known about the sensory characteristics of CM and their potential impact on consumer acceptance. To this end, a structured scoping review of existing, peer-reviewed literature on the sensory evaluation of CM was conducted according to the PRISMA-ScR and Joanna Briggs Institute guidelines. Among the included studies (N = 26), only 5 conducted research activities that could be termed "sensory evaluation," with only 4 of those 5 studies evaluating actual CM products in some form. The remaining 21 studies based their conclusions on the sensory characteristics of CM and consequent consumer acceptance to a set of hypothetical CM products and consumption experiences, often with explicitly positive information framing. In addition, many consumer acceptance studies in the literature have the explicit goal to increase the acceptance of CM, with some authors (researchers) acting as direct CM industry affiliates; this may be a source of bias on the level of consumer acceptance toward these products. By separating what is known about CM sensory characteristics and consumer acceptance from what is merely speculated, the current review reported realistic expectations of CM's sensory characteristics within the promissory narratives of CM proponents.

Neuropsychology consultation to identify learning disorders in children and adolescents: a proposal based on lessons learned during the COVID-19 pandemic.

Learning disorders are common neurodevelopmental conditions, occurring both idiopathically and in the context of other medical conditions. They are frequently comorbid with other neurodevelopmental and psychiatric conditions. Delayed identification and treatment have been associated with significant negative psychosocial consequences. The need for pediatric neuropsychologists to efficiently screen for learning disorders is likely to increase in the months and years following the COVID-19 pandemic, which has severely disrupted access to educational services, especially for children who also face racial and economic disparities. In this paper, we describe a consultation model that can be used to screen for learning disorders and can be completed using both in-person and telemedicine visits. Implementation may result in earlier intervention for struggling children, increase access to neuropsychological services without increasing wait times for comprehensive evaluations, and provide opportunities for collaborations with other health professionals (e.g., pediatricians, therapists, psychiatrists, and neurologists).

Transcriptomic changes during stage progression of mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, which in the early patch/plaque stages runs an indolent course. However, ~25% of patients with MF develop skin tumours, a hallmark of progression to the advanced stage, which is associated with high mortality. The mechanisms involved in stage progression are poorly elucidated. OBJECTIVES: We sought to address the hypothesis of MF cell trafficking between skin lesions by comparing transcriptomic profiles of skin samples in different clinical stages of MF. METHODS: We performed whole-transcriptome and whole-exome sequencing of malignant MF cells from skin biopsies obtained by laser-capture microdissection. We compared three types of MF lesions: early-stage plaques (ESP, n = 12) as well as plaques and tumours from patients in late-stage disease [late-stage plaques (LSP, n = 10) and tumours (TMR, n = 15)]. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine pathway changes specific for different lesions which were linked to the recurrent somatic mutations overrepresented in MF tumours. RESULTS: The key upregulated pathways during stage progression were those related to cell proliferation and survival (MEK/ERK, Akt-mTOR), T helper cell (Th)2/Th9 signalling [interleukin (IL)4, STAT3, STAT5, STAT6], meiomitosis (CT45A1, CT45A3, STAG3, GTSF1, REC8) and DNA repair (PARP1, MYCN, OGG1). Principal coordinate clustering of the transcriptome revealed extensive gene expression differences between early (ESP) and advanced-stage lesions (LSP and TMR). LSP and TMR showed remarkable similarities at the level of the transcriptome, which we interpreted as evidence of cell percolation between lesions via haematogenous self-seeding. CONCLUSIONS: Stage progression in MF is associated with Th2/Th9 polarization of malignant cells, activation of proliferation, survival, as well as increased genomic instability. Global transcriptomic changes in multiple lesions may be caused by haematogenous cell percolation between discrete skin lesions.

Assessing the feasibility of a rapid, high-volume cervical cancer screening programme using HPV self-sampling and digital colposcopy in rural regions of Yunnan, China.

OBJECTIVE: Implementation of a novel, rapid, high-volume, see-and-treat cervical cancer screening programme using self-swab human papillomavirus (HPV) testing and digital colposcopy in underserved regions of Yunnan China. DESIGN: 480-980 women per day self-swabbed for high-risk HPV (hrHPV+). Four careHPV machines (Qiagen) were run simultaneously to test the specimens. All hrHPV+ patients were contacted the same day and digital colposcopy was performed with the enhanced visual assessment system (MobileODT). Digital images were obtained, and all suspected lesions were biopsied and then treated. SETTING: Rural and underserved areas of the Yunnan province, Kunming municipality. PARTICIPANTS: 3600 women, mean age 50.2 years, who had never been screened for cervical cancer. The women were of the Yi, Hui, Dai and Han ethnicities. INTERVENTIONS: Cryotherapy was performed on all lesions suspicious for cervical intraepithelial neoplasia (CIN) 1 and loop electrosurgical excision procedure was performed on all lesions suspicious for ≥CIN2. Endocervical curettage was performed if the transformation zone was not fully visualised. RESULTS: 216 women (6%) were hrHPV+. 168 underwent same-day colposcopy (23 CIN1, 17≥CIN2). Digital colposcopy was able to identify 15 of 16 (93.8%)≥CIN2 lesions. CONCLUSIONS: This study illustrates a high-volume, rapid and practical strategy that can be used to screen and treat an ethnically diverse group of Chinese women. First, HPV self-sampling allows large numbers of women to be screened rapidly and relatively inexpensively. Only hrHPV+ women will then require further evaluation. Digital colposcopy is then performed on hrHPV+ women with a portable digital colposcope. The high-resolution images obtained can facilitate appropriate same-day treatment as they are able to accurately distinguish between CIN1 and ≥CIN2 lesions.

Differences in Fecal Gut Microbiota, Short-Chain Fatty Acids and Bile Acids Link Colorectal Cancer Risk to Dietary Changes Associated with Urbanization Among Zimbabweans.

The incidence of colorectal cancer (CRC) is gradually rising in sub-Saharan Africa. This may be due to dietary changes associated with urbanization, which may induce tumor-promoting gut microbiota composition and function. We compared fecal microbiota composition and activity in 10 rural and 10 urban Zimbabweans for evidence of a differential CRC risk. Dietary intake was assessed by a food frequency questionnaire. Fecal microbiota composition, metabolomic profile, functional microbial genes were analyzed, and bile acids and short chain fatty acids quantified. Animal protein intake was higher among urban volunteers, but carbohydrate and fiber intake were similar. Bacteria related to Blautia obeum, Streptococcus bovis, and Subdoligranulum variabile were higher in urban residents, whereas bacteria related to Oscillospira guillermondii and Sporobacter termitidis were higher in rural volunteers. Fecal levels of primary bile acids, cholic acid, and chenodeoxycholic acid (P < 0.05), and secondary bile acids, deoxycholic acid (P < 0.05) and ursodeoxycholic acid (P < 0.001) were higher in urban residents. Fecal levels of acetate and propionate, but not butyrate, were higher in urban residents. The gut microbiota composition and activity among rural and urban Zimbabweans retain significant homogeneity (possibly due to retention of dietary fiber), but urban residents have subtle changes, which may indicate a higher CRC risk.

Short communication: Mycosporine-like amino acids protect natamycin against photodegradation in milk exposed to fluorescent or light-emitting diode light.

Natamycin has been used as a natural antimicrobial in dairy products, but the poor light stability of natamycin can limit usefulness in food products. Mycosporine-like amino acids are strong UV absorbers and might be useful as an additive to decrease light-induced degradations. Therefore, the objective of this study was to evaluate the photoprotective effect of mycosporine-like amino acids (MAA) in cow milk stored under 2 lighting conditions in retail commercial display cabinets with fluorescent and high intensity light-emitting diode illumination. When milk was exposed to both fluorescent and light-emitting diode light, natamycin degradation was very fast, and only 17.1 ± 0.9% of its original concentration was observed after 8 d at 4.0°C. On the other hand, by adding MAA into milk, natamycin was retained at 82.2 ± 0.9% and 92.2 ± 0.9% when low and high MAA levels were used, respectively. However, high MAA levels resulted in color changes. Therefore, MAA at low levels had a photoprotective effect for natamycin stability in cow milk exposed to light in refrigerated glass containers.

Packaging modifications for protecting flavor of extended-shelf-life milk from light.

The effectiveness of titanium dioxide (TiO2)-loaded high-density polyethylene (HDPE) to reduce light-induced oxidation of extended-shelf-life milk (2% total fat) was studied. The objective was to determine differences over time in sensory quality, vitamin retention, and oxidative chemistry as a function of packaging and retail light exposure duration. Effectiveness of packaging for protecting milk quality was assessed by sensory evaluation (triangle tests, untrained panel), changes in volatile compounds, thiobarbituric reactive substances (TBARS), and riboflavin concentration. Milk (2%) was stored in HDPE packages consisting of TiO2 at 3 levels (low: 0.6%; medium: 1.3%; high: 4.3%) at 3 °C for up to 43 d. Light-protected (translucent, foil-wrapped) and light-exposed (translucent) HDPE packages served as controls. The high TiO2-HDPE package provided protection similar to light-protected control package through d 22 of light exposure, with less consistent performance by the medium TiO2 package. The TBARS increased in all treatments during storage. Under the experimental conditions used, a TBARS value of 1.3mg/L could be considered the limiting sensory threshold for differentiating oxidized milk from light-protected milk. Riboflavin concentration decreased 10.5% in the light-protected control and 28.5% in the high TiO2 packaged milk past 29 d of light exposure, but losses were greater than 40% for all other packages. The high TiO2 package protected riboflavin concentration from degradation and controlled aldehyde concentration throughout the test period.

Advance preferences regarding thrombolysis in patients at risk for stroke: a cross-sectional study.

BACKGROUND: It is difficult to obtain informed consent for thrombolysis in stroke patients given the emergency setting, the need for a speedy decision and the effects of neurological deficits. AIM: To determine the advance preferences for thrombolysis of patients at risk for stroke following discussion of the potential risks and benefits. DESIGN: Cross-sectional survey. METHODS: Data on benefits and risks of thrombolysis within 3 h and between 3 and 4.5 h after stroke were presented orally, in writing and pictorially to patients attending geriatric and stroke services in a teaching hospital with specified stroke risk factors and preferences for thrombolysis were recorded. RESULTS: Of the 121 participants, 108 (89.3%; 95% confidence interval [CI] 82.4-93.7) would opt for thrombolysis within the 3-h period and 100 (82.6%; 95% CI 74.9-88.4) within the 3- to 4.5-h period after acute stroke (P = 0.04, McNemar's test for correlated proportions). Previous stroke or transient ischaemic attack was more common among those who agreed to thrombolysis (54.1% vs. 30.4%, P = 0.04) and those who opted for thrombolysis were significantly more likely to agree to have their preferences recorded and used in the event of a stroke than those who refused thrombolysis (88.8% vs. 30.4%, P = 0.002). CONCLUSION: Advance discussion of the potential risks and benefits of thrombolysis in at-risk patients may improve decision making if thrombolysis is being considered and the patient can no longer make a decision.

The National Single Assessment Tool (SAT) a pilot study in older persons care-survey results.

Following a consultation and review process, the interRAI suite of assessment tools was chosen as the most suitable instrument for assessment of the care needs of older people in Ireland. We used previously validated questionnaires to examine the usability, practicality and acceptability of these tools to professionals, carers and clients in rural and urban acute, long-term care and community settings. Of the 45 professionals, 42-44 (93-98%) agreed or strongly agreed with 14 of 15 positive statements regarding the acceptability, clinical value and ease of use of the interRAl tools; 39 (87%) felt the terminology was consistent and familiar, although 35 (78%) felt some areas would require further explanation. Responses from carers (n = 15) and clients (n = 68) were similarly overwhelmingly positive regarding the experience of being assessed using these tools. These results support the clinical utility and practicality of using this approach to assess older people in Irish clinical practice.

Effects of mineral content of bovine drinking water: does iron content affect milk quality?

The composition of water given to dairy cattle is often ignored, yet water is a very important nutrient and plays a major role in milk synthesis. The objective of this study was to study effects of elevated levels of iron in bovine drinking water on milk quality. Ferrous lactate treatments corresponding to 0, 2, 5, and 12.5mg/kg drinking water concentrations were delivered through the abomasum at 10 L/d to 4 lactating dairy cows over 4 periods (1 wk infusion/period) in a Latin square design. On d 6 of infusion, milk was collected, processed (homogenized, pasteurized), and analyzed. Mineral content (Fe, Cu, P, Ca) was measured by inductively coupled plasma mass spectrometry. Oxidative stability of whole processed milk was measured by the thiobarbituric acid reactive substances (TBARS) assay for malondialdehyde (MDA) and sensory analysis (triangle test) within 72 h of processing and after 7d of storage (4°C). Significant sensory differences between processed milks from cows receiving iron and the control infusion were observed. No differences in TBARS (1.46±0.04 mg of MDA/kg) or mineral content (0.22±0.01 mg/kg Fe) were observed. A 2-way interaction (iron treatment by cow) for Ca, Cu, and Fe concentrations was seen. While iron added directly to milk causes changes in oxidation of milk, high levels of iron given to cattle have subtle effects that initially may not be obvious.

Oxidative stability of an extended shelf-life dairy-based beverage system designed to contribute to heart health.

Skim milk, butter-derived aqueous phase, butter oil, and fish oil (3 levels) were used to produce UHT pasteurized n-3 fatty acid-fortified beverages (3.1% fat, 3.9% protein, and 11.5% total solids) with targeted deliveries of 200, 500, and 800 mg of eicosapentaenoic acid and docosahexaenoic acid (combined total) per 250 mL (8 fl oz) serving. Microbial quality, emulsion stability, and oxidation of lipids over 35 d of storage at 4 °C were evaluated. Conjugated diene hydroperoxides were below 1% throughout storage and were found at highest concentrations around d 21 of storage for all formulations. Volatile analysis indicated an increase in 1-penten-3-ol in the n-3 fortified dairy-based beverage systems during storage. Triangle tests were conducted to determine if consumers could detect a difference in aroma, compared with commercially processed aseptically packaged milk. The beverage system with targeted delivery of 500 mg of eicosapentaenoic acid + docosahexaenoic acid per 250-mL serving was not different in aroma compared with commercially available UHT processed milk. This formulation delivered 432 mg of heart-healthy n-3 fatty acids per 250-mL serving on d 35 and was microbiologically and physically stable throughout the 35-d refrigerated storage period.

Consumer perception and sensory effect of oxidation in savory-flavored yogurt enriched with n-3 lipids.

The objective of this study was to determine the effects of different oils (butter, fish, and oxidized fish) on sensory characteristics of a savory [chile-lime (CL)] low-fat yogurt using descriptive (unstructured line scales, 5 attributes) and affective (hedonic) sensory testing methods. Yogurts were each manufactured at low [1.1-1.2% total fat; 0.43% added oil (wt/wt)] or high [1.6% total fat; 1% added oil (wt/wt)] levels of fish oil, with high levels of fish oil targeted to deliver 145 mg of docosahexaenoic acid+eicosapentaenoic acid/170 g of yogurt. In a preliminary study, untrained panelists (n=31), using triangle tests, did not discriminate between low levels of fish and butter oils in unflavored yogurts but could discern yogurt with oxidized fish oil, even at the low level. Trained panelists (n=12) described lower lime and acid flavor characteristics in CL-flavored yogurts containing 1% oxidized fish oil compared with yogurts containing low levels of oxidized fish oil and low or high levels of butter and fish oils. Oxidized flavor was higher in CL-flavored yogurts with oxidized fish oil (low and high) and with the high level of fish oil. Consumer ratings (n=100; 9-point hedonic scale; 9="like extremely) of overall acceptability and flavor acceptability were bimodally distributed, with overall means between 4 and 5 ("neither like nor dislike") for CL-flavored yogurt with butter or fish oils (high level). The upper 50% of responses for yogurt with butter or fish oil were 6.51 and 6.31, respectively, for overall acceptability ("like slightly"), and 7.02 and 6.56, respectively, for flavor acceptability. A large segment of consumers may be interested in incorporating heart-healthy n-3 lipids in their diets through frequent consumption of a savory yogurt enriched with n-3 fatty acids.

Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome.

BACKGROUND AND AIMS: Teduglutide, a GLP-2 analogue, may restore intestinal structural and functional integrity by promoting repair and growth of the mucosa and reducing gastric emptying and secretion, thereby increasing fluid and nutrient absorption in patients with short bowel syndrome (SBS). This 24-week placebo-controlled study evaluated the ability of teduglutide to reduce parenteral support in patients with SBS with intestinal failure. METHODS: In 83 patients randomised to receive subcutaneous teduglutide 0.10 mg/kg/day (n = 32), 0.05 mg/kg/day (n = 35) or placebo (n = 16) once daily, parenteral fluids were reduced at 4-week intervals if intestinal fluid absorption (48 h urine volumes) increased ≥ 10%. Responders were subjects who demonstrated reductions of ≥ 20% in parenteral volumes from baseline at weeks 20 and 24. The primary efficacy end point, a graded response score (GRS), took into account higher levels and earlier onset of response, leading to longer duration of response. The intensity of the response was defined as a reduction from baseline in parenteral volume (from 20% to 100%), and the duration of the response was considered the response at weeks 16, 20 and 24. The results were tested according to a step-down procedure starting with the 0.10 mg/kg/day dose. RESULTS: Using the GRS criteria, teduglutide in a dose of 0.10 mg/kg/day did not have a statistically significant effect compared with placebo (8/32 vs 1/16, p=0.16), while teduglutide in a dose of 0.05 mg/kg/day had a significant effect (16/35, p = 0.007). Since parenteral volume reductions were equal (353 ± 475 and 354 ± 334 ml/day), the trend towards higher baseline parenteral volume (1816 ± 1008 vs 1374 ± 639 ml/day, p=0.11) in the 0.10 mg/kg/day group compared with the 0.05 mg/kg/day group may have accounted for this discrepancy. Three teduglutide-treated patients were completely weaned off parenteral support. Serious adverse events were distributed similarly between active treatment groups and placebo. Villus height, plasma citrulline concentration and lean body mass were significantly increased with teduglutide compared with placebo. CONCLUSIONS: Teduglutide was safe, well tolerated, intestinotrophic and suggested pro-absorptive effects facilitating reductions in parenteral support in patients with SBS with intestinal failure. ClinicalTrials.gov number NCT00172185.

Controlled release of α-tocopherol, quercetin, and their cyclodextrin inclusion complexes from linear low-density polyethylene (LLDPE) films into a coconut oil model food system.

Polymer additive migration into a food product is dependent upon numerous factors including the original concentration of the additive in the polymer, its solubility in the food, its diffusion coefficient in the polymer, its partition coefficient between the polymer and food, temperature, and time. The limited solubility of quercetin in linear low-density polyethylene (LLDPE) did not allow release from the film due to phase segregation of the quercetin in the bulk polymer. Increasing the molecular weight of α-tocopherol by ß-cyclodextrin inclusion complexation can greatly reduce its diffusion coefficient in LLDPE. Ziegler-Natta and metallocene LLDPE contain different crystalline structure morphologies and diffusion path networking arrangements that allow for differences in additive release rates. Effective controlled-release packaging should combine ß-cyclodextrin complexation of additives and polymer morphology control to target delivery of an optimal antioxidant concentration to achieve prolonged activity, resulting in extended shelf life foods.

Constraints on adaptation: explaining deviation from optimal sex ratio using artificial neural networks.

Determining processes constraining adaptation is a major challenge facing evolutionary biology, and sex allocation has proved a useful model system for exploring different constraints. We investigate the evolution of suboptimal sex allocation in a solitary parasitoid wasp system by modelling information acquisition and processing using artificial neural networks (ANNs) evolving according to a genetic algorithm. Theory predicts an instantaneous switch from the production of male to female offspring with increasing host size, whereas data show gradual changes. We found that simple ANNs evolved towards producing sharp switches in sex ratio, but additional biologically reasonable assumptions of costs of synapse maintenance, and simplification of the ANNs, led to more gradual adjustment. Switch sharpness was robust to uncertainty in fitness consequences of host size, challenging interpretations of previous empirical findings. Our results also question some intuitive hypotheses concerning the evolution of threshold traits and confirm how neural processing may constrain adaptive behaviour.

Comparison of quality attributes of shell eggs subjected to directional microwave technology.

Microwaves have been shown to cause thermal as well as nonthermal destruction of pathogens such as Salmonella, which can be found in shell eggs. The objective of this study was to determine if using microwave technology would cause detrimental quality effects in shell eggs. Treatments included control (no treatment) and microwave-treated (20 s) shell eggs. There were no differences in mineral content, fatty acid profile, Haugh units, broken-out score, yolk index, emulsion stability, pH of whole egg, and foaming capacity between 2 treatments (P >or= 0.05). At 0 and 30 d, there were no noticeable differences in H(2)O activity between 2 treatments. The foaming stability and albumen thermocoagulation of microwave-treated eggs were significantly higher than control eggs (P or= 0.05). Therefore, microwave technology can be applied to shell eggs without causing detrimental effects to quality.

Controlling light oxidation flavor in milk by blocking riboflavin excitation wavelengths by interference.

Milk packaged in glass bottles overwrapped with iridescent films (treatments blocked either a single visible riboflavin [Rb] excitation wavelength or all visible Rb excitation wavelengths; all treatments blocked UV Rb excitation wavelengths) was exposed to fluorescent lighting at 4 degrees C for up to 21 d and evaluated for light-oxidized flavor. Controls consisted of bottles with no overwrap (light-exposed treatment; represents the light barrier properties of the glass packaging) and bottles overwrapped with aluminum foil (light-protected treatment). A balanced incomplete block multi-sample difference test, using a ranking system and a trained panel, was used for evaluation of light oxidation flavor intensity. Volatiles were evaluated by gas chromatography and Rb degradation was evaluated by fluorescence spectroscopy. Packaging overwraps limited production of light oxidation flavor over time but not to the same degree as the complete light block. Blocking all visible and UV Rb excitation wavelengths reduced light oxidation flavor better than blocking only a single visible excitation wavelength plus all UV excitation wavelengths. Rb degraded over time in all treatments except the light-protected control treatment and only minor differences in the amount of degradation among treatments was observed. Hexanal production was significantly higher in the light-exposed control treatment compared to the light-protected control treatment from day 7; it was only sporadically significantly higher in the 570 nm and 400 nm block treatments. Pentanal, heptanal, and an unidentified volatile compound also increased in concentration over time, but there were no significant differences in concentration among the packaging overwrap treatments for these compounds.

Effect of raisin consumption on oxidative stress and inflammation in obesity.

AIM: Oxidative stress can initiate increased inflammation that elevates risk for cardiovascular disease. The objective of this study was to determine the effects of daily consumption of raisins on markers of oxidative stress, inflammation and endothelial activation in response to an acute high-fat meal in overweight individuals. METHODS: Seventeen overweight men and women consumed 90 g raisins or isocaloric placebo (264 kcal/day) for 14 days in a randomized, crossover design while following a low-flavonoid diet. The oxidative [urinary 8-iso-prostaglandin-F(2alpha) (8-epi PGF(2alpha)) and serum oxygen radical absorbance capacity (ORAC)], inflammatory (serum C-reactive protein and interleukin-6), endothelial (serum soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1, sVCAM-1) and metabolic [free fatty acids (FFAs), triacylglycerol, glucose and insulin] response to four high-fat (53%) meals was tested pre- and postintervention. RESULTS: Urinary 8-epi PGF(2alpha) decreased (-22%) and fasting ORAC increased (+3%) after both interventions combined. Fasting protein-free ORAC was modestly (+3.5%) higher during the raisin than the placebo intervention. Neither the meals nor the raisins consistently induced fasted markers of inflammation or endothelial dysfunction. Gender influenced postprandial metabolic responses in that males responded with higher serum FFAs, sVCAM-1 and glucose compared with females. CONCLUSIONS: Serum antioxidant capacity was modestly increased by daily raisin consumption, but this did not alter fasted or postprandial inflammatory response in these relatively healthy but overweight individuals. Providing all food in regular pattern reduced measures of oxidative stress.

Phase I trial of three-weekly docetaxel, carboplatin and oral lenalidomide (Revlimid) in patients with advanced solid tumors.

INTRODUCTION: Lenalidomide is an immunomodulatory derivative of thalidomide with significantly greater in vitro activity and a different toxicity profile. In preclinical trials it has shown synergy with chemotherapy. PATIENTS AND METHODS: Primary objective of this study was to determine the maximum tolerated doses of docetaxel and carboplatin when combined with oral lenalidomide in a standard phase I study design. Between September 2004 and May 2005, 14 patients with pathologically proven solid tumors, < or =2 prior chemotherapy regimens, performance status ECOG 0/1, and adequate organ function were enrolled. Dose limiting toxicities (DLT) were defined as > or = grade 3 non-hematological, or grade 4 hematological toxicity. No growth factors were used during cycle 1. RESULTS: Three of four patients treated at dose level 1, docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, and lenalidomide 10 mg orally daily on Days 1-14 of a 21 day cycle experienced DLT (grade 3 electrolyte changes in two patients, and grade 4 neutropenia in one patient). Ten patients were treated at dose level -1, docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, and lenalidomide 5 mg orally daily on Days 1-14 of a 21 day cycle with one DLT (Grade 4 neutropenia). There were no treatment-related deaths or irreversible toxicities. Of the 14 response-evaluable patients, five achieved a partial response (5 out of 9 patients with non-small cell lung cancer. CONCLUSIONS: Docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, with lenalidomide 5 mg orally daily on Days 1-14 days of a 21 day cycle is the maximum tolerated dose without the use of prophylactic growth factors. This combination is active and further evaluation in a phase II trial is warranted.