Strain Comparison in Rats Differentiates Strain-Specific from More General Correlates of Noise-Induced Hearing Loss and Tinnitus.

Experiments in rodent animal models help to reveal the characteristics and underlying mechanisms of pathologies related to hearing loss such as tinnitus or hyperacusis. However, a reliable understanding is still lacking. Here, four different rat strains (Sprague Dawley, Wistar, Long Evans, and Lister Hooded) underwent comparative analysis of electrophysiological (auditory brainstem responses, ABRs) and behavioral measures after noise trauma induction to differentiate between strain-dependent trauma effects and more consistent changes across strains, such as frequency dependence or systematic temporal changes. Several hearing- and trauma-related characteristics were clearly strain-dependent. Lister Hooded rats had especially high hearing thresholds and were unable to detect a silent gap in continuous background noise but displayed the highest startle amplitudes. After noise exposure, ABR thresholds revealed a strain-dependent pattern of recovery. ABR waveforms varied in detail among rat strains, and the difference was most prominent at later peaks arising approximately 3.7 ms after stimulus onset. However, changes in ABR waveforms after trauma were small compared to consistent strain-dependent differences between individual waveform components. At the behavioral level, startle-based gap-prepulse inhibition (gap-PPI) was used to evaluate the occurrence and characteristics of tinnitus after noise exposure. A loss of gap-PPI was found in 33% of Wistar, 50% of Sprague Dawley, and 75% of Long Evans rats. Across strains, the most consistent characteristic was a frequency-specific pattern of the loss of gap-PPI, with the highest rates at approximately one octave above trauma. An additional range exhibiting loss of gap-PPI directly below trauma frequency was revealed in Sprague Dawley and Long Evans rats. Further research should focus on these frequency ranges when investigating the underlying mechanisms of tinnitus induction.

Living with consequences of stroke and risk factors for unhealthy diet- experiences among stroke survivors and caregivers in Nairobi, Kenya.

BACKGROUND: Stroke prevalence is increasing in sub-Saharan Africa and has been partly attributed to the rapid economic and population growth that have contributed to changes in lifestyle and increased the prevalence of modifiable risk factors for stroke. Healthy diet is important in stroke management and secondary stroke prevention. The aim was to explore the clinical characteristics and functioning after stroke and the experiences of nutritional aspects among stroke survivors and caregivers in Nairobi, Kenya. METHODS: A cross-sectional study with qualitative and quantitative methods involving two rounds of data collection was utilised. In the first round, data on demographics and clinical characteristics were collected for 30 people poststroke during a seminar organized by the Kenya Stroke Association. In the second round, nine participants then agreed to be interviewed together with their caregivers and asked to describe their own experiences and their household eating patterns after suffering a stroke. The food frequency questionnaire and anthropometric measurements of weight, height and waist measurements were used. The self-reported data were analyzed using descriptive statistics and the transcribed interview texts used a constructivist-based theory. RESULTS: The results give an insight in the life situation for people living with consequences after stroke and their caregivers in Nairobi. The participants were aware that they were overweight and that this indicated an increased risk for the development of cardiovascular diseases. A core category emerged: The caregiver as the main definer of health and enabler of healthy diet among persons who have had a stroke. Healthy diets and provided information on eating healthy were lacking from the healthcare professionals, whereupon the responsibility for managing a healthy diet had shifted to the caregivers. CONCLUSIONS: Support needs to be given to people with stroke and their caregivers to achieve a healthy diet. The importance of healthy eating as a way of reducing the risk of suffering a stroke needs to be communicated by health care. The Kenyan food-based dietary guidelines need to be more implemented and accessible as well as an overall secondary stroke prevention program.

Rats genetically selected for low and high aerobic capacity exhibit altered soleus muscle myofilament functions.

Aerobic exercise capacity is critical to bodily health. As a model to investigate the mechanisms that determine health and disease, we employed low (LCR) and high (HCR) capacity running rat models selectively bred to concentrate the genes responsible for divergent aerobic running capacity. To investigate the skeletal muscle contribution to this innate difference in running capacity we employed an approach combining examination of the myofilament protein composition and contractile properties of the fast fiber extensor digitorum longus (EDL) and slow fiber soleus (SOL) muscles from LCR and HCR rats. Intact muscle force experiments demonstrate that SOL, but not EDL, muscles from LCR rats exhibit a three times greater decrease in fatigued force. To investigate the mechanism of this increased fatigability in the LCR SOL muscle, we determined the myofilament protein composition and functional properties. Force-Ca2+ measurements demonstrate decreased Ca2+ sensitivity of single skinned SOL muscle fibers from LCR compared with that of HCR rats. Segregating SOL fibers into fast and slow types demonstrates that the decreased Ca2+ sensitivity in LCR SOL results from a specific decrease in slow-type SOL fiber Ca2+ sensitivity such that it was similar to that of fast-type fibers. These results identify that the altered myofilament contractile properties of LCR SOL slow-type fibers result in a fast muscle type Ca2+ sensitivity and the LCR muscle phenotype. Overall our findings demonstrate alterations of the myofilament proteins could contribute to fatigability of the SOL muscle and the decreased innate aerobic running performance of LCR compared with HCR rats.

Changes in fermentation and animal performance during recovery from classical diet-induced milk fat depression using corn with differing rates of starch degradability.

Diet-induced milk fat depression (MFD) is a multifactorial disorder that can be triggered by a variety of conditions. Feeding high amounts of starch and unsaturated fatty acids has been shown to reduce milk fat yield and composition, as well as alter ruminal biohydrogenation patterns. However, little is known about how starch degradability in the rumen influences recovery from diet-induced MFD and if production of milk fat-inhibiting isomers will persist following an episode of MFD. The objective of this study was to evaluate production performance and ruminal fermentation in cows recovering from MFD when corn with a low or high starch degradability is fed. Six ruminally fistulated Holstein cows were used in a crossover design with 2 periods. During each period, MFD was induced for 10 d by feeding a diet with low fiber, high starch, and high unsaturated fatty acid. The polyunsaturated fatty acid concentration of the diet during the induction phase was modified primarily through inclusion of soybean oil. Following induction, cows were switched to either a high degradable starch recovery diet (HDS) or a low degradable starch recovery diet (LDS) for 18 d. The 7-h starch degradability was 66.5% for LDS and 87.8% for HDS. Milk was collected every 3 d for component and fatty acid analysis. On d 0, 4, 7, 10, 16, 22, and 28 of each period, ruminal pH and rumen fluid were collected every 2 h. Milk fat yield and composition was reduced during MFD induction and progressively increased by day in both HDS and LDS during recovery. Dry matter intake was similar among treatments and increased steadily over time during recovery. Preformed fatty acids were greater for HDS-fed animals, and de novo fatty acid in milk fat was greater for LDS-fed animals. Milk trans-10 C18:1 tended to be greater for HDS, and trans-10,cis-12 conjugated linoleic acid was significantly greater for HDS. cis-9,trans-11 conjugated linoleic acid was not affected by starch degradability during recovery. Total volatile fatty acids, butyrate, and valerate tended to differ or differed with recovery treatment, but ruminal pH and ammonia concentration were unaffected. The HDS diet responded similarly to the LDS diet during recovery with regard to milk fat percentage, but milk and fat yield tended to consistently be lower in HDS. When considering approaches to ameliorate diet-induced MFD, the degradability of the starch within rations should be evaluated. Although animal performance was similar, some trans fatty acid isomers were persistent in the milk through the recovery phase with HDS-fed animals, suggesting that milk fat synthesis might be potentially inhibited and biohydrogenation pathways modified in the rumen following an episode of MFD.

Beneficial effects of running and milk protein supplements on Sirtuins and risk factors of metabolic disorders in rats with low aerobic capacity.

BACKGROUND: Physical activity and dietary intake of dairy products are associated with improved metabolic health. Dairy products are rich with branched chain amino acids that are essential for energy production. To gain insight into the mechanisms underlying the benefit of the sub-chronic effects of running and intake of milk protein supplements, we studied Low Capacity Runner rats (LCR), a rodent exercise model with risk for metabolic disorders. We especially focused on the role of Sirtuins, energy level dependent proteins that affect many cellular metabolic processes. METHODS: Forty-seven adult LCR female rats sedentary or running voluntarily in wheels were fed normal chow and given supplements of either whey or milk protein drink (PD)-supplemented water, or water only for 21 weeks. Physiological responses were measured in vivo. Blood lipids were determined from serum. Mitochondrial markers and Sirtuins (Sirt1-7) including downstream targets were measured in plantaris muscle by western blotting. RESULTS: For the first 10 weeks whey-drinking rats ran about 50% less compared to other groups; still, in all runners glucose tolerance improved and triglycerides decreased. Generally, running induced a ∼six-fold increase in running capacity and a ∼8% decrease in % body fat. Together with running, protein supplements increased the relative lean mass of the total body weight by ∼11%. In comparison with sedentary controls, running and whey increased HDL (21%) and whey, with or without running, lowered LDL (-34%). Running increased mitochondrial biogenesis and Sirtuins 3 and 4. When combined with exercise, both whey and milk protein drink induced about a 4-fold increase in Sirt3, compared to runners drinking water only, and about a 2-fold increase compared to the respective sedentary group. Protein supplements, with or without running, enhanced the phosphorylation level of the acetyl-coA-carboxylase, suggesting increased fat oxidation. Both supplemented diets increased Sirt5 and Sirt7 without an additional effect from exercise. Running diminished and PD supplement increased Sirt6. CONCLUSION: We demonstrate in rats new sub-chronic effects of milk proteins on metabolism that involve Sirtuins and their downstream targets in skeletal muscle. The results show that running and milk proteins act on reducing the risk factors of metabolic disorders and suggest that the underlying mechanisms may involve Sirtuins. Notably, we found that milk protein supplements have some favorable effects on metabolism even without running.

A novel D2O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle.

Current methods to quantify in vivo RNA dynamics are limited. Here, we developed a novel stable isotope (D2O) methodology to quantify RNA synthesis (i.e., ribosomal biogenesis) in cells, animal models, and humans. First, proliferating C2C12 cells were incubated in D2O-enriched media and myotubes ±50 ng/ml IGF-I. Second, rat quadriceps (untrained, n = 9; 7-wk interval-"like" training, n = 13) were collected after ~3-wk D2O (70 atom %) administration, with body-water enrichment monitored via blood sampling. Finally, 10 (23 ± 1 yr) men consumed 150-ml D2O followed by 50 ml/wk and undertook 6-wk resistance exercise (6 × 8 repetitions, 75% 1-repetition maximum 3/wk) with body-water enrichment monitored by saliva sampling and muscle biopsies (for determination of RNA synthesis) at 0, 3, and 6 wk. Ribose mole percent excess (r-MPE) from purine nucleotides was analyzed via GC-MS/MS. Proliferating C2C12 cell r-MPE exhibited a rise to plateau, whereas IGF-I increased myotube RNA from 76 ± 3 to 123 ± 3 ng/µl and r-MPE by 0.39 ± 0.1% (both P < 0.01). After 3 wk, rat quadriceps r-MPE had increased to 0.25 ± 0.01% (P < 0.01) and was greater with running exercise (0.36 ± 0.02%; P < 0.01). Human muscle r-MPE increased to 0.06 ± 0.01 and 0.13 ± 0.02% at 3/6 wk, respectively, equating to synthesis rates of ~0.8%/day, increasing with resistance exercise to 1.7 ± 0.3%/day (P < 0.01) and 1.2 ± 0.1%/day (P < 0.05) at 3/6 wk, respectively. Therefore, we have developed and physiologically validated a novel technique to explore ribosomal biogenesis in a multimodal fashion.

[Allergic contact dermatitis of the scalp]. / Kontaktallergien der Kopfhaut.

Contact allergy represents an important differential diagnosis to other skin diseases of the scalp. The typical efflorescences, spreading in the periphery, pruritus, and the clinical history support the differential diagnosis. Since the scalp is particularly resistant to contact dermatitis, allergens applied to this area often produce dermatitis of the eyelids, ears and neck. Nevertheless, potent allergens such as para-phenylendiamine can also cause severe reactions of the scalp. The most important allergens eliciting contact allergy of the scalp are found in bleaches and dyes, shampoos and conditioners, products for perm waves and straighteners as well as topical drugs. Besides active ingredients or drugs, vehicles and preservative agents represent additional allergens. The use of topical steroids and oral antihistamines usually results in rapid resolution of the dermatitis, systemic steroids are only necessary in severe cases. Epicutaneous patch testing on the basis of available series combined with the ingredients of the suspected elicitors confirms the diagnosis and facilitates allergen avoidance as well as the selection of alternative products.

Inhibition of cross-reactive carbohydrate determinants (CCDs) enhances the accuracy of in vitro allergy diagnosis.

BACKGROUND: Cross-reactive carbohydrate determinants (CCDs) as they occur on natural allergens from plants and insects influence the measurement of antigen-specific IgE-antibodies in the context of in vitro allergy diagnosis. When positive results are based solely on the reaction of CCDs with anti-CCD IgE, results must be rated as false-positive. A generally applicable solution to this problem has not yet been presented. METHODS/PATIENTS: Sera of patients for whom an assumed allergy should be verified or ruled out were tested with three methods for specific IgE determination (a multiallergen teststrip format, a single allergen test and an allergen-component array) in the absence and presence of a novel, semi-synthetic CCD-blocker. The study was not prospective and for many patients unequivocal clinical data were missing; the data section thus focusses on few, well-defined patient sera. RESULTS: More than 20% of all patients were tested positive for IgE-anti-CCD antibodies and hence against a multitude of similarly glycosylated allergen extracts in a strip-based multiallergen test. Incubation of these positive sera with the CCD-blocker led to significant reductions of read-out values and in many cases to negative test results. The inhibitory efficiency was highest for the allergen strip test and for the component array. Results remained positive for relevant allergens for which a true sensitization had been indicated by skin tests or other means. The CCD-blocker did not alter the read-outs for unglycosylated allergens or - with CCD-negative sera - for all allergens. CONCLUSION: Elimination of CCD-specific IgE antibodies by means of a synthetic CCD-blocker drastically reduced the number of false-positive in vitro test results without compromising the sensitivity for relevant IgE interactions. Thus, the herein described CCD-blocker constitutes a valuable tool for increasing the test specificity of routine in vitro allergy diagnosis.

Precision-feeding dairy heifers a high rumen-undegradable protein diet with different proportions of dietary fiber and forage-to-concentrate ratios.

The addition of dietary fiber can alter nutrient and N utilization in precision-fed dairy heifers and may further benefit from higher inclusion levels of RUP. The objective of this experiment was to determine the effects of feeding a high-RUP diet when dietary fiber content was manipulated within differing forage-to-concentrate ratios (F:C) on nutrient utilization of precision-fed dairy heifers. Six rumen-cannulated Holstein heifers (555.4 ± 31.4 kg BW; 17.4 ± 0.1 mo) were randomly assigned to 2 levels of forage, high forage (HF; 60% forage) or low forage (LF; 45% forage), and to a fiber proportion sequence (low fiber: 100% oat hay and silage [OA], 0% wheat straw [WS]; medium fiber: 83.4% OA, 16.6% WS; and high fiber: 66.7% OA, 33.3% WS) administered according to a split-plot 3 × 3 Latin square design (21-d periods). Similar levels of N intake (1.70 g N/kg BW) and RUP (55% of CP) were provided. Data were analyzed as a split-plot, 3 × 3 Latin square design using a mixed model with fixed effects of period and treatment. A repeated measures model was used with data that had multiple measurements over time. No differences were observed for DM, OM, NDF, or ADF apparent digestibility coefficients (dC) between HF- and LF-fed heifers. Heifers receiving LF diets had greater starch dC compared to HF heifers. Increasing the fiber level through WS addition resulted in a linear reduction of OM dC. There was a linear interaction for DM dC with a concurrent linear interaction in NDF dC. Nitrogen intake, dC, and retention did not differ; however, urine and total N excretion increased linearly with added fiber. Predicted microbial CP flow (MP) linearly decreased with WS inclusion mainly in LF heifers, as indicated by a significant interaction between F:C and WS. Rumen pH linearly increased with WS addition, although no F:C effect was detected. Ruminal ammonia concentration had an opposite linear effect with respect to MP as WS increased. Diets with the higher proportion of fiber benefited the most from a high RUP supply, complementing the substantial reduction in predicted MP caused by the incremental dietary fiber concentration. These results suggest that RUP supplementation is a practical method for reestablishing optimal ruminal N balance in the event of increased dietary fiber through forage inclusion in precision-fed dairy heifer diets.

Precision-feeding dairy heifers a high rumen-degradable protein diet with different proportions of dietary fiber and forage-to-concentrate ratios.

The objective of this experiment was to determine the effects of feeding a high-rumen-degradable protein (RDP) diet when dietary fiber content is manipulated within differing forage-to-concentrate ratio (F:C) on nutrient utilization of precision-fed dairy heifers. Six cannulated Holstein heifers (486.98±15.07kg of body weight) were randomly assigned to 2 F:C, low- (45% forage; LF) and high-forage (90% forage; HF) diets and to a fiber proportion sequence [33% grass hay and wheat straw (HS), 67% corn silage (CS; low fiber); 50% HS, 50% CS (medium fiber); and 67% HS, 33% CS (high fiber)] within forage proportion administered according to a split-plot, 3×3 Latin square design (16-d periods). Heifers fed LF had greater apparent total-tract organic matter digestibility coefficients (dC), neutral detergent fiber, and cellulose than those fed LC diets. Substituting CS with HS resulted in a linear reduction in dry matter, organic matter, and cellulose dC. Nitrogen dC was not different between F:C or with increasing proportions of HS in diets, but N retention tended to decrease linearly as HS was increased in the diets. Predicted microbial protein flow to the duodenum decreased linearly with HS addition and protozoa numbers HS interacted linearly, exhibiting a decrease as HS increased for LF, whereas no effects were observed for HF. Blood urea N increased linearly as HS was incorporated. The LF-fed heifers had a greater ruminal volatile fatty acids concentration. We noted a tendency for a greater dry matter, and a significantly higher liquid fraction turnover rate for HF diets. There was a linear numerical increase in the liquid and solid fraction turnover rate as fiber was added to the diets. Rumen fermentation parameters and fractional passages (solid and liquid) rates support the reduction in dC, N retention, and microbial protein synthesis observed as more dietary fiber is added to the rations of dairy heifers precision-fed a constant proportion of rumen-degradable protein.

Gut microbiota are linked to increased susceptibility to hepatic steatosis in low-aerobic-capacity rats fed an acute high-fat diet.

Poor aerobic fitness is linked to nonalcoholic fatty liver disease and increased all-cause mortality. We previously found that rats with a low capacity for running (LCR) that were fed an acute high-fat diet (HFD; 45% kcal from fat) for 3 days resulted in positive energy balance and increased hepatic steatosis compared with rats that were highly aerobically fit with a high capacity for running (HCR). Here, we tested the hypothesis that poor physiological outcomes in LCR rats following acute HFD feeding are associated with alterations in cecal microbiota. LCR rats exhibited greater body weight, feeding efficiency, 3 days of body weight change, and liver triglycerides after acute HFD feeding compared with HCR rats. Furthermore, compared with HCR rats, LCR rats exhibited reduced expression of intestinal tight junction proteins. Cecal bacterial 16S rDNA revealed that LCR rats had reduced cecal Proteobacteria compared with HCR rats. Microbiota of HCR rats consisted of greater relative abundance of Desulfovibrionaceae and unassigned genera within this family, suggesting increased reduction of endogenous mucins and proteins. Although feeding rats an acute HFD led to reduced Firmicutes in both strains, short-chain fatty acid-producing Phascolarctobacterium was reduced in LCR rats. In addition, Ruminococcae and Ruminococcus were negatively correlated with energy intake in the LCR/HFD rats. Predicted metagenomic function suggested that LCR rats had a greater capacity to metabolize carbohydrate and energy compared with HCR rats. Overall, these data suggest that the populations and metabolic capacity of the microbiota in low-aerobically fit LCR rats may contribute to their susceptibility to acute HFD-induced hepatic steatosis and poor physiologic outcomes.

Changes in fermentation and biohydrogenation intermediates in continuous cultures fed low and high levels of fat with increasing rates of starch degradability.

Excessive levels of starch in diets for lactating dairy cattle is a known risk factor for milk fat depression, but little is known about how this risk is affected by differences in rates of starch degradability (Kd) in the rumen. The objective of this study was to compare accumulation of biohydrogenation intermediates causing milk fat depression, including conjugated linoleic acid (CLA), when corn with low or high Kd were fed to continuous cultures. Diets contained (dry matter basis) 50% forage (alfalfa pellets and grass hay) and 50% concentrate, with either no added fat (LF) or 3.3% added soybean oil (HF). Within both the LF and HF diets, 3 starch degradability treatments were obtained by varying the ratio of processed (heat and pressure treatments) and unprocessed corn sources, giving a total of 6 dietary treatments. Each diet was fed to dual-flow continuous fermenters 3 times a day at 0800, 1600, and 2400h. Diets were fed for four 10-d periods, with 7d for adaptation and 3d for sample collection. Orthogonal contrasts were used in the GLIMMIX procedure of SAS to test the effects of fat, starch degradability, and their interaction. Acetate and acetate:propionate were lower for HF than for LF but daily production of trans-10 18:1 and trans-10,cis-12 CLA were higher for HF than for LF. Increasing starch Kd from low to high increased culture pH, acetate, and valerate but decreased butyrate and isobutyrate. Changes in biohydrogenation intermediates (expressed as % of total isomers) from low to high starch Kd included reductions in trans-11 18:1 and cis-9,trans-11 CLA but increases in trans-10 18:1 and trans-10,cis-12 CLA. The results show that increasing the starch Kd in continuous cultures while holding starch level constant causes elevation of biohydrogenation intermediates linked to milk fat depression.

Comparison of Cancer Diagnoses Between the US Solid Organ Transplant Registry and Linked Central Cancer Registries.

US transplant centers are required to report cancers in transplant recipients to the transplant network. The accuracy and completeness of these data, collected in the Scientific Registry of Transplant Recipients (SRTR), are unknown. We compared diagnoses in the SRTR and 15 linked cancer registries for colorectal, liver, lung, breast, prostate and kidney cancers; melanoma; and non-Hodgkin lymphoma (NHL). Among 187 384 transplants, 9323 cancers were documented in the SRTR or cancer registries. Only 36.8% of cancers were in both, with 47.5% and 15.7% of cases additionally documented solely in cancer registries or the SRTR, respectively. Agreement between the SRTR and cancer registries varied (kappa = 0.28 for liver cancer and kappa = 0.52-0.66 for lung, prostate, kidney, colorectum, and breast cancers). Upon evaluation, some NHLs documented only in cancer registries were identified in the SRTR as another type of posttransplant lymphoproliferative disorder. Some SRTR-only cases were explained by miscoding (colorectal cancer instead of anal cancer, metastases as lung or liver cancers) or missed matches with cancer registries, partly due to recipients' outmigration from catchment areas. Estimated sensitivity for identifying cancer was 52.5% for the SRTR and 84.3% for cancer registries. In conclusion, SRTR cancer data are substantially incomplete, limiting their usefulness for surveillance and research.

Nucleus accumbens cocaine-amphetamine regulated transcript mediates food intake during novelty conflict.

Obesity is a persistent and pervasive problem, particularly in industrialized nations. It has come to be appreciated that the metabolic health of an individual can influence brain function and subsequent behavioral patterns. To examine the relationship between metabolic phenotype and central systems that regulate behavior, we tested rats with divergent metabolic phenotypes (Low Capacity Runner: LCR vs. High Capacity Runner: HCR) for behavioral responses to the conflict between hunger and environmental novelty using the novelty suppressed feeding (NSF) paradigm. Additionally, we measured expression of mRNA, for peptides involved in energy management, in response to fasting. Following a 24-h fast, LCR rats showed lower latencies to begin eating in a novel environment compared to HCR rats. A 48-h fast equilibrated the latency to begin eating in the novel environment. A 24-h fast differentially affected expression of cocaine-amphetamine regulated transcript (CART) mRNA in the nucleus accumbens (NAc), where 24-h of fasting reduced CART mRNA in LCR rats. Bilateral microinjections of CART 55-102 peptide into the NAc increased the latency to begin eating in the NSF paradigm following a 24-h fast in LCR rats. These results indicate that metabolic phenotype influences how animals cope with the conflict between hunger and novelty, and that these differences are at least partially mediated by CART signaling in the NAc. For individuals with poor metabolic health who have to navigate food-rich and stressful environments, changes in central systems that mediate conflicting drives may feed into the rates of obesity and exacerbate the difficulty individuals have in maintaining weight loss.