Reduced bone breakage and increased bone strength in free range laying hens fed omega-3 polyunsaturated fatty acid supplemented diets

INTRODUCTION The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are the immediate precursors to a number of important mediators of immunity, inflammation and bone function, with products of omega-6 generally thought to promote inflammation and favour bone resorption. Western diets generally provide a 10 to 20-fold deficit in omega-3 PUFAs compared with omega-6, and this is thought to have contributed to the marked rise in incidence of disorders of modern human societies, such as heart disease, colitis and perhaps osteoporosis. Many of our food production animals, fed on grains rich in omega-6, are also exposed to a dietary deficit in omega-3, with perhaps similar health consequences. Bone fragility due to osteoporotic changes in laying hens is a major economic and welfare problem, with our recent estimates of breakage rates indicating up to 95% of free range hens suffer breaks during lay. METHODS Free range hens housed in full scale commercial systems were provided diets supplemented with omega-3 alpha linolenic acid, and the skeletal benefits were investigated by comparison to standard diets rich in omega-6. RESULTS There was a significant 40-60% reduction in keel bone breakage rate, and a corresponding reduction in breakage severity in the omega-3 supplemented hens. There was significantly greater bone density and bone mineral content, alongside increases in total bone and trabecular volumes. The mechanical properties of the omega-3 supplemented hens were improved, with strength, energy to break and stiffness demonstrating significant increases. Alkaline phosphatase (an osteoblast marker) and tartrate-resistant acid phosphatase (an osteoclast marker) both showed significant increases with the omega-3 diets, indicating enhanced bone turnover. This was corroborated by the significantly lower levels of the mature collagen crosslinks, hydroxylysyl pyridinoline, lysyl pyridinoline and histidinohydroxy-lysinonorleucine, with a corresponding significant shift in the mature:immature crosslink ratio. CONCLUSIONS The improved skeletal health in laying hens corresponds to as many as 68million fewer hens suffering keel fractures in the EU each year. The biomechanical and biochemical evidence suggests that increased bone turnover has enhanced the bone mechanical properties, and that this may suggest potential benefits for human osteoporosis.

Comparison of randomized treatments for late whiplash

BACKGROUND: To compare 4 different treatment strategies in patients with late whiplash syndrome. METHODS: Patients were randomly assigned to one of the following treatment groups: infiltration, physiotherapy, or medication. Group allocation was stratified according to gender, age, and education. Additionally, patients of each group were randomized 1:1 to cognitive-behavioral therapy (CBT) or no CBT. Patients were assessed at baseline, after an 8-week treatment period, and 3 and 6 months later. Main outcome measures were subjective outcome rating, pain intensity, and working ability. RESULTS: Of 91 enrolled patients, 73 completed the study; 62% were women. After treatment, 47 patients (64%) were subjectively improved (48%), or free of symptoms (16%), with a preponderance of women (73% vs 50%, p = 0.047). There was no difference regarding outcomes among the 3 treatment groups in men and women. The most robust difference was achieved with CBT, associated with a higher rate of recovery (23% vs 9%), and improvement (53% vs 42%) (p = 0.024), and with a gender difference (p = 0.01). All treatments significantly improved pain intensity and working ability. CONCLUSION: Intensive therapy in late whiplash syndrome can achieve improvement of different outcome measures including working ability in two-thirds of patients, more effective in women, persisting beyond 6 months in half. Additional cognitive-behavioral therapy was the most effective treatment modality. Classification of evidence: This interventional study provides Class III evidence that CBT used as an adjunct to infiltration, medication, or physiotherapy increases improvement rates in persons with late whiplash syndrome.

[Verification of normative values for the Swiss version of the Freiburg speech intelligibility test.]

BACKGROUND AND OBJECTIVE: In the Swiss version of the Freiburg speech intelligibility test five test words from the original German recording which are rarely used in Switzerland have been exchanged. Furthermore, differences in the transfer functions between headphone and loudspeaker presentation are not taken into account during calibration. New settings for the levels of the individual test words in the recommended recording and small changes in calibration procedures led us to make a verification of the currently used normative values.PATIENTS AND METHODS: Speech intelligibility was measured in 20 subjects with normal hearing using monosyllabic words and numbers via headphones and loudspeakers.RESULTS: On average, 50% speech intelligibility was reached at levels which were 7.5 dB lower under free-field conditions than for headphone presentation. The average difference between numbers and monosyllabic words was found to be 9.6 dB, which is considerably lower than the 14 dB of the current normative curves.CONCLUSIONS: There is a good agreement between our measurements and the normative values for tests using monosyllabic words and headphones, but not for numbers or free-field measurements.

Use of outdoor ranges by laying hens in different sized flocks.

In studies assessing outdoor range use of laying hens, the number of hens seen on outdoor ranges is inversely correlated to flock size. The aim of this study was to assess individual ranging behavior on a covered (veranda) and an uncovered outdoor run (free-range) in laying hen flocks varying in size. Five to ten percent of hens (aged 9–15 months) within 4 small (2–2500 hens), 4 medium (5–6000), and 4 large (≥9000) commercial flocks were fitted with radio frequency identification (RFID) tags. Antennas were placed at both sides of all popholes between the house and the veranda and the veranda and the free-range. Ranging behavior was directly monitored for approximately three weeks in combination with hourly photographs of the free-range for the distribution of hens and 6h long video recordings on two parts of the free-range during two days. Between 79 and 99% of the tagged hens were registered on the veranda at least once and between 47 and 90% were registered on the free-range at least once. There was no association between the percentage of hens registered outside the house (veranda or free-range) and flock size. However, individual hens in small and medium sized flocks visited the areas outside the house more frequently and spent more time there than hens from large flocks. Foraging behavior on the free-range was shown more frequently and for a longer duration by hens from small and medium sized flocks than by hens from large flocks. This difference in ranging behavior could account for the negative relationship between flock size and the number of hens seen outside at one point of time. In conclusion, our work describes individual birds’ use of areas outside the house within large scale commercial egg production.

Normal Thyroid Function and the Risk of Atrial Fibrillation: the Rotterdam Study

CONTEXT Hyperthyroidism is an established risk factor for atrial fibrillation (AF), but information concerning the association with variations within the normal range of thyroid function and subgroups at risk is lacking. OBJECTIVE This study aimed to investigate the association between normal thyroid function and AF prospectively and explore potential differential risk patterns. DESIGN, SETTING, AND PARTICIPANTS From the Rotterdam Study we included 9166 participants ≥ 45 y with TSH and/or free T4 (FT4) measurements and AF assessment (1997-2012 median followup, 6.8 y), with 399 prevalent and 403 incident AF cases. MAIN OUTCOME MEASURES Outcome measures were 3-fold: 1) hazard ratios (HRs) for the risk of incident AF by Cox proportional-hazards models, 2) 10-year absolute risks taking competing risk of death into account, and 3) discrimination ability of adding FT4 to the CHARGE-AF simple model, an established prediction model for AF. RESULTS Higher FT4 levels were associated with higher risks of AF (HR 1.63, 95% confidence interval, 1.19-2.22), when comparing those in the highest quartile to those in lowest quartile. Absolute 10-year risks increased with higher FT4 in participants ≤ 65 y from 1-9% and from 6-12% in subjects ≥ 65 y. Discrimination of the prediction model improved when adding FT4 to the simple model (c-statistic, 0.722 vs 0.729; P = .039). TSH levels were not associated with AF. CONCLUSIONS There is an increased risk of AF with higher FT4 levels within the normal range, especially in younger subjects. Adding FT4 to the simple model slightly improved discrimination of risk prediction.

Association between sentinel lymph node excision with or without preoperative SPECT/CT and metastatic node detection and disease-free survival in melanoma

Malignant melanoma has become an increasing interdisciplinary public health challenge worldwide. Sentinel lymph node excision (SLNE) is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes.

Free abdominal fluid without obvious solid organ injury upon CT imaging: an actual problem or simply over-diagnosing?

Whereas a non-operative approach for hemodynamically stable patients with free intraabdominal fluid in the presence of solid organ injury is generally accepted, the presence of free fluid in the abdomen without evidence of solid organ injury not only presents a challenge for the treating emergency physician but also for the surgeon in charge. Despite recent advances in imaging modalities, with multi-detector computed tomography (CT) (with or without contrast agent) usually the imaging method of choice, diagnosis and interpretation of the results remains difficult. While some studies conclude that CT is highly accurate and relatively specific at diagnosing mesenteric and hollow viscus injury, others studies deem CT to be unreliable. These differences may in part be due to the experience and the interpretation of the radiologist and/or the treating physician or surgeon.A search of the literature has made it apparent that there is no straightforward answer to the question what to do with patients with free intraabdominal fluid on CT scanning but without signs of solid organ injury. In hemodynamically unstable patients, free intraabdominal fluid in the absence of solid organ injury usually mandates immediate surgical intervention. For patients with blunt abdominal trauma and more than just a trace of free intraabdominal fluid or for patients with signs of peritonitis, the threshold for a surgical exploration - preferably by a laparoscopic approach - should be low. Based on the available information, we aim to provide the reader with an overview of the current literature with specific emphasis on diagnostic and therapeutic approaches to this problem and suggest a possible algorithm, which might help with the adequate treatment of such patients.

Effects of a short-term overfeeding with fructose or glucose in healthy young males

Consumption of simple carbohydrates has markedly increased over the past decades, and may be involved in the increased prevalence in metabolic diseases. Whether an increased intake of fructose is specifically related to a dysregulation of glucose and lipid metabolism remains controversial. We therefore compared the effects of hypercaloric diets enriched with fructose (HFrD) or glucose (HGlcD) in healthy men. Eleven subjects were studied in a randomised order after 7 d of the following diets: (1) weight maintenance, control diet; (2) HFrD (3.5 g fructose/kg fat-free mass (ffm) per d, +35 % energy intake); (3) HGlcD (3.5 g glucose/kg ffm per d, +35 % energy intake). Fasting hepatic glucose output (HGO) was measured with 6,6-2H2-glucose. Intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) were measured by 1H magnetic resonance spectroscopy. Both fructose and glucose increased fasting VLDL-TAG (HFrD: +59 %, P < 0.05; HGlcD: +31 %, P = 0.11) and IHCL (HFrD: +52 %, P < 0.05; HGlcD: +58 %, P = 0.06). HGO increased after both diets (HFrD: +5 %, P < 0.05; HGlcD: +5 %, P = 0.05). No change was observed in fasting glycaemia, insulin and alanine aminotransferase concentrations. IMCL increased significantly only after the HGlcD (HFrD: +24 %, NS; HGlcD: +59 %, P < 0.05). IHCL and VLDL-TAG were not different between hypercaloric HFrD and HGlcD, but were increased compared to values observed with a weight maintenance diet. However, glucose led to a higher increase in IMCL than fructose.

Complication and failure rates in patients treated for chronic periodontitis and restored with single crowns on teeth and/or implants

Objectives: To assess the biological and technical complication rates of single crowns on vital teeth (SC-V), endodontically treated teeth without post and core (SC-E), with a cast post and core (SC-PC) and on implants (SC-I). Material and methods: From 392 patients with chronic periodontitis treated and documented by graduate students during the period from 1978 to 2002, 199 were reexamined during 2005 for this retrospective cohort study, and 64 of these patients were treated with SCs. Statistical analysis included Kaplan–Meier survival functions and event rates per 100 years of object-time. Poisson regression was used to compare the four groups of crowns with respect to the incidence rate ratio of failures, and failures and complications combined over 10 years and the entire observation period. Results: Forty-one (64%) female and 23 (36%) male patients participated in the reexamination. At the time of seating the crowns, the mean patient age was 46.8 (range 24–66.3) years. One hundred and sixty-eight single unit crowns were incorporated. Their mean follow-up time was 11.8 (range 0.8–26.4) years. During the time of observation, 22 biological and 11 technical complications occurred; 19 SC were lost. The chance for SC-V (56) to remain free of any failure or complication was 89.3% (95% confidence interval [CI] 76.1–95.4) after 10 years, 85.8% (95% CI 66–94.5) for SC-E (34), 75.9% for SC-PC (39), (95% CI 58.8–86.7) and 66.2% (95% CI 45.1–80.7) for SC-I (39). Over 10 years, 95% of SC-I remained free of failure and demonstrated a cumulative incidence of failure or complication of 34%. Compared with SC-E, SC-I were 3.5 times more likely to yield failures or complications and SC-PC failed 1.7 times more frequently than did SC-E. SC-V had the lowest rate of failures or complications over the 10 years. Conclusions: While SCs on vital teeth have the best prognosis, those on endodontically treated teeth have a slightly poorer prognosis over 10 years. Crowns on teeth with post and cores and implant-supported SCs displayed the highest incidence of failures and complications.

Reference values of mechanical and thermal pain tests in a pain-free population

Quantitative sensory tests are widely used in human research to evaluate the effect of analgesics and explore altered pain mechanisms, such as central sensitization. In order to apply these tests in clinical practice, knowledge of reference values is essential. The aim of this study was to determine the reference values of pain thresholds for mechanical and thermal stimuli, as well as withdrawal time for the cold pressor test in 300 pain-free subjects. Pain detection and pain tolerance thresholds to pressure, heat and cold were determined at three body sites: (1) lower back, (2) suprascapular region and (3) second toe (for pressure) or the lateral aspect of the leg (for heat and cold). The influences of gender, age, height, weight, body-mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short-Form 36 (SF-36) were analyzed by multiple regressions. Quantile regressions were performed to define the 5th, 10th and 25th percentiles as reference values for pain hypersensitivity and the 75th, 90th and 95th percentiles as reference values for pain hyposensitivity. Gender, age and/or the interaction of age with gender were the only variables that consistently affected the pain measures. Women were more pain sensitive than men. However, the influence of gender decreased with increasing age. In conclusion, normative values of parameters related to pressure, heat and cold pain stimuli were determined. Reference values have to be stratified by body region, gender and age. The determination of these reference values will now allow the clinical application of the tests for detecting abnormal pain reactions in individual patients.

Sensitive and selective detection of free FXIII activation peptide: a potential marker of acute thrombotic events

Coagulation factor XIII (FXIII) stabilizes fibrin fibers and is therefore a major player in the maintenance of hemostasis. FXIII is activated by thrombin resulting in cleavage and release of the FXIII activation peptide (AP-FXIII). The objective of this study was to characterize the released AP-FXIII and determine specific features that may be used for its specific detection. We analyzed the structure of bound AP-FXIII within the FXIII A-subunit and interactions of AP-FXIII by hydrogen bonds with both FXIII A-subunit monomers. We optimized our previously developed AP-FXIII ELISA by using 2 monoclonal antibodies. We determined high binding affinities between the antibodies and free AP-FXIII and demonstrated specific binding by epitope mapping analyses with surface plasmon resonance and enzyme-linked immunosorbent assay. Because the structure of free AP-FXIII had been characterized so far by molecular modeling only, we performed structural analysis by nuclear magnetic resonance. Recombinant AP-FXIII was largely flexible both in plasma and water, differing significantly from the rigid structure in the bound state. We suggest that the recognized epitope is either occluded in the noncleaved form or possesses a structure that does not allow binding to the antibodies. On the basis of our findings, we propose AP-FXIII as a possible new marker for acute thrombotic events.

Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses

The lower intestine of adult mammals is densely colonized with nonpathogenic (commensal) microbes. Gut bacteria induce protective immune responses, which ensure host-microbial mutualism. The continuous presence of commensal intestinal bacteria has made it difficult to study mucosal immune dynamics. Here, we report a reversible germ-free colonization system in mice that is independent of diet or antibiotic manipulation. A slow (more than 14 days) onset of a long-lived (half-life over 16 weeks), highly specific anticommensal immunoglobulin A (IgA) response in germ-free mice was observed. Ongoing commensal exposure in colonized mice rapidly abrogated this response. Sequential doses lacked a classical prime-boost effect seen in systemic vaccination, but specific IgA induction occurred as a stepwise response to current bacterial exposure, such that the antibody repertoire matched the existing commensal content.

Intensity modulated radiation therapy or stereotactic fractionated radiotherapy for infratentorial ependymoma in children: a multicentric study

This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8-60). The median follow-up for surviving patients was 4.8 years (range, 1.3-8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques.

High-dose melphalan with or without stem cell support before myeloablative allo-SCT for remission induction in patients with advanced relapsed or refractory AML

Treatment strategies for relapsed/refractory AML are limited and disappointing. Recently, high-dose melphalan (HDM) chemotherapy and autologous hematopoietic SCT (HSCT) has been proposed for AML re-induction. We investigated the impact of HDM remission induction in highly advanced relapsed/refractory AML patients planned for allogeneic HSCT. A total of 23 patients with relapsed/refractory AML were prospectively scheduled for HDM with or without stem cell support followed by myeloablative allogeneic HSCT. Patients included nine individuals with a history of previous HSCT (seven allogeneic, two autologous). A total of 18 patients (78%) achieved a leukemia-free state and an additional four had substantial reduction of the initial leukemia burden warranting treatment continuation. There were no differences between patients with or without immediate stem cell support regarding mucositis or other organ toxicity. A total of 20 patients proceeded to myeloablative allogeneic HSCT. Outcome of allogeneic HSCT was poor: 11 patients (55%) relapsed, 7 patients (35%) died from TRM and only 2 patients (10%) were alive at the last follow-up. Our study shows that HDM is effective in inducing a leukemia-free state in patients with highly advanced relapsed/refractory AML. Leukemia burden reduction with HDM, however, did not translate into improved OS.

Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study

In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction activity in patients with relapsed AML. Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were randomized between 3 cycles of GO (6 mg/m(2) every 4 weeks) or no postremission therapy (control) to assess whether GO would improve outcome. The 2 treatment groups (113 patients receiving GO vs 119 control patients) were comparable with regard to age (60-78 years, median 67 years), performance status, and cytogenetics. A total of 110 of 113 received at least 1 cycle of GO, and 65 of 113 patients completed the 3 cycles. Premature discontinuation was mainly attributable to incomplete hematologic recovery or intercurrent relapse. Median time to recovery of platelets 50 x 10(9)/L and neutrophils 0.5 x 10(9)/L after GO was 14 days and 20 days. Nonhematologic toxicities were mild overall, but there was 1 toxic death caused by liver failure. There were no significant differences between both treatment groups with regard to relapse probabilities, nonrelapse mortality, overall survival, or disease-free survival (17% vs 16% at 5 years). Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points. The HOVON-43 study is registered at The Netherlands Trial Registry (number NTR212) and at http://www.controlled-trials.com as ISRCTN77039377.