Investigating the efficacy of purified tannin extracts from underutilized temperate forages in reducing enteric methane emissions in vitro.

The study investigated how the concentration and composition of purified tannin extracts, at various inclusion rates, affect the ruminal in vitro fermentation parameters. Tannin extracts were isolated from four different forage species: birdsfoot trefoil (Lotus corniculatus), sulla (Hedysarum coronarium), big trefoil (Lotus pedunculatus), and salad burnet (Sanguisorba minor). Plants extracts were purified by Sephadex LH-20 gel chromatography and analyzed by UPLC-ESI-MS/MS. The results showed a large variation among the extracts from different species in terms of tannin composition and structural features. The extracts from salad burnet were dominated by hydrolysable tannins, comprising mainly ellagitannins. The extracts derived from sulla and big trefoil contained predominantly proanthocyanidins (PA), primarily composed of prodelphinidins with high mean degree of polymerisation (mDP). Birdsfoot trefoil extracts comprised procyanidin-rich PAs with low mDP. To determine whether the combined presence of tannins and flavonoid together lead to synergistic or antagonistic effects, the tannin extracts were incubated both with or without rutin at concentrations of 10, 20, and 30 g/kg DM, using a base substrate of perennial ryegrass (Lolium perenne, control). In general, all the tannin extracts decreased methane (CH4) production compared to the control, while no significant effect of rutin was observed on both gas (GP) and CH4 production, neither pure, nor in the simultaneous presence of tannins. The highest CH4 reduction (15%, at 30 g/kg DM) was observed from sulla and big trefoil extracts compared to control, but this was also supplemented with a concomitant reduction in GP (11%) indicating a reduction in feed digestibility. The extracts from birdsfoot trefoil and salad burnet reduced CH4 by up to 12% without significantly reducing GP, indicating the importance of tannin composition on ruminal fermentation.

Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review.

Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. BACKGROUND: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. METHODS: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). RESULTS: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. CONCLUSION: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.

The importance of hyperosmolarity in diabetic ketoacidosis.

AIM: Diabetic ketoacidosis is a hyperglycaemic emergency that is often treated in intensive care units (ICUs) despite having a low mortality and good prognosis. Current risk stratification is based primarily on acidosis, but it has been suggested that hyperosmolarity may also be an important marker of increased severity. Our aim was to evaluate the relationship between raised serum osmolarity and adverse clinical outcomes in ICU admissions for ketoacidosis. METHODS: Retrospective review of prospectively collected data for adult admissions with ketoacidosis in the Australian and New Zealand Intensive Care Society Adult Patient Database over a 15-year period (2004-2018). Exclusions were readmissions and records with critical missing data. Serum hyperosmolarity was defined as > 320 mosm/l. The primary outcome was hospital mortality; secondary outcomes were ICU mortality and other adverse clinical events. RESULTS: Some 17 379 admissions were included in the study population. People with hyperosmolarity had fourfold increased mortality, a higher incidence of renal failure and need for mechanical ventilation, and prolonged ICU and hospital length of stay. The relationship with mortality remained highly significant even after adjusting for severity of acidosis, hospital type, year of admission, time to ICU, and a modified Australia and New Zealand Risk of Death propensity score. CONCLUSIONS: Although adults with ketoacidosis have a good prognosis overall, hyperosmolarity was independently associated with a significantly higher incidence of multiple adverse outcomes including mortality. Whether or not this is directly causal, it may have practical applications to improve risk stratification and identify individuals at risk of adverse outcomes.

Diffuse osteosclerosis as a presentation of recurrent breast cancer: role of endothelin 1.

We report a 46-yr-old woman with a history of breast cancer who presented with diffuse myalgias, bone pain, and osteosclerosis. She was found to have recurrent breast cancer producing endothelin-1. INTRODUCTION: Acquired osteosclerosis can be caused by various disorders. Endothelin -1 is believed to contribute to osteosclerosis caused by breast cancer. METHODS: Although the bone marrow biopsy did not reveal breast cancer, she developed skin lesions consistent with metastatic breast cancer. She ultimately died from progressive disease. At autopsy immunohistochemistry for endothelin-1 was performed on a section from the L5 vertebral body. RESULTS: The section from the L5 vertebral body showed small foci of cells consistent with metastatic carcinoma and a prominent sclerotic response. Immunohistochemistry for endothelin-1 was strongly positive. CONCLUSIONS: Recurrent breast cancer may present with diffuse osteosclerosis. Endothelin-1 may be a paracrine factor responsible for increased bone formation and osteosclerosis.

An audit of perioperative blood transfusions in a regional hospital to rationalise a maximum surgical blood ordering schedule.

Appropriate preoperative blood typing and cross-matching is an important quality improvement target to minimise costs and rationalise the use of blood bank resources. This can be facilitated using a maximum surgical blood ordering schedule (MSBOS) for specific operations. It is recommended that individual hospitals develop a site-specific MSBOS based on institutional data, but this is challenging in non-tertiary centres without electronic databases. Our aim was to audit our perioperative blood transfusions to develop a site-specific MSBOS. A retrospective audit of blood transfusions in surgical patients in our regional referral hospital was conducted using five years' coded administrative data. Procedures with higher transfusion rates warranting preoperative testing (type and screen with or without subsequent cross-matching) were identified. There were about 15,000 eligible surgical procedures performed in our institution over the audit period. The need for preoperative testing was identified for only a few procedures, namely laparotomy, bowel resection, major amputation, joint arthroplasty, hip/femur fracture and humerus surgery, and procedures for obstetric complications. We observed a reduction in transfusion rates over time for total joint arthroplasty. The use of coding data represents an efficient method by which centres without electronic anaesthesia information management systems can conduct large-scale audits to develop a site-specific MSBOS. This would represent a significant improvement for hospitals that currently base preoperative testing recommendations on expert opinion alone. As many procedures in regional centres have very low transfusion rates, hospitals with a similar case mix to ours could consider selectively auditing higher-risk operations where local data is most likely to alter testing recommendations.

Ruminal degradation of quercetin and its influence on fermentation in ruminants.

The aim of the present study was to investigate the ruminal degradation of the flavonol quercetin and to determine its potential antimicrobial effects on ruminal fermentation in cows. Ruminal degradation of quercetin (0 or 100µmol/L, respectively) as well as its influence on ruminal gas production (0, 50, or 100µmol of quercetin equivalents/L, respectively, either applied as aglycone or as its glucorhamnoside rutin) using concentrate, grass hay, and straw as substrates were investigated in vitro using the Hohenheim gas test. Additionally, the influence of quercetin on ruminal concentrations of volatile fatty acids and their molar ratio in rumen-fistulated, nonlactating cows (n=5) after intraruminal application of quercetin as aglycone or as rutin (0, 10, or 50mg of quercetin equivalents/kg of BW, respectively) was evaluated. Quercetin was rapidly and extensively degraded, whereby the disappearance of quercetin was accompanied by the simultaneous appearance of 2metabolites 3,4-dihydroxyphenylacetic acid and 4-methylcatechol. In vitro total gas and methane production were not reduced by the addition of quercetin aglycone or rutin, respectively, using concentrate, grass hay, and straw as substrates. As expected, however, effects of the substrates used were detected on total gas and methane production. Highest gas production was found with concentrate, whereas values obtained with grass hay and straw were lower. Relative methane production was highest with grass hay compared with concentrate and straw (27.1 vs. 25.0 and 25.5%). After intraruminal application of the quercetin aglycone or rutin, respectively, neither total concentration nor the molar ratio of volatile fatty acids in the rumen fluid were influenced. Results of the present study show that quercetin underlies rapid ruminal degradation, whereby 3,4-dihydroxyphenylacetic acid and 4-methylcatechol are the main metabolites, whereas the latter one most likely is formed by dehydroxylation from 3,4-dihydroxyphenylacetic acid. Regarding antimicrobial effects of quercetin, results obtained indicate that fermentation processes in the forestomachs are not substantially influenced by quercetin or rutin, respectively. With regard to potential health-promoting effects of quercetin, its application in cows, especially in the form of the better available rutin, might not be accompanied by negative effects on ruminal fermentation.

Can vitamin D metabolite measurements facilitate a "treat-to-target" paradigm to guide vitamin D supplementation?

UNLABELLED: Substantial variability exists in the serum 25(OH)D increase observed in response to vitamin D supplementation. Measurement of circulating cholecalciferol and 24,25(OH)2D, as indicators of vitamin D absorption and degradation, respectively, account for approximately half of the variation in serum 25(OH)D observed following supplementation. INTRODUCTION: Vitamin D supplementation produces a variable response in serum 25(OH)D. This variability likely reflects, in part, differences in vitamin D absorption and/or degradation. Despite this variation in response, virtually all expert recommendations endorse a fixed vitamin D supplementation dose, an approach also used in most prospective studies. Such utilization of a single vitamin D dose does not assure attaining any pre-specified target 25(OH)D level, thereby compromising clinical care and prospective supplementation trials. This study begins addressing this weakness by exploring the feasibility of vitamin D metabolite measurements to predict serum 25(OH)D level attained following supplementation. METHODS: Ninety-one community-dwelling postmenopausal women with baseline 25(OH)D of 10-30 ng/mL received oral vitamin D3, 2300 or 2500 IU, daily for 4-6 months. Serum 25(OH)D, cholecalciferol (D3), and 24,25(OH)2D were measured before and at the end of supplementation to determine if metabolite concentrations allow prediction of the 25(OH)D level attained. RESULTS: From baseline and follow-up data, we derived a multiple linear regression model predicting posttreatment 25(OH)D as follows: final 25(OH)D = 8.3 + (1.05*initial 25(OH)D) - (7.7*initial 24,25(OH)2D) + (0.53*final D3) + (4.2*final 24,25(OH)2D). This model has an adjusted R(2) = 0.55, thus accounting for approximately half of the observed variance in the final 25(OH)D level. CONCLUSIONS: The contributions of circulating cholecalciferol and 24,25(OH)2D to this predictive model can be considered as indicators of intestinal absorption and clearance, respectively. This paradigm requires further study; it may allow efficient "treat-to-25(OH)D-target" strategies useful in optimizing prospective studies and clinical practice.

[Turkish patient with syncope and accompanying vegetative symptoms with bradycardia after eating pontin honey]. / Türkischer Patient mit Synkope und vegetativer Begleitsymptomatik bei Bradykardie nach Genuss von pontischem Honig.

A 52-year-old man with Turkish background presented with nausea, emesis, one experience of syncope with loss of consciousness for a few seconds, and documented sinus bradycardia. During monitoring, several phases of bradycardia were observed. After 24 h of monitoring, the patient was free of complaints. The patient's wife reported regular consumption of pontin honey. Because of the anamnesis and the typical characteristics, grayanotoxin poisoning was diagnosed. Typical symptoms of this poisoning are hypotension, bradycardia, syncope, and loss of consciousness. When these symptoms are found and a typical anamnesis exists, this kind of intoxication has to been taken into consideration as part of the differential diagnosis.

What analytic method should clinicians use to derive spine T-scores and predict incident fractures in men? Results from the MrOS study.

UNLABELLED: In this study, the area under the curve was highest when using the lowest vertebral body T-score to diagnose osteoporosis. In men for whom hip imaging is not possible, the lowest vertebral body T-score improves the ability to diagnose osteoporosis in men who are likely to have an incident fragility fracture. INTRODUCTION: Spine T-scores have limited ability to predict fragility fracture. We hypothesized that using lowest vertebral body T-score to diagnose osteoporosis would better predict fracture. METHODS: Among men enrolled in the Osteoporotic Fractures in Men Study, we identified cases with incident clinical fracture (n = 484) and controls without fracture (n = 1,516). We analyzed the lumbar spine bone mineral density (BMD) in cases and controls (n = 2,000) to record the L1-L4 (referent), the lowest vertebral body, and International Society for Clinical Densitometry (ISCD)-determined T-scores using a male normative database and the L1-L4 T-score using a female normative database. We compared the ability of method to diagnose osteoporosis and, therefore, to predict incident clinical fragility fracture, using area under the receiver operator curves (AUCs) and the net reclassification index (NCI) as measures of diagnostic accuracy. ISCD-determined T-scores were determined in only 60 % of participants (n = 1,205). RESULTS: Among 1,205 men, the AUC to predict incident clinical fracture was 0.546 for L1-L4 male, 0.542 for the L1-L4 female, 0.585 for lowest vertebral body, and 0.559 for ISCD-determined T-score. The lowest vertebral body AUC was the only method significantly different from the referent method (p = 0.002). Likewise, a diagnosis of osteoporosis based on the lowest vertebral body T-score demonstrated a significantly better net reclassification index (NRI) than the referent method (net NRI +0.077, p = 0.005). By contrast, the net NRI for other methods of analysis did not differ from the referent method. CONCLUSION: Our study suggests that in men, the lowest vertebral body T-score is an acceptable method by which to estimate fracture risk.

Standardized ileal digestibility of amino acids in alfalfa meal, sugar beet pulp, and wheat bran compared to wheat and protein ingredients for growing pigs.

A total of 11 (8 + 3 for replacement) barrows with an initial BW of 23 kg and fitted with a simple T-cannula at the distal ileum were used in 2 consecutive experiments (Exp. 1 and Exp. 2) to determine the standardized ileal digestibility (SID) of AA in 7 assay feed ingredients according to 2 consecutive duplicated 4 × 4 Latin square designs. In Exp. 1, 3 corn starch-based assay diets were formulated to contain 170 g CP/kg (as-fed basis) from either soybean meal (SBM), canola meal (CM), or meat-and-bone meal (MBM) and 1 assay diet that contained 136 g CP/kg (as-fed basis) from wheat as commonly used feed ingredients for pigs. In Exp. 2, the pigs were fed 4 assay diets formulated to contain 170 g CP/kg (as-fed basis) from either the same SBM as in Exp. 1 or a combination of this SBM and alfalfa meal (AM), sugar beet pulp (SB), or wheat bran (WB) to compare the SID of AA in these feed ingredients with those used in Exp. 1. The SID of AA in CM was lower compared to SBM (P < 0.05) with intermediate values for MBM and wheat. Among fiber rich feed ingredients, SID values were lower in SB compared to WB (P < 0.05) with intermediate values for AM. In AM, SID values ranged between 29 and 45% for Lys, Cys, Thr, and Phe and between 51 and 71% for Arg, His, Ile, Leu, Met, and Val. In SB, SID values ranged between -21 and 46% for Cys, Thr, Phe, and Val and between 51 and 61% for Arg, His, Ile, Leu, Lys, and Met. In WB, SID values were between 55 and 64% for Lys, Cys, Phe, Thr, and Val and between 68 and 80% for Arg, His, Ile, Leu, and Met. The SID values in WB, SB, and AM provided in the present study may improve diet formulation when these feed ingredients are used in diet formulation for pigs.

Clinical, genetic and environmental factors associated with congenital vertebral malformations.

Congenital vertebral malformations (CVM) pose a significant health problem because they can be associated with spinal deformities, such as congenital scoliosis and kyphosis, in addition to various syndromes and other congenital malformations. Additional information remains to be learned regarding the natural history of congenital scoliosis and related health problems. Although significant progress has been made in understanding the process of somite formation, which gives rise to vertebral bodies, there is a wide gap in our understanding of how genetic factors contribute to CVM development. Maternal diabetes during pregnancy most commonly contributes to the occurrence of CVM, followed by other factors such as hypoxia and anticonvulsant medications. This review highlights several emerging clinical issues related to CVM, including pulmonary and orthopedic outcome in congenital scoliosis. Recent breakthroughs in genetics related to gene and environment interactions associated with CVM development are discussed. The Klippel-Feil syndrome which is associated with cervical segmentation abnormalities is illustrated as an example in which animal models, such as the zebrafish, can be utilized to provide functional evidence of pathogenicity of identified mutations.

Bioavailability of the flavonol quercetin in cows after intraruminal application of quercetin aglycone and rutin.

The bioavailability of quercetin has been intensively investigated in monogastric species, but knowledge about its bioavailability in ruminants does not exist. Thus, the aim of the present study was to determine the bioavailability of quercetin in nonlactating cows equipped with indwelling catheters placed in one jugular vein after intraruminal and additionally after i.v. application, respectively. Quercetin was administered intraruminally in equimolar amounts, either in the aglycone form or as its glucorhamnoside rutin, each at 2 dosages [10 and 50 mg of quercetin/kg of body weight (BW)]. In a second trial, 0.8 mg of quercetin aglycone/kg of BW was applied i.v. Blood samples were drawn 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 h after intraruminal application and every 5 min (first hour), every 10 min(second hour), and at 3 and 6h after i.v. bolus application, respectively. Quercetin and quercetin metabolites with an intact flavonol structure (isorhamnetin, tamarixetin, and kaempferol) in plasma samples were analyzed by HPLC with fluorescence detection. After intraruminal application of quercetin and rutin, respectively, quercetin and its methylated (isorhamnetin, tamarixetin) and dehydroxylated (kaempferol) derivatives were present in plasma mainly as conjugated forms, whereas free quercetin and its derivatives were scarcely detected. For rutin, the relative bioavailability of total flavonols (sum of conjugated and nonconjugated quercetin and its conjugated and nonconjugated derivatives after intake of 50 mg/kg of BW) was 767.3% compared with quercetin aglycone (100%). Absolute bioavailability of total flavonols was only 0.1 and 0.5% after quercetin aglycone and rutin applications, respectively. Our data demonstrate that bioavailability of quercetin from rutin is substantially higher compared with that from quercetin aglycone in cows after intraruminal (or oral) application, unlike in monogastric species.

Effects of formic acid and phytase supplementation on digestibility and use of phosphorus and zinc in growing pigs.

Two studies, arranged according to a 4 × 4 Latin square design, were conducted to assess effects of dietary acidification on fungal 3-phytase (PHY) efficacy in growing pigs. In Exp. 1, effects of supplementing 500 units/kg feed of PHY and 4.7 g/kg HCOOH either alone or in combination on the use of P and Zn in growing pigs fed a pelleted diet based on wheat (Triticum aestivum), barley (Hordeum vulgare), and soybean (Glycine max) meal were investigated. In Exp. 2 the same dietary treatments were fed except that PHY supplementation was increased to 1000 units/kg. In both experiments, PHY supplementation increased (P < 0.05) P digestibility and retention. A PHY × HCOOH supplementation interaction on P balance was observed (P < 0.05), indicating that the combination of the additives may increase P digestibility and retention. Effects of HCOOH and PHY on Zn use followed a similar pattern. Supplementation of 1000 units/kg of PHY further increased P and Zn retention compared to supplementation of 500 units/kg. In conclusion, the present study indicated that HCOOH supplementation to diets with microbial PHY may increase PHY efficacy.

Introduction of guidelines to facilitate enteral nutrition in a surgical intensive care unit is associated with earlier enteral feeding.

PURPOSE: Patients treated postoperatively in surgical intensive care units often receive delayed enteral nutrition. We hypothesized that the introduction of guidelines promoting early enteral nutrition is associated with earlier enteral feeding. METHODS: Enteral nutrition guidelines were created by the consensus of a multidisciplinary team consisting of intensivists, nurses, nutritionists, and surgeons. The guidelines were implemented through repeated staff education. We prospectively compared data on nutritional support in the surgical intensive care unit of a tertiary care center before (pre-intervention period, from January 27 to April 30, 2008) and after (post-intervention period, from May 1st to August 15th, 2008) implementation of the guidelines. The primary outcome was time to enteral feeding (oral or tube feeding). RESULTS: 146 patients were evaluated during the pre-period and 141 patients during the post-period. Patients during the two time periods had similar demographics and clinical characteristics. None of the patients were without nutrition for longer than 7 days. Oral or feeding tube nutrition was started earlier in the post-period (median 1 vs. 2 days, p < 0.001). There was no difference in the percentages of patients receiving parenteral nutrition (7.4 vs. 10%, p = 0.360). There was no increase in aspiration events in the post-period (8 vs. 9.4%, p = 0.606). CONCLUSIONS: Introduction of guidelines to facilitate enteral nutrition in a surgical intensive care unit was associated with earlier enteral feeding.

"Evidence-based" or "logic-based" medicine?

Low trauma fractures are the cardinal manifestation of osteoporosis. Their occurrence supersedes bone mineral density in deciding whether specific therapy is warranted. We therefore disagree with the notion that a densitometric threshold for treatment should be applied to patients over age 50 who suffer low trauma distal radius fracture.

Complete AV block in Lyme carditis: an important differential diagnosis.

Lyme disease is a tick-borne spirochetal infection that may affect the heart. Cardiac manifestations include conduction disturbances and other pathologies of the heart. We report on a 37-year old male, who was admitted to the emergency department because of dizziness and generalized tiredness. Physical examination and the initial laboratory values revealed no abnormalities. The patient's electrocardiogram on admission revealed newly diagnosed bradycardia due to atrioventricular heart block. The ventricular heart rate was 35/min. The patient was admitted to the ICU. Lyme serology and Western blot were positive for Borrelia antibodies. After institution of antibiotic therapy with ceftriaxone, atrioventricular heart block resolved rapidly. We therefore have to assume that in this patient Lyme carditis was the cause of third-degree AV block.