Avaliação nutricional e metabólica de borregas alimentadas com níveis crescentes de aminoácidos protegidos / [Nutritional and metabolic evaluation of feeding lambs with growing levels of protein amino acids]

Objetivou-se avaliar a inclusão de níveis de lisina e metionina protegidas na dieta sobre os parâmetros nutricionais e metabólicos energéticos e hepáticos de borregas em crescimento. Utilizaram-se cinco borregas ½ sangue Dorper x Santa Inês, com aproximadamente oito meses de idade e peso médio de 50 ± 2,3kg, distribuídas em esquema quadrado latino 5x5 (cinco tratamentos, cinco animais e cinco períodos). Os tratamentos consistiram na inclusão de diferentes níveis de lisina e metionina protegidas da degradação ruminal (MicroPEARLS LM®) na ração, sendo: 0g, 8g, 16g, 24g e 32g por dia. A dieta era composta por silagem de milho e concentrado na relação 30V:70C. Realizou-se um ensaio de digestibilidade para determinar consumo e digestibilidade da matéria seca (CMS/DGMS), balanço de nitrogênio e metabólitos sanguíneos. O CMS (kg/dia) em relação ao peso metabólico apresentou equação linear positiva, sendo maior no tratamento que ofertou 32g de aminoácidos por dia, assim como o nitrogênio ingerido e o balanço de nitrogênio, sendo positivo em todos os tratamentos. Não houve diferença (P>0,05) para a digestibilidade da MS e o metabolismo energético e hepático. Lisina e metionina protegidas da degradação ruminal podem ser incluídas na ração de borregas em crescimento até 32g/dia sem causar efeitos negativos na digestibilidade da MS e no metabolismo.(AU)

The objective was to evaluate the inclusion of protected lysine and methionine levels on the diet, over the nutritional parameters and energetic and hepatic metabolites of growing lambs. Five lambs ½ blood Dorper x Santa Inês, with approximately eight months of age and average weight of 50kg, were distributed in a 5x5 latin square scheme (five treatments and five replicates). The treatments consisted of the inclusion of different levels of lysine and methionine protected from ruminal degradation (MicroPEARLS LM®) in the diet, being: 0g, 8g, 16g, 24g and 32g. The diet was composed of corn silage and concentrated 30V:70C in the ratio. A digestibility assay was performed to determine dry matter intake and digestibility (DMI/DDMI), nitrogen balance and blood metabolites. The DMI (kg/day) in relation to the metabolic weight had a positive linear equation, being higher in treatment 32g, as well as the ingested nitrogen and nitrogen balance, being positive in all treatments. There was no difference (P>0.05) for the digestibility of DM, energetic and hepatic metabolism. Lysine and methionine protected from ruminal degradation can be included in the diet of growing lambs up to 32g without causing negative effects on DM digestibility and metabolism.(AU)

Effects of treatments for drooling on caries risk in children and adolescents with cerebral palsy.

BACKGROUND: Neuromuscular impairment makes individuals with cerebral palsy (CP) more prone to drooling. Among the treatment options, there are procedures that interfere with saliva production. It is imperative to evaluate the effect of the different modalities since the reduction in salivary flow rate/production may exacerbate the risk of dental caries. MATERIAL AND METHODS: The aim of this study was to compare the effects of different treatments for drooling on caries risk and salivary parameters in children and adolescents with CP. STUDY DESIGN: A total of 142 children and adolescents with CP, aged 6 to 18 years, were assigned to groups based on the different treatments they had received for drooling: G1-anticholinergic drugs (n = 18), G2-botulinum toxin injection (n = 16), G3-salivary glands surgery (n = 16), G4-no treatment (n = 42), and G5-non-drooling subjects (n = 50). All participants were evaluated on the Simplified Oral Hygiene Index, and for the prevalence of dental caries (decayed, missing, and filled teeth index and white spot lesions). Unstimulated whole saliva was collected, and salivary flow rate and osmolality were measured. Chi-square, ANOVA and Poisson regression were calculated. Prevalence ratios and their respective 95 % confidence intervals were obtained. The significance level was fixed at 5%. RESULTS: No differences were found in the decayed, missing, and filled teeth index (p = 0.128) and Simplified Oral Hygiene Index (p = 0.674) among the different groups. G3 presented significantly higher percentages of WSL (p < 0.001), lower values of salivary flow rate (p < 0.001), and higher values of osmolality (p < 0.001). The white spot lesion prevalence ratio was higher only for G3 (Prevalence ratio = 14.36; IC 95% = 4.64-44.40; p < 0.001). CONCLUSIONS: Children and adolescents with CP who had received surgical treatment for drooling exhibited higher number of white spot lesions because of the reduced salivary flow rate and higher salivary osmolality.

Development and validation of a clinical prediction model for patient-reported pain and function after primary total knee replacement surgery.

To develop and validate a clinical prediction model of patient-reported pain and function after undergoing total knee replacement (TKR). We used data of 1,649 patients from the Knee Arthroplasty Trial who received primary TKR across 34 centres in the UK. The external validation included 595 patients from Southampton University Hospital, and Nuffield Orthopaedic Centre (Oxford). The outcome was the Oxford Knee Score (OKS) 12-month after TKR. Pre-operative predictors including patient characteristics and clinical factors were considered. Bootstrap backward linear regression analysis was used. Low pre-operative OKS, living in poor areas, high body mass index, and patient-reported anxiety or depression were associated with worse outcome. The clinical factors associated with worse outcome were worse pre-operative physical status, presence of other conditions affecting mobility and previous knee arthroscopy. Presence of fixed flexion deformity and an absent or damaged pre-operative anterior cruciate ligament (compared with intact) were associated with better outcome. Discrimination and calibration statistics were satisfactory. External validation predicted 21.1% of the variance of outcome. This is the first clinical prediction model for predicting self-reported pain and function 12 months after TKR to be externally validated. It will help to inform to patients regarding expectations of the outcome after knee replacement surgery.

Do foot & ankle assessments assist the explanation of 1 year knee arthroplasty outcomes?

OBJECTIVE: Whilst a number of risk factors for poor patient reported outcome measures (PROMs) following knee arthroplasty (KA) have been identified, unexplained variability still remains. The role of pre-operative foot and ankle status on such outcomes has not been investigated. The aim of this study was therefore to determine the association of clinical foot and ankle assessments with patient reported outcomes 1 year following KA. DESIGN: One hundred and fifteen participants from the Clinical Outcomes in Arthroplasty Study (COASt), underwent detailed foot and ankle assessments at baseline, prior to KA (2012-2014) and were followed up for self-reported outcomes 1 year after surgery. RESULTS: Thirty nine percent of subjects reported foot pain at baseline. Mean pre-operative Oxford Knee Score (OKS; 0 [worst] to 48 [best outcome]) was 21 and post-operative OKS score was 38. In fully adjusted analysis pre-operative foot pain was significantly associated with 1 year outcome (risk ratio [RR] 0.78 95% confidence interval [95% CI] 0.62, 0.98). No significant association was observed between ankle dorsiflexion or foot posture and outcome. CONCLUSIONS: Patients with pre-operative foot pain are more likely to have poorer clinically important outcomes 1 year following KA than patients without foot pain. Static ankle dorsiflexion and foot posture do not further explain post-operative KA outcomes. Consideration should also be given to address pre-operative foot pain when attempting to achieve a good clinical outcome for KA.

Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23†years follow-up of a population-based cohort of middle-aged women.

UNLABELLED: To assess whether joint pain or radiographic osteoarthritis (ROA) of the knee and hand is associated with all-cause and disease-specific mortality in middle-aged women. METHODS: Four subgroups from the prospective community-based Chingford Cohort Study were identified based on presence/absence of pain and ROA at baseline: (Pain-/ROA-; Pain+/ROA-; Pain-/ROA+; Pain+/ROA+). Pain was defined as side-specific pain in the preceding month, while side-specific ROA was defined as Kellgren-Lawrence grade ≥2. All-cause, cardiovascular disease (CVD) and cancer-related mortality over the 23-year follow-up was based on information collected by the Office for National Statistics. Associations between subgroups and all-cause/cause-specific mortality were assessed using Cox regression, adjusting for age, body mass index, typical cardiovascular risk factors, occupation, past physical activity, existing CVD disease, glucose levels and medication use. RESULTS: 821 and 808 women were included for knee and hand analyses, respectively. Compared with the knee Pain-/ROA- group, the Pain+/ROA- group had an increased risk of CVD-specific mortality (HR 2.93 (95% CI 1.47 to 5.85)), while the knee Pain+/ROA+ group had an increased HR of 1.97 (95% CI 1.23 to 3.17) for all-cause and 3.57 (95% CI 1.53 to 8.34) for CVD-specific mortality. We found no association between hand OA and mortality. CONCLUSION: We found a significantly increased risk of all-cause and CVD-specific mortality in women experiencing knee pain with or without ROA but not ROA alone. No relationship was found between hand OA and mortality risk. This suggests that knee pain, more than structural changes of OA is the main driver of excess mortality in patients with OA.

The histone deacetylase sirtuin 2 is a new player in the regulation of platelet function.

BACKGROUND: Histone deacetylases (HDACs) play a key role in signaling in many cell types. However, little is known about the participation of HDACs, particularly sirtuins (SIRTs), in platelet reactivity. OBJECTIVE: To investigate the role of HDACs in platelets, we examined the effects of SIRT inhibition on platelet function and protein acetylation in human platelets. METHODS: We used washed platelets obtained from healthy subjects. Cambinol (SIRT1 and SIRT2 inhibitor), AGK2 (specific SIRT2 inhibitor) and EX527 (specific SIRT1 inhibitor) were used as SIRT inhibitors. Platelets were stimulated with collagen, thrombin, or U46619, and platelet responses were determined according to optical aggregometry findings, dense granule release, and cytosolic calcium levels (Fura-2AM fluorescence). Protein acetylation and phosphorylation were assessed by immunoblotting. RESULTS: SIRT inhibition remarkably reduced platelet responses (aggregation, granule release, and cytosolic calcium level; P < 0.05). SIRT2 was present in platelets at the level of mRNA and protein, and its specific inhibition reduced platelet responses. The acetylated protein pattern observed in resting platelets changed during platelet aggregation. Inhibition of SIRT2 increased the acetylation of Akt kinase, which in turn blocked agonist-induced Akt phosphorylation and glycogen synthase kinase-3ß phosphorylation, which are markers of Akt activity. Finally, collagen-induced aggregation provoked Akt acetylation. CONCLUSIONS: Regulation of protein acetylation by SIRT2 plays a central role in platelet function. The effects of SIRT2 are mediated in part by the acetylation and inhibition of Akt. These results open a new avenue for research into the control of platelet function, and may help to identify new therapeutic targets.

killerFLIP: a novel lytic peptide specifically inducing cancer cell death.

One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killerFLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using electron microscopy demonstrated that killerFLIP-E triggers cell death accompanied by rapid (within minutes) plasma membrane permeabilization. Studies of the structure of the active core of killerFLIP (-E) indicated that it possesses amphiphilic properties and self-assembles into micellar structures in aqueous solution. The biochemical properties of killerFLIP are comparable to those of cationic lytic peptides, which participate in defense against pathogens and have also demonstrated anticancer properties. We show that the pro-cell death effects of killerFLIP are independent of its sequence similarity with c-FLIPL as killerFLIP-induced cell death was largely apoptosis and necroptosis independent. A killerFLIP-E variant containing a scrambled c-FLIPL motif indeed induced similar cell death, suggesting the importance of the c-FLIPL residues but not of their sequence. Thus, we report the discovery of a promising synthetic peptide with novel anticancer activity in vitro and in vivo.

A genomic-scale search for regulatory binding sites in the integration host factor regulon of Escherichia coli K12

We examined general aspects of the DNA-protein interaction between the integration host factor (IHF) global regulator and its regulatory binding sites in the Escherichia coli K12 genome. Two models were developed with distinct weight matrices for the regulatory binding sites recognized by IHF. Using these matrices we performed a genome scale scan and built a set of computationally predicted binding sites for each of the models. The sites found by the model associated with repetitive sequences had a higher score in the sequence to matrix alignment. They were also more rare than the other sites. The sites not associated with repeats rapidly tended to become undistinguishable from the background as statistical stringency was relaxed. We compared our results to the known sites documented in RegulonDB and found new members of the IHF Regulon. The two models exhibit clearly distinct affinity patterns (scores in the sequence to matrix alignments and in the number of regulatory sites), as we vary the stringency of the statistical confidence parameters. We suggest that these differences may play an important role in the dynamics of the network. We concluded that IHF may regulate two genes encoding ATP-dependent RNA helicases. This interaction is not described in RegulonDB, even as a computational prediction. IHF may also regulate RNA modification processes.

Naso-ethmoid schwannoma with intracranial extension: case report.

Intranasal schwannomas are rare lesions, specially when they present with an intracranial extension. The fifth case in the medical literature of a naso-ethmoid schwannoma with extension into the anterior cranial fossa is presented. The magnetic resonance findings and the details of the combined intracranial / transfacial operative approach used are described. The possible origin and the clinical characteristics of this rare lesion are reviewed.

Downregulation of human platelet reactivity by neutrophils. Participation of lipoxygenase derivatives and adhesive proteins.

Unstimulated neutrophils inhibited activation and recruitment of thrombin- or collagen-stimulated platelets in an agonist-specific manner. This occurred under conditions of close physical cell-cell contact, although biochemical adhesion between the cells as mediated by P-selectin was not required. Moreover, in the presence of monoclonal P-selectin antibodies that blocked biochemical platelet-neutrophil adhesion, thrombin-stimulated platelets were more efficiently downregulated by neutrophils. This suggested a prothrombotic role for P-selectin under these circumstances. The neutrophil downregulatory effect on thrombin-stimulated platelets was amplified by lipoxygenase inhibition with 5,8,11,14-eicosatetraynoic acid. In contrast, the neutrophil inhibitory effect on platelets was markedly reduced by platelet-derived 12S-hydroxy-5,8-cis, 10-trans, 14-cis-eicosatetraenoic acid (12S-HETE), as well as by the platelet-neutrophil transcellular product, 12S,20-dihydroxy-5,8,10,14-eicosatetraenoic acid (12S,20-DiHETE), but not by another comparable metabolite, 5S,12S-dihydroxy-6-trans, 8-cis, 10-trans, 14-cis-eicosatetraenoic acid (5S,12S-DiHETE), or the neutrophil-derived hydroxy acid leukotriene B4. The neutrophil downregulatory effect on thrombin-induced platelet reactivity was enhanced by aspirin treatment. This may represent a novel action of aspirin as an inhibitor of platelet function. These results provide in vitro biochemical and functional evidence for the thromboregulatory role of neutrophils and emphasize the multicellular aspect of hemostasis and thrombosis.

Erythrocytes metabolically enhance collagen-induced platelet responsiveness via increased thromboxane production, adenosine diphosphate release, and recruitment.

Erythrocytes promoted platelet reactivity in a plasma medium, as demonstrated in an in vitro system that independently evaluated the biochemistry of platelet activation and recruitment. The prothrombotic erythrocyte effects were metabolically regulated, as evidenced by lack of activity of ATP-depleted or glutaraldehyde-fixed erythrocytes. They occurred in the absence of cell lysis as verified by lactate dehydrogenase assays, and had an absolute requirement for platelet activation. The presence of erythrocytes induced a twofold increase in platelet thromboxane B2 (TXB2) synthesis upon collagen stimulation, indicating that erythrocytes modulated platelet eicosanoid formation. Cell-free releasates from stimulated platelet-erythrocyte suspensions, which exhibited increased recruiting capacity, contained 6.9-fold more ADP and 4.9-fold more ATP than releasates from stimulated platelets alone. Following aspirin ingestion, TXB2 formation was blocked, but erythrocyte promotion of platelet reactivity persisted at those doses of collagen that reinduced platelet activation. Moreover, when platelet mixtures consisted of as little as 10% obtained before aspirin plus 90% obtained post-aspirin ingestion, significant erythrocyte enhancement of platelet reactivity occurred, even at low agonist concentrations. These erythrocyte effects would decrease the therapeutic potential of inhibition of platelet cyclooxygenase by aspirin. The erythrocyte-induced modulation of platelet biochemistry and function emphasizes the importance of cell-cell interactions in stimulus-response coupling.

Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. A new approach to platelet activation and recruitment.

Erythrocytes are known to influence hemostasis. Bleeding times are prolonged in anemia and corrected by normalizing the hematocrit. We now demonstrate that intact erythrocytes modulate biochemical and functional responsiveness of activated platelets. A two-stage procedure, permitting studies of cell-cell interactions and independently evaluating platelet activation and recruitment within 1 min of stimulation, was developed. Erythrocytes increased platelet serotonin release despite aspirin treatment, enzymatic adenosine diphosphate removal, protease inhibition, or combinations thereof. The data suggested that erythrocyte enhancement of platelet reactivity can reduce the therapeutic effectiveness of aspirin. Erythrocytes metabolically modified platelet arachidonate or eicosapentaenoate release and eicosanoid formation. They promoted significant increases in cyclooxygenase and lipoxygenase metabolites upon platelet stimulation with collagen or thrombin. However, with ionophore, erythrocytes strongly reduced platelet lipoxygenation. These erythrocyte modulatory effects were stimulus-specific. Activated platelet-erythrocyte mixtures, with or without aspirin, promoted 3-10-fold increases in extracellular free fatty acid, which would be available for transcellular metabolism. Erythrocyte-induced increases in free eicosapentaenoate may contribute to antithrombotic and anti-inflammatory effects of this fish oil derivative. These results provide biochemical insight into erythrocyte contributions to thrombosis and hemostasis, and support the concept of thrombus formation as a multicellular event.

Effect of smoking on plasma and platelet fatty acid composition in middle-aged men.

The effect of tobacco cigarette smoking on plasma and platelet fatty acid composition was studied in 219 male subjects. The effect of tobacco on plasma malondialdehyde-like material (MDA-LM) was also evaluated. In the total fatty acid percentage composition in plasma, an increase in the saturated fatty acids at the expense of polyunsaturated fatty acids was observed in those subjects who smoked more than 20 cigarettes/day. In the total fatty acid composition of platelets, an increase in myristic acid (14:0) and palmytoleic acid (16:1) was found. Additionally, when the fatty acid composition of the different platelet lipid fractions was evaluated, an increase in 14:0 and 16:0 + 16:1 was observed in phospholipids. Finally, the plasma MDA-LM level was significantly higher in those subjects who smoked more than 10 cigarettes/day. The biochemical variations found in this study may be compatible with the greater incidence of CHD observed in smokers.

Influencia do estado nutricional na produtividade de trabalhadores da construcao civil no municipio do Rio de Janeiro. / Influence of nutritional status in the productivity of civil construction workers of Rio de Janeiro

Os autores tentam descobrir os fatores predisponentes para o alto numero de acidentes de trabalho e a consequencia baixa de produtividade dos trabalhadores da construcao civil na cidade do Rio de Janeiro. Foram estudados 320 individuos, escolhidos de maneira aleatoria em varias obras da cidade. Realizados exames medicolaboratoriais e inquerito alimentar. Os resultados evidenciaram insuficiencia nutricional e uma tendencia a hipoglicemia.As consequencias do achado sao discutidas e feitas algumas sugestoes

[Radiological appearances of cancer of the gastric stump (author's transl)]. / Aspects radiologiques du cancer du moignon gastrique

The authors report 35 cases of primary carcinoma of the gastric stump, describing the technique they use for radiography, noting the main diagnosis signs and discussing the importance of the various methods for their study. They emphasize the importance of periodic post-operative control in these cases.