Trichiasis removal using dermatological punch: A case report.

Entropion, a common malposition of the eyelid, can lead to trichiasis and corneal damage. This article presents a clinical case in which, following initial surgery to correct entropion, the use of a dermatological punch was chosen to definitively eliminate persistent trichiasis. This relatively unknown yet effective approach proved to be a quick and straightforward alternative with positive outcomes, emphasizing the importance of considering innovative approaches to recurrent challenges in clinical practice.

Discovery of serum biomarkers for diagnosis of tuberculosis by NMR metabolomics including cross-validation with a second cohort.

BACKGROUND: Tuberculosis (TB) is a disease with worldwide presence and a major cause of death in several developing countries. Current diagnostic methodologies often lack specificity and sensitivity, whereas a long time is needed to obtain a conclusive result. METHODS: In an effort to develop better diagnostic methods, this study aimed at the discovery of a biomarker signature for TB diagnosis using a Nuclear Magnetic Resonance based metabolomics approach. In this study, we acquired 1H NMR spectra of blood serum samples of groups of healthy subjects, individuals with latent TB and of patients with pulmonary and extra-pulmonary TB. The resulting data were treated with uni- and multivariate statistical analysis. RESULTS: Six metabolites (inosine, hypoxanthine, mannose, asparagine, aspartate and glutamate) were validated by an independent cohort, all of them related with metabolic processes described as associated with TB infection. CONCLUSION: The findings of the study are according with the WHO Target Product Profile recommendations for a triage test to rule-out active TB.

Effects of condensed tannin-amended cassava silage blend diets on feeding behavior, digestibility, nitrogen balance, milk yield and milk composition in dairy goats.

Condensed tannins (CTs) are phenolic compounds derived from secondary plant metabolism that act as part of the plant's chemical defense system against pathogen invasion and herbivorous attack. This study aimed to evaluate the intake, digestibility, nitrogen (N) balance, production and composition of milk from goats fed cassava silage with added levels of CTs. Eight Anglo-Nubian goats with a mean BW of 40 ±â€¯2.0 kg were distributed in a double Latin square design with four levels of CTs (0, 25, 50 and 75 g/kg DM) with four 20-day periods with 15 days of adaptation and five evaluation days for each period. No differences were observed in DM, NDF, CP intake and feed conversion (grams of DM intake (DMI) per gram of milk produced); however, when expressed as percent of BW, DMI showed a quadratic increase to 29.1 g/kg. As the level of supplemented CTs increased in the diet, the CP digestibility (P = 0.023), NDF (P = 0.044), non-fiber carbohydrates (NFC; P = 0.032) and total digestible nutrients (P = 0.033) exhibited a linear decrease. Furthermore, the addition of CTs to cassava silage induced a linear increase in N-fecal excretion (P = 0.014) and a positive quadratic effect on N-retained (P = 0.014) and N-balance (P = 0.024) as well as a positive quadratic trend in N-digested (P = 0.092). Milk urea N (P = 0.023) decreased linearly. The addition of CTs to cassava silage had a positive quadratic effect on ruminating time (P = 0.011). In addition, comparing the use or non-use from the orthogonal contrast test, the inclusion of CTs in goat diet increased water and N-intake, CP and NDF digestibility, spent time eating and ruminating and N-balance and decreased milk production corrected3.5%, fat milk content, milk urea N and dry defatted extract of milk. Thus, adding CTs to cassava silage at 25 g/kg total DM promoted goats' greater use of the diet without impairing feed conversion and the quality of goat milk produced. Dietary levels of 50 and 75 g/kg total DM are not recommended because under the conditions of this study, they reduced the productive efficiency of dairy goats.

Peptidylarginine deiminase type 2 is over expressed in the glaucomatous optic nerve.

PURPOSE: To determine levels of Peptidyl arginine deiminase 2 (PAD2) and its product protein-bound citrulline in cadaver eyes that suffered from normal tension glaucoma (NTG) compared to primary open angle glaucoma (POAG), and controls. METHODS: Western analysis, ELISA, and immunohistochemical analysis were performed with human tissues. RESULTS: We report over expression of PAD2 and higher levels of its product protein-bound citrulline in the optic nerve of normal tension glaucoma patients (NTG). CONCLUSIONS: This is the first report demonstrating that like in POAG, NTG also possesses elevated levels of both PAD2 and protein-bound citrulline.

Active and prospective latent tuberculosis are associated with different metabolomic profiles: clinical potential for the identification of rapid and non-invasive biomarkers.

Although 23% of world population is infected with Mycobacterium tuberculosis (M. tb), only 5-10% manifest the disease. Individuals surely exposed to M. tb that remain asymptomatic are considered potential latent TB (LTB) cases. Such asymptomatic M. tb.-exposed individuals represent a reservoir for active TB cases. Although accurate discrimination and early treatment of patients with active TB and asymptomatic M. tb.-exposed individuals are necessary to control TB, identifying those individuals at risk of developing active TB still remains a tremendous clinical challenge. This study aimed to characterize the differences in the serum metabolic profile specifically associated to active TB infected individuals or to asymptomatic M. tb.-exposed population. Interestingly, significant changes in a specific set of metabolites were shared when comparing either asymptomatic house-hold contacts of active TB patients (HHC-TB) or active TB patients (A-TB) to clinically healthy controls (HC). Furthermore, this analysis revealed statistically significant lower serum levels of aminoacids such as alanine, lysine, glutamate and glutamine, and citrate and choline in patients with A-TB, when compared to HHC-TB. The predictive ability of these metabolic changes was also evaluated. Although further validation in independent cohorts and comparison with other pulmonary infectious diseases will be necessary to assess the clinical potential, this analysis enabled the discrimination between HHC-TB and A-TB patients with an AUC value of 0.904 (confidence interval 0.81-1.00, p-value < 0.0001). Overall, the strategy described in this work could provide a sensitive, specific, and minimally invasive method that could eventually be translated into a clinical tool for TB control.

ABACUS, a direct method for protein NMR structure computation via assembly of fragments.

The ABACUS algorithm obtains the protein NMR structure from unassigned NOESY distance restraints. ABACUS works as an integrated approach that uses the complete set of available NMR experimental information in parallel and yields spin system typing, NOE spin pair identities, sequence specific resonance assignments, and protein structure, all at once. The protocol starts from unassigned molecular fragments (including single amino acid spin systems) derived from triple-resonance (1)H/(13)C/(15)N NMR experiments. Identifications of connected spin systems and NOEs precede the full sequence specific resonance assignments. The latter are obtained iteratively via Monte Carlo-Metropolis and/or probabilistic sequence selections, molecular dynamics structure computation and BACUS filtering (A. Grishaev and M. Llinás, J Biomol NMR 2004;28:1-10). ABACUS starts from scratch, without the requirement of an initial approximate structure, and improves iteratively the NOE identities in a self-consistent fashion. The procedure was run as a blind test on data recorded on mth1743, a 70-amino acid genomic protein from M. thermoautotrophicum. It converges to a structure in ca. 15 cycles of computation on a 3-GHz processor PC. The calculated structures are very similar to the ones obtained via conventional methods (1.22 A backbone RMSD). The success of ABACUS on mth1743 further validates BACUS as a NOESY identification protocol.

1H-NMR assignment and solution structure of human acidic fibroblast growth factor activated by inositol hexasulfate.

A major fragment of human acidic fibroblast growth factor of 132 amino acid residues is shown to be as active and stable as the 139 residue molecule initially described, and commonly used in physiological studies. It is shown that inositol hexasulfate is a good substitute for heparin in both activating and protecting acidic fibroblast growth factor. The complex between the shortened form of the protein and inositol hexasulfate was used to determine the structure of activated acidic fibroblast growth factor in solution. The 1H-NMR spectrum of the complex was totally assigned, and a low-resolution, three-dimensional structure of the protein computed. The global fold of the activated acidic fibroblast growth factor is similar to that proposed for a crystallized variant of the protein obtained by genetic engineering whose activity is not dependent on heparin. The inositol hexasulfate binds to the protein through the positively charged groups of Lys126, Lys127, Arg133 and Lys142 side-chains. The computed three-dimensional structure suggests that inositol hexasulfate may stabilize and activate the protein by conferring rigidity to the hairpin involving beta-strands 10 and 11.

Three-dimensional structure of acidic fibroblast growth factor in solution: effects of binding to a heparin functional analog.

Acidic and basic fibroblast growth factors (aFGF and bFGF; FGFs) are paradigms of a group of nine closely related proteins known as the fibroblast growth factor family. FGFs induce mitosis in most mesoderm- and neuroectoderm-derived cells, and appear to be involved in diseases caused by anomalous cell proliferation. In vitro assays show that binding to heparin-like glycosaminoglycans is required to elicit the mitogenic activity of these proteins. It has been shown that myo-inositol hexasulfate (MIHS) emulates heparin in the mitogenesis assays of aFGF, and a low-resolution three-dimensional structure in solution of this protein bound to MIHS has been reported. Here we describe the 1H-NMR three-dimensional structure in solution of the free aFGF. Comparison of this structure with that of the protein bound to MIHS, upgraded to a level of refinement equivalent to that of the free protein, shows that MIHS binding causes some slight conformational changes with an increase in the definition of the structure. In addition, amide exchange H/2H rates of the most protected protons, and exchange data of the intermediate and fast-exchanging ones show that the free protein is less stable (< or = 2 kcal/mol) and more flexible in terms of local unfolding equilibria, respectively, than the MIHS-bound one. Thus, MIHS binding to aFGF causes a decrease of its flexibility, which translates into an enhancement of the definition of its three-dimensional structure. The increase of aFGF rigidity affects regions that include those involved in recognizing the cell membrane receptor. Thus, our data suggest that enhancement of structural definition may play a key role in the modulation of the affinity of aFGF by its receptor, and, consequently, of its specific mitogenic activity.

Genetic polymorphism for human platelet thermostable phenol sulfotransferase (TS PST) activity.

Platelet TS PST basal activity and thermal stability were measured in blood samples from 237 individuals in 50 nuclear families. Significant correlations were found among first degree relatives, confirming the previously reported familial aggregation of TS PST basal activity and thermal stability. Commingling analysis of basal TS PST activity provided evidence for multiple component distributions, and after transformation to remove skewness, segregation analysis supported a major gene hypothesis. For TS PST thermal stability, commingling analysis also provided evidence for multiple component distributions. However, segregation analyses were equivocal with regard to the presence of a major gene for thermal stability, since support for a major gene model depended on skewness. Bivariate commingling analysis, which examined thermal stability by simultaneously considering basal activity and activity after heating, suggested that genotypes, as defined by the inferred component distributions for TS PST activity, differ in thermal stability. A three-allele model is proposed as one hypothesis that may account for the combined results of basal activity and thermal stability. The results of this study indicate that a major gene polymorphism in conjunction with polygenic inheritance plays an important role in the regulation of both level of activity and thermal stability of this important drug-metabolizing enzyme in humans.

n-3 Fatty acids plus oleic acid and vitamin supplemented milk consumption reduces total and LDL cholesterol, homocysteine and levels of endothelial adhesion molecules in healthy humans.

BACKGROUND AND AIMS: Numerous studies suggest n -3 polyunsaturated fatty acids (n -3 PUFA) and oleic acid intake have beneficial effects on health including risk reduction of coronary heart disease. The purpose of this study was to evaluate the effect of a commercially available skimmed milk supplemented with n -3 PUFA, oleic acid, and vitamins E, B(6), and folic acid (Puleva Omega3) on risk factors for cardiovascular disease. (CVD). METHODS: Thirty volunteers were given 500 ml/day of semi-skimmed milk for 4 weeks and then 500 ml/day of the n -3 enriched milk for 8 further weeks. Plasma and LDL lipoproteins were obtained from volunteers at the beginning of the study (T(pre)), and at 4, 8 and 12 weeks. RESULTS: The consumption of n -3 enriched milk produced a significant decrease in plasma concentration of total and LDL cholesterol accompanied by a reduction in plasma levels of homocysteine. Plasma and LDL oxidability and vitamin E concentration remained unchanged throughout the study. A significant reduction in plasma levels of vascular cell adhesion molecule 1, and an increase in plasma concentration of folic acid were also observed. CONCLUSION: Daily intake of n -3 PUFA and oleic acid supplemented skimmed milk plus folic acid and B-type vitamins has favourable effects on risk factors for CVD.

Direct intrafollicular insemination. A case report.

This is the first case report of a documented pregnancy initiated with a new assisted reproductive technique based on direct insemination of a preovulatory follicle with ultrasonographic guidance using a transvaginal probe in women with at least one patent fallopian tube and controlled ovarian stimulation.

Vaginal gamete intrafallopian transfer. Experience with 14 cases.

A procedure utilizing transvaginal aspiration of stimulated gametes followed by transcervical, ultrasound-guided catheterization of the tubal ostia was performed as a modification of the standardized gamete intrafallopian transfer (GIFT) technique. Among 14 patients with 16 cycles there were four normal, intrauterine pregnancies and one ectopic pregnancy. In two patients the beta-human gonadotropin level rose significantly and then started to fall; the patients aborted spontaneously. The procedure can be performed with a higher degree of patient acceptance than can traditional GIFT, and the success rate in this small series was promising.

[Interactions between foodstuffs and statins]. / Interacciones entre los alimentos y las estatinas.

The existence of interactions between different drugs or between drugs and the diet is becoming better and better known. Statins are medicines currently in widespread use for the treatment of hyperlipidaemias. Diet has a great influence on the prevention and/or treatment of these pathologies as the therapeutic strategy used comprises appropriate diet and, if this does not succeed, pharmacological therapy is begun in combination with dietary advice. For this reason it is necessary to be aware of the potential interactions between this kind of medication and foodstuffs in order to avoid alterations in the therapeutic benefits and even the onset of adverse side effects. All of the statins are absorbed orally, so the impact of food intake on administration is extremely important to achieve an appropriate therapeutic effect. Many of the interactions of statins lie in their metabolism through cytochrome P-450 (except for pravastatin), thus making them candidates for interaction with certain foodstuffs or compounds contained in them, such as in the case of grapefruit juice. This paper reviews the drug-nutrient interactions with special attention to the interactions specific to statins and the mechanism of these interactions is described so as to contribute to their avoidance and thus improve this form of treatment in individuals with hyperlipidaemia.

[Origin and elimination of fibrous elements seen in CRL antirabies vaccine for human use]. / Origen y eliminación de elementos fibrosos observados en vacuna antirrábica CRL de uso humano.

The present work describes the discovery of an organoleptic alteration in some batchs of suckling mouse brain rabies vaccine for human use, produced in the Central Laboratory of Public Health of the Province of Buenos Aires. This alteration consists in the appearance of fibrous particles, light-white, slightly perceptible, suspended in the diluent. The production procedure is that of Fuenzalida and Palacios (4), with the modifications proposed by the Panamerican Zoonoses Center (Larghi and col.) (6), which include a refrigerated centrifugation of the viral suspension to 17,000 g during 10 minutes. This alteration caused 20% or more of dosis loss and a decrease in vaccine potency (2). In order to determine the origin of this alteration, we controlled the homogenization systems, the elements employed, the production of experimental batchs with diversity of isotonizators (dextrose-sucrose) and preservatives, the utilization of glass filters in the treatment of water, all drugs employed, variation of pH of diluent solutions, double centrifugation, the glass employed (ampoules, flasks), pumps of dispensation and wash systems (3) (5). We conclude that the alterations are produced by partial freezing of the infected brain suspension to 10% in water, during the last part of the centrifugation. Particles are formed by irreversible precipitation of a proteic nature (1) (7). It is recommended that during the production of this vaccine the temperature be maintained between 3 to 5 degrees C carefully avoiding freezing the brain suspension in distilled water.

[The communication process in the care of patients during echocardiography]. / O processo de comunicação no cuidado do paciente submetido ao eco-stress: algumas reflexões.

The article reviews some aspects of the communication process, its basic concepts, how it is approached in the theories of the nurses, and proposes to make reflections on the communication in the context of the patient undergoing the stress-echo study. Our goal is to emphasize and to rescue some important aspects related to the communication in health allies area, which is practiced in a constant manner in the daily practices of the nurse. Finally, this paper wishes to emphasize the importance of the knowledge of this process, incorporating it to the practice.

[Postoperative care after heart surgery. Report of experiences]. / Assistência de enfermagem em pós operatório de cirurgia cardíaca--relato de experiência.

The objective of the authors is to describe the nursing care for patients in post-operative cardiac surgery at Hospital de Clínicas de Porto Alegre, emphasizing some important points to be observed for the best qualification and organization of the routines nowadays used. The nursing care is divided in many stages, all of them important, going from the unit organization, the patient admission in a critical moment, until the assistance to the patient discharge. The conclusion is that: it's very important, for an integral assistance to the patient, an adequated organization of the service, a good relation between multiprofessional staff, training staff, and specific staff for this nursing care.

[Systemic arterial hypertension: clinical aspects and aspects of care]. / Hipertensão arterial sistêmica: aspectos clínicos e assistenciais.

This article is a literature review about the concepts of systemic arterial hypertension, it's incidence, the diagnostic methods and used treatments. It emphasizing the nurse's role in the patients care, based on the authors' nursing practice at Hospital de Clínicas Porto Alegre. The authors describe measures to prevent and promote health, as well as advanced actions during hypertension crisis and emergency cases.

Nosocomial infections with metallo-beta-lactamase-producing Pseudomonas aeruginosa: molecular epidemiology, risk factors, clinical features and outcomes.

BACKGROUND: Metallo-ß-lactamases (MBLs) have emerged as one of the most important bacterial resistance mechanisms because of their ability to hydrolyse virtually all ß-lactam agents. MBL-producing Pseudomonas aeruginosa (MBL-PA) are an important cause of nosocomial infections, particularly in intensive care units (ICUs), where they are associated with serious infections and present a significant clinical risk. AIM: To assess the molecular epidemiology, risk factors and outcomes of nosocomial infections caused by MBL-PA in a teaching hospital in Southern Brazil. METHODS: From January 2001 to December 2008, 142 carbapenem-resistant P. aeruginosa strains were isolated from distinct clinical samples from hospitalized patients. These isolates were screened for MBLs, and underwent polymerase chain reaction, sequencing and pulsed-field gel electrophoresis (PFGE). Patients infected with carbapenem-resistant MBL-PA were considered as cases, and patients infected with non-MBL-PA were considered as controls. FINDINGS: Eighty-four of 142 patients with positive carbapenem-resistant P. aeruginosa cultures met the criteria of the Centers for Disease Control and Prevention for infection. Fifty-eight patients were infected with MBL-PA (69%) and 26 patients were infected with non-MBL-PA (31%). Multi-variate analysis revealed that ICU stay [P = 0.003, odds ratio (OR) 4.01, 95% confidence interval (CI) 1.15-14.01] and urinary tract infection (P = 0.001, OR 9.67, 95% CI 1.72-54.48) were important risk factors for MBL-PA infection. Patients infected with MBL-PA showed faster onset of infection (P = 0.002) and faster progression to death (P = 0.04). CONCLUSIONS: These results showed the severity of MBL-PA infections, and demonstrated the urgent need for strategies to improve infection control measures to prevent an increase in these nosocomial infections.

GSK3-SCF(FBXW7) targets JunB for degradation in G2 to preserve chromatid cohesion before anaphase.

JunB, an activator protein-1 (AP-1) transcription factor component, acts either as a tumor suppressor or as an oncogene depending on the cell context. In particular, JunB is strongly upregulated in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) where it enhances cell proliferation. Although its overexpression is linked to lymphomagenesis, the mechanisms whereby JunB promotes neoplastic growth are still largely obscure. Here, we show that JunB undergoes coordinated phosphorylation-dependent ubiquitylation during the G2 phase of the cell cycle. We characterized a critical consensus phospho-degron that controls JunB turnover and identified GSK3 and SCF(FBXW7) as, respectively, the kinase and the E3 ubiquitin ligase responsible for its degradation in G2. Pharmacological or genetic inactivation of the GSK3-FBXW7-JunB axis induced accumulation of JunB in G2/M and entailed transcriptional repression of the DNA helicase DDX11, leading to premature sister chromatid separation. This abnormal phenotype due to dysregulation of the GSK3ß/JunB/DDX11 pathway is phenocopied in ALK-positive ALCL. Thus, our results reveal a novel mechanism by which mitosis progression and chromatid cohesion are regulated through GSK3/SCF(FBXW7)-mediated proteolysis of JunB, and suggest that JunB proteolysis in G2 is an essential step in maintaining genetic fidelity during mitosis.

Avaliação clínica de ovinos após a ingestão de elevada quantidade de manga / Clinical evaluation of sheep after high ingestion of mango fruit

Objetivou-se avaliar clinicamente os efeitos da administração intrarruminal de duas quantidades distintas de manga em ovinos. Foram utilizados sete ovinos machos, hígidos, que não receberam carboidratos não fibrosos por, pelo menos, seis meses previamente ao período experimental, quando se avaliou pH ruminal, total de protozoários no suco de rúmen, pH urinário, pH sanguíneo estimado e parâmetros vitais nos tempos zero, 12, 16, 20 e 24 após a administração da manga. Os sete ovinos foram distribuídos aleatoriamente em dois grupos e receberam 0,625% ou 1,875% da MS de manga/kg/PV (M1 e M2, respectivamente), distribuídos em delineamento cross-over, com uma parcela perdida, e 30 dias de washout. Os ovinos M2 apresentaram valores médios para pH ruminal significativamente inferiores a M1 a partir do tempo T12 (5,1 e 6,9, respectivamente), o que indica ocorrência de acidose ruminal. Os animais tratados com M1 não apresentaram alterações sistêmicas, ao passo que os ovinos tratados com M2 apresentaram acidose metabólica leve, detectada por meio do pH urinário ácido (4,8). A ingestão apenas de manga in natura na quantidade de 1,875% da MS de manga/kg/PV mostrou-se capaz de provocar acidose ruminal em ovinos, levando-os a: ligeira depressão, aumento da frequência cardíaca, diminuição dos movimentos ruminais e diarreia em alguns casos.(AU)

The aim of this study is to clinically evaluate the effects of intra ruminal administration of two different amounts of mango in sheep. The sample was of seven male healthy sheep, which did not receive non-fibrous carbohydrates for at least six months prior to the trial. Rumen fluid pH, total of protozoa in the rumen fluid, urine pH, estimated blood pH, and vital parameters were evaluated at the following times: zero, 12, 16, 20 and 24 hours after administration of the mango. The seven sheep were randomly divided into two groups and received either 0.625% or 1.875% of the dry matter of the pulp and mango peel per kg body weight (M1 and M2, respectively), distributed in cross-over design with a lost portion and 30 days washout. Sheep treated with M2 showed significantly lower average values for ruminal pH than the M1 since T12 (5.1 and 6.9, respectively), indicating the occurrence of ruminal acidosis. The animals treated with M1 showed no systemic changes, while the sheep treated with M2 had mild metabolic acidosis, detected through the lower urinary pH (4.8). The in natura mango ingestion in the amount of 1.875% of the dry matter of mango per kg of body weight proved to provoke rumen acidosis in sheep, leading these animals to: slight depression, rise in heart rate, diminished rumen movement, and diarrhea in some cases.(AU)