Value of Diaphragm Ultrasonography for Extubation: A Single-Blinded Randomized Clinical Trial.

Introduction: Daily evaluation of mechanically ventilated (MV) patients is essential for successful extubation. Proper withdrawal prevents complications and reduces the cost of hospitalization in the intensive care unit (ICU). Diaphragm ultrasonography (DUS) has emerged as a potential instrument for determining whether a patient is ready to be extubated. This study compared the efficacy rate of extubation using a standard withdrawal protocol and DUS in patients with MV. Methods: A randomized, parallel, single-blind, controlled study was conducted on ICU patients undergoing MV. Patients were randomly assigned to either the control (conventional weaning protocol) group or intervention (DUS-guided weaning) group in a 1 : 1 ratio. The primary outcome measure was the rate of reintubation and hospital mortality. Results: Forty patients were randomized to the trial. The mean age of the sample was 70 years, representing an older population. The extubation success rate was 90% in both groups. There was no reintubation in the first 48 hours and only two reintubations in both groups between the second and seventh days. The hospital mortality risk in patients with acute kidney injury was positively correlated with age and the need for hemodialysis. Discussion. This study demonstrates the usefulness of DUS measurement protocols for withdrawing MV. The rate of reintubation was low for both cessation methods. As a parameter, the diaphragm thickness fraction comprehensively evaluates the diaphragm function. The results demonstrate that DUS has the potential to serve as a noninvasive tool for guiding extubation decisions. In conclusion, using DUS in patients with respiratory failure revealed no difference in reintubation rates or mortality compared with the conventional method. Future research should concentrate on larger, multicentered, randomized trials employing a multimodal strategy that combines diaphragmatic parameters with traditional clinical withdrawal indices.

The effect of litter materials on broiler performance: a systematic review and meta-analysis.

1. Divergence in outcomes from studies on the effects of litter materials on body weight, feed intake, feed conversion and mortality in broilers has led to a need for a meta-analysis to quantify their effects.2. A systematic search of published quantitative research relating to wood shavings and alternative bedding litters was conducted using databases.3. Means, standard deviations and sample sizes were extracted from each study. The response variables were analysed using the standardised mean difference (SMD, control treatment minus alternative litters).4. The literature demonstrated that alternative materials have no impact on feed intake in broilers, compared to wood shavings (SMD = 0.064, 95% CI = -0.101-0.229, P = 0.44).5. There was a positive overall effect of wood shavings on body weight (SMD = 0.253, 95% CI = 0.073-0.433, P = 0.006), feed conversion (SMD = -0.169, 95% CI = -0.327 - -0.012, P = 0.03) and mortality (SMD = -1.069, 95% CI = -1.983 - -0.155, P = 0.02) of broilers, compared to other litter types.6. Subgroup meta-analysis revealed that straw, when used as an alternative litter material to wood shavings, may be responsible for lower body weight (SMD = 0.654, 95% CI = 0.162-1.146, P = 0.009), worse feed conversion (SMD = -0.487, 95% CI = -0.828 - -0.145, P = 0.005) and higher mortality rates of broilers (SMD = -3.25, 95% CI = -5.681 - -0.819, P = 0.009). Rice husks impaired body weight compared to wood shavings (SMD = 0.535, 95% CI = 0.065-1.004, P = 0.02).7. It was concluded that different litter types do not affect the broilers' feed intake. Conversely, broilers kept on straw showed lower body weights, worse feed conversion and higher mortality rates, in comparison to wood shavings. Rice husks decreased body weight compared to wood shavings.

Temperature dependence of the Raman spectrum of 1-(4-chlorophenyl)-3-(2-thienyl)prop-2-en-1-one.

The heterocyclic chalcone containing thiophene ring 1-(4-chlorophenyl)-3-(2-thienyl)prop-2-en-1-one, C13H9ClOS was synthesized and investigated using experimental techniques such as nuclear magnetic resonance (1H and 13C NMR), Fourier transform infrared spectroscopy (FTIR) at room temperature, differential scanning calorimeter (DSC) from room temperature to 500K and Raman scattering at the temperature range 10-413K in order to study its structure and vibrational properties as well as stability and possible phase transition. Density functional theory (DFT) calculations were performed to determine the vibrational spectrum viewing to improve the knowledge of the material properties. A reasonable agreement was observed between theoretical and experimental Raman spectrum taken at 10K since anharmonic effects of the molecular motion is reduced at low temperatures, leading to a more comprehensive assignment of the vibrational modes. Increasing the temperature up to 393K, was observed the typical phonon anharmonicity behavior associated to changes in the Raman line intensities, line-widths and red-shift, in special in the external mode region, whereas the internal modes region remains almost unchanged due its strong chemical bonds. Furthermore, C13H9ClOS goes to melting phase transition in the temperature range 393-403K and then sublimates in the temperature range 403-413K. This is denounced by the disappearance of the external modes and the absence of internal modes in the Raman spectra, in accordance with DSC curve. The enthalpy (ΔH) obtained from the integration of the endothermic peak in DSC curve centered at 397K is founded to be 121.5J/g.

Habitat monitoring and genotoxicity in Ucides cordatus (Crustacea: Ucididae), as tools to manage a mangrove reserve in southeastern Brazil.

In Brazil, the state of São Paulo contains both preserved areas (Juréia-Itatins Ecological Station) and extremely impacted ones (Cubatão Municipality). This study evaluated the concentrations of five metals (Cu, Cd, Cr, Pb, and Hg) in two mangroves with different levels of anthropogenic impact and the apparent genotoxicity to Ucides cordatus. Water and sediment samples were obtained, and metal concentrations were determined with an atomic absorption spectrophotometer. The genotoxic impact was quantified based on the number of micronucleated cells per 1,000 analyzed (MN‰), using hemolymph slides stained with Giemsa. Metal concentrations in water were below the detection limit, except for lead, although no significant difference was observed between the areas (P > 0.05). Sediment from Cubatão had higher concentrations of Cd, Pb, Cr, and Cu than sediment from Juréia-Itatins (P < 0.05), but no significant differences in metal concentrations were detected among depth strata of the sediment (P > 0.05). Crabs from Cubatão had a 2.6 times higher mean frequency of micronucleated cells (5.2 ± 1.8 MN‰) than those from Juréia-Itatins (2.0 ± 1.0 MN‰; P < 0.0001). The more-polluted conditions found in the mangrove sediments of Cubatão were reflected in the micronucleus assay, demonstrating their genotoxic effect; however, genetic damage should be attributed to a synergistic effect with other kinds of pollutants previously recorded in different environments of Cubatão. U. cordatus proved to be an excellent bioindicator of mangrove pollution. This study established, for the first time, the normal frequency of MN‰ in a population of this species within an ecological station.

A myosin-Va tail fragment sequesters dynein light chains leading to apoptosis in melanoma cells.

Previous studies proposed that myosin-Va regulates apoptosis by sequestering pro-apoptotic Bmf to the actin cytoskeleton through dynein light chain-2 (DLC2). Adhesion loss or other cytoskeletal perturbations would unleash Bmf, allowing it to bind and inhibit pro-survival Bcl2 proteins. Here, we demonstrated that overexpression of a myosin-Va medial tail fragment (MVaf) harboring the binding site for DLC2 dramatically decreased melanoma cell viability. Morphological and molecular changes, including surface blebbing, mitochondrial outer membrane permeabilization, cytochrome-c and Smac release, as well as caspase-9/-3 activation and DNA fragmentation indicated that melanoma cells died of apoptosis. Immobilized MVaf interacted directly with DLCs, but complexed MVaf/DLCs did not interact with Bmf. Overexpression of DLC2 attenuated MVaf-induced apoptosis. Thus, we suggest that, MVaf induces apoptosis by sequestering DLC2 and DLC1, thereby unleashing the pair of sensitizer and activator BH3-only proteins Bmf and Bim. Murine embryonic fibroblasts (MEFs) lacking Bim and Bmf or Bax and Bak were less sensitive to apoptosis caused by MVaf expression than wild-type MEFs, strengthening the putative role of the intrinsic apoptotic pathway in this response. Finally, MVaf expression attenuated B16-F10 solid tumor growth in mice, suggesting that this peptide may be useful as an apoptosis-inducing tool for basic and translational studies.

Functional VEGF haplotypes affect the susceptibility to hypertension.

We examined whether vascular endothelial growth factor (VEGF) polymorphisms (C-2578A, G-1154A and G-634C) are associated with hypertension, response to antihypertensive therapy and nitric oxide (NO) formation. Substudy 1 compared the distribution of VEGF genotypes and haplotypes in 178 patients with arterial hypertension (100 whites and 78 blacks) and 186 healthy controls (115 whites and 71 blacks). Substudy 2 compared the distribution of VEGF markers in 82 patients with controlled hypertension, 89 patients with resistant hypertension and 101 normotensive (NT) patients. In substudy 3, plasma nitrite/nitrate (NOx) levels were determined (chemiluminescence assay) in 64 NT subjects and 48 hypertensive (HTN) subjects, and the distribution of VEGF markers was compared in subjects having low NOx with subjects having high NOx. Although the substudy 1 showed no differences in genotypes or allele distributions for the three VEGF polymorphisms between NT and HTN subjects, the 'C-A-G' haplotype was more common in white NT subjects than in the white HTN subjects, and the 'C-A-C' haplotype was more frequent in black and white HTN subjects than in black and white NT subjects. The substudy 2 showed similar results, with no differences between responsive and resistant HTN subjects. The substudy 3 showed that the 'C-A-G' haplotype, which had a protective effect against hypertension, was significantly more common in subjects with higher NOx concentrations than in subjects with lower NOx concentrations. VEGF haplotypes are associated with hypertension, and the haplotype associated with normotension was more common in subjects with increased NO formation, possibly offering a mechanistic clue for our findings.

Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children.

OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) is involved in the atherosclerotic process and functional polymorphisms in the MMP-9 gene affect MMP-9 expression/activity, and are associated with cardiovascular diseases. However, no study has tested the hypothesis that functional MMP-9 polymorphisms could affect MMP-9 levels in obese children. We investigated whether three MMP-9 gene polymorphisms (C-1562T (rs3918242), 90(CA)((14-24)) (rs2234681) and Q279R (rs17576)), or haplotypes, affect MMP-9 levels in obese children. METHODS: We studied 175 healthy control children and 127 obese children. Plasma MMP-9, tissue inhibitor of MMPs (TIMP)-1 and adiponectin concentrations were measured using enzyme-linked immunosorbent assay. RESULTS: We found similar MMP-9 genotypes, allelic and haplotypes distributions in the two study groups (P>0.05). However, we found lower plasma MMP-9 concentrations in obese subjects carrying the CC or the QQ genotypes for the C-1562T and the Q279R polymorphisms, respectively, in obese children compared with children with the other genotypes, or with non-obese children with the same genotypes (all P<0.05). Moreover, we found lower MMP-9 levels and lower MMP-9/TIMP-1 ratios (which reflect net MMP-9 activity) in obese children carrying the H2 haplotype (which combines the C, H and Q alleles for the three polymorphisms, respectively) when compared with obese children carrying the other haplotypes, or with non-obese children carrying the same haplotype (P<0.05). CONCLUSIONS: Our findings show that MMP-9 genotypes and haplotypes affect MMP-9 levels in obese children and adolescents, and suggest that genetic factors may modify relevant pathogenetic mechanisms involved in the development of cardiovascular complications associated with obesity in childhood.

eNOS haplotypes affect the responsiveness to antihypertensive therapy in preeclampsia but not in gestational hypertension.

Variations of the endothelial nitric oxide synthase (eNOS) gene have been associated with hypertensive disorders of pregnancy. We examined whether eNOS polymorphisms affect the therapeutic responses of women with gestational hypertension (GH) or preeclampsia (PE). We studied 304 hypertensive pregnant women (152 GH and 152 PE), who were stratified according to clinical and laboratorial parameters of therapeutic responsiveness. We compared the frequencies of three eNOS genetic polymorphisms (T-786C, Glu298Asp and b/a intron 4) in responsive and nonresponsive PE and GH patients. We found no significant differences in genotype or allele distributions when responsive and nonresponsive groups were compared (both PE or GH; all P>0.05). However, the eNOS haplotype distribution differed in PE (but not in GH)-responsive and -nonresponsive groups (P=0.0003). The 'C-Glu-a' and 'T-Asp-a' hapotypes were associated with responsiveness and nonresponsiveness to therapy, respectively (both P<0.001), thus suggesting that eNOS haplotypes affect the responsiveness to antihypertensive therapy in PE.

Living donor liver transplantation: usefulness of hemostatic and prothrombotic screening in potential donors.

Bleeding and thrombosis are serious complications of living donor liver transplantation (LDLT). The aim of this paper was to describe the results of a screening for coagulation disorders, including for thrombophilic factors, in potential living liver graft donors and to evaluate thrombotic and bleeding events in donors and recipients, during and after the procedure. From January 2001 to January 2007, 41 LDLTs were performed at our institution. We performed systematic screening for bleeding or prothrombotic states among 188 potential donors, 38 (20.2%) of whom showed at least one abnormality. We rejected potential donors with factor V Leiden, prothrombin mutation G20210A, and deficiencies in anticoagulant proteins (protein C, protein S, and antithrombin) or coagulation factors. Bleeding and thrombotic events in donors and recipients of the 41 LDLTs were evaluated during 7 days to 70 months follow-up. No major bleeding events were detected in the donors. Neither donor nor recipient experienced venous thrombosis or pulmonary embolism. Among all recipients, six suffered hepatic artery thrombosis including five in the first month probably related to surgery. Deep venous thrombosis and pulmonary embolism are well-known complications of hepatic surgery; Prothrombotic abnormalities in the donor can be transmitted to the recipient, leading to increased risk of serious postoperative events. Although the cost-effectiveness is not definitely established, we recommend systematic screening for hemostatic and prothrombotic disorders to prevent more morbidity of a procedure that already has high risks of bleeding and thrombosis.

The association between the VAL34LEU mutation in the factor XIII gene and deep venous thrombosis in young people

Background. A mutation in the coagulation FXIII has been described: a G to T transition in exon 2 of the FXIII A-subunitgene, which results in the substitution of Leucine for Valine at amino acid position 34 (FXIII Val34Leu). The higher level ofactivity of the Leu34 enzyme would be expected to be associated with increased resistance of the fibrin clot to plasmin degradation. Evidence is conflicting regarding the association of FXIII Val34Leu polymorphism with risk of venous thrombosis. The aim of this study was to evaluate the association of the Val34Leu mutation in the Factor XIII gene with deep venous thrombosis(DVT) in young people. Methods. The prevalence of the FXIII Val34Leu mutation was investigated in a population of 50 consecutive and unrelated patients with an objectively documented first episode of DVT under 40 years old and in a random control group of 45 healthy subjects, using DNA analysis. Results. The distribution of genotypes amongst patients was 64% Val/Val, 36% Val/Leu and 0% Leu/Leu, corresponding to a frequency of 18% for the Leu allele. In the control group the results were respectively 48.9%, 46.7% and 4.4%, corresponding to a frequency of 27.8% for the Leu allele (p= 0.150). The odds ratio (OR) was 0.54 (95% CI: 0.24-1.22 ).Conclusion. Data from this study suggests that the Val34Leu polymorphism offers a protective effect against a first episode of deep venous thrombosis in young people (AU)

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The association between the C677T mutation in the 5.10 methylenetertrahydrofolate reductase gene and deep venous thrombosis in young people

PURPOSE. To evaluate the association between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and deep venous thrombosis (DVT) in young people. METHODS. The prevalence of the C677T mutation in the MTHFR gene was investigated in a population of 97 consecutive and unrelated patients with an objectively documented first episode of DVT under 40 years old and in a control group of 100 healthy subjects, using DNA analysis. FINDINGS. The frequency of genotypes amongst patients was 0.10 TT, 0.44 CT and 0.46 CC and in the control group the results were respectively 0.11, 0.40 and 0.49. The odds ratio (OR) for homozygous genotype 677TT was 1.0 (95% CI: 0.4- 2.6), which was not statistically significant (p=0.86). CONCLUSION. In this study, the C677T mutation in the MTHFR gene, including the homozygous mutant genotype, was not associated with an increased risk of deep venous thrombosis in young people (AU)

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Griscelli syndrome-type 2 in twin siblings: case report and update on RAB27A human mutations and gene structure.

Griscelli syndrome (GS) is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1, Elejalde), RAB27A (GS2) or MLPH (GS3) genes. Typical features of all three subtypes of this disease include pigmentary dilution of the hair and skin and silvery-gray hair. Whereas the GS3 phenotype is restricted to the pigmentation dysfunction, GS1 patients also show primary neurological impairment and GS2 patients have severe immunological deficiencies that lead to recurrent infections and hemophagocytic syndrome. We report here the diagnosis of GS2 in 3-year-old twin siblings, with silvery-gray hair, immunodeficiency, hepatosplenomegaly and secondary severe neurological symptoms that culminated in multiple organ failure and death. Light microscopy examination of the hair showed large, irregular clumps of pigments characteristic of GS. A homozygous nonsense mutation, C-T transition (c.550C>T), in the coding region of the RAB27A gene, which leads to a premature stop codon and prediction of a truncated protein (R184X), was found. In patient mononuclear cells, RAB27A mRNA levels were the same as in cells from the parents, but no protein was detected. In addition to the case report, we also present an updated summary on the exon/intron organization of the human RAB27A gene, a literature review of GS2 cases, and a complete list of the human mutations currently reported in this gene. Finally, we propose a flow chart to guide the early diagnosis of the GS subtypes and Chédiak-Higashi syndrome.

Griscelli syndrome-type 2 in twin siblings: case report and update on RAB27A human mutations and gene structure

Griscelli syndrome (GS) is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1, Elejalde), RAB27A (GS2) or MLPH (GS3) genes. Typical features of all three subtypes of this disease include pigmentary dilution of the hair and skin and silvery-gray hair. Whereas the GS3 phenotype is restricted to the pigmentation dysfunction, GS1 patients also show primary neurological impairment and GS2 patients have severe immunological deficiencies that lead to recurrent infections and hemophagocytic syndrome. We report here the diagnosis of GS2 in 3-year-old twin siblings, with silvery-gray hair, immunodeficiency, hepatosplenomegaly and secondary severe neurological symptoms that culminated in multiple organ failure and death. Light microscopy examination of the hair showed large, irregular clumps of pigments characteristic of GS. A homozygous nonsense mutation, C-T transition (c.550C>T), in the coding region of the RAB27A gene, which leads to a premature stop codon and prediction of a truncated protein (R184X), was found. In patient mononuclear cells, RAB27A mRNA levels were the same as in cells from the parents, but no protein was detected. In addition to the case report, we also present an updated summary on the exon/intron organization of the human RAB27A gene, a literature review of GS2 cases, and a complete list of the human mutations currently reported in this gene. Finally, we propose a flow chart to guide the early diagnosis of the GS subtypes and Chédiak-Higashi syndrome.

Genetic polymorphisms and risk of recurrent deep venous thrombosis in young people: prospective cohort study.

OBJECTIVE: To determine the incidence of deep venous thrombosis (DVT) recurrence in young people, and its association with some genetic polymorphisms (FV G1691A, FII G20210A, MTHFR C677T, PAI-1 4G/5G). DESIGN: Prospective cohort study. METHODS: A database was established prospectively to follow-up a cohort of unselected patients who had had a first episode of objectively proven DVT under the age of 40 years. All patients had DNA analysis for heritable thrombophilia. We excluded patients with deficiency of antithrombin, protein C or protein S, malignant disease, antiphospholipid syndrome, or a requirement for long-term antithrombotic treatment. The end-point was objective evidence of symptomatic DVT recurrence. RESULTS: Eighty-seven patients were enrolled in the study. Mean duration of follow-up was 4.07 years. At 2 years, the cumulative recurrence rate was 19.3%. The risk of risk was not related to presence or absence of laboratory evidence of genetic polymorphisms: FV G1619A (HR 1.26 [95%CI: 0.64-2.46]; p = 0.51), FII G20210A (HR 0.81 [95%CI: 0.35-1.89]; p = 0.62), MTHFR C677T (HR 1.26 [95%CI: 0.56-2.81]; p = 0.58), PAI-1 4G/5G (0.84 [95%CI: 0.35-2.05]; p = 0.71). CONCLUSION: In this study, the risk of recurrent deep venous thrombosis in young people was not related with the presence of FV G1691A, FII G20210A, MTHFR C677T or PAI-1 4G/5G polymorphisms.

Review article: colon cleansing preparation for gastrointestinal procedures.

Adequate cleansing is essential for reliable diagnostic and surgical colon procedures. Accuracy and safety depend on good preparation. Patient compliance is enhanced by simplicity and well-tolerated methods. Several methods are available. Diet and cathartic regimens utilize clear liquids or diets designed to leave a minimal colonic residue. Laxatives, cathartics and enemas are employed. Gut lavage solutions are osmotically balanced electrolyte lavage products. Oral sodium phosphate solutions and tablets are available and are attractive because of good efficacy with a small volume of administration. For colonoscopy and colon surgery preparation, these methods have been proven safe and effective. For barium enema X-ray, lavage requires an adjunctive agent such as bisacodyl to enhance barium coating. Overall, all regimens are well-tolerated. This review discusses the development and clinical experience with various colon cleansing regimens.

Experiencia clínica prospectiva con glimepirida en pacientes con Diábetes Mellitus tipo 2 en Venezuela / Prospective clinical experience with Glimipiride tolerance in patient with diagnosis of diabetes mellitus type 2 in Venezuela

El objetivo del trabajo fue evaluar la eficacia y tolerancia de glimepirida en pacientes con diagnóstico de Diábetes Mellitus tipo 2 en Venezuela. Mediante un estudio multicéntrico abierto, no randomizado, prospectivo, de Glimepirida en pacientes diabéticos tipo 2. Dosis de inicio: 1 mg de glimepirida, de acuerdo a las respuesta se aumenta la dosis en 1 mg cada 2 semanas hasta alcanzar una glicemia en ayunas menor o igual a 140 mg/dl. El período total de observación fue de 12 semanas. Se realizó un control cada dos semanas. Se estudió una muestra de 258 pacientes diabéticos tipo 2 que no estaban controlados adecuadamente con dieta, ejercicios y/o tratamiento hipoglicemiante, quienes recibieron glimepirida por primera vez o cambiaron su tratamiento a glimepirida. Todos los datos se analizaron mediante la prueba T de Student con dos colas. Se consideró resultado estadísticamente significativo a los valores de p<0.05 en lo que se refiere a disminución de glicemia por cada consulta. Al inicio del estudio la glicemia en ayunas se encontraba en valores de 225,55 ñ 67 mg/dl. Al término del estudio la glicemia obtenida fue 127,80 ñ 42 mg/dl. La glicemia disminuyo en promedio un 44 por ciento luego de 12 semanas de tratamiento. 93 por ciento de casos lograron control adecuado de la glicemia. No se presentaron efectos secundarios en 91 por ciento de los casos. Ocurrieron reacciones adversas en 21 pacientes (9 por ciento de los casos), de los cuales 11 casos corresponden a episodios de hipoglicemia. La hipoglicemia fue leve o moderada en todos los casos no ameritando hospitalización. Glimepirida demostró eficacia terapéutica al disminuir los niveles de glicemia en ayunas a valores menores o iguales a 140 mg/dl en el 79,53 por ciento de los pacientes, significativo estadísticamente, con un excelente perfíl de seguridad (91 por ciento de los casos no reportaron efectos secundarios