Cri-du-Chat Syndrome: Revealing a Familial Atypical Deletion in 5p.

Introduction: Cri-du-chat syndrome is generally diagnosed when patients present a high-pitched cry at birth, microcephaly, ocular hypertelorism, and prominent nasal bridge. The karyotype is useful to confirm deletions in the short arm of chromosome 5 (5p-) greater than 10 Mb. In cases of smaller deletions, it is necessary to resort to other molecular techniques such as fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA) or genomic array. Case Presentation: We report a family with an atypical deletion in 5p (mother and 2 children) and variable phenotypes compared with the literature. We applied a P064 MLPA kit to evaluate 5p- in the mother and the 2 children, and we used the Infinium CytoSNP-850K BeadChip genomic array to evaluate the siblings, an 11-year-old boy and a 13-year-old girl, to better define the 5p breakpoints. Both children presented a high-pitched cry at birth, but they did not present any of the typical physical features of 5p- syndrome. The MLPA technique with 5 probes for the 5p region revealed that the patients and their mother presented an atypical deletion with only 4 probes deleted (TERT_ex2, TERT_ex13, CLPTM1L, and IRX4). The genomic array performed in the siblings' samples revealed a 6.2-Mb terminal deletion in 5p15.33p15.32, which was likely inherited from their mother, who presented similar molecular features, seen in MLPA. Discussion: The sparing of the CTNND2 gene, which is associated with cerebral development, in both siblings may explain why these 2 patients had features such as better communication skills which most patients with larger 5p deletions usually do not present. In addition, both patients had smaller deletions than those found in patients with a typical 5p- phenotype. This report demonstrates the utility of genomic arrays as a diagnostic tool to better characterize atypical deletions in known syndromes such as 5p- syndrome, which will allow a better understanding of the genotype-phenotype correlations.

Perinatal mental health and recommendations for integral care in gyneco-obstetric hospitals.

Mental health is defined as the ability by which individuals recognize their own abilities and cope with the normal stress of life, work productively and fruitfully, contribute to their communities and enjoy the greatest possible well-being. Therefore, it is essential as a part of the health of the individual and its constant evaluation. Recently, special attention has been drawn to the study of the mental health of women, given the greater probability to suffer depression and anxiety disorders during and after pregnancy. The most vulnerable state occurs in adolescence, pregnancy, puerperium and perimenopause; Adequate mental health during pregnancy has shown beneficial effects in the resolution of pregnancy and in the health of the newborn. Regarding this paper, the fundamental aspects in the definition of perinatal mental health were reviewed, its determinants, the main mental disorders in this vital period, its role in perinatal outcomes and the importance of its evaluation. Some basic recommendations for adequate mental health care in gyneco-obstetric hospitals are also proposed.

La salud mental es la aptitud por la cual los individuos reconocen sus habilidades y son capaces de hacer frente al estrés normal de la vida, trabajar de forma productiva y fructífera, contribuir a sus comunidades y gozar del mayor bienestar posible. Por ello, es fundamental para la salud integral del individuo y su evaluación constante. Recientemente se ha prestado especial atención a la salud mental de las mujeres, puesto que se ha observado una mayor propensión a sufrir depresión y trastornos de ansiedad durante y posterior al embarazo. El estado de mayor vulnerabilidad sucede en la adolescencia, el embarazo, el puerperio y la perimenopausia. Una adecuada salud mental durante la gestación ha mostrado efectos benéficos en la resolución del embarazo y en la salud del recién nacido. En este trabajo se revisan aspectos fundamentales en la definición de salud mental perinatal, sus determinantes, los principales trastornos mentales en este periodo vital, su papel en los resultados perinatales y la importancia de su evaluación. Se exponen también algunas recomendaciones básicas para la atención adecuada de la salud mental en los hospitales ginecoobstétricos.

1H qNMR-Based Metabolomics Discrimination of Covid-19 Severity.

The coronavirus disease 2019 (Covid-19), which caused respiratory problems in many patients worldwide, led to more than 5 million deaths by the end of 2021. Experienced symptoms vary from mild to severe illness. Understanding the infection severity to reach a better prognosis could be useful to the clinics, and one study area to fulfill one piece of this biological puzzle is metabolomics. The metabolite profile and/or levels being monitored can help predict phenotype properties. Therefore, this study evaluated plasma metabolomes of 110 individual samples, 57 from control patients and 53 from recent positive cases of Covid-19 (IgM 98% reagent), representing mild to severe symptoms, before any clinical intervention. Polar metabolites from plasma samples were analyzed by quantitative 1H NMR. Glycerol, 3-aminoisobutyrate, formate, and glucuronate levels showed alterations in Covid-19 patients compared to those in the control group (Tukey's HSD p-value cutoff = 0.05), affecting the lactate, phenylalanine, tyrosine, and tryptophan biosynthesis and d-glutamine, d-glutamate, and glycerolipid metabolisms. These metabolic alterations show that SARS-CoV-2 infection led to disturbance in the energetic system, supporting the viral replication and corroborating with the severe clinical conditions of patients. Six polar metabolites (glycerol, acetate, 3-aminoisobutyrate, formate, glucuronate, and lactate) were revealed by PLS-DA and predicted by ROC curves and ANOVA to be potential prognostic metabolite panels for Covid-19 and considered clinically relevant for predicting infection severity due to their straight roles in the lipid and energy metabolism. Thus, metabolomics from samples of Covid-19 patients is a powerful tool for a better understanding of the disease mechanism of action and metabolic consequences of the infection in the human body and may corroborate allowing clinicians to intervene quickly according to the needs of Covid-19 patients.

Epidemiological analysis of perinatal depression.

Perinatal depression is a commonly underdiagnosed problem which not only severely affects maternal mental and physical health, but also affects the newborn on a physical, mental and cognitive level with serious repercussions on adult life. Despite efforts to obtain useful information to dimension the problem, most experts in the field agree that this disorder is more frequent than estimated. Thus, the improvement in obtaining information on perinatal mental health will not only allow for a better dimensioning of the problem, but will also allow for better decision making in public mental health to reduce morbidity and mortality and the burden of disease associated with perinatal depression.

La depresión perinatal es un problema habitualmente subdiagnosticado que no sólo afecta de manera importante la salud mental y física materna, sino también al recién nacido en los aspectos físico, mental y cognitivo, con serias repercusiones en la vida adulta. A pesar de los esfuerzos para obtener información útil para dimensionar el problema, la mayoría de los expertos en el tema coinciden en señalar que este trastorno es más frecuente de lo que se estima. La mejora en la obtención de información en salud mental perinatal permitirá dimensionar mejor el problema y una adecuada toma de decisiones en salud mental pública para disminuir la morbimortalidad y la carga de la enfermedad asociada a la depresión perinatal.

Breastfeeding and COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has affected all dimensions of health care, including exclusive breastfeeding assurance and its promotion. The risk of contagion and the consequences of the pandemic have raised concerns among future mothers or in those who are already breastfeeding due to the risk of possible transmission of the virus through breast milk, although active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not yet been detected in breast milk. The fear of contagion has favored mother-child isolation policies. So far, there is no evidence of vertical transmission, and the risk of horizontal transmission in the infant is similar to that of the general population. In infants with COVID-19, breastfeeding can even favorably change the clinical course of the disease.

La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha afectado a todas las dimensiones de la atención en salud, entre ellas el aseguramiento de la lactancia materna exclusiva y su promoción. El riesgo de contagio y las consecuencias de la pandemia han provocado preocupación entre las futuras madres o las que se ya encuentran lactando debido al riesgo de una posible transmisión del virus a través de la leche materna. Aunque aún no se ha detectado el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) activo en la leche materna. El miedo al contagio ha favorecido las políticas de aislamiento madre-hijo. Hasta el momento no existe evidencia de transmisión vertical y el riesgo de transmisión horizontal en el lactante es similar al de la población general. En lactantes con COVID-19 la lactancia materna incluso puede cambiar favorablemente el curso clínico de la enfermedad.

Lactancia materna y COVID-19 / Breastfeeding and COVID-19

Resumen La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha afectado a todas las dimensiones de la atención en salud, entre ellas el aseguramiento de la lactancia materna exclusiva y su promoción. El riesgo de contagio y las consecuencias de la pandemia han provocado preocupación entre las futuras madres o las que se ya encuentran lactando debido al riesgo de una posible transmisión del virus a través de la leche materna. Aunque aún no se ha detectado el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) activo en la leche materna. El miedo al contagio ha favorecido las políticas de aislamiento madre-hijo. Hasta el momento no existe evidencia de transmisión vertical y el riesgo de transmisión horizontal en el lactante es similar al de la población general. En lactantes con COVID-19 la lactancia materna incluso puede cambiar favorablemente el curso clínico de la enfermedad.

Abstract The COVID-19 pandemic has affected the health attention in all dimensions, one of them, the exclusive breastfeeding assurance and her promotion. The high risk of contagion and the pandemic consequences have raised a number of concerns in future mothers or those who are breastfeeding because of the risk of a possible transmission of the virus through breast milk. Although SARS-CoV2 has no evidence of being active on breast milk, the fear of contagion has favored mother-child isolation policies. At this point, there are no evidence of vertical transmission and the risk of horizontal transmission in the infant is similar to the general population. Breastfeeding in newborn with COVID-19, can even favorably change the clinical course of the disease.

Leadership problems in the management of health institutions.

In health institutions, physicians or other health professionals frequently occupy senior management positions, usually without any administrative expertise. In such a way that an excellent clinician can become a lousy leader and administrator. In this article, the administrative and organizational consequences of a bad exercise of leadership are displayed, interpreting the phenomenon from the classical and contemporary theories of leadership and exposing the problems that top management in health frequently faces in hospitals. Leadership is not innate; it is a skill that can be developed. Leading and managing health institutions is a science and an art that should be learned from undergraduate and perfected in the postgraduate course. Unless the health professional has a solid administrative and political career, holding senior positions in the hospital is a fortuitous matter.

En las instituciones de salud es frecuente que los médicos u otros profesionales de la salud ocupen altos cargos directivos, habitualmente sin ninguna experiencia administrativa, de tal modo que un excelente clínico se puede convertir en un pésimo líder y administrador. En este artículo se abordan las consecuencias administrativas y organizativas de un mal ejercicio del liderazgo, interpretando el fenómeno desde las teorías clásicas y contemporáneas del liderazgo y exponiendo los problemas que la alta dirección en salud enfrenta frecuentemente en los hospitales. El liderazgo no es innato, es una habilidad que puede ser desarrollada. Liderar y administrar instituciones de salud es una ciencia y un arte que bien debiese aprenderse desde el pregrado y perfeccionarse en el posgrado, puesto que, a menos que el profesional de la salud posea una sólida carrera administrativa y política, el ocupar altos cargos de responsabilidad es un asunto fortuito.

Influence of interleukins on prognosis of patients with oral squamous cells carcinoma / Influência de interleucinas no prognóstico de pacientes portadores de carcinoma de células escamosas intraoral

ABSTRACT Squamous cell carcinoma is a malignant neoplasm that affects the structures and tissues of the oral cavity. Interleukins (IL) synthesized from a tumor modulate a cascade reaction that may influence the prognosis of the disease. We aim to investigate in the literature whether interleukins are mediators that negatively or positively influence the prognosis of patients with oral squamous cell carcinoma. A systematic review study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) instructions. PubMed (including MedLine), Scopus, Web of Science, SciELO and Latin American and Caribbean Health Sciences (LILACS) databases were used as the primary sources for the study; OpenGrey and OpenThesis were used to search for "gray literature". The search conducted in seven general databases resulted in a set of 858 studies, while the search conducted in two databases for gray literature resulted in 82 studies, totaling 940 studies. From these, 15 studies were selected for this systematic review (eight studies presented low bias risk; four studies presented moderate bias risk; and three studies presented high risk of bias). Although they may act on the anti-tumor immune response pathways, the IL evaluated in the present systematic review (IL-4, IL-6, IL-8, IL-10, IL-12 and IL-13) tend to present a response associated with the intensification of carcinogenesis and poor prognosis in patients with oral squamous cell carcinoma.

RESUMEN El carcinoma de células escamosas es una neoplasia maligna que afecta las estructuras y los tejidos de la cavidad oral. Interleucinas (IL) sintetizadas a partir de un tumor modulan una cascada de reacciones que puede influenciar el pronóstico de la enfermedad. Nuestro objetivo es investigar en la literatura si las IL son mediadoras que influyen negativamente o positivamente en el pronóstico de pacientes con carcinoma oral de células escamosas. Un estudio de revisión sistemática fue realizado bajo las instrucciones del Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Las bases de datos PubMed (incluyendo MedLine), Scopus, Web of Science, SciELO y Latin American and Caribbean Health Sciences (LILACS) fueron usadas como fuentes primarias de estudio; OpenGrey y OpenThesis, para pesquisar la literatura gris. La búsqueda realizada en siete bases de datos generales resultó en un conjunto de 858 estudios, mientras la búsqueda realizada en dos bases de datos para literatura gris resultó en 82 estudios, totalizando 940 investigaciones. Entre ellas, 15 fueron elegidas para la presente revisión sistemática (ocho estudios presentaron bajo riesgo de sesgo; cuatro, riesgo moderado; tres, riesgo alto). A pesar de poder actuar en vías de respuesta inmune antitumoral, las IL evaluadas en esta revisión (IL-4, IL-6, IL-8, IL-10, IL-12, y IL-13) suelen presentar una respuesta asociada a la intensificación del proceso de carcinogénesis y al pronóstico desfavorable en pacientes portadores de carcinoma oral de células escamosas.

RESUMO O carcinoma de células escamosas é uma neoplasia maligna que afeta as estruturas e os tecidos da cavidade oral. Interleucinas (IL) sintetizadas a partir de um tumor modulam uma cascata de reações que poderá influenciar o prognóstico da doença. Objetiva-se investigar na literatura se as interleucinas são mediadores que influenciam negativamente ou positivamente o prognóstico de pacientes com carcinoma de células escamosas intraoral. Um estudo de revisão sistemática foi realizado segundo as instruções do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). As bases de dados PubMed (incluindo MedLine), Scopus, Web of Science, SciELO e Latin American and Caribbean Health Sciences (LILACS) foram utilizadas como fontes de estudo primárias; OpenGrey e OpenThesis, utilizadas para pesquisar a "literatura cinzenta". A busca realizada em sete bases de dados gerais resultou em um conjunto de 858 estudos, enquanto a realizada em duas bases de dados para literatura cinza, em 82 estudos, totalizando 940 pesquisas. Destas, 15 foram selecionadas para a presente revisão sistemática (oito estudos apresentaram baixo risco de viés; quatro, moderado risco de viés; e três, alto risco de viés). Apesar de poderem atuar nas vias de resposta imune antitumoral, as IL avaliadas nesta revisão (IL-4, IL-6, IL-8, IL-10, IL-12 e IL-13) tendem a apresentar uma resposta associada à intensificação do processo de carcinogênese e ao prognóstico desfavorável em pacientes portadores do carcinoma de células escamosas intraoral.

Increased chemical acetylation of peptides and proteins in rats after daily ingestion of diacetyl analyzed by Nano-LC-MS/MS.

BACKGROUND: Acetylation alters several protein properties including molecular weight, stability, enzymatic activity, protein-protein interactions, and other biological functions. Our previous findings demonstrating that diacetyl/peroxynitrite can acetylate L-lysine, L-histidine, and albumin in vitro led us to investigate whether diacetyl-treated rats suffer protein acetylation as well. METHODS: Wistar rats were administered diacetyl daily for four weeks, after which they were sacrificed, and their lung proteins were extracted to be analysed by Nano-LC-MS/MS (Q-TOF). A C18 reversed-phase column and gradient elution with formic acid/acetonitrile solutions from 2 to 50% over 150 min were used to separate the proteins. Protein detection was performed using a microTOF-Q II (QTOF) equipped with captive source and an electrospray-ionization source. The data from mass spectrometry were processed using a Compass 1.7 and analyzed using Protein Scape, software that uses Mascot algorithms to perform protein searches. RESULTS: A set of 3,162 acetylated peptides derived from 351 acetylated proteins in the diacetyl-treated group was identified. Among them, 23 targeted proteins were significantly more acetylated in the diacetyl-treated group than in the PBS control. Protein acetylation of the group treated with 540 mg/kg/day of diacetyl was corroborated by Western blotting analysis. CONCLUSIONS: These data support our hypothesis that diacetyl exposure in animals may lead to the generation of acetyl radicals, compounds that attach to proteins, affecting their functions and triggering adverse health problems.

Pharmacokinetic and clinical effects of two bupivacaine concentrations on axillary brachial plexus block / Efeitos farmacocinéticos e clínicos de duas concentrações de bupivacaína no bloqueio do plexo braquial via axilar

Abstract Introduction: The risk of systemic bupivacaine toxicity is a persistent problem, which makes its pharmacokinetic study fundamental for regional anesthesia safety. There is little evidence of its influence on plasma peak at different concentrations. The present study compares two bupivacaine concentrations to establish how the concentration affects this drug plasma peak in axillary brachial plexus block. Postoperative latency and analgesia were also compared. Methods: 30 patients were randomized. In the 0.25% Group, 0.25% bupivacaine (10 mL) was injected per nerve. In the 0.5% Group, 0.5% bupivacaine (5 mL) was injected per nerve. Peripheral blood samples were collected during the first 2 h after the blockade. For sample analyses, high performance liquid chromatography mass spectrometry was used. Results: Plasma peak occurred 45 min after the blockade, with no difference between groups at the assessed time-points. Plasma peak was 933.97 ± 328.03 ng.mL−1 (mean ± SD) in 0.25% Group and 1022.79 ± 253.81 ng.mL−1 in 0.5% Group (p = 0.414). Latency was lower in 0.5% Group than in 0.25% Group (10.67 ± 3.71 × 17.33 min ± 5.30, respectively, p = 0.004). No patient had pain within the first 4 h after the blockade. Conclusion: For axillary brachial plexus block, there was no difference in bupivacaine plasma peak despite the use of different concentrations with the same local anesthetic mass. The concentration inversely influenced latency.

Resumo Introdução: O risco de intoxicação sistêmica pelo uso da bupivacaína é um problema persistente e torna seu estudo farmacocinético fundamental para a segurança da anestesia regional. São escassas as evidências sobre a influência de diferentes concentrações no pico plasmático desse fármaco. O presente estudo compara duas concentrações de bupivacaína para estabelecer como a concentração afeta o pico plasmático desse fármaco no bloqueio do plexo braquial via axilar. Também se compararam latência e analgesia pós-operatória. Métodos: Foram randomizados 30 pacientes. No Grupo 0,25%, injetaram-se 10 mL de bupivacaína 0,25% por nervo. No Grupo 0,5%, injetaram-se 5 mL de bupivacaína 0,5% por nervo. Amostras de sangue periférico foram colhidas durante as duas primeiras horas após o bloqueio. Para análise das amostras, usou-se a cromatografia líquida de alta frequência acoplada ao espectrômetro de massas. Resultados: O pico plasmático ocorreu 45 minutos após o bloqueio, sem diferença entre os grupos nos tempos avaliados. O pico plasmático (média ± DP) foi 933,97 ± 328,03 ng.mL−1 no Grupo 0,25% e 1.022,79 ± 253,81 ng.mL−1 no Grupo 0,5% (p = 0,414). O Grupo 0,5% apresentou menor latência com relação ao Grupo 0,25% (10,67 ± 3,71 × 17,33 min ± 5,30; respectivamente; p = 0,004). Nenhum paciente apresentou dor nas primeiras quatro horas após o bloqueio. Conclusão: Para o bloqueio do plexo braquial via axilar, não foi detectada diferença no pico plasmático de bupivacaína apesar do uso de diferentes concentrações, com a mesma massa de anestésico local. A concentração influenciou inversamente a latência.

[Pharmacokinetic and clinical effects of two bupivacaine concentrations on axillary brachial plexus block]. / Efeitos farmacocinéticos e clínicos de duas concentrações de bupivacaína no bloqueio do plexo braquial via axilar.

INTRODUCTION: The risk of systemic bupivacaine toxicity is a persistent problem, which makes its pharmacokinetic study fundamental for regional anesthesia safety. There is little evidence of its influence on plasma peak at different concentrations. The present study compares two bupivacaine concentrations to establish how the concentration affects this drug plasma peak in axillary brachial plexus block. Postoperative latency and analgesia were also compared. METHODS: 30 patients were randomized. In the 0.25% Group, 0.25% bupivacaine (10mL) was injected per nerve. In the 0.5% Group, 0.5% bupivacaine (5mL) was injected per nerve. Peripheral blood samples were collected during the first 2hours after the blockade. For sample analyses, high performance liquid chromatography mass spectrometry was used. RESULTS: Plasma peak occurred 45minutes after the blockade, with no difference between groups at the assessed time-points. Plasma peak was 933.97 ± 328.03 ng.mL-1 (mean ± SD) in 0.25% Group and 1022.79 ± 253.81 ng.mL-1 in 0.5% Group (p = 0.414). Latency was lower in 0.5% Group than in 0.25% Group (10.67 ± 3.71 × 17.33min ± 5.30, respectively, p = 0.004). No patient had pain within the first 4hours after the blockade. CONCLUSION: For axillary brachial plexus block, there was no difference in bupivacaine plasma peak despite the use of different concentrations with the same local anesthetic mass. The concentration inversely influenced latency.

Use of yeast (Pichia kudriavzevii) as a novel feed additive to ameliorate the effects of aflatoxin B1 on broiler chicken performance.

The aim of this study was to evaluate the efficacy of autochthonous Pichia kudriavzevii as a novel bioadsorbent for aflatoxin B1 (AFB1). The selection of this yeast was based on the AFB1 adsorption capacity previously demonstrated in vitro (Magnoli et al. 2016). One-day-old Cobb broilers (n = 160) were randomly assigned to four dietary treatments (T1: basal diet (B); T2: B + 0.1% yeast; T3: B + AFB1, 100 µg/kg; T4: B + 0.1% yeast + AFB1, 100 µg/kg). Performance parameters (average daily weight gain body, average daily consumption, feed conversion ratio, carcass weight, and dead weight), biochemical parameters (albumin, globulin, and albumin/globulin), liver pathological changes, and AFB1 residual levels in the liver and excreta were evaluated. Significant differences (P < 0.05) in performance parameters were observed among treatments and controls: T3 group showed the lowest average daily body weight gain value while in T4 group, the value of this parameter increased significantly (P < 0.05). T3 and T4 groups showed the lowest and highest values for average daily feed consumption, respectively. The feed conversion ratio (FC) showed no significant differences among treatments. T3 group showed the lowest dead weight and carcass weight compared with T1 group. The biochemical parameters showed no significant differences among treatments. T3 group showed macroscopic and microscopic liver changes compared to the control. Aflatoxin B1 levels (µg/g) were detected in broiler livers and showed significant differences among treatments (P < 0.05). In conclusion, native P. kudriavzevii incorporation (0.1%) in broiler diets containing AFB1 was shown to be effective in ameliorating the adverse effects of AFB1 on production.

Complete Genome Sequence of Herbaspirillum hiltneri N3 (DSM 17495), Isolated from Surface-Sterilized Wheat Roots.

We report the complete genome sequence of Herbaspirillum hiltneri N3 (DSM 17495), a member of the genus Herbaspirillum of the Betaproteobacteria. The genome is contained in a single chromosome, and analysis revealed that N3 lacks the whole nitrogen fixation (nif) gene cluster, confirming its inability to fix nitrogen.

Impact of postprandial glycaemia on health and prevention of disease.

Postprandial glucose, together with related hyperinsulinemia and lipidaemia, has been implicated in the development of chronic metabolic diseases like obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In this review, available evidence is discussed on postprandial glucose in relation to body weight control, the development of oxidative stress, T2DM, and CVD and in maintaining optimal exercise and cognitive performance. There is mechanistic evidence linking postprandial glycaemia or glycaemic variability to the development of these conditions or in the impairment in cognitive and exercise performance. Nevertheless, postprandial glycaemia is interrelated with many other (risk) factors as well as to fasting glucose. In many studies, meal-related glycaemic response is not sufficiently characterized, or the methodology with respect to the description of food or meal composition, or the duration of the measurement of postprandial glycaemia is limited. It is evident that more randomized controlled dietary intervention trials using effective low vs. high glucose response diets are necessary in order to draw more definite conclusions on the role of postprandial glycaemia in relation to health and disease. Also of importance is the evaluation of the potential role of the time course of postprandial glycaemia.

Methylmalonate impairs mitochondrial respiration supported by NADH-linked substrates: involvement of mitochondrial glutamate metabolism.

The neurodegeneration that occurs in methylmalonic acidemia is proposed to be associated with impairment of mitochondrial oxidative metabolism resulting from methylmalonate (MMA) accumulation. The present study evaluated the effects of MMA on oxygen consumption by isolated rat brain mitochondria in the presence of NADH-linked substrates (α-ketoglutarate, citrate, isocitrate, glutamate, malate, and pyruvate). Respiration supported either by glutamate or glutamate plus malate was significantly inhibited by MMA (1-10 mM), whereas no inhibition was observed when a cocktail of NADH-linked substrates was used. Measurements of glutamate transport revealed that the inhibitory effect of MMA on respiration maintained by this substrate is not due to inhibition of its mitochondrial uptake. In light of this result, the effect of MMA on the activity of relevant enzymes involved in mitochondrial glutamate metabolism was investigated. MMA had minor inhibitory effects on glutamate dehydrogenase and aspartate aminotransferase, whereas α-ketoglutarate dehydrogenase was significantly inhibited by this metabolite (K(i) = 3.65 mM). Moreover, measurements of α-ketoglutarate transport and mitochondrial MMA accumulation indicated that MMA/α-ketoglutarate exchange depletes mitochondria from this substrate, which may further contribute to the inhibition of glutamate-sustained respiration. To study the effect of chronic in vivo MMA treatment on mitochondrial function, young rats were intraperitoneally injected with MMA. No significant difference was observed in respiration between isolated brain mitochondria from control and MMA-treated rats, indicating that in vivo MMA treatment did not lead to permanent mitochondrial respiratory defects. Taken together, these findings indicate that the inhibitory effect of MMA on mitochondrial oxidative metabolism can be ascribed to concurrent inhibition of specific enzymes and lower availability of respiratory substrates.

Single-site laparoscopic (SSL) cholecystectomy in human cadavers using a novel percutaneous instrument platform and a magnetic anchoring and guidance system (MAGS): reestablishing the "critical view".

INTRODUCTION: SSL introduces ergonomic challenges while establishing the critical view during dissection of the Triangle of Calot (TOC). This study investigates the use of a novel percutaneous instrument platform and MAGS in performing SSL cholecystectomy with a technique that closely mimics four-port cholecystectomy. METHODS: SSL cholecystectomy was performed on four female cadavers via a 15-18-mm incision made at the umbilicus for introduction of these devices and the working port. MAGS comprises an internal effector with a retractable monopolar cautery hook coupled across the abdominal wall to an external magnet held by the surgeon. The novel grasper was introduced percutaneously in the RUQ and comprises a 3-mm transabdominal shaft mated to a 5-mm end effector intracorporeally. Retraction was accomplished using the percutaneous grasper to manipulate the fundus and a standard 5-mm grasper at the umbilicus for the infundibulum. Dissection was performed by using a combination of the MAGS and a standard Maryland dissector. Total procedure time, time from procedure start to obtain a critical view of the TOC and clipping and dividing the cystic duct/artery, time for dissection of the gallbladder from the liver bed, and thickness of the abdominal wall at the umbilicus were measured. RESULTS: The critical view was obtained in each case, and all four procedures were completed successfully. Mean procedure time was 40 (range, 33-51) min; time from procedure start to obtaining the critical view and clipping and dividing the cystic duct/artery was 33 (range, 28-38) min, and time for dissection of the gallbladder from the liver bed was 6.7 (range, 3-13) min. The mean abdominal wall thickness was 1.9 (range, 1.5-2) cm. CONCLUSIONS: The use of a novel graspers and MAGS overcomes the limitations of SSL cholecystectomy and improves surgeon dexterity. Making SSL feel more like traditional laparoscopy will enable a wider adoption of this procedure in the community.

Óleo essencial de Thymus vulgaris sobre o crescimentode Streptococcus mutans / Effect of the Thymus vulgaris essential oil on the growth of Streptococcus mutans

The traditional Mediterranean herb thyme (Thymus vulgaris) is a source of an essential oil that has been shown to possess antimicrobial activity against many microorganisms. A considerable part of the general population has dental caries and Streptococcus mutans is one of the microorganisms responsible. The aim of this study was to assess the effect of the essential oil extracted from thyme on the growth of S. mutans, the main bacterium involved in the etiology of dental caries, as well as to incorporate this oil into a toothpaste formulation for preliminary assessment. The broth dilution technique was used in threefold tests for antibacterial activity. The concentrations tested were 1%, 5% and 10% essential oil diluted in ethanol or mineral oil. The controls were triclosan at 0.25% and 0.5%, chlorhexidine digluconate at 0.06% and 0.12%, and ethanol. The 1% solution of thyme essential oil in ethanol proved to be the most efficient against Streptococcus mutans and may be considered viable as an ingredient of toothpaste, both with regard to cost and to the sensory profile of the product. Also, analyses of the characteristics of the formulation indicated that the product is stable.

Thymus vulgaris (tomilho) é uma fonte de óleo essencial que tem demonstrado atividade antimicrobiana. Uma parcela considerável da população tem apresentado problemas dentários, tais como a cárie, na qual o Streptococcus mutans é um microrganismo de fundamental importância. O objetivo deste trabalho foi avaliar o efeito do óleo essencial de tomilho sobre o crescimento do Streptococcus mutans, a principal bactéria relacionada com a etiologia da cárie dentária, bem como veicular este óleo essencial em uma formulação de creme dental para estudo preliminar. O método empregado foi diluição em caldo. As concentrações utilizadas de óleo essencial foram 1%, 5% e 10% de óleo essencial diluído em etanol ou óleo mineral. Os controles foram triclosan a 0,25% e 0,5%, bem como digluconato de clorexidina a 0,06% e 0,12%. A amostra contendo 1% de óleo essencial de tomilho diluída em etanol foi a mais eficaz, sendo efetiva contra Streptococcus mutans e, portanto considerada viável em relação ao custo e ao sensorial conferido ao produto, sendo que a formulação avaliada foi considerada estável.

Generation of singlet oxygen by the glyoxal-peroxynitrite system.

Diacetyl, methylglyoxal, and glyoxal are α-dicarbonyl catabolites prone to nucleophilic additions of amino groups of proteins and nucleobases, thereby triggering adverse biological responses. Because of their electrophilicity, in aqueous medium, they exist in a phosphate-catalyzed dynamic equilibrium with their hydrate forms. Diacetyl and methylglyoxal can be attacked by peroxynitrite (k(2) ≈ 1.0 × 10(4) M(-1) s(-1) and k(2) ≈ 1.0 × 10(5) M(-1) s(-1), respectively), a potent biological nucleophile and oxidant, yielding the acetyl radical from the homolysis of peroxynitrosocarbonyl adducts, and acetate or formate ions, respectively. We report here that glyoxal also reacts with peroxynitrite, yielding formate ion at rates at least 1 order of magnitude greater than does methylglyoxal. A triplet EPR signal (1:2:1; a(H) = 0.78 mT) attributable to hydrated formyl radical was detected by direct flow experiments. In the presence of the spin trap 2-methyl-2-nitrosopropane, the EPR spectrum displays the di-tert-butyl nitroxide signal, another signal assignable to the spin trapping adduct with hydrogen radical (a(N) = a(H) = 1.44 mT), probably formed from formyl radical decarbonylation, and a third EPR signal assignable to the formyl radical adduct of the spin trap (a(N) = 0.71 mT and a(H) = 0.14 mT). The novelty here is the detection of singlet oxygen ((1)Δ(g)) monomol light emission at 1270 nm during the reaction, probably formed by subsequent dioxygen addition to formyl radical and a Russell reaction of nascent formylperoxyl radicals. Accordingly, the near-infrared emission increases upon raising the peroxynitrite concentration in D(2)O buffer and is suppressed upon addition of O(2) ((1)Δ(g)) quenchers (NaN(3), l-His, H(2)O). Unequivocal evidence of O(2) ((1)Δ(g)) generation was also obtained by chemical trapping of (18)O(2) ((1)Δ(g)) with anthracene-9,10-divinylsulfonate, using HPLC/MS/MS for detection of the corresponding 9,10-endoperoxide derivative. Our studies add insights into the molecular events underlying nitrosative, oxidative, and carbonyl stress in inflammatory processes and aging-associated maladies.

"Chopstick" surgery: a novel technique improves surgeon performance and eliminates arm collision in robotic single-incision laparoscopic surgery.

INTRODUCTION: Single-incision laparoscopic surgery (SILS) is limited by the coaxial arrangement of the instruments. A surgical robot with wristed instruments could overcome this limitation, but the arms often collide when working coaxially. This study tests a new technique of "chopstick" surgery to enable use of the robotic arms through a single incision without collision. METHODS: Experiments were conducted utilizing the da Vinci S robot (Intuitive Surgical, Inc., Sunnyvale, CA) in a Fundamentals of Laparoscopic Surgery (FLS) box trainer with three laparoscopic ports (1 x 12 mm, 2 x 5 mm) introduced through a single "incision." Pilot work determined the optimal setup for SILS to be a triangular port arrangement with 2-cm trocar distance and remote center at the abdominal wall. Using this setup, five experienced robotic surgeons performed three FLS tasks utilizing either a standard robotic arm setup or the chopstick technique. The chopstick arrangement crosses the instruments at the abdominal wall so that the right instrument is on the left side of the target and the left instrument on the right. This results in separation of the robotic arms outside the box. To correct for the change in handedness, the robotic console is instructed to drive the "left" instrument with the right-hand effector and the "right" instrument with the left. Performances were compared while measuring time, errors, number of clutching maneuvers, and degree of instrument collision (Likert scale 1-4). RESULTS: Compared with the standard setup, the chopstick configuration increased surgeon dexterity and global performance through significantly improved performance times, eliminating instrument collision, and decreasing number of camera manipulations, clutching maneuvers, and errors during all tasks. CONCLUSION: Chopstick surgery significantly enhances the functionality of the surgical robot when working through a small single incision. This technique will enable surgeons to utilize the robot for SILS and possibly for intraluminal or transluminal surgery.

Microwave-assisted solid-phase peptide synthesis at 60 degrees C: alternative conditions with low enantiomerization.

Several conditions have been used in the coupling reaction of stepwise SPPS at elevated temperature (SPPS-ET), but we have elected the following as our first choice: 2.5-fold molar excess of 0.04-0.08 M Boc or Fmoc-amino acid derivative, equimolar amount of DIC/HOBt (1:1) or TBTU/DIPEA (1:3), 25% DMSO/toluene, 60 degrees C, conventional heating. In this study, aimed to further examine enantiomerization under such condition and study the applicability of our protocols to microwave-SPPS, peptides containing L-Ser, L-His, L-Cys and/or L-Met were manually synthesized traditionally, at 60 degrees C using conventional heating and at 60 degrees C using microwave heating. Detailed assessment of all crude peptides (in their intact and/or fully hydrolyzed forms) revealed that, except for the microwave-assisted coupling of L-Cys, all other reactions occurred with low levels of amino acid enantiomerization (<2%). Therefore, herein we (i) provide new evidences that our protocols for SPPS at 60 degrees C using conventional heating are suitable for routine use, (ii) demonstrate their appropriateness for microwave-assisted SPPS by Boc and Fmoc chemistries, (iii) disclose advantages and limitations of the three synthetic approaches employed. Thus, this study complements our past research on SPPS-ET and suggests alternative conditions for microwave-assisted SPPS.