Factors to Predict Positive Results of Gonadotropin Releasing Hormone Stimulation Test in Girls with Suspected Precocious Puberty

Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty

Does Doxycycline work in synergy with cisplatin and oxaliplatin in colorectal cancer?

Background: In recent years, apart from antibacterial properties, doxycycline is reported to have cytotoxic and anti-proliferative actions in various cancers including colorectal cancer. Colorectal cancer constitutes one of the most common cancers in the western population. Apart from surgery, chemotherapy plays crucial role in the treatment of colorectal cancer. Cisplatin and oxaliplatin are most commonly used platinum compounds for the cancer chemotherapy. This study has looked for any impact of doxycycline on the cytotoxic effects of platinum compounds in colorectal cancer including its mechanisms of actions.Methods: HT 29 colorectal cancer cells were used for this study. These cells were treated with cisplatin and oxaliplatin with or without doxycycline treatment. The caspase 3 gene expression was quantitated by gel electrophoresis and qualitated by real time polymerase chain reactions. The caspase 3 activity was assessed in HT 29 cells with fluorescence kit.Results: The results revealed increased caspase 3 gene expressions and activities in HT 29 cells treated with cisplatin, oxaliplatin and doxycycline; however the combination of doxycycline with cisplatin and oxaliplatin did not report increased caspase 3 gene expressions and activity compared to cisplatin and oxaliplatin alone.Conclusion: We concluded that doxycycline has role in apoptosis induction in the colorectal cancer. However, it did not show any synergy with platinum compounds in the colorectal cancer cells. This study also pointed towards possible caspase-independent actions of doxycycline with cisplatin and oxaliplatin. However, further work is required to underpin the mechanisms of actions of doxycycline

Nitrosothiols in the immune system: Signaling and protection

Antioxidants and Redox Signaling 18.3 (2013): 288-308Significance: In the immune system, nitric oxide (NO) has been mainly associated with antibacterial defenses exerted through oxidative, nitrosative, and nitrative stress and signal transduction through cyclic GMP-dependent mechanisms. However, S-nitrosylation is emerging as a post-translational modification (PTM) involved in NO-mediated cell signaling. Recent Advances: Precise roles for S-nitrosylation in signaling pathways have been described both for innate and adaptive immunity. Denitrosylation may protect macrophages from their own S-nitrosylation, while maintaining nitrosative stress compartmentalized in the phagosomes. Nitrosothiols have also been shown to be beneficial in experimental models of autoimmune diseases, mainly through their role in modulating T-cell differentiation and function. Critical Issues: Relationship between S-nitrosylation, other thiol redox PTMs, and other NO-signaling pathways has not been always taken into account, particularly in the context of immune responses. Methods for assaying S-nitrosylation in individual proteins and proteomic approaches to study the S-nitrosoproteome are constantly being improved, which helps to move this field forward. Future Directions: Integrated studies of signaling pathways in the immune system should consider whether S-nitrosylation/denitrosylation processes are among the PTMs influencing the activity of key signaling and adaptor proteins. Studies in pathophysiological scenarios will also be of interest to put these mechanisms into broader contexts. Interventions modulating nitrosothiol levels in autoimmune disease could be investigated with a view to developing new therapiesFinanced by the Spanish Government grants CSD2007-00020 (RosasNet, Consolider-Ingenio 2010 programme), CP07/00143 (Miguel Servet programme), and PS09/00101; and PI10/0213

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

Preventing problematic internet use during the COVID-19 pandemic: consensus guidance

As a response to the COVID-19 pandemic, many governments have introduced steps such as spatial distancing and “staying at home” to curb its spread and impact. The fear resulting from the disease, the ‘lockdown’ situation, high levels of uncertainty regarding the future, and financial insecurity raise the level of stress, anxiety, and depression experienced by people all around the world. Psychoactive substances and other reinforcing behaviors (e.g., gambling, video gaming, watching pornography) are often used to reduce stress and anxiety and/or to alleviate depressed mood. The tendency to use such substances and engage in such behaviors in an excessive manner as putative coping strategies in crises like the COVID-19 pandemic is considerable. Moreover, the importance of information and communications technology (ICT) is even higher in the present crisis than usual. ICT has been crucial in keeping parts of the economy going, allowing large groups of people to work and study from home, enhancing social connectedness, providing greatly needed entertainment, etc. Although for the vast majority ICT use is adaptive and should not be pathologized, a subgroup of vulnerable individuals are at risk of developing problematic usage patterns. The present consensus guidance discusses these risks and makes some practical recommendations that may help diminish them

Dexmedetomidine sedation in ICU

Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is the newest agent introduced for sedation in intensive care unit (ICU). The sedation strategy for critically ill patients has stressed light sedation with daily awakening and assessment for neurologic, cognitive, and respiratory functions, since Society of Critical Care Medicine (SCCM) guidelines were presented in 2002. The traditional GABAergic agents, including benzodiazepines and propofol, have some limitations for safe sedatives in this setting, due to an unfavorable pharmacokinetic profile and to detrimental adverse effects (such as lorazepam associated propylene glycol intoxication and propofol infusion syndrome). DEX produces it's sedative, analgesic and cardiovascular effects through α2 receptors on the locus ceruleus (LC). Activities of LC, the tuberomammillary nucleus (TMN) are depressed and activity of the ventrolateral preoptic nucleus (VLPO) is increased during DEX sedation, which is similar in features to normal non-REM (NREM) sleep. At the same time, perifornical orexinergic activity is maintained, which might be associated with attention. This mechanism of action produces a normal sleep-like, cooperative sedation. The characteristic feature of sedation, together with a concomitant opioid sparing effect, may decrease the length of time spent on a ventilator, length of stay in ICU, and prevalence and duration of delirium, as the evidence shown from several comparative studies. In addition, DEX has an excellent safety profile. In conclusion, DEX is considered as a promising agent optimized for sedation in ICU

A Família e Educação em Saúde

O Curso de Pós-graduação em Atenção Básica em Saúde da Família, na modalidade a distância, em Mato Grosso do Sul, faz a opção metodológica de trabalhar de forma permanente o contexto real de práticas em que seus estudantes trabalhadores estão inseridos. O curso – que tem seu sistema instrucional baseado na Educação à Distância – tem o objetivo de formar profi ssionais médicos, enfermeiros e cirurgiões-dentistas integrantes das Equipes de Saúde da Família. É organizado por meio de um conjunto de cadernos, apresentados em diferentes mídias e utiliza ferramentas interativas. A Unidade de Ensino III deste curso intitula-se: A Família e Educação em Saúde e é composta por dois módulos de aprendizagem: Módulo 1 - Promoção da Saúde e Intersetorialidade na Abordagem Familiar. Módulo 2 - A Família no contexto da Atenção Primária à Saúde. O Módulo 1, Promoção da Saúde e Intersetorialidade na Abordagem Familiar, traz a discussão de como fazer abordagens de promoção e educação em saúde dirigidas ao indivíduo, à família e à comunidade. O módulo está organizado em seis seções: a primeira discute a interface Promoção de Saúde/ Educação em Saúde e a infl uência do processo histórico na compreensão do binômio Saúde/Doença. A segunda seção apresenta a evolução do processo de educação em Saúde. A terceira seção traz a discussão da necessidade de realizar Promoção em Saúde para melhorar a qualidade de vida da população. A quarta seção traz a discussão do papel do profi ssional de saúde como agente facilitador no processo de Educação em Saúde. Na seção cinco discute-se a Educação em Saúde e ações interdisciplinares. E a seção seis mostra as técnicas de Educação em saúde. O módulo tem o objetivo dar a você, desta forma, ferramentas para escolher a melhor estratégia de abordagem no processo de educação em saúde de acordo com a situação local, fatores de risco e população-alvo, além de ajudá-lo a planejar a realização de uma proposta promotora/educadora em saúde. O módulo 2: A Família no Contexto da Atenção Primária à Saúde está dividido em cinco seções. A primeira seção apresenta as políticas voltadas à atenção das famílias. A segunda seção discute conceito de família, as funções e estrutura das famílias e as transformações da família contemporânea. A terceira seção discute as situações de vulnerabilidade a que as famílias estão expostas e apresenta as etapas para se trabalhar com famílias. A quarta seção traz as tecnologias de abordagem familiar. E, fi nalmente, a quinta seção discute as ferramentas para se realizar a abordagem familiar. Com a apresentação e discussão destes conteúdos você terá a oportunidade de fazer uma refl exão a respeito de seus conhecimentos e começar a aplicar estas ferramentas na atenção de sua população. Este módulo tem os seguintes objetivos: promover a mudança do foco de atenção das equipes de saúde da família e a atenção às doenças para uma abordagem centrada no indivíduo e sua família. Estes dois módulos são fundamentais para que você tenha instrumentos efi cazes para manter e recuperar a saúde de sua comunidade. Efetivar o conceito que a estratégia de saúde da família apresenta é muito mais amplo que atender os doentes de sua área. A estratégia de saúde da família só cumprirá sua fi nalidade a partir do momento que sua população adscrita seja capaz de construir um modo de vida saudável garantindo a saúde de todos os membros da comunidade.MINISTÉRIO DA SAÚD

Expression of oestrogen receptors, ERα, ERβ, and ERβ variants, in endometrial cancers and evidence that prostaglandin F may play a role in regulating expression of ERα

<p>Abstract</p> <p>Background</p> <p>Endometrial cancer is the most common gynaecological malignancy; risk factors include exposure to oestrogens and high body mass index. Expression of enzymes involved in biosynthesis of oestrogens and prostaglandins (PG) is often higher in endometrial cancers when compared with levels detected in normal endometrium. Oestrogens bind one of two receptors (ERα and ERβ) encoded by separate genes. The full-length receptors function as ligand-activated transcription factors; splice variant isoforms of ERβ lacking a ligand-binding domain have also been described. PGs act in an autocrine or paracrine manner by binding to specific G-protein coupled receptors.</p> <p>Methods</p> <p>We compared expression of ERs, progesterone receptor (PR) and cyclooxygenase-2 (COX-2) in stage 1 endometrial adenocarcinomas graded as well (G1), moderately (G2) or poorly (G3) differentiated (n ≥ 10 each group) using qRTPCR, single and double immunohistochemistry. We used endometrial adenocarcinoma cell lines to investigate the impact of PGF2α on expression of ERs and PR.</p> <p>Results</p> <p>Full length ERβ (ERβ1) and two ERβ variants (ERβ2, ERβ5) were expressed in endometrial cancers regardless of grade and the proteins were immunolocalised to the nuclei of cells in both epithelial and stromal compartments. Immunoexpression of COX-2 was most intense in cells that were ERα^neg/low. Expression of PR in endometrial adenocarcinoma (Ishikawa) cell lines and tissues broadly paralleled that of ERα. Treatment of adenocarcinoma cells with PGF2α reduced expression of ERα but had no impact on ERβ1. Cells incubated with PGF2α were unable to increase expression of PR mRNA when they were incubated with E2.</p> <p>Conclusion</p> <p>We have demonstrated that ERβ5 protein is expressed in stage 1 endometrial adenocarcinomas. Expression of three ERβ variants, including the full-length protein is not grade-dependent and most cells in poorly differentiated cancers are ERβ^pos/ERα^neg. We found evidence of a link between COX-2, its product PGF2α, and expression of ERα and PR that sheds new light on the cross talk between steroid and PG signalling pathways in this disease.</p

Computing the wavefunction from trajectories: particle and wave pictures in quantum mechanics and their relation

We discuss the particle method in quantum mechanics which provides an exact scheme to calculate the time-dependent wavefunction from a single-valued continuum of trajectories where two spacetime points are linked by at most a single orbit. A natural language for the theory is offered by the hydrodynamic analogy, in which wave mechanics corresponds to the Eulerian picture and the particle theory to the Lagrangian picture. The Lagrangian model for the quantum fluid may be developed from a variational principle. The Euler-Lagrange equations imply a fourth-order nonlinear partial differential equation to calculate the trajectories of the fluid particles as functions of their initial coordinates using as input the initial wavefunction. The admissible solutions are those consistent with quasi-potential flow. The effect of the superposition principle is represented via a nonclassical force on each particle. The wavefunction is computed via the standard map between the Lagrangian coordinates and the Eulerian fields, which provides the analogue in this model of Huygens principle in wave mechanics. The method is illustrated by calculating the time-dependence of a free Gaussian wavefunction. The Eulerian and Lagrangian pictures are complementary descriptions of a quantum process in that they have associated Hamiltonian formulations that are connected by a canonical transformation. The de Broglie-Bohm interpretation, which employs the same set of trajectories, should not be conflated with the Lagrangian version of the hydrodynamic interpretation. The theory implies that the mathematical results of the de Broglie-Bohm model may be regarded as statements about quantum mechanics itself rather than about its interpretation.Comment: 26 page