Asymmetric post-translational modifications regulate the nuclear translocation of STAT3 homodimers in response to leukemia inhibitory factor.

STAT3 is a pleiotropic transcription factor overactivated in 70% of solid tumours. We have recently reported that inactivating mutations on residues susceptible to post-translational modifications (PTMs) in only one of the monomers (i.e. asymmetric) caused changes in the cellular distribution of STAT3 homodimers. Here, we used more controlled experimental conditions, i.e. without the interference of endogenous STAT3 (STAT3-/- HeLa cells) and in the presence of a defined cytokine stimulus (Leukemia Inhibitory Factor, LIF), to provide further evidence that asymmetric PTMs affect the nuclear translocation of STAT3 homodimers. Time-lapse microscopy for 20 min after LIF stimulation showed that S727 dephosphorylation (S727A) and K685 inactivation (K685R) slightly enhanced the nuclear translocation of STAT3 homodimers, while K49 inactivation (K49R) delayed STAT3 nuclear translocation. Our findings suggest that asymmetrically modified STAT3 homodimers could be a new level of STAT3 regulation and, therefore, a potential target for cancer therapy.

Sacsin Deletion Induces Aggregation of Glial Intermediate Filaments.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder commonly diagnosed in infants and characterized by progressive cerebellar ataxia, spasticity, motor sensory neuropathy and axonal demyelination. ARSACS is caused by mutations in the SACS gene that lead to truncated or defective forms of the 520 kDa multidomain protein, sacsin. Sacsin function is exclusively studied on neuronal cells, where it regulates mitochondrial network organization and facilitates the normal polymerization of neuronal intermediate filaments (i.e., neurofilaments and vimentin). Here, we show that sacsin is also highly expressed in astrocytes, C6 rat glioma cells and N9 mouse microglia. Sacsin knockout in C6 cells (C6Sacs-/-) induced the accumulation of the glial intermediate filaments glial fibrillary acidic protein (GFAP), nestin and vimentin in the juxtanuclear area, and a concomitant depletion of mitochondria. C6Sacs-/- cells showed impaired responses to oxidative challenges (Rotenone) and inflammatory stimuli (Interleukin-6). GFAP aggregation is also associated with other neurodegenerative conditions diagnosed in infants, such as Alexander disease or Giant Axonal Neuropathy. Our results, and the similarities between these disorders, reinforce the possible connection between ARSACS and intermediate filament-associated diseases and point to a potential role of glia in ARSACS pathology.

"Inflammatory peritonitis in a child with COVID-19″.

COVID-19 is the disease caused by SARS-COV-2 coronavirus infection (Severe acute respiratory syndrome coronavirus 2). Although its most prevalent symptoms are respiratory, there are descriptions of gastrointestinal manifestations in children, but the presentation as an acute abdomen is rare. We report the case of a 6-month-old infant who was admitted with a diagnosis of intestinal obstruction and generalized peritonitis with no apparent cause, in whom a SARS-CoV-2 rt-PCR search was positive. We have not found descriptions of similar cases in the literature so far.

Health-Related Quality of Life Outcomes in Head and Neck Cancer: Results From a Prospective, Real-World Data Study With Brazilian Patients Treated With Intensity Modulated Radiation Therapy, Conformal and Conventional Radiation Techniques.

PURPOSE: To compare global health-related quality of life (HRQoL) and overall survival (OS) in patients with head and neck cancer treated with intensity modulated radiation therapy (IMRT), conformal radiation therapy (3DCRT) or conventional radiation therapy (2DRT). METHODS AND MATERIALS: In this real-world, multi-institutional and prospective study, HRQoL outcomes were assessed using the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Head and Neck 43 (H&N43) questionnaires. Item response theory was used to generate a global HRQoL score, based on the 71 questions from both forms. The effect of treatment modality on HRQoL was studied using multivariate regression analyses. Survival was estimated using the Kaplan-Meyer method, and groups were compared by the log-rank test. RESULTS: Five hundred and seventy patients from 13 institutions were included. Median follow-up was 12.2 months. Concerning the radiation technique, 29.5% of the patients were treated with 2DRT, 43.7% received 3DCRT, and 26.8% were treated with IMRT. A higher proportion of patients receiving 2DRT had a treatment interruption of more than 5 days (69% vs 50.2% for 3DCRT and 42.5% for IMRT). IMRT had a statistically significant positive effect on HRQoL compared with 3DCRT (ß= 2.627, standard error = 0.804, P = .001) and 2DRT had a statistically significant negative effect compared with 3DCRT (ß= -5.075, standard error = 0.926, P < .001). Patients receiving 2DRT presented a worse OS (P = .01). There were no differences in OS when IMRT was compared with 3DCRT. CONCLUSIONS: IMRT provided better HRQoL than 3DCRT, which provided better HRQoL than 2DRT. Patients receiving 2DRT presented a worse OS, which might be related to more frequent treatment interruptions.

Can asymmetric post-translational modifications regulate the behavior of STAT3 homodimers?

Signal transducer and activator of transcription 3 (STAT3) is a ubiquitous and pleiotropic transcription factor that plays essential roles in normal development, immunity, response to tissue damage and cancer. We have developed a Venus-STAT3 bimolecular fluorescence complementation assay that allows the visualization and study of STAT3 dimerization and protein-protein interactions in living cells. Inactivating mutations on residues susceptible to post-translational modifications (PTMs) (K49R, K140R, K685R, Y705F and S727A) changed significantly the intracellular distribution of unstimulated STAT3 dimers when the dimers were formed by STAT3 molecules that carried different mutations (ie they were "asymmetric"). Some of these asymmetric dimers changed the proliferation rate of HeLa cells. Our results indicate that asymmetric PTMs on STAT3 dimers could constitute a new level of regulation of STAT3 signaling. We put forward these observations as a working hypothesis, since confirming the existence of asymmetric STAT3 homodimers in nature is extremely difficult, and our own experimental setup has technical limitations that we discuss. However, if our hypothesis is confirmed, its conceptual implications go far beyond STAT3, and could advance our understanding and control of signaling pathways.

Evidence on the Use of Mobile Apps During the Treatment of Breast Cancer: Systematic Review.

BACKGROUND: Cancer is a major cause of morbidity, disability, and mortality worldwide, and breast cancer is the most common cause of death in women. Different modalities of cancer treatment can have adverse effects that reduce the quality of life of patients and lead to treatment interruptions, if not managed properly. The use of mobile technologies has brought innovative possibilities for improving health care. Mobile apps can help individuals manage their own health and well-being and may also promote healthy lifestyles and information access. OBJECTIVE: The aim of this study was to identify available evidence on the use of mobile apps to provide information and facilitate communication regarding self-care management related to the adverse effects of toxicities owing to breast cancer therapy. METHODS: This systematic review includes studies which were identified using a search strategy adapted for each electronic database: CINAHL, Cochrane Library, LILACS, LIVIVO, PubMed, SCOPUS, and Web of Science. In addition, a gray literature search was performed using Google Scholar. All the electronic database searches were conducted on April 17, 2019. Two investigators independently reviewed the titles and abstracts of the studies identified and then read the full text of all selected papers. The quality of the included studies was analyzed by the Cochrane Collaboration Risk of Bias Tool and the Methodological Index for Non-Randomized Studies. RESULTS: A total of 9 studies which met the eligibility criteria-3 randomized clinical trials and 6 nonrandomized studies published in English from 2010 to 2018-were considered for this systematic review; 396 patients with breast cancer, as well as 40 experts in the medical and nursing fields, and 3 software engineers were included. CONCLUSIONS: The evidence from the studies included in this systematic review is currently limited but suggests that mobile apps for women with breast cancer might be an acceptable information source that can improve patient well-being; they can also be used to report symptoms and adverse treatment-related effects and promote self-care. There is a need to test more evidence-based apps in future randomized clinical trials.

Use of stereotactic body radiation therapy for oligometastatic recurrent prostate cancer: A systematic review.

The purpose of this study is to evaluate the effectiveness and safety of stereotactic body radiation therapy (SBRT) in the management of oligometastatic recurrent prostate cancer (PCa) by means of a systematic review. Six databases were searched (CENTRAL, Embase, LILACS, PubMed, Scopus and Web of Science). Additionally, hand-searching and grey literature search were performed. The main outcomes were progression-free survival (PFS) and toxicity rates. Androgen deprivation therapy-free survival (ADT-FS), local control, pattern of recurrence, cancer-specific survival and overall survival were also assessed. Risk of bias and quality of evidence were judged with the aid of specific tools. Fourteen studies were included, involving 661 patients and 899 lesions (561 nodal, 336 bone, 2 liver). Median PFS and ADT-FS were around 1 to 3 years. Local control rates varied from 82 to 100% among researches with low risk of bias. Acute and late grade 2 toxicity was observed in 2.4% and 1.1% of the patients, respectively. One case of acute and two cases of late grade 3 toxicity were registered. Only one randomized study addresses this topic. Although it does not meet all the eligibility criteria, it is useful for the discussion. A quantitative analysis was not possible, nor were subgroup analyses, due to the significant heterogeneity of the interventions and outcomes reported. Longer follow-up period is required. SBRT seems to be a safe approach to metastatic lesions that might provide disease control and defer androgen deprivation therapy (ADT). Local control is better when higher radiation doses are employed.

Divertículo traqueal: um relato de caso e revisão da literatura / Tracheal diverticulum: a case report and literature review

Divertículo traqueal é uma patologia benigna caracterizada por invaginações únicas ou múltiplas na parede da traqueia. Condição rara, com poucos casos relatados na literatura mundial. Tem etiologias congênita ou adquirida. A maioria dos pacientes são completamente assintomáticos durante toda a sua vida, o que justifica um pequeno número de casos na literatura. O diagnóstico é feito por Tomografia Computadorizada (preferencialmente helicoidal) de pescoço. O caso relato é de uma mulher de 55 anos, portadora de asma brônquica de difícil controle atendida no ambulatório de cirurgia torácica de um hospital público brasileiro com quadro de tosse crônica e dispneia intermitentes há cerca de dois anos. Propedêutica com broncoscopia e endoscopia digestiva alta sem achados anormais. Tomografia computadorizada de pescoço multislice detectou formação cística de conteúdo aéreo projetada para a direita da traqueia. Submetida a cervicotomia exploradora e ressecção de formação cística, ovóide, posterior ao lobo direito da tireóide, com comunicação com a traquéia. Estudo histopatológico evidenciou lesão constituída de epitélio respiratório, achado que corroborou o diagnóstico de divertículo traqueal. Essa patologia foi identificada como de causa adquirida no caso relatado, devido ao quadro de tosse crônica pela asma brônquica de difícil controle, achados compatíveis com a literatura mundial. (AU)

Tracheal diverticulum is a benign pathology characterized by single or multiple invaginations in the trachea wall. It is a rare condition, with few cases reported in the world literature. Tracheal diverticulum can be either congenital or acquired. Most patients are completely asymptomatic throughout the life, which justifies a small number of cases reported in the literature. The diagnosis is made by computed tomography multi-slice of the neck. The case report is of a asthmatic 55-year-old female, with a 2-year history of repeatedly cough and dyspnea met in thoracic surgery clinic of a brazilian public hospital. Workup with bronchoscopy and endoscopy with no abnormal findings. Computed tomography multi-slice detected a paratracheal air cyst located at the right posterolateral aspect of the trachea. The patient underwent exploratory cervicotomy and resection of a cystic lesion, ovoid, posterior the right lobe of the thyroid, with communication with the trachea. The final pathological report: respiratory epithelium in the cyst wall, a finding that corroborates the diagnosis of tracheal diverticulum. In the case reported, the tracheal diverticulum was determined as acquired, due to chronic cough by asthma, findings consistent with the literature. (AU)

Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin.

Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antiproliferative, oncolytic and neuroprotective properties. Here, we present evidence that the N-acetyl side chain plays a key role in melatonin's antiproliferative effect in HT22 and sw-1353 cells, but it does so at the expense of antioxidant and neuroprotective properties. Removal of the N-acetyl group enhances the antioxidant and neuroprotective properties of the indole, but it can lead to toxic methamphetamine-like effects in several cell lines. Inhibition of NFkB mimicked melatonin's antiproliferative and antioxidant effects, but not neuroprotection. Our results strongly suggest that neuroprotective and antiproliferative effects of melatonin rely on different parts of the molecule and are likely mediated by different mechanisms. We also predict that melatonin metabolism by target cells could determine whether melatonin inhibits cell proliferation, prevents toxicity or induces cell death (e.g. apoptosis or autophagy). These observations could have important implications for the rational use of melatonin in personalized medicine.

IL-10 release by bovine epithelial cells cultured with Trichomonas vaginalis and Tritrichomonas foetus.

Trichomonas vaginalis and Tritrichomonas foetus are parasitic protists of the human and bovine urogenital tracts, respectively. Several studies have described the cytotoxic effects of trichomonads on urogenital tract epithelial cells. However, little is known about the host cell response against trichomonads. The aim of this study was to determine whether T. foetus and T. vaginalis stimulated the release of the cytokine interleukin (IL)-10 from cultured bovine epithelial cells. To characterise the inflammatory response induced by these parasites, primary cultures of bovine oviduct epithelial cells were exposed to either T. vaginalis or T. foetus. Within 12 h after parasite challenge, supernatants were collected and cytokine production was analysed. Large amounts of IL-10 were detected in the supernatants of cultures that had been stimulated with T. foetus. Interestingly, T. vaginalis induced only a small increase in the release of IL-10 upon exposure to the same bovine cells. Thus, the inflammatory response of the host cell is species-specific. Only T. foetus and not T. vaginalis induced the release of IL-10 by bovine oviduct epithelial cells.

IL-10 release by bovine epithelial cells cultured with Trichomonas vaginalis and Tritrichomonas foetus

Trichomonas vaginalis and Tritrichomonas foetus are parasitic protists of the human and bovine urogenital tracts, respectively. Several studies have described the cytotoxic effects of trichomonads on urogenital tract epithelial cells. However, little is known about the host cell response against trichomonads. The aim of this study was to determine whether T. foetus and T. vaginalis stimulated the release of the cytokine interleukin (IL)-10 from cultured bovine epithelial cells. To characterise the inflammatory response induced by these parasites, primary cultures of bovine oviduct epithelial cells were exposed to either T. vaginalis or T. foetus. Within 12 h after parasite challenge, supernatants were collected and cytokine production was analysed. Large amounts of IL-10 were detected in the supernatants of cultures that had been stimulated with T. foetus. Interestingly, T. vaginalis induced only a small increase in the release of IL-10 upon exposure to the same bovine cells. Thus, the inflammatory response of the host cell is species-specific. Only T. foetus and not T. vaginalis induced the release of IL-10 by bovine oviduct epithelial cells.

Trichomonas vaginalis and Tritrichomonas foetus: interaction with fibroblasts and muscle cells - new insights into parasite-mediated host cell cytotoxicity.

Trichomonas vaginalis and Tritrichomonas foetus are parasitic, flagellated protists that inhabit the urogenital tract of humans and bovines, respectively. T. vaginalis causes the most prevalent non-viral sexually transmitted disease worldwide and has been associated with an increased risk for human immunodeficiency virus-1 infection in humans. Infections by T. foetus cause significant losses to the beef industry worldwide due to infertility and spontaneous abortion in cows. Several studies have shown a close association between trichomonads and the epithelium of the urogenital tract. However, little is known concerning the interaction of trichomonads with cells from deeper tissues, such as fibroblasts and muscle cells. Published parasite-host cell interaction studies have reported contradictory results regarding the ability of T. foetus and T. vaginalis to interact with and damage cells of different tissues. In this study, parasite-host cell interactions were examined by culturing primary human fibroblasts obtained from abdominal biopsies performed during plastic surgeries with trichomonads. In addition, mouse 3T3 fibroblasts, primary chick embryo myogenic cells and L6 muscle cells were also used as models of target cells. The parasite-host cell cultures were processed for scanning and transmission electron microscopy and were tested for cell viability and cell death. JC-1 staining, which measures mitochondrial membrane potential, was used to determine whether the parasites induced target cell damage. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling staining was used as an indicator of chromatin damage. The colorimetric crystal violet assay was performed to ana-lyse the cytotoxicity induced by the parasite. The results showed that T. foetus and T. vaginalis adhered to and were cytotoxic to both fibroblasts and muscle cells, indicating that trichomonas infection of the connective and muscle tissues is likely to occur; such infections could cause serious risks to the infected host.

Trichomonas vaginalis and Tritrichomonas foetus: interaction with fibroblasts and muscle cells - new insights into parasite-mediated host cell cytotoxicity

Trichomonas vaginalis and Tritrichomonas foetus are parasitic, flagellated protists that inhabit the urogenital tract of humans and bovines, respectively. T. vaginalis causes the most prevalent non-viral sexually transmitted disease worldwide and has been associated with an increased risk for human immunodeficiency virus-1 infection in humans. Infections by T. foetus cause significant losses to the beef industry worldwide due to infertility and spontaneous abortion in cows. Several studies have shown a close association between trichomonads and the epithelium of the urogenital tract. However, little is known concerning the interaction of trichomonads with cells from deeper tissues, such as fibroblasts and muscle cells. Published parasite-host cell interaction studies have reported contradictory results regarding the ability of T. foetus and T. vaginalis to interact with and damage cells of different tissues. In this study, parasite-host cell interactions were examined by culturing primary human fibroblasts obtained from abdominal biopsies performed during plastic surgeries with trichomonads. In addition, mouse 3T3 fibroblasts, primary chick embryo myogenic cells and L6 muscle cells were also used as models of target cells. The parasite-host cell cultures were processed for scanning and transmission electron microscopy and were tested for cell viability and cell death. JC-1 staining, which measures mitochondrial membrane potential, was used to determine whether the parasites induced target cell damage. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling staining was used as an indicator of chromatin damage. The colorimetric crystal violet assay was performed to ana-lyse the cytotoxicity induced by the parasite. The results showed that T. foetus and T. vaginalis adhered to and were cytotoxic to both fibroblasts and muscle cells, indicating that trichomonas infection of the connective and muscle tissues is likely to occur; such infections could cause serious risks to the infected host.

Interaction of Trichomonas vaginalis and Tritrichomonas foetus with keratin: an important role in parasite infection.

Trichomonas vaginalis and Tritrichomonas foetus are human and bovine parasites, respectively, that provoke the sexually transmitted disease trichomoniasis. These extracellular parasites adhere to the host epithelial cell surface. Although mucinases and proteases have been described as important proteins for parasite adhesion to epithelial cells, no studies have examined the role of the keratin molecules that cornify the vaginal epithelium. Here, we investigated the interaction of T. vaginalis and T. foetus with human keratin in vitro; additionally, adherence assays were performed in cattle with T. foetus to elucidate whether trichomonads were able to interact with keratin in vivo. We demonstrated that both T. vaginalisand T. foetusinteracted directly with keratin. Additionally, the trichomonads ingested and digested keratin, shedding new light on the Trichomonas infection process.

Interaction of Trichomonas vaginalis and Tritrichomonas foetus with keratin: an important role in parasite infection

Trichomonas vaginalis and Tritrichomonas foetus are human and bovine parasites, respectively, that provoke the sexually transmitted disease trichomoniasis. These extracellular parasites adhere to the host epithelial cell surface. Although mucinases and proteases have been described as important proteins for parasite adhesion to epithelial cells, no studies have examined the role of the keratin molecules that cornify the vaginal epithelium. Here, we investigated the interaction of T. vaginalis and T. foetus with human keratin in vitro; additionally, adherence assays were performed in cattle with T. foetus to elucidate whether trichomonads were able to interact with keratin in vivo. We demonstrated that both T. vaginalisand T. foetusinteracted directly with keratin. Additionally, the trichomonads ingested and digested keratin, shedding new light on the Trichomonas infection process.

Equipe interdisciplinar reduz infecção sanguínea relacionada ao cateter venoso central em Unidade de Terapia Intensiva Pediátrica / Interdisciplinary task-force reduces catheter-related bloodstream infection in a Pediatric Intensive Care Unit

OBJETIVO: Avaliar o impacto de intervenções interdisciplinares nos indicadores de infecção de corrente sanguínea relacionada ao cateter venoso central e microrganismos isolados, em uma Unidade de Terapia Intensiva Pediátrica. MÉTODOS: Estudo de intervenção do tipo antes e depois. Foi criado um programa educativo e constituída uma equipe interdisciplinar de intervenção composta por médicos e enfermeiros da unidade e do Serviço de Controle de Infecção Hospitalar. As intervenções foram compostas por medidas diretas e indiretas educativas e processuais. O período pré-intervenção (Fase 1), de junho de 2003 a maio de 2004, foi comparado ao período pós-intervenção nas Fases 2 (junho de 2004 a maio de 2005) e 3 (junho de 2005 a maio de 2006). As taxas de infecção foram comparadas por ANOVA, sendo significante p<0,05. RESULTADOS: Foram avaliados 1.234 pacientes entre 1º de junho de 2003 e 31 de maio de 2006. A densidade de incidência de infecção de corrente sanguínea relacionada ao cateter venoso central foi de 22,72 por 1.000 dias de cateter na Fase 1; diminuiu para 6,81 e 5,87 nas Fases 2 e 3, respectivamente (p<0,01) e não houve diferença entre as Fases 2 e 3. Os Gram-positivos representaram 57 por cento dos microrganismos isolados no período pré-intervenção e 45 e 58 por cento, respectivamente, nos períodos pós-intervenção. CONCLUSÕES: A abordagem educacional interdisciplinar e o estabelecimento de normas para inserção e intervenção no processo de manutenção de cateteres reduziram as taxas de infecção da corrente sanguínea relacionada ao cateter venoso central em uma Unidade de Terapia Intensiva Pediátrica.

OBJECTIVE: To determine the impact of interdisciplinary interventions on central venous catheter-related bloodstream infections rates in a Pediatric Intensive Care Unit (PICU) and on the bloodstream infection organisms. METHODS: Interventional study type before-and-after. An educational program was performed and an interdisciplinary team of interventions was created. This team was formed by nurses and doctors of the PICU and of the Infection Control Committee. The interventions were composed by direct and indirect educational and procedural measures. Task-force interventions were developed from Jun/2003 to May/2004. This pre-intervention period (Phase 1) was compared with two post-intervention periods: Phases 2 (Jun/2004 to May/2005) and 3 (Jun/2005 to May/2006). Central venous catheter-related bloodstream infection rates during the three periods were compared by ANOVA, being significant p<0.05. RESULTS: 1,234 patients were studied from June 1st 2003 to May 31, 2006. The number of central venous catheter-related bloodstream infections was 22.72 per 1,000 catheter-days in Phase 1, and 6.81 and 5.87 in Phases 2 and 3 respectively (Phase 1 vs Phase 2 and 3; p<0.001). Gram-positive organisms were isolated in 57 percent of bloodstream infections in Phase 1, and 45 and 58 percent in Phases 2 and 3, respectively. CONCLUSIONS: The interdisciplinary educational approach and the central venous catheter insertion policies were effective to reduce central venous catheter-related bloodstream infections in the Pediatric Intensive Care Unit.

Estridor na sala de parto / Stridor in the delivery room

OBJETIVO: Ressaltar a importância do estridor por anel vascular em recém-nascidos. DESCRIÇÃO DE CASO: Caso 1: recém-nascido a termo do sexo feminino, com história prévia de poli-hidrâmnio, apresentou estridor na sala de parto e necessidade de intubação orotraqueal com parâmetros ventilatórios moderados. Trouxe melhora do quadro respiratório após a inserçào de cânula traqueal além do habitual, o que motivou a investigação de compressão traqueal extrínseca. Realizado diagnóstico de duplo arco aórtico, seguido de cirurgia corretiva com boa evolução. Caso 2: menina de sete meses com estridor desde o nascimento e diagnóstico prévio de laringomalácia, com diversas internações anteriores por doenças respiratórias. Na última internação, houve melhora dos sintomas após a intubação seletiva do brônquio principal direito, sugerindo compressão extrínseca da traqueia. Após a confirmação do diagnóstico de anel vascular, foi submetida à correção cirúrgica, porém evoluiu a óbito. COMENTÁRIOS: O anel vascular não é a principal causa de estridor em recém-nascidos, mas deve ser considerado no diagnóstico diferencial. O baixo índice de suspeição dessa alteração leva a atrasos no tratamento e, como consequência, aumenta o risco de traqueomalácia e dismotilidade esofágica mesmo após a correção cirúrgica.

OBJECTIVE: To underline the importance of vascular rings causing stridor in newborns infants. CASE DESCRIPTION: Case 1: term female newborn infant with prenatal history of polyhydramnios that presented stridor in the delivery room. She was treated with endotracheal intubation and moderate ventilator settings. She improved her respiratory distress after the insertion of the endotracheal tube deeper than usual. This fact prompted the investigation of extrinsic tracheal compression. A double aortic arch was diagnosed, which had satisfactory surgical outcome. Case 2: a seven-month old girl with stridor since birth and previous diagnosis of laryngomalacia had several hospital admissions due to respiratory distress. In her last hospital stay, she improved after a selective intubation of the right main bronchus, suggesting the presence of extrinsic tracheal compression. After the diagnosis of a vascular ring, she was submitted to the surgical correction, but she died soon after surgery. COMMENTS: Vascular rings are not the main cause of upper airway obstruction in newborn infants but they should be considered in the differencial diagnosis. The low index of suspicion delays diagnosis and treatment and increases the risk of tracheomalacia and esophageal dysmotility, even after surgical repair.

Cell death induction in Giardia lamblia: effect of beta-lapachone and starvation.

Giardia lamblia is a protozoan that parasitizes the small intestine of vertebrates. It is a cause of intestinal infection and diarrhea and infects millions of people worldwide. This protozoan presents many characteristics common to eukaryotic cells but it lacks organelles found in most eukaryotes (e.g., peroxisomes, typical Golgi complex and mitochondria). Also it presents mitosomes, a relic organelle that appears to be a mitochondrial remnant. Cell death in Giardia was induced by the drug beta-Lapachone and by starvation. Giardia behavior was followed by scanning, transmission and fluorescence microscopy, quantification of cell metabolism using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide), changes in lipid rafts, using DiIC(16) and cholera toxin. Cell shrinkage, chromatin condensation, membrane blebbing and vacuolization provided ultrastructural evidence of apoptosis, whereas the myelinic figures in large vacuoles and LC-3 staining suggested an autophagic process. Lipids rafts were altered by drug treatment and co-localized with regions containing membrane blebbing. The treatment with beta-Lap induced encystation. A search for sequence similarities in databases and protein alignments was carried out. Although Giardia is an amitochondrial organism, it presented some autophagic-like cell death characteristics and several, but not all, apoptotic characteristics, induced by beta-Lapachone and starvation.