Rational Identification of a Colorectal Cancer Targeting Peptide through Phage Display

Colorectal cancer is frequently diagnosed at an advanced stage due to the absence of early clinical indicators. Hence, the identification of new targeting molecules is crucial for an early detection and development of targeted therapies. This study aimed to identify and characterize novel peptides specific for the colorectal cancer cell line RKO using a phage-displayed peptide library. After four rounds of selection plus a negative step with normal colorectal cells, CCD-841-CoN, there was an obvious phage enrichment that specifically bound to RKO cells. Cell-based enzyme-linked immunosorbent assay (ELISA) was performed to assess the most specific peptides leading to the selection of the peptide sequence CPKSNNGVC. Through fluorescence microscopy and cytometry, the synthetic peptide RKOpep was shown to specifically bind to RKO cells, as well as to other human colorectal cancer cells including Caco-2, HCT 116 and HCT-15, but not to the normal non-cancer cells. Moreover, it was shown that RKOpep specifically targeted human colorectal cancer cell tissues. A bioinformatics analysis suggested that the RKOpep targets the monocarboxylate transporter 1, which has been implicated in colorectal cancer progression and prognosis, proven through gene knockdown approaches and shown by immunocytochemistry co-localization studies. The peptide herein identified can be a potential candidate for targeted therapies for colorectal cancer.info:eu-repo/semantics/publishedVersio

Brain functional connectivity is altered in patients with Takotsubo Syndrome

Takotsubo syndrome (TTS) is an acute, reversible cardiomyopathy. The central autonomic nervous system (ANS) is believed to play a role in this disease. The aim of the present study was to investigate the patterns of brain functional connectivity in a sample of patients who had experienced a previous episode of TTS. Brain functional connectivity, both at rest and in response to the stressful stimulus of topical cold stimulation, was explored using functional magnetic resonance imaging (fMRI), network-based statistics (NBS) and graph theory analysis (GTA) in a population consisting of eight patients with a previous episode of TTS and eight sex- and age-matched controls. At rest, a network characterized by increased connectivity in the TTS group compared to controls and comprising elements of the central ANS was identified. GTA revealed increased local efficiency, clustering and strength in regions of the bilateral hippocampus in subjects with a previous episode of TTS. When stressed by local exposure to cold, the TTS group differed significantly from both a pre-stress baseline interval and from the control group, showing increased connectivity in a network that included the left amygdala and the right insula. Based on the results, patients with TTS display a reorganization of cortical and subcortical networks, including areas associated with the emotional response and autonomic regulation. The findings tend to support the hypothesis that a deregulation of autonomic control at the central level plays a significant role in this syndrome.info:eu-repo/semantics/publishedVersio

The correlation between serum vascular endothelial growth factor (VEGF) and tumor VEGF receptor 3 in colorectal cancer

PURPOSE: Despite plasma biomarkers offering a number of advantages over tissue-based markers, the relationship between serum vascular endothelial growth factor (VEGF) and VEGF receptor (VEGF-R) tumor expression in colorectal cancer (CRC) is still unclear. This study was designed to establish the relationship between the concentration of serum VEGF and tumor VEGF-R expression in patients with CRC. METHODS: A prospective study of consecutive patients undergoing elective colorectal surgery during 1 year. Preoperative VEGF was determined by enzyme-linked immunosorbent assay and VEGF-R3 by immunochemistry. RESULTS: The initial sample included 134 patients with CRC diagnosis. Results showed significant association of serum values of VEGF with VEGF-R3 expression (P < 0.001), even in the presence of confounders (sex, age, body mass index, tumor location, and surgical approach). The estimated effect size was high (η2 = 0.35). CONCLUSION: Serum VEGF has a significant correlation with tumoral VEGF-R3 expression in CRC.info:eu-repo/semantics/publishedVersio

Accuracy of the new rapid test for monitoring adalimumab levels

The loss of response to adalimumab (ADL) has been related to low serum concentrations at trough. Currently, most methods commercially available for the quantification of ADL are enzyme-linked immunosorbent assay (ELISA) based, with a turnaround time of approximately 8 h, delaying the target dosage adjustment to the subsequent infusion. In this study, we aimed to evaluate the performance of the newly available rapid-test ADL quantification assay by comparing it with three established ELISA methods, using spiked samples and a set of clinical samples.info:eu-repo/semantics/publishedVersio

Eosinophilic fasciitis: an atypical presentation of a rare disease

Eosinophilic fasciitis, or Shulman's disease, is a rare disease of unknown etiology. It is characterized by peripheral eosinophilia, hypergammaglobulinemia, and high erythrocyte sedimentation rate. The diagnosis is confirmed by a deep biopsy of the skin. The first line of treatment is corticotherapy. We present a rare case of eosinophilic fasciitis in a 27-year-old woman with an atypical presentation with symmetrical peripheral edema and a Groove sign. The patient responded well to treatment with corticosteroids at high doses and, in this context, was associated with hydroxychloroquine and azathioprine. After two and a half years, peripheral eosinophilia had increased, and more of her skin had hardened. At that time, the therapy was modified to include corticoids, methotrexate, and penicillamine. It is of great importance to publicize these cases that allow us to gather experience and better treat our patients.info:eu-repo/semantics/publishedVersio

Endoscopic Submucosal Dissection for the Treatment of Superficial Epithelial Gastric Neoplasia in a Portuguese Centre

BACKGROUND: The emergence of endoscopic submucosal dissection (ESD) made possible en bloc resection of neoplastic gastric lesions, regardless of lesion size, with reduced rates of complications and recurrence. This technique has become the preferred method for curative resection, instead of conventional endoscopic mucosal resection and surgery, when distant metastases have negligible risk. In Western countries experience with this technique has evolved quickly, with an increasing number of case series reported in the literature. This study aims to report the short- and long-term outcomes of ESD in gastric epithelial neoplastic lesions by a single operator in a Portuguese centre. METHODS: A retrospective analysis of all gastric ESDs in a tertiary specialised unit during a 5-year period, between May 2012 and September 2017, was performed. RESULTS: A total of 114 ESDs of gastric epithelial lesions were performed during this period; 96.5% of them were removed en bloc and 87.6% with R0 resection. A curative treatment was achieved in 83.2% of the cases. Complications occurred in 13.2% of the procedures, including early and delayed bleeding in 12 patients (10.5%) and one perforation (0.9%). With a median follow-up period of 12 months (interquartile range [IQR] = 18), 6 cases of recurrence at the previous ESD site were diagnosed: 4 residual lesions and 2 local recurrences in previous R0 resections. Residual lesions occurred more often in patients with larger lesions (median = 40.0 mm, IQR = 26 vs. median = 20.0 mm, IQR = 15, p = 0.008) and with positive horizontal margins (HMs) after resection (50.0 vs. 0.0%, Fisher exact test, p < 0.001). The cumulative incidence of metachronous gastric lesions at 34 months was 16.1%. All new lesions were effectively treated using an endoscopic technique. The disease-specific survival at 12 months was 100%. CONCLUSION: This study showed that ESD is an effective resection technique for gastric lesions with a good safety profile, confirming other European series. Regardless, high en bloc resection positive HM is still a problem in some specimens resected by ESD. Endoscopic surveillance can detect local recurrence and new lesions during early stages, potentially treatable by endoscopy.info:eu-repo/semantics/publishedVersio

Magnetic resonance imaging of cerebellar cysts in a neonate with congenital cytomegalovirus infection

Congenital cytomegalovirus infection is one of the most common congenital viral infections in the world. Brain magnetic resonance imaging plays a key role in evaluating brain involvement and establishing prognosis; several characteristic features have been described. We present a description of cerebellar cysts in a neonate with polymerase chain reaction-confirmed cytomegalovirus congenital infection, and discuss the differential diagnosis and potential pathophysiological mechanisms.info:eu-repo/semantics/publishedVersio

Quality of life in elderly Portuguese war veterans with post-traumatic stress symptoms

BACKGROUND: Studies show that post-traumatic stress symptoms among Portuguese veterans who participated in Colonial War (1961-75) are high, even though 43 years have gone by since the end of the war. AIMS: This study analyzed the role of family type, personality traits, and social support as predictors of post-traumatic stress symptoms and quality of life in war veterans, and whether satisfaction with social support was a mediator between neuroticism/post-traumatic stress symptoms and quality of life. METHOD: A cross-sectional study was conducted including 230 war veterans with a mean age of 60 years (SD=3.82). RESULTS: Results indicated a high prevalence of post-traumatic stress symptoms as well as high neuroticism, 16.5 (SD=4.41); 81% of veterans presented high psychological distress, suggesting emotional disturbance and 71% belonged to extreme families (families with cohesion and adaptability problems). Results showed that age (β=-0.166, p<0.05), social support (β=-0.184, p<0.01), and neuroticism (β=0.325, p<0.001) predicted post-traumatic stress symptoms. Age, professional status, social support, post-traumatic stress symptoms, family type, neuroticism, and extroversion predicted different dimensions of quality of life. Finally, a path analysis showed that satisfaction with social support was a mediator in the relationship between neuroticism and quality of life (β=-0.066; p<0.01) and between post-traumatic stress symptoms and quality of life (β=-0.108; p<0.01). CONCLUSION: Four decades after the Colonial War have passed, there is still a high prevalence of post-traumatic stress symptoms. Screening elderly veterans who present post-traumatic stress symptoms, for the presence of neuroticism traits, and assessing family type and social support, should be a standard practice in health care services, especially in the oldest and those who are retired. Social support should be promoted in order to enhance quality of life in this population.info:eu-repo/semantics/publishedVersio

Easy resolution of severe obstructive kidney injury

Chronic constipation is a common diagnosis with a high prevalence in the elderly. Constipation affects the quality of life of sick individuals, bringing several clinical complications.info:eu-repo/semantics/publishedVersio

Prevalência de Crianças Portuguesas Expostas ao Fumo Ambiental do Tabaco em Casa e no Carro

Introduction: Children’s exposure to secondhand smoke is a cause of serious health problems and infant morbidity. This is the first nationally representative study conducted in Portugal to describe the prevalence of children exposed to secondhand smoke at home and in the car. Material and Methods: This is a descriptive cross-sectional study with a representative sample of 2396 Portuguese children aged 0 to 9 years old, stratified by age and administrative region NUTS II. Questionnaires were administered between January and September 2016. Results: Results showed that 6.1% of mothers and 11.2% of fathers reported smoking at home. It was found that 4.5% of mothers and 8.3% of fathers reported smoking in the car. Results also showed that 5.4% of children were double exposed to secondhand smoke at home and in the car. Children whose parents were smokers and had a lower level of education were more exposed to secondhand smoke at home. Discussion: Children’s exposure to secondhand smoke has been decreasing in Portugal. Parental smoking and a low educational level were risk factors for children’s exposure to secondhand smoke at home. Conclusion: The main source of children’s exposure to secondhand smoke is parental smoking. As such, it is crucial to implement effective measures to control parental smoking. It is necessary to promote smoking cessation among parents and to ban smoking inside the car.info:eu-repo/semantics/publishedVersio