Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

A new approach for blood pressure estimation based on phonocardiogram

Continuous and non-invasive measurement of blood pressure (BP) is of great importance particularly for patients in critical state. To achieve continuous and cuffless BP monitoring, pulse transit time (PTT) has been reported as a potential parameter. Nevertheless, this approach remains very sensitive, cumbersome and disagreeable in ambulatory measurement. This paper proposes a new approach to estimate blood pressure through PCG signal by exploring the correlation between PTT and diastolic duration (S21). In this purpose, an artificial neural network was developed using as input data: (systolic duration, diastolic duration, heart rate, sex, height and weight). According to the NN decision, the mean blood pressure was measured and consequently the systolic and the diastolic pressures were estimated. The proposed method is evaluated on 37 subjects. The obtained results are satisfactory, where, the error in the estimation of the systolic and the diastolic pressures compared to the commercial blood pressure device was in the order of 6 .48 ± 4.48 mmHg and 3 .91 ± 2.58 mmHg, respectively, which are very close to the AAMI standard, 5 ± 8 mmHg. This shows the feasibility of estimating of blood pressure using PCG.

Proliferating Trichilemmal Tumor of the Knee Mimicking Prepatellar Bursitis on Ultrasonogram: A Case Report

Proliferating trichilemmal tumor is a rare benign tumor of skin appendage. It is usually solitary, more common in women after the fourth decade of life, and almost exclusively confined to the scalp and back of the neck. We report herein an unusual case of proliferating trchilemmal tumor which occurred on the knee.

The how's and why's of evidence based plasma therapy

Although traditionally fresh frozen plasma (FFP) has been the product of choice for reversing a significant coagulopathy, the modern blood bank will have several different plasma preparations which should all be equally efficacious in reversing a significant coagulopathy or arresting coagulopathic bleeding. Emerging evidence suggests that for a stable patient, transfusing plasma for an INR< or =1.5 does not confer a hemostatic benefit while unnecessarily exposing the patient to the risks associated with plasma transfusion. This review will discuss the various plasma products that are available and present some of the current literature on the clinical uses of plasma.

Métodos de investigación molecular en la detección de mutaciones germinativas en cáncer colorrectal hereditário / Molecular research methods in the detection of germinal mutations in hereditary colorectal cancer

El cáncer colorrectal (CCR) es una de las principales causas de muerte por neoplasia en países sudamericanos. Las formas hereditarias de CCR son, poliposis adenomatosa familiar (FAP) y cáncer colorrectal hereditario sin poliposis (HNPCC) o Síndrome de Lynch (SL), que es la forma más común. La detección de mutaciones en los genes de reparo de ADN (MMR) y en el gen APC permite el desarrollo de estrategias de prevención. Algunas de estas metodologías de diagnóstico molecular son aplicadas para la investigación y detección de mutaciones en estos genes, tales como el Test de la Proteína Truncada (PTT), Análisis de polimorfismos de conformación de cadena simple (SSCP), Cromatografia liquida desnaturante de alta performance (DHPLC) y Reacción en Cadena de la Polimerasa (PCR) en tiempo real (qPCR).

Colorectal cancer (CRC) is one of the main causes of death in South American countries. The hereditary forms of CRC are, familial adenomatous (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome (LS), which is the most common form. The detection of mutations in the DNA repair genes (MMR) and in the APC genes enables the development of prevention strategies. Some of these methods for molecular diagnosis are applied in research and the detection of mutations of these genes, such as the partial thromboplastin time test (PTT), the single strand conformational polymorphism test (SSCP), the Denaturing High Performance Liquid Chromatography test (DHPLC) and the Polymerase Chain Reaction (PCR) in real time (qPCR).

Development of a Wearable Pulse Transit Time Monitoring Device / 대한의료정보학회지

OBJECTIVES: We have developed a non.intrusive continuous PTT monitoring system, using a wearable device and wireless communication technology. METHODS: Pulse transit time (PTT) is a non.invasive measurement that shows promise in the continuous monitoring of blood pressure (BP) and the assessment of arterial stiffness. It has potential applications in wearable health monitoring devices. Generally, PTT is measured from the electrocardiogram (ECG) Rwave to a characteristic point on the peripheral pulse by photoplethysmography. However, for home healthcare applications, a system needs to be wearable and wireless. ECG and PPG were sampled at 1200 Hz and transmitted to a personal computer (PC) using Bluetooth communications. Heart rate (HR) and PTT were calculated by the PC from the signals received and waveforms of ECG, PPG, PTT and HR were displayed. RESULTS: In this study, we implemented a system that could be adapted to the wrist and measured ECG and a Photoplethysmogram (PPG). CONCLUSIONS: The wearable continuous PTT monitoring system developed in this study could be useful in home cardiovascular healthcare.

Efecto de la vitamina E en el proceso de hemostasia de individuos sanos / Effect of vitamin E in haemostasis of healthy individuals

La vitamina E (VE) es una vitamina liposoluble que actúa como antioxidante y ha sido asociada a tiempos prolongados de sangramiento en individuos sanos. El objetivo del siguiente trabajo fue evaluar el efecto de la VE en el proceso de coagulación de personas sanas. Fueron incluidos en el estudio 211 individuos sanos sin historia de enfermedades que comprometieran la hemostasia y separados en dos grupos dependiendo de la ingesta o no de VE. Los datos epidemiológicos de cada paciente así como el tiempo de protrombina (PT) y el tiempo parcial de tromboplastina (PTT) fueron recolectados. Todos los datos fueron analizados mediante el programa estadístico SPSS versión 13.0 y las medias comparadas usando la prueba estadística t de student. 114 individuos consumian al menos 400mgrs diarios de VE por un lapso no menor de 3 meses (75 mujeres y 39 hombres, edad promedio de 53.82+1.7 años) y 97 individuos que no consumian VE (55 mujeres y 42 hombres, edad media de 54.29+1.9 años) fueron incluidos como grupo control. El grupo que consumía VE mostró valores de PT estadísticamente mayores que los controles (p=0.001) (14.3+0.23seg y 13.2+0.23seg respectivamente). Así mismo, los valores de PTT del grupo VE estuvieron estadísticamente por encima de los pacientes control (p<0.0001) (31.19+0.33seg y 28.69+0.18seg respectivamente). El presente estudio sugiere que el consumo contínuo de VE podría alterar los valores de PT y PTT en individuos sanos y por tal razón modificar el proceso de coagulación normal

Vitamin E (VE) is a fat-soluble vitamin that acts as an antioxidant and it has been associated to prolonged bleeding in healthy individuals. The aim of this study was to evaluate the effect of VE in haemostasis. 211 healthy individuals were included and separated into groups depending on the VE ingest. Epidemiological data, prothrombin time (PT) and activated partial thromboplastin time (PTT) were collected. Data was analysed using SPSS 13.0 and means compared by t student test. 114 individuals consuming VE regularly (75 women and 39 men, mean age 53.82+1.7 years) and 97 controls (55 women and 42 men, mean age 54.29+1.9 years) were evaluated. VE group showed PT values significantly higher (p=0.001) than controls (14.3+0.23sec and 13.2+0.23sec respectively), as well as statically augmented PTT times (p<0.0001) (31.19+0.33sec 28.69+0.18sec respectively). VE may alter PT and PTT values in healthy people and therefore modifies haemostasis

A Comparative Coagulopathic Study for Treatment of Vasospasm by Using Low- and High-molecular Weight Hydroxyethyl Starches

OBJECTIVE: High-molecular-weight hydroxyethyl starch (HES) compromises blood coagulation more than does low-molecular-weight HES. We compared the effects of low- and high-molecular-weight HES for the treatment of vasospasm and investigated the dose relationship with each other. METHODS: Retrospectively, in a series of consecutive 102 patients with subarachnoid hemorrhage (SAH), 35 patients developed clinical symptoms of vasospasm of these fourteen patients were treated with low-molecularweight HES for volume expansion while the other 21 received high-molecular-weight HES as continuous intravenous infusion. Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen level, and platelet count were all measured prior to initiation, during treatment and after termination of therapy for symptomatic vasospasm. The total dose of HES ranged from 5 L to 14 L and median infusion duration was 10 days. RESULTS: A more pronounced PTT prolongation was observed in high-molecular-weight HES group compared with low-molecular-weight HES group. No other coagulation parameters were altered. Dosage (=duration) shows a positive correlation with PTT. Clinically, significant bleeding episodes were noted in four patients who received high-molecular-weight HES. CONCLUSION: Coagulopathy was developed in direct proportion to molecular weight of starch and dosages. We propose the extreme caution in the administration of HES solution for the vasospasm treatment.

Germline Mutation of BRCA2 Gene in Korean Breast / Ovarian Cancer Families / 대한암학회지

PURPOSE: Recent discovery of BRCA1 and BRCA2 genes has made it possible to perform presymptomatic diagnosis in hereditary breast/ovarian cancer families. We have previously reported germline mutations of the BRCA1 gene in Korean hereditary breast/ovarian cancer families. In that study two out of 13 families were found to have germline mutations in BRCA1 gene. One was a nonsense mutation in codon 1815, and the other was a frameshift mutation due to 2 base-pair deletion in codon 1701 of BRCA1 gene. This study was intended to identify germline mutations of the BRCA2 gene in Korean breast/ovarian cancer families. MATERIALS AND METHODS: Peripheral blood DNA was obtained from 10 breast cancer patients registered at the Korean Hereditary Tumor Registry with positive family history of breast and/or ovarian cancer. Exons 11 and 27 of the BRCA2 gene(together accounting for 50% of the coding region of the BRCA2 gene) were amplified by polymerase chain reaction(PCR) and screened for mutations by in vitro transcription/translation method. For confirmation of the mutations, automatic sequencing of the PCR products displaying abnormal truncated protein bands was perfomed. RESULT: We identified an abnormal truncated protein in the exon 11 of the BRCA2 gene from a member of hereditary breast cancer family, SNU-B4. Sequencing analysis revealed a 4 bp deletion in codons 1248-49 of the exon 11, resulting in frameshift that led to premature stop codon and truncation of the protein product. CONCLUSION: We have identified a germline mutation from a Korean hereditary breast cancer family. So far only one case of the same mutation has been registered in Database of BRCA2 mutation (BIC) by a commercial genetic diagnosis company, Myriad Genetics, Inc. Identification of the germline mutation in BRCA2 gene should aid in the accurate presymptomatic diagnosis of the at-risk members in this family.

Avaliação da coagulação sanguínea em gestantes da maternidade escola Assis Chateaubriand - MEAC / Blood coagulation on pregnant women in the maternidade escola Assis Chateaubriand - MEAC

Com o objetivo de avaliar a coagulação sanguinea em gestantes da maternidade Escol a ASsis Chateaumbriand (MEAC), no periodo de 25 de janeiro a 25 de maio de 1992, foi analisado o plasma de 22 gestantes e 30 mulheres não grávidas que serviu como grupo de controle. Ficou evidenciado que os testes hemostáticos (tempo de protrombina, tempo parcial de de tromboplastina e tempo de trombina) resultaram em um aumento da coagulação com a diminuição da média dos tempos de coagulação, quando comparado ao grupo controle. O número de plaquetas dominuiu, com média de 175.545/mm3 na 26a semana para 148.727/mm3 na 36a semana de gestação. A concentração do fibrinogênio aumentou consideravelmente de 310mg/dl para 465,4mg/dl. Diante deste resultado, ficou evidente que o estudo é concordante com a literatura, onde as mudanças hemostáticas durante a gravidez levam a um estado de hipercoagulabilidade.