Relationship between Meta-Cognitive Beliefs and Mindfulness with Ruminative Thoughts in Students

The purpose of this study was to investigate the relationship among meta-cognitive beliefs, mindfulness and ruminative thoughts in post-secondary students. The Mindful Attention Awareness Scale (MAAS) and Ruminative Response Style Scale (RRS) were completed by 381 students who were selected using multi-stage cluster sampling from the Islamic Azad University of Bojnoord, Iran. The results showed a negative correlation between metacognitive beliefs and rumination (P < 0.01), while positive and significant correlation with mindfulness and ruminative thoughts (P < 0.01).     

Adjustment process in Iranian women with breast cancer

Breast cancer is a devastating event for a woman. Physical changes and psychological problems, treatment to improve the patient's condition, and increased survival rates compared with other cancers manifest the importance of quality of life in these patients. This quality of life is affected by how the patients adjust to their situation. Hence, to understand adjustment to breast cancer, this research aimed to investigate the experience from the patients' perspective and how they interact with others and interpret their experiences in adjusting to the disease. A qualitative research approach based on grounded theory was used. The data were the result of 45 interviews with patients in different phases of their illness trajectory during 1 year, 6 interviews with families, and 10 observation sessions. The main categories that emerged were perceived threat to live, religious aspects, supportive dimensions, will to recover, increase in endurance, barriers to efforts leading to health, living with the disease with tolerance, and inhibitors and facilitators of tolerance. These main categories were understood as passages to reach evolutionary peaceful coexistence. Adjustment to breast cancer has positive evolutional process, and its direction is toward better adjustment. By positive mental reconstruction, the patients feel that they can live with their disease.     

Three simple steps during closed laparoscopic entry may minimize major injuries

Objectives  To describe three steps: (1) the initial Veress pressure (VIP-Pressure), (2) transient high-pressure pneumoperitoneum (HIP-Entry) prior to trocar/cannula insertion, and (3) visual entry with a trocarless cannula during closed laparoscopic entry, which may reduce major injuries. Design  Prospective observational cohort study (Canadian Task Force Classification II-2). Setting  University-affiliated teaching hospital. Interventions  VIP-Pressure. During laparoscopic entry, the initial VIP pressure was measured and correlated against the body habitus and parity of 365 consecutive women. HIP-Entry was performed in 2,498 consecutive cases. In 100 women, the CO₂ volume, heart rate, blood pressure, oxygen saturation, and pulmonary compliance were recorded at pressures of 10, 15, 20, 25, and 30 mmHg. Visual entry with a trocarless blunt cannula was performed in 776 women. The cannula, housing a 0° laparoscope, was rotated clockwise applying minimal downward force. Measurements and results  VIP-Pressure. Pneumoperitoneum was established after one, two or three Veress needle attempts at the umbilicus in 82.4%, 10.9%, and 4.0% of women, respectively. In seven (2.2%), pneumoperitoneum was established at the left upper quadrant (LUQ) during the fourth attempt, and in two (0.6%) entry was abandoned. Median initial Veress pressure was 4 mmHg (range 2–10 mmHg). The VIP pressure correlated positively with women’s weight (r = 0.518, p < 0.001) and body mass index (BMI) (r = 0.545, p < 0.001), and negatively with parity (r = −0.179, p < 0.001). HIP-Entry. The abdomen was insufflated to 25−30 mmHg prior to primary trocar/cannula insertion. There were no changes in cardiovascular parameters between 15 and 30 mmHg. A 21% decrease in pulmonary compliance from 15 to 30 mmHg was of no clinical significance. No injury has been experienced with the visual cannula in 776 cases. Conclusions  (1) A VIP-Pressure (<10 mmHg) indicates intraperitoneal placement of the Veress needle. (2) The use of transient HIP-Entry does not adversely affect cardiopulmonary function in healthy women. (3) Visual cannula offers an additional step towards safer entry.     

Dendritic cell paucity in mismatch repair–proficient colorectal cancer liver metastases limits immune checkpoint blockade efficacy

Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair–proficient (pMMR) CRCs make up about 95% of metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models of orthotopic pMMR CRC liver metastasis accurately recapitulate the inefficacy of ICB therapy in patients, whereas the same pMMR CRC tumors are sensitive to ICB therapy when grown subcutaneously. To reveal local, nonmalignant components that determine CRC sensitivity to treatment, we compared the microenvironments of pMMR CRC cells grown as liver metastases and subcutaneous tumors. We found a paucity of both activated T cells and dendritic cells in ICB-treated orthotopic liver metastases, when compared with their subcutaneous tumor counterparts. Furthermore, treatment with Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 ligand (Flt3L) plus ICB therapy increased dendritic cell infiltration into pMMR CRC liver metastases and improved mouse survival. Lastly, we show that human CRC liver metastases and microsatellite stable (MSS) primary CRC have a similar paucity of T cells and dendritic cells. These studies indicate that orthotopic tumor models, but not subcutaneous models, should be used to guide human clinical trials. Our findings also posit dendritic cells as antitumor components that can increase the efficacy of immunotherapies against pMMR CRC.

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment in recent years. Anti–PD1 (anti–programmed cell-death protein 1) and anti–CTLA-4 (anti–cytotoxic T lymphocyte-associated protein 4) are two main types of ICB therapies that can be particularly effective (1). Metastatic melanoma, which was previously an incurable disease, now has cure rates of more than 50% when patients are treated with a combination of anti–PD1 and anti–CTLA-4 (2). However, ICB therapy is only effective in less than 15% of patients who receive the therapy (3), and efforts are ongoing to uncover the underlying mechanisms of intrinsic and acquired resistance.Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States (4) and in the world (5). Metastatic spread, especially to the liver, is a major cause of mortality in patients with CRC (6). The efficacy of ICB therapy in metastatic CRCs has been limited to patients with mismatch repair–deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, where a 55% objective response rate has been achieved (7). However, dMMR or MSI-H metastatic CRCs represent only about 5% of total metastatic CRC cases. The remaining 95% are mismatch repair–proficient (pMMR) or microsatellite stable (MSS) tumors (8), which are typically unresponsive to ICB therapy (8). Therefore, there is an urgent need to better understand the resistance mechanisms in pMMR and MSS metastatic CRCs, and improve the efficacy of treatments against this disease.Preclinical mouse models of cancer are effective tools for studying and improving cancer therapy. MC38 and CT26 are syngeneic mouse CRC cell lines commonly used in preclinical immunocompetent mouse models of cancer. In most preclinical studies, these cells are injected under the skin into the hind flank of mice, where they grow as subcutaneous tumors. When treated with ICB therapies such as anti–PD1 and/or anti–CTLA-4, these tumors have been shown to respond well (9, 10). However, MC38 and CT26 lack coding somatic mutations in the DNA mismatch repair genes and should be considered as pMMR CRC cell lines (11, 12). Hence, experimental preclinical models using subcutaneously implanted pMMR CRC cell lines fail to recapitulate the disease resistance to ICB therapy that is observed in patients.We hypothesized that orthotopic pMMR CRC mouse models, where pMMR CRC cells are implanted in the colon to represent primary colon tumors or in the liver to represent liver metastases, would more accurately recapitulate progression of the human disease and its response to ICB treatment in the clinic. Indeed, we report here strikingly different sensitivities to ICB treatment for pMMR CRC tumors grown orthotopically when compared with their subcutaneous counterparts. We further take advantage of these differences to define local nonmalignant components that determine the sensitivity of pMMR CRCs to treatment.     

In Vitro Analysis of CsA-Induced Hepatotoxicity in HepG2 Cell Line: Oxidative Stress and α2 and β1 Integrin Subunits Expression

Background

Cyclosporine A (CsA)-induced hepatotoxicity could be due to a reduction in α2β1 integrin expression that may either be from the direct effect of CsA itself or from reactive oxygen species (ROS) overproduction.

Objectives

In this study we aimed to identify the cellular mechanisms underlying CsA-induced hepatic injury by investigating the activation patterns of the antioxidant enzymes, using HepG2 as an in vitro model.

Materials and Methods

HepG2 cells were cultured with different concentrations of CsA (0, 0.1, 1, 10 μg/ml) for 72 h. Effect of CsA on, 1) cellular integrity, 2) glutathione reductase (GR) and glutathione peroxidase (GPx) activity, 3) cellular levels of glutathione (GSH), 4) intracellular ROS, 5) ALT and AST activities, 6) urea production and 7) α2β1 integrin expression were assayed.

Results

CsA treatment demonstrated a dose dependent increase in intracellular levels of ROS, GPx activity and decrease in GSH levels (P<0.05). GR activity was mildly attenuated in 1 and 10 µg/ml concentrations of CsA. Alanine aminotranferase (ALT) and aspartate aminotransferase (AST) levels increased in CsA treated cells, while urea synthesis was significantly decreased following treatment with higher concentrations of CsA (P<0.05). Significant down-regulation of β1integrin expression was observed in 1 and 10 µg/ml CsA treated cells while α2 integrin mRNA was significantly down-regulated in all CsA treated cells.

Conclusions

The observed reduction of α2β1 integrin expression following CsA treatment could be proposed as a possible pathway of CsA-induced hepatotoxicity. Further studies are required to elucidate whether this attenuated expression is due to the direct effect of CsA or caused by overproduction of ROS.     

Immunophenotypic Characterization of Peripheral Blood T-Lymphocytes and Their Subpopulations in Tuberculosis Patients before and after Treatments

Tuberculosis is a chronic mycobacterial infection. The main effector cells against mycobacterium tuberculosis are CD4+ T lymphocytes. Our objective in this research was to evaluate the quantity of T lymphocytes and their subpopulations before and after treatments with combination of 4 drugs (Rifampcin, Isoniaside, pyrasinamide, Ethambutal) for 2 months directly in sputum-positive tuberculosis patients. Twenty patients as cases and twenty healthy people were selected as controls. Flow cytometry was used for TCD3+, TCD4+ and TCD8+ lymphocytes by using monoclonal antibodies. Our results indicated that there was alteration in cell mediated immunity during tuberculosis showing itself as decrease in TCD3+ and TCD4+ lymphocytes and increase in TCD8+ lymphocytes. The changes in TCD3+ and TCD4+ but not in TCD8+ were reversible after 2 months of treatment.