In vitro metabolism of ferroquine (SSR97193) in animal and human hepatic models and antimalarial activity of major metabolites on Plasmodium falciparum.

Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.     

Autonomous histopathological regression of primary tumours associated with specific immune responses to cancer antigens

Spontaneous histopathological regression of cancer has been reported. The involvement of the immune system in such regression has been advocated, leading to the theory of immunological surveillance against cancer. A prediction of this theory is that common tumour antigens can be recognized upon repeated exposure by cell-mediated immunity, which leads to tumour regression and the subsequent appearance of tumour antigen-loss variants. However, no direct evidence has been provided in non-viral-induced experimental animal models of primary malignancy or in human primary cancer. This study examined two groups of melanoma patients where histopathological regression of the primary tumour was observed. Many of the 23 patients with multiple (> or =3) primary melanomas showed significant regression of their last melanoma (median 33%, mean 40) compared with matched melanomas from patients with a single primary melanoma (median 0%, mean 12) (p=0.0080), or compared with their first primary melanoma (p=0.0013). Regression was consistent with an 'immunization effect' seen in murine tumour transplantation studies, where inoculation with > or =3 asynchronous tumours induces transplantation rejection on subsequent challenge. A significant decrease in the expression of the melanoma common tumour antigen MART-1 in the last primary tumour from multiple melanoma patients (median 8%, mean 24) versus matched single melanoma patients (median 79%, mean 68) (p=0.0041) and in the last versus first tumour in multiple primary patients was found (p=0.0083). Metastases from 17 patients whose primary skin melanomas had completely regressed (occult primary melanoma) also showed significant MART-1 loss (median 0%, mean 11) compared with matched metastases from patients with non-regressing primary melanoma (median 51%, mean 50) (p=0.0013). MART-1 antigen-loss variants observed in the multiple primary and occult primary patients correlated with the presence of peripheral blood MART-1-specific cytotoxic T lymphocytes (CTLs) (p=0.03). No similar effects were observed with two other melanoma antigens, gp100 and CD63. Thus, in two groups of human melanoma patients, evidence is provided for histopathological tumour regression associated with cancer immune surveillance.     

Meta-Analysis and Systematic Review of Micro- and Macro-Nutrient Intakes and Trajectories of Macro-Nutrient Supply in the Eastern Mediterranean Region

The Eastern Mediterranean Region (EMR) is experiencing a nutrition transition, characterized by the emergence of overnutrition and micro-nutrient deficiencies. No previous study has comparatively examined nutrient intake in adults across countries in the EMR. This review examined the adequacy of nutrients in adults living in the EMR. Moreover, it analyzed the food balance sheets (FBS) for 1961–2018 to identify the trajectory of energy supply from macro-nutrients in the EMR. A systematic search was conducted from January 2012 to September 2020. Only observational studies were retained with a random sampling design. An assessment of the methodological quality was conducted. Levels of nutrient daily intake and their adequacy compared to the daily reference intake of the Institute of Medicine were reported across the region. No studies were identified for half of the region’s countries. Although nutrient energy intake was satisfactory overall, fat and carbohydrate intake were high. Intake of vitamin D, calcium, potassium, zinc, and magnesium were below that recommended. The analysis of the FBS data allowed for the identification of four linear patterns of trajectories, with countries in the EMR best fitting the ‘high-energy-supply from carbohydrate’ group. This systematic review warrants multi-sectorial commitment to optimize nutrient intake.     

Prospective randomized controlled trial evaluating cap-assisted colonoscopy vs standard colonoscopy

AIM: To study the significance of cap-fitted colonoscopy in improving cecal intubation time and polyp detection rate. METHODS: This study was a prospective randomized controlled trial conducted from March 2008 to February 2009 in a tertiary referral hospital at Sydney. The primary end point was cecal intubation time and the secondary endpoint was polyp detection rate. Consecutive cases of total colonoscopy over a 1-year period were recruited. Randomization into either standard colonoscopy (SC) or cap-assist...     

TAVI: How to best predict postprocedural outcomes?

• Baseline risk scores for TAVI patients, including STS and EuroSCORE, might not predict long‐term outcomes.
• Including postprocedural data might improve risk stratification.
• The ACEF‐7 risk score includes the lowest creatinine clearance in the first 7 postprocedural days and appears to be a good predictor of worse long‐term outcomes.

     

A randomized single-blind trial of whole versus split-dose polyethylene glycol-electrolyte solution for colonoscopy preparation

BACKGROUND: Colonoscopy preparation regimens are often poorly tolerated because they require use of large-volume bowel preparation solution and diet restrictions for adequate cleansing. This study evaluated the efficacy and tolerability of a split-dose polyethylene glycol-electrolyte solution plus bisacodyl and a regular diet. METHODS: A total of 187 patients (104 men, 83 women; age range 18-91 years) were randomly assigned to receive either 3 L of polyethylene glycol-electrolyte solution (n = 96; Group A) with a liquid diet on the day before colonoscopy, or 2 L of polyethylene glycol-electrolyte solution, one tablet of bisacodyl, and a minimally restricted diet on the day before colonoscopy, and then 1 L of the same solution on the day of colonoscopy (n = 91; Group B). Acceptability, adverse events, and willingness to retake the preparation were assessed by questionnaire. The quality of the preparation was graded by an endoscopist, blinded to the type of preparation, by using a previously described scale (excellent to poor). RESULTS: There were 96 patients in Group A and 91 in Group B. Colon cleansing was significantly better in Group B with regard to the overall quality of the preparation (p lt; 0.05). Compliance was significantly higher in Group B as evidenced by the lower number of patients who discontinued the preparation (4 vs. 15; p = 0.02) because of side effects such as nausea or vomiting. The degree of discomfort, adverse events, and willingness to retake the preparation were not significantly different between the groups. CONCLUSIONS: Colonic preparation with split-dose polyethylene glycol-electrolyte provided better quality colon cleansing and higher compliance, with less dietary restrictions, than preparation with whole-dose polyethylene glycol-electrolyte.     

Lifestyle Patterns Are Associated with Elevated Blood Pressure among Qatari Women of Reproductive Age: A Cross-Sectional National Study

Women of childbearing age are particularly vulnerable to the adverse effects of elevated blood pressure (BP), with dietary and lifestyle habits being increasingly recognized as important modifiable environmental risk factors for this condition. Using data from the National STEPwise survey conducted in Qatar in year 2012, we aimed to examine lifestyle patterns and their association with elevated BP among Qatari women of childbearing age (18–45 years). Socio-demographic, lifestyle, dietary, anthropometric and BP data were used (n = 747). Principal component factor analysis was applied to identify the patterns using the frequency of consumption of 13 foods/food groups, physical activity level, and smoking status. Multivariate logistic regression analyses were used to evaluate the association of the identified lifestyle patterns with elevated BP and to examine the socio-demographic correlates of these patterns. Three lifestyle patterns were identified: a “healthy” pattern characterized by intake of fruits, natural juices, and vegetables; a “fast food & smoking” pattern characterized by fast foods, sweetened beverages, and sweets, in addition to smoking; and a “traditional sedentary” pattern which consisted of refined grains, dairy products, and meat in addition to low physical activity. The fast food & smoking and the traditional & sedentary patterns were associated with an approximately 2-fold increase in the risk of elevated BP in the study population. The findings of this study highlight the synergistic effect that diet, smoking and physical inactivity may have on the risk of elevated BP among Qatari women.