A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress

Cisplatin and its platinum analogs, carboplatin and oxaliplatin, are some of the most widely used cancer chemotherapeutics. Although cisplatin and carboplatin are used primarily in germ cell, breast and lung malignancies, oxaliplatin is instead used almost exclusively to treat colorectal and other gastrointestinal cancers. Here we utilize a unique, multi-platform genetic approach to study the mechanism of action of these clinically established platinum anti-cancer agents, as well as more recently developed cisplatin analogs. We show that oxaliplatin, unlike cisplatin and carboplatin, does not kill cells through the DNA-damage response. Rather, oxaliplatin kills cells by inducing ribosome biogenesis stress. This difference in drug mechanism explains the distinct clinical implementation of oxaliplatin relative to cisplatin, and it might enable mechanistically informed selection of distinct platinum drugs for distinct malignancies. These data highlight the functional diversity of core components of front-line cancer therapy and the potential benefits of applying a mechanism-based rationale to the use of our current arsenal of anti-cancer drugs

Body mass index in individuals with HIV infection and factors associated with thinness and overweight/obesity

A cross-sectional study was conducted using body mass index (BMI) to estimate the prevalence of thinness and overweight/obesity and associated factors in 2,018 individuals with HIV/AIDS attending health services referral centers. The dependent variable was classified as thinness, overweight/obesity and eutrophy. Multinomial logistic regression analyses were performed considering eutrophy as the reference level. The prevalence of thinness was 8.8% and of overweight/obesity, 32.1%. The variables associated with thinness were anemia and CD4 cell count 40 years and diabetes, and the variables identified as decreasing likelihood of overweight/obesity were having no long-term partner, smoking, presence of an opportunistic disease, anemia, and albumin levels Estudo seccional para estimar a prevalência de magreza e sobrepeso/obesidade e fatores associados em 2.018 indivíduos com HIV/AIDS, atendidos em serviços de referência em Recife, Pernambuco, Brasil, utilizando o índice de massa corporal. A variável dependente foi classificada como magreza, sobrepeso/obesidade e eutrofia. Realizou-se análise de regressão logística multinomial considerando-se como referência os eutróficos. A prevalência de magreza foi de 8,8% e a de sobrepeso/obesidade de 32,1%. Permaneceram associados à magreza ter anemia e contagem de células TCD4 40 anos e presença de diabetes, e aqueles inversamente associados com sobrepeso/obesidade: não ter companheiro fixo, tabagismo, história recente de doença oportunista, anemia e níveis de albumina < 3,5mg/dL. O principal desvio nutricional observado foi o sobrepeso/obesidade, superando a magreza. Os indivíduos mais velhos com diabetes devem ser alvos de intervenções nutricionais e de estilo de vida

Prevalence of Methicillin-resistant Staphylococcus aureus in the Surgical Wards of the Port-of-Spain General Hospital, Trinidad and Tobago

Objective: Methicillin-resistant Staphylococcus aureus (MRSA) is associated with soft tissue infections in surgical patients. In severe cases, it may result in pneumonia, septicaemia and osteomyelitis. Limited data are available with regard to its prevalence and associations in the Caribbean. This study aimed to assess the prevalence of MRSA in patients hospitalized in the surgical wards of the Port-of-Spain General Hospital (POSGH), Trinidad and Tobago, and determine associated risk factors. Methods: Over the period of April 1 to August 1, 2013, all patients from the surgical wards of the POSGH who had had wound swabs taken were identified. Demographic data included duration of hospital stay, surgical and medical history, antibiotic use and type of wound swab. Microbiological reports were then retrieved and analyses done. Results: A total of 153 patients had wound swabs taken. There were 38 patients (24%) infected with Staphylococcus aureus, with 15 (39.5%) growing MRSA. Increased susceptibility to MRSA was associated with age, gender, ethnicity, duration of hospital stay, co-morbidities, previous antibiotic use, previous surgery and the type of wound (p &lt; 0.05). Conclusion: The prevalence of MRSA in the surgical wards of the POSGH was 39.5% of Staphylococcus aureus isolates. Risk factors included the age range of 60–69 years, patients with co-morbidities, hospital stays of longer than one week, previous surgery and prior use of antibiotics. We recommend more awareness of this problem in the practice of Caribbean medicine to improve infection rates.</jats:p

The breast cancer stem cell potency of copper(<scp>ii</scp>) complexes bearing nonsteroidal anti-inflammatory drugs and their encapsulation using polymeric nanoparticles

This is the first report to demonstrate that polymeric nanoparticles can be used to effectively deliver CSC-potent metal complexes into CSCs.</p