Atovaquone: An Inhibitor of Oxidative Phosphorylation as Studied in Gynecologic Cancers.

Oxidative phosphorylation is an active metabolic pathway in cancer. Atovaquone is an oral medication that inhibits oxidative phosphorylation and is FDA-approved for the treatment of malaria. We investigated its potential anti-cancer properties by measuring cell proliferation in 2D culture. The clinical formulation of atovaquone, Mepron, was given to mice with ovarian cancers to monitor its effects on tumor and ascites. Patient-derived cancer stem-like cells and spheroids implanted in NSG mice were treated with atovaquone. Atovaquone inhibited the proliferation of cancer cells and ovarian cancer growth in vitro and in vivo. The effect of atovaquone on oxygen radicals was determined using flow and imaging cytometry. The oxygen consumption rate (OCR) in adherent cells was measured using a Seahorse XFe96 Extracellular Flux Analyzer. Oxygen consumption and ATP production were inhibited by atovaquone. Imaging cytometry indicated that the majority of the oxygen radical flux triggered by atovaquone occurred in the mitochondria. Atovaquone decreased the viability of patient-derived cancer stem-like cells and spheroids implanted in NSG mice. NMR metabolomics showed shifts in glycolysis, citric acid cycle, electron transport chain, phosphotransfer, and metabolism following atovaquone treatment. Our studies provide the mechanistic understanding and preclinical data to support the further investigation of atovaquone's potential as a gynecologic cancer therapeutic.

Percutaneous foot surgery for the treatment of brachymetatarsia: A case report.

BACKGROUND: The term brachimetatarsia refers to an abnormal shortening of the metatarsal bones as a result of early closure of the growth plate. The deformity, which may be congenital, idiopathic or secondary to surgery or trauma, may result in functional as well as cosmetic alterations, which require correction by an orthopedic surgeon. The purpose of this report is to illustrate the possibility of treating this condition by means of a minimally invasive technique which affords results as satisfactory as those of conventional techniques but with fewer complications. We report on the case of a 35-year-old female with a diagnosis of congenital brachymetatarsia, with bilateral involvement of the fourth toe. METHODS: We present our experience of surgical correction of brachymetatarsia using percutaneous surgery. The surgical technique is illustrated by a case report with a follow-up of 2 years. RESULTS: Radiographic and cosmetic correction of the deformity were satisfactory after 9 weeks of treatment. No complications were observed during follow-up. CONCLUSIONS: Although minimally invasive surgery for treatment of brachymetatarsia is a relatively unknown or explored procedure, it provides good clinical and radiological results in experienced hands. In addition, it causes little trauma to the soft tissues, reduces operative time and allows patients a better and faster functional recovery, offering clear advantages over other techniques used for correcting this bone malformation.

New deep ocean Iravadiidae of the genus Ceratia (Caenogastropoda: Truncatelloidea) from an underwater canyon and adjacent regions of the southwestern Atlantic (northeastern Brazil).

Previous studies on the mollusks from Brazilian underwater canyons have addressed the record and description of new species of aplacophorans, bivalves, scaphopods and/or gastropods (Leal & Simone 2000; Absalão 2010; Corrêa et al. 2014). Leal & Simone (2000) described a new bathyal gastropod of the family Pseudococculinidae collected from the continental slope and Doce River Canyon (960 m) off the state of Espírito Santo (southeastern Brazil). Absalão (2010) reported a number of species of gastropods, bivalves and scaphopods from Campos Basin off the state of Rio de Janeiro (southeastern Brazil). It is likely that some of these species reported by Absalão (2010) were collected from underwater canyons in the northern portion of the Campos Basin. Corrêa et al. (2014) recorded two species of aplacophorans of the genus Falcidens Salvini-Plawen, 1968 obtained from the continental slope and underwater canyons of Campos Basin. Certainly more species of mollusks were studied from Brazilian underwater canyons, but not duly mentioned in publications (i.e., the region of canyons may have been referred to as the continental slope or deep sea).

Evaluation of the effect of dietary virgin olive oil on blood pressure and lipid composition of serum and low-density lipoprotein in elderly type 2 diabetic subjects.

Dietary virgin olive oil may help to reduce blood pressure in hypertensive individuals, but little is known about the effect on type 2 diabetic patients. For the present study, 17 type 2 diabetic elderly subjects and 23 healthy elderly controls received a diet rich in virgin olive oil for 4 weeks. Blood pressure, biochemical parameters, low-density lipoprotein (LDL), and oxidized LDL lipids and fatty acids were measured. Systolic blood pressure was reduced after virgin olive oil consumption in both controls and diabetic patients. Although the biochemical parameters were not modified, the intervention protected LDL from oxidation and restored the levels of dihomo-gamma-linolenic acid (20:3, n-6) in serum cholesterol esters and phospholipids of diabetic patients. In conclusion, the present study provides new evidence of the effects of dietary virgin olive oil on blood pressure and LDL oxidation in type 2 diabetics. It is likely that the components responsible for the observed effects are the monounsaturated fatty acids and the presence of antioxidants in the oil, but this needs further investigation.

Outcome prediction in terms of functional disability and mortality at 1 year among ICU-admitted severe stroke patients: a prospective epidemiological study in the south of the European Union (Evascan Project, Andalusia, Spain).

OBJECTIVES: To analyse 1-year mortality and functional disability outcomes and resource use in critical stroke patients admitted to ICU. DESIGN AND SETTING: Multi-centre, prospective, observational study in 28 Spanish hospitals. PATIENTS. Patients admitted for acute stroke from March-August 1999. INTERVENTION: Collection of data on: severity by Apache III and Glasgow Coma Score; neurological lesion, hospital and 1-year mortality; functional disability at 1 year by Barthel Index and Glasgow Outcome Scale; ICU length of stay, life support techniques, and neurosurgical interventions. MEASUREMENT AND RESULTS: We studied 132 patients: 21% with subarachnoid haemorrhage (SAH), 58% intracerebral haemorrhage (ICH), 20% ischaemic stroke (ISC); Apache III 63+/-29 ICU stay 13+/-12 days; 74% required mechanical ventilation. Hospital and 1-year mortality was 33% (22%:ISC, 32%:SAH, 37%:ICH) and 53.8% (66%:ISC, 39%:SAH, 54%:ICH), respectively. Age, APACHE III, and diagnosis defined hospital mortality. Age, APACHE III, and Glasgow Coma Score defined 1-year mortality. Barthel Index score improved ( P<0.001) between discharge and 1 year; 73% of patients presented severe disability at discharge vs. 26% at 1 year; 8% minimal/no disability at discharge vs. 43.3% at 1 year. Only 17% of subarachnoid haemorrhage patients presented severe disability at 1 year. Admission Apache III and hospital-discharge Barthel Index scores were related to functional outcome at 1 year. CONCLUSIONS: Critical stroke patients are characterized by high severity of illness, elevated resource consumption, and poor outcomes that are mainly influenced by severity and age. Glasgow Coma Score-measured neurological severity is the main determinant of future functional capacity, which is greater at 1 year.

Actividad sanitaria durante la operación Alfa-Charlie en Centroamérica

En el presente artículo se expone la actividad sanitaria desarrollada por el Servicio de Sanidad del Buque "Pizarro" en diferentes países de Centroamérica en enero de 1999, afectados por el huracán "Mitch" (AU)