Chronic acidosis rewires cancer cell metabolism through PPARα signaling

The mechanisms linking tumor microenvironment acidosis to disease progression are not understood. Here, we used mammary, pancreatic, and colon cancer cells to show that adaptation to growth at an extracellular pH (pH_e) mimicking acidic tumor niches is associated with upregulated net acid extrusion capacity and elevated intracellular pH at physiological pH_e, but not at acidic pH_e. Using metabolic profiling, shotgun lipidomics, imaging and biochemical analyses, we show that the acid adaptation-induced phenotype is characterized by a shift toward oxidative metabolism, increased lipid droplet-, triacylglycerol-, peroxisome content and mitochondrial hyperfusion. Peroxisome proliferator-activated receptor-α (PPARA, PPARα) expression and activity are upregulated, at least in part by increased fatty acid uptake. PPARα upregulates genes driving increased mitochondrial and peroxisomal mass and β-oxidation capacity, including mitochondrial lipid import proteins CPT1A, CPT2 and SLC25A20, electron transport chain components, peroxisomal proteins PEX11A and ACOX1, and thioredoxin-interacting protein (TXNIP), a negative regulator of glycolysis. This endows acid-adapted cancer cells with increased capacity for utilizing fatty acids for metabolic needs, while limiting glycolysis. As a consequence, the acid-adapted cells exhibit increased sensitivity to PPARα inhibition. We conclude that PPARα is a key upstream regulator of metabolic changes favoring cancer cell survival in acidic tumor niches.     

Transoral robotic surgery for squamous cell carcinoma of the oropharynx in a primarily human papillomavirus-negative patient population

Transoral robotic surgery (TORS) is one of the main treatment options for non-locally advanced primary oropharyngeal cancer in the United States. However,     

Taxonomic Characterization and Secondary Metabolite Profiling of Aspergillus Section Aspergillus Contaminating Feeds and Feedstuffs

Xerophilic fungal species of the genus Aspergillus are economically highly relevant due to their ability to grow on low water activity substrates causing spoilage of stored goods and animal feeds. These fungi can synthesize a variety of secondary metabolites, many of which show animal toxicity, creating a health risk for food production animals and to humans as final consumers, respectively. Animal feeds used for rabbit, chinchilla and rainbow trout production in Argentina were analysed for the presence of xerophilic Aspergillus section Aspergillus species. High isolation frequencies (>60%) were detected in all the studied rabbit and chinchilla feeds, while the rainbow trout feeds showed lower fungal charge (25%). These section Aspergillus contaminations comprised predominantly five taxa. Twenty isolates were subjected to taxonomic characterization using both ascospore SEM micromorphology and two independent DNA loci sequencing. The secondary metabolite profiles of the isolates were determined qualitatively by HPLC-MS. All the isolates produced neoechinulin A, 17 isolates were positive for cladosporin and echinulin, and 18 were positive for neoechinulin B. Physcion and preechinulin were detected in a minor proportion of the isolates. This is the first report describing the detailed species composition and the secondary metabolite profiles of Aspergillus section Aspergillus contaminating animal feeds.     

Head-to-head comparison between the EQ-5D-5L and the EQ-5D-3L in general population health surveys

Background

The EQ-5D has been frequently used in national health surveys. This study is a head-to-head comparison to assess how expanding the number of levels from three (EQ-5D-3L) to five in the new EQ-5D-5L version has improved its distribution, discriminatory power, and validity in the general population.

Methods

A representative sample (N?=?7554) from the Catalan Health Interview Survey 2011–2012, aged ≥18, answered both EQ-5D versions, and we evaluated the response redistribution and inconsistencies between them. To assess validity of this redistribution, we calculated the mean of the Visual Analogue Scale (VAS), which measures perceived health. The discriminatory power was examined with Shannon Indices, calculated for each dimension separately. Spanish preference value sets were applied to obtain utility indices, examining their distribution with statistics of central tendency and dispersion. We estimated the proportion of individuals reporting the best health state in EQ-5D-5L and EQ-5D-3L within groups of specific chronic conditions and their VAS mean.

Results

A very small reduction in the percentage of individuals with the best health state was observed, from 61.8% in EQ-5D-3L to 60.8% in EQ-5D-5L. In contrast, a large proportion of individuals reporting extreme problems in the 3 L version moved to severe problems (level 4) in the 5 L version, particularly for pain/discomfort (75.5%) and anxiety/depression (66.4%). The average proportion of inconsistencies was 0.9%. The pattern of the perceived health VAS mean confirmed the hypothesis established a priori, supporting the validity of the observed redistribution. Shannon index showed that absolute informativity was higher in the 5 L version for all dimensions. The means (SD) of the Spanish EQ-5D-3L and EQ-5D-5L indices were 0.87 (0.25) and 0.89 (0.22). The proportion of individuals with the best health state within each specific chronic condition was very similar, regardless of the EQ-5D version (≤?30% in half of the 28 chronic conditions).

Conclusion

Although the proportion of individuals with the best possible health state is still very high, our findings support that the increase of levels provided by the EQ-5D-5L contributed to the validity and discriminatory power of this new version to measure health in general population, as in the national health surveys.

     

Facial nerve paralysis following mandibular trauma: a case report

A strong posteriorly directed force applied to the mandible resulting in fracture, can also displace the mandibular condyle towards the external auditory canal or superiorly against the mandibular fossa, causing its penetration into the middle cranial fossa or even the fracture of the temporal bone. We report the case of a 30-year-old male patient victim of a bicycle accident that developed facial expression muscles paralysis on the left side soon after the trauma. On physical examination he presented left side postauricular ecchymosis, diminished muscular tonus of the left mouth angle and difficulty to close the left eye, he did not present clinical signs of facial fractures. The neurological and CT scan examination revealed fracture of the left temporal bone with total facial expression muscles paralysis. The patient was referred to the neurosurgical team for evaluation and they opted for a conservative treatment. After 3 months the patient showed a marked improvement with almost normal facial expression muscle movements. The trauma dynamics and treatment details are discussed.     

Immediate provisionalization on a new implant design for esthetic restoration and preserving crestal bone

PURPOSE: This article describes how the concept of platform switching has been incorporated into a new implant design as a method of reducing crestal bone loss and maintaining the gingival papillae. A 6-month study of the effects of this implant on bone loss is described. MATERIALS: Ten new platform switched implants were placed into fresh anterior maxillary extraction sites in 3 men and 7 women, ranging in age between 29 and 45 years old, and immediately provisionalized. The adjoining bone height was evaluated with digital radiography on the day after implant placement, and at 15 days, 1, 2, 3, and 6 months later. RESULTS: After 6 months, the mean bone loss on the mesial of the central-incisor implants was 0.05 mm. The mean bone loss was 0.07 mm on the distal of the central incisor implants, 0.07 mm on the mesial of the lateral-incisor implants, and 0.06 mm on the distal of the lateral-incisor implants. CONCLUSIONS: An implant design that incorporates the concept of platform switching is a simple and effective way to control circumferential bone loss around dental implants, helping to ensure a predictable esthetic result.     

Diagnostic accuracy of the Phototest for cognitive impairment and dementia in Argentina

Phototest is a simple, easy and very brief test with theoretical advantages over available dementia screening tests in Spain. The objective of this study was to estimate the diagnostic accuracy of the Phototest for cognitive impairment and dementia and to compare it with that of the MMSE and the Clock Drawing Test (CDT) in an Argentine population. A phase II cross-sectional study of diagnostic tests evaluation was performed in a sample of 30 controls, 61 with amnestic mild cognitive impairment (a-MCI), and 56 with mild Alzheimer type dementia (DAT). The diagnostic accuracy (DA) was assessed in relation to the clinical diagnosis by calculating the area under the ROC curve (UAC), Sensitivity (Sn), and Specificity (Sp).The DA of the Phototest for a-MCI and DAT (0.93 and 0.97 [UAC]) was higher than that of the MMSE and the CDT. The cut-off points of 27/28 for DAT (Sn = 89.29 [78.1–96.0], Sp = 96.67 [82.8–99.9]) and 30/31 for a-MCI (Sn = 85.25 [73.8–93.0], Sp = 90.00 [73.5–97.9]) maximized the sum of Sn and Sp. Phototest correlates significantly with MMSE and CDT. The Phototest is an efficient instrument for the detection of mild dementia or MCI, with good accuracy and good correlation with tests measuring overall cognitive impairment.     

Diabetes Mellitus and Renal Transplantation in Adults: Is There Enough Evidence for Diagnosis,Treatment, and Prevention of New-Onset Diabetes After Renal Transplantation?

BackgroundNew-onset diabetes after renal transplantation (NODAT) is one of the most frequent metabolic complications after transplantation; it is present in ～25% of kidney transplant recipients, increasing their cardiovascular risk and inducing graft damage. The medical approach of this entity is still a matter of controversy, so our aim was to review the evidence available and offer a practical approach for diagnosis, treatment, and follow-up.MethodsA systematic review of the literature in the Medline, Embase, Cochrane, and Lilacs databases was carried out with the use of the terms “Diabetes Mellitus,” “Kidney Transplantation,” “Drug Therapy,” “Prognosis,” “Therapeutics,” and “Risk Factors.” Randomized controlled trials, meta-analyses, and observational studies were included.ResultsThe main risk factors were elevated body mass index, family history of diabetes, recipient >60 years old, hepatitis C virus infection, and treatment with tacrolimus/corticosteroids or sirolimus. Some small studies suggest that thiazolidinediones, sulfonylureas, glinides, and dipeptidyl peptidase 4 inhibitors could be useful in the treatment of the disease. NODAT constitutes a prognostic factor for the renal transplant. Although there is a higher risk of developing diabetes in kidney transplant recipients than in the general population, both populations share the same diagnostic criteria.ConclusionsThere is no consensus on the treatment regimen for these patients. It is necessary to review the diagnostic criteria and the screening methods for NODAT, given the higher susceptibility of kidney transplant recipients to develop this entity; therefore, an earlier intervention could be implemented to decrease the negative effects that this disease has on the kidney graft and the recipient.