A method to enhance 2D ion chamber array patient specific quality assurance for IMRT. Diaz Moreno RM, Venencia D, Garrigo E, Pipman Y. Australas Phys Eng Sci Med. 2016 Nov 21. [Epub ahead of print]

Gamma index comparison has been established as a method for patient specific quality assurance in IMRT. Detector arrays can replace radiographic film systems to record 2D dose distributions and fulfill quality assurance requirements. These electronic devices present spatial resolution disadvantages with respect to films. This handicap can be partially overcome with a multiple acquisition sequence of adjacent 2D dose distributions. The detector spatial response influence can also be taken into account through the convolution of the calculated dose with the detector spatial response. A methodology that employs both approaches could allow for enhancements of the quality assurance procedure. 35 beams from different step and shoot IMRT plans were delivered on a phantom. 2D dose distributions were recorded with a PTW-729 ion chamber array for individual beams, following the multiple acquisition methodology. 2D dose distributions were also recorded on radiographic films. Measured dose distributions with films and with the PTW-729 array were processed with the software RITv5.2 for Gamma index comparison with calculated doses. Calculated dose was also convolved with the ion chamber 2D response and the Gamma index comparisons with the 2D dose distribution measured with the PTW-729 array was repeated. 3.7 ± 2.7% of points surpassed the accepted Gamma index when using radiographic films compared with calculated dose, with a minimum of 0.67 and a maximum of 13.27. With the PTW-729 multiple acquisition methodology compared with calculated dose, 4.1 ± 1.3% of points surpassed the accepted Gamma index, with a minimum of 1.44 and a maximum of 11.26. With the PTW- multiple acquisition methodology compared with convolved calculated dose, 2.7 ± 1.3% of points surpassed the accepted Gamma index, with a minimum of 0.42 and a maximum of 5.75. The results obtained in this work suggest that the comparison of merged adjacent dose distributions with convolved calculated dose represents an enhancement in the methodology for IMRT patient specific quality assurance with the PTW-729 ion chamber array.

Association between non-perfusion parameters and presence of ischemia in gated-SPECT myocardial perfusion imaging studies. Peix A, Cabrera LO, Padrón K, Rodríguez L, Fernández J, López G, et al.

Background Combined assessment of perfusion and function improves diagnostic and prognostic power of gated-SPECT in patients with coronary artery disease. The aim of this study was to investigate whether the presence of stress-induced ischemia is associated with abnormal resting left ventricular (LV) function and intraventricular dyssynchrony. Methods and Results Gated-SPECT myocardial perfusion imaging (MPI) at rest and 15 min post-stress was performed in 101 patients, who were divided into three groups: those with stress-induced ischemia (Group 1, n = 58), those with normal scans (Group 2, n = 28), and those with scar but no ischemia (Group 3, n = 15). More extensive perfusion defects were found in patients of Groups 1 and 3 [Summed stress score (SSS): 13 ± 8 and 21 ± 9, respectively]. In Group 2, the mean SSS was 1.5. The mean change in LV ejection fraction (LVEF at stress – LVEF at rest) was higher in Group 1 v. Group 2 patients: -5.54% ± 6.24% vs -2.46% ± 5.56%, p = 0.02. Group 3 patients also had higher values, similar to Group 1: -6.47% ± 8.82%. Patients with ischemia had almost 50% higher end-diastolic volumes than patients with normal MPI. Similarly, end-systolic volumes were almost twice as high in this group (p < 0.0001). In addition, the histogram bandwidth, a measure of intraventricular dyssynchrony, was greater in Group 1. Conclusions Baseline differences in left ventricular volumes and degree of dyssynchrony are associated with inducible ischemia on stress testing in a gated-SPECT MPI. Stress-induced ischemia increases the degree of intraventricular dyssynchrony.

Corticomuscular Coherence: A Novel Tool to Assess the Pyramidal Tract Dysfunction in Spinocerebellar Ataxia Type 2. Velázquez-Pérez L, Tünnerhoff J, Rodríguez-Labrada R, Torres-Vega R, Belardinelli P, Medrano-Montero J, et al. Cerebellum. 2016 Oct 11. [Epub ahead of print]

Clinical signs of corticospinal tract dysfunction are a common feature of spinocerebellar ataxia type 2 (SCA2) patients. The objective of this study is to assess dysfunction of the corticospinal tract in SCA2 using corticomuscular coherence. Testing corticomuscular coherence and rating of ataxia severity and non-ataxia symptoms were performed in 19 SCA2 patients and 24 age-matched controls. Central motor conduction times (CMCT) to upper and lower right limbs were obtained for the SCA2 group using transcraneal magnetic stimulation (TMS). SCA2 patients exhibited a significant reduction of corticomuscular coherence for lower limbs, but not for upper limbs. This difference remained significant, even when excluding those individuals with clinical signs of corticospinal tract dysfunction. Corticomuscular coherence for lower limbs correlated inversely with CMCT to tibialis anterior muscle. Corticomuscular coherence could be a valuable electrophysiological tool to assess the corticospinal tract involvement in SCA2, even in the absence of clinical signs of corticospinal tract dysfunction.

Eating Behaviors in Cuban Adults: Results from an Exploratory Transcultural Study. Front Psychol. 2016 Sep 26;7:1455. eCollection 2016. Rodríguez-Martín BC, Innamorati M, Imperatori C, Fabbricatore M, Harnic D, Janiri L, et al.

This study aims to investigate eating behaviors in Cuban adults and compare them with those of a developed Western country, Italy. The study also aimed to determine the overall accuracy of a predictive model intended to define variables which could be used to discriminate between nationalities. Participants were 283 normal weight individuals from Cuba (n = 158) and Italy (n = 125). Italians had higher scores for restrained eating on the questionnaire than Cubans with a considerable effect size. This trend was also found for emotional eating and binge eating, as well as number of current dieters, despite the fact that effect sizes were small. On the other hand, Cubans, when compared to Italians reported higher scores for food thought suppression with reward responsiveness and restrained eating emerging as significant predictors of between-country differences. To conclude, eating behaviors in Cubans could be different from those reported in European countries, perhaps as a consequence of Cuba’s recent history.

Diversity and bias through dopamine D2R heteroreceptor complexes. Borroto-Escuela DO, Fuxe K. Curr Opin Pharmacol. 2016 Nov 10;32:16–22. DOI: 10.1016/j.coph.2016.10.004. [Epub ahead of print]

The D2R is a hub receptor interacting with a large number of other GPCRs. A2AR activation of the antagonistic A2AR-D2R interaction not only leads to inhibition of the Gi/o signaling but also to an increase in β-arrestin2 signaling over the D2R protomer. Hallucinogenic 5-HT2AR agonists can produce a biased agonist state at the 5-HT2AR protomer of D2R-5-HT2AR heteroreceptor complexes with increased D2R recognition and Gi/o mediated signaling. Allosteric receptor-receptor interactions in D2-NTR1 heteroreceptor complexes inhibit D2R function and can switch G protein coupling. These large numbers of D2R heterocomplexes and their allosteric receptor-receptor interactions produce a marked increase in diversity and bias of the participating D2R protomers opening a promised land for drug development in schizophrenia, addiction and Parkinson’s disease.

Endoscopic versus laparoscopic treatment for choledocholithiasis: a prospective randomized controlled trial. Barreras González JE, Torres Peña R, Ruiz Torres J, Martínez Alfonso MA, Brizuela Quintanilla R, Morera Pérez M. Endosc Int Open. 2016 Nov;4(11):E1188–E93.

Background and study aims Overall, 5 % to 15 % of patients undergoing cholecystectomy for cholelithiasis have concomitant bile duct stones, and the incidence of choledocholithiasis increases with age. There is no clear consensus on the best therapeutic approach (endoscopic versus surgical). Patients and methods A prospective randomized controlled clinical trial was performed to compare three treatment options for patients with choledocholithiasis at the National Center for Minimally Invasive Surgery in Havana, Cuba from November 2007 to November 2011. The patients were randomized in three groups. Group I: patients who underwent intraoperative cholangiography (IOC) to confirm the choledocholithiasis followed by laparoscopic cholecystectomy (LC) associated with intraoperative endoscopic retrograde cholangiopancreatography (ERCP), group II: patients who underwent preoperative ERCP followed by LC during the same hospital admission and group III: patients who underwent IOC to confirm the choledocholithiasis followed by LC associated with laparoscopic common bile duct exploration (LCBDE). Results A total of 300 patients with suspected choledocholithiasis were included in the trial and were randomized. As a result, a total of 134 patients were diagnosed with the presence of choledocholithiasis and treated during the study period. There were no significant differences in success rates of ductal stone clearance, but retained stone, postoperative complications and length of hospital stay were better in group I. Conclusions Intraoperative ERCP/ES shows a higher rate of common bile duct stones clearance, a shorter hospital stay, and lower morbidity, but further research with a larger study population is necessary to determine the additional benefits of this procedure. The results to date suggests that in appropriate patients, single-stage treatments are the best options.

“Hearing faces and seeing voices”: Amodal coding of person identity in the human brain. Awwad Shiekh Hasan B, Valdes-Sosa M, Gross J, Belin P. Sci Rep. 2016 Nov 24;6:37494. DOI: 10.1038/srep37494

Recognizing familiar individuals is achieved by the brain by combining cues from several sensory modalities, including the face of a person and her voice. Here we used functional magnetic resonance (fMRI) and a whole-brain, searchlight multi-voxel pattern analysis (MVPA) to search for areas in which local fMRI patterns could result in identity classification as a function of sensory modality. We found several areas supporting face or voice stimulus classification based on fMRI responses, consistent with previous reports; the classification maps overlapped across modalities in a single area of right posterior superior temporal sulcus (pSTS). Remarkably, we also found several cortical areas, mostly located along the middle temporal gyrus, in which local fMRI patterns resulted in identity “cross-classification”: vocal identity could be classified based on fMRI responses to the faces, or the reverse, or both. These findings are suggestive of a series of cortical identity representations.

Improvement in liver histology due to lifestyle modification is independently associated with improved kidney function in patients with non-alcoholic steatohepatitis. Vilar-Gomez E, Calzadilla-Bertot L, Friedman SL, Gra-Oramas B, Gonzalez-Fabian L, Villa-Jiménez O, et al.
Aliment Pharmacol Ther. 2016 Nov 16. DOI: 10.1111/apt.13860. [Epub ahead of print]

Background Several recent studies have shown a strong association between non-alcoholic steatohepatitis (NASH) and chronic kidney disease. Aim To examine the relationship between changes in liver histology and renal function in patients with NASH. Methods The present analysis represents a post hoc analysis of a recently published trial that included 261 patients with NASH who were treated with lifestyle modifications during 52 weeks. Kidney function was evaluated through Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rates (eGFR, mL/min/1.73 m2) overtime. We explored correlations between the kidney function and improvement in histological outcomes at 52 weeks. Results Interestingly, a one-stage reduction in fibrosis (r = 0.20, P < 0.01) and resolution of NASH (r = 0.17, P < 0.01) were significantly correlated with an improvement in the kidney function. The eGFR values significantly increased in patients with fibrosis improvement (+7.6 ± 6.5 mL/min/1.73 m2), compared to those without fibrosis improvement (−1.98 ± 6.4 mL/min/1.73 m2) (P < 0.01) at end of treatment (EOT). Likewise, NASH resolution was associated with an increase in eGFR compared with patients without NASH resolution (2.32 ± 7.8 mL/min/1.73 m2 vs. −1.04 ± 5.9 mL/min/1.73 m2, P = 0.04) at EOT. After controlling for the confounders, the association between fibrosis improvement, NASH resolution and eGFR change remained significant (P < 0.05 for both). Conclusions Improvement in liver histology due to lifestyle modification is independently associated with improved kidney function in NASH. As new drugs for NASH emerge, studies should address whether improvement in histology in response to pharmacotherapies yield the same improvement in kidney function as weight loss.

Morbidity, utilization of curative care and service entry point preferences in metropolitan Centro Habana, Cuba. Rodríguez A, Díaz A, Balcindes S, García R, Vos P, Stuyft PV. Cad Saude Publica. 2016 Nov;32(10):e00108914. DOI: 10.1590/0102-311X00108914

First-line health services with a primary health care approach are a strong trigger for adequate health-care-seeking behavior. Research on the association between prevalence of chronic diseases and acute illnesses and use of health services emphasizes the importance of socioeconomic determinants in such patterns of utilization. In a cross-sectional study of 408 families in Centro Habana, Cuba, home interviews were conducted between April and June 2010 to analyze socio-demographic determinants of acute and chronic health problems and use of formal health services. Bivariate and logistic regression models were used. 529 persons reported a chronic disease. During the previous month, 155 of the latter reported an exacerbation and 50 experienced an unrelated acute health problem. 107 persons without chronic diseases reported acute health problems. Age was the strongest determinant of chronic disease prevalence. Adult women and the elderly were more likely to report acute problems. Acute patients with underlying chronic disease used formal services more often. No socio-demographic variable was associated with services use or consultation with the family physician. While the family physician is defined as the system’s entry-point, this was the case for only 54% of patients that had used formal services, thus compromising the physician’s role in counseling patients and summarizing their health issues. The importance of chronic diseases highlights the need to strengthen the family physician’s pivotal role. New economic policies in Cuba, stimulating self-employment and private initiative, may increase the strain on the exclusively public health care system. Still, the Cuban health system has demonstrated its ability to adapt to new challenges, and the basic premises of Cuba’s health policy are expected to be preserved.

Mycobacterium smegmatis proteoliposome induce protection in a murine progressive pulmonary tuberculosis model. Tirado Y, Puig A, Álvarez N, Borrero R, Aguilar A, Camacho F, et al. Tuberculosis. 2016 Dec;101:44–8.

Tuberculosis (TB) remains an important cause of mortality and morbidity. The TB vaccine, BCG, is not fully protective against the adult form of the disease and is unable to prevent its transmission although it is still useful against severe childhood TB. Hence, the search for new vaccines is of great interest. In a previous study, we have shown that proteoliposomes obtained from Mycobacterium smegmatis (PLMs) induced cross reactive humoral and cellular response against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLMs, a murine model of progressive pulmonary TB was used. Animals immunized with PLMs with and without alum (PLMs/PLMsAL respectively) showed protection compared to non-immunized animals. Mice immunized with PLMsAL induced similar protection as that of BCG. Animals immunized with BCG, PLMs and PLMsAL showed a significant decrease in tissue damage (percentage of pneumonic area/lung) compared to non-immunized animals, with a more prominent effect in BCG vaccinated mice. The protective effect of the administration of PLMs in mice supports its future evaluation as experimental vaccine candidate against Mtb.

The association of low birth weight with serum C reactive protein in 3-year-old children living in Cuba: A population-based prospective study. Venero-Fernández J, Fundora Hernández H, Batista-Gutiérrez L, Suárez-Medina R, de la C Mora-Faife E, García-García G, et al. Am J Hum Biol. 2016 Nov 18. DOI: 10.1002/ajhb.22936. [Epub ahead of print]

Objective Low birthweight is associated with a decreased risk of childhood leukemia and an increased risk of both cardiovascular disease and all-cause mortality in adult life. Possible biological mediators include systemic innate immunity and inflammation. We tested the hypothesis that birthweight was inversely associated with serum high sensitivity C reactive protein assay (hsCRP), a measure of both innate immunity and systemic inflammation. Methods Data on birthweight and current anthropometric measures along with a range of exposures were collected at 1 and 3 years of age in a population-based cohort study of young children living in Havana, Cuba. A total of 986 children aged 3-years-old provided blood samples that were analyzed for serum hsCRP levels. Results Nearly 49% of children had detectable hsCRP levels in their serum. Lower birthweight was linearly associated with the natural log of hsCRP levels (beta coefficient -0.70 mg L-1 per kg increase in birthweight, 95% CI: -1.34 to -0.06). This was attenuated but still present after adjustment for the child’s sex and municipality (-0.65 mg L-1 per kg birthweight; 95% CI: -1.38 to +0.08). There were no associations between growth from birth or anthropometric measures at 3 years and systemic inflammation. Conclusions Birthweight was inversely associated with serum hsCRP levels in children aged 3 years living in Cuba. These observations provide a potential mechanism that is present at the age of 3 years to explain the association between low birthweight and both decreased childhood leukemia and increased cardiovascular disease in adults.