Breast cancer (BC) is a global public health problem attributed to varying risk factors. The designing of a targeted screening program focused on at-risk women can be cost-effective in reducing its burden. A hospital based case control study was conducted on 138 cases of breast cancer and 169 healthy controls to investigate the reproductive and non-reproductive risk factors for breast cancer in Pakistani women. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed with unconditional logistic regression. Almost all i.e. 97.83% of cases were married (OR=5.03),70.29% were illiterate (OR=1.88), 73.19% were aged >35 years (OR=0.632) and 81.16% belonged to the poor class(OR=1.81). Early age at menarche (OR, 2.55; 95% CI 1.50-4.31, P=0.0001), hormone replacement therapy (OR=2.057, 95% CI 1.283-3.295, P= 0.002) early pregnancy (OR,2.23, 95% CI 1.29-3.88, P=0.004), history of miscarriage (OR, 2.11, 95% CI 1.32-3.39,P=0.002) & oral contraceptive use (OR, 2.76, 95% CI 1.54-4.92, P= 0.006) were significantly associated with BC. The study highlights the dire need for effective public health programs for high-risk women to address this highly fatal disease.
Le cancer du sein (BC) est un problème de santé publique mondial attribué à divers facteurs de risque. La conception d\'un programme de dépistage ciblé axé sur les femmes à risque peut s\'avérer rentable pour réduire son fardeau. Une étude cas-témoins en milieu hospitalier a été menée sur 138 cas de cancer du sein et 169 témoins sains pour étudier les facteurs de risque reproductifs et non reproductifs du cancer du sein chez les femmes pakistanaises. Les rapports de cotes (OR) et les intervalles de confiance (IC) à 95 % ont été calculés par régression logistique inconditionnelle. La quasi-totalité soit 97,83% des cas étaient mariés (OR=5,03), 70,29% étaient analphabètes (OR=1,88), 73,19% étaient âgés de >35 ans (OR=0,632) et 81,16% appartenaient à la classe pauvre (OR=1,81). . Âge précoce aux premières règles (OR = 2,55 ; IC à 95 % 1,50-4,31, P = 0,0001), traitement hormonal substitutif (OR = 2,057, IC à 95 % 1,283-3,295, P = 0,002) grossesse précoce (OR , 2,23, IC à 95 % 1,29-3,88, P=0,004), les antécédents de fausse couche (OR, 2,11, IC à 95 % 1,32-3,39, P=0,002) et l\'utilisation de contraceptifs oraux (OR, 2,76, IC à 95 % 1,54-4,92, P= 0,006) étaient significativement associé à la Colombie-Britannique. L\'étude souligne le besoin urgent de programmes de santé publique efficaces destinés aux femmes à haut risque afin de lutter contre cette maladie hautement mortelle.

Nasopharyngeal Carcinoma (NPC) is an upper respiratory tract cancer prevalent in Southeast Asia and related to chronic EBV infection. microRNAs (miRNAs) regulate gene expression implicated in NPC\'s carcinogenesis. However, this circulating RNA molecule\'s role and clinical utility remain unknown. Therefore, this study examined the circulation of miRNAs and their association with clinical data.
160 plasma samples of NPC and 80 non-tumor samples were extracted to evaluate and validate the gene expressions. Quantification expression was performed using relative quantification of qPCR analysis level expression methods. The intrinsic cellular roles involving biological signaling in NPC\'s oncogenesis using Ingenuity Pathways Analysis (IPA) were also used.
The results of the quantification significance profiling of NPC samples revealed decreased miR- 29c-3p (fold change 1.16; p<0.05) and increased 195-5p expression (fold change 1.157; p<0.05). Furthermore, the validation of hsa-miR-29c-3p expression on plasma NPC with known tumor vs. non-tumor and significant changes was also performed using a fold change of 4.45 (medians of 31.45 ± 1.868 and 24.96 ± 1.872, respectively; p<0.0005). miR-29c had a 2.14 fold change correlated with T primary status with a median of 31.99±1.319 and 31.35±2.412, respectively (p<0.05). Stage status with fold change 1.99 also had median levels of 31.98±1.105 and 31.21 ± 2.355, respectively (p-value <0.05). Furthermore, the node\'s status for the lower expression of miR-29c with fold change 1.17 had median levels of 32.78 ± 2.221 and 31.33 ± 1.689, respectively (p-value of 0.7). Bioinformatics analysis established the roles and functions of miR-29 in NPC progression, cell death and survival, cellular development, cellular function, and cell maintenance by inhibiting COL4A, PI3K, VEGFA, JUN, and CDK6.
Overall, we conclude that decreased miR-29c expression is associated with poor clinical status and might inhibit NPC\'s five target genes.

A greater comprehension of factors contributing to pleasure from food-related experiences could increase understanding of underlying processes around different eating behaviours. We explored drivers of food pleasure and whether certain consumer characteristics were associated with specific food pleasure profiles. This study aimed to investigate (1) how Danish consumers vary in terms of primary drivers of food pleasure, and (2) how differences in food pleasure are related to specific sociodemographic, lifestyle, health and eating behavioural personality traits. Three-hundred and fifty-five respondents (mean age 33.3 years) rated the importance of different drivers of food pleasure, along with sociodemographic, lifestyle, health and eating behaviour variables. Segmentation analysis was performed based on emerging food pleasure dimensions, and profiling of segments was conducted by multivariate regression analysis and calculations of odds ratios. The results demonstrated that five specific consumer segments could be defined, \'Sensory-pleasure Seekers\' (50%), \'Internal-pleasure Seekers\' (34%), \'Contextual-pleasure Seekers\' (17%), \'Exploratory-pleasure seekers\' (13%) and \'Confirming-pleasure seekers\' (5%), each with specific characteristics. Importantly, this research indicates that a link between mental health, personality, eating behaviour and perceived food pleasure is evident. These insights contribute to the comprehension of the complex nature of food choices of importance to accommodating public health issues.

A riboswitch is a type of RNA molecule that regulates important biological functions by changing structure, typically under ligand-binding. We assess the extent that these ligand-bound structural alternatives are present in the Boltzmann sample, a standard RNA secondary structure prediction method, for three riboswitch test cases. We use the cluster analysis tool RNAStructProfiling to characterize the different modalities present among the suboptimal structures sampled. We compare these modalities to the putative base pairing models obtained from independent experiments using NMR or fluorescence spectroscopy. We find, somewhat unexpectedly, that profiling the Boltzmann sample captures evidence of ligand-bound conformations for two of three riboswitches studied. Moreover, this agreement between predicted modalities and experimental models is consistent with the classification of riboswitches into thermodynamic versus kinetic regulatory mechanisms. Our results support cluster analysis of Boltzmann samples by RNAStructProfiling as a possible basis for de novo identification of thermodynamic riboswitches, while highlighting the challenges for kinetic ones.

Quantitative metrics are used to develop profiles of health care institutions, including hospitals, nursing homes, and dialysis clinics. These profiles serve as measures of quality of care, which are used to compare institutions and determine reimbursement, as a part of a national effort led by the Center for Medicare and Medicaid Services in the United States. However, there is some concern about how misclassification in case-mix factors, which are typically accounted for in profiling, impacts results. We evaluated the potential effect of misclassification on profiling results, using 20 744 patients from 2740 dialysis facilities in the US Renal Data System. In this case study, we compared 30-day readmission as the profiling outcome measure, using comorbidity data from either the Center for Medicare and Medicaid Services Medical Evidence Report (error-prone) or Medicare claims (more accurate). Although the regression coefficient of the error-prone covariate demonstrated notable bias in simulation, the outcome measure-standardized readmission ratio-and profiling results were quite robust; for example, correlation coefficient of 0.99 in standardized readmission ratio estimates. Thus, we conclude that misclassification on case-mix did not meaningfully impact overall profiling results. We also identified both extreme degree of case-mix factor misclassification and magnitude of between-provider variability as 2 factors that can potentially exert enough influence on profile status to move a clinic from one performance category to another (eg, normal to worse performer).

Direct-injection mass spectrometry (DIMS) techniques have evolved into powerful methods to analyse volatile organic compounds (VOCs) without the need of chromatographic separation. Combined to chemometrics, they have been used in many domains to solve sample categorization issues based on volatilome determination. In this paper, different DIMS methods that have largely outperformed conventional electronic noses (e-noses) in classification tasks are briefly reviewed, with an emphasis on food-related applications. A particular attention is paid to proton transfer reaction mass spectrometry (PTR-MS), and many results obtained using the powerful PTR-time of flight-MS (PTR-ToF-MS) instrument are reviewed. Data analysis and feature selection issues are also summarized and discussed. As a case study, a challenging problem of classification of dark chocolates that has been previously assessed by sensory evaluation in four distinct categories is presented. The VOC profiles of a set of 206 chocolate samples classified in the four sensory categories were analysed by PTR-ToF-MS. A supervised multivariate data analysis based on partial least squares regression-discriminant analysis allowed the construction of a classification model that showed excellent prediction capability: 97% of a test set of 62 samples were correctly predicted in the sensory categories. Tentative identification of ions aided characterisation of chocolate classes. Variable selection using dedicated methods pinpointed some volatile compounds important for the discrimination of the chocolates. Among them, the CovSel method was used for the first time on PTR-MS data resulting in a selection of 10 features that allowed a good prediction to be achieved. Finally, challenges and future needs in the field are discussed.

The instrumental characterization of volatile organic compounds (VOCs) is essential to have a precise, reliable, and reproducible estimation of food aroma and, therefore, of the overall product quality. In this report, we introduce four analytical approaches based on PTR-MS (proton transfer reaction-mass spectrometry) technology suitable to fully investigate the complexity of apple aroma. In our opinion, these proposed methodologies can be applied, with slight modification, to every kind of fruit for destructive and nondestructive rapid VOC fingerprinting.

We discovered a constitutively activating mutation (CAM) V308E for the neurotensin NT1 receptor. Molecular dynamics (MD) performed for the CAM NT1-V308E exhibiting a high spontaneous activity, and for the wild-type NT1 without basal activity, show dramatic conformational changes for the CAM. To test if the two MD models could be valuable active and inactive templates for building molecular models for other class-A GPCR, supposed active and inactive models were built by homology for the cholecystokinin CCK1 receptor. Virtual screening of a corporate library with 250 000 compounds was performed with the two CCK1 models, and a differential virtual screening analysis (DVS), led us to isolate 250 predicted agonists and 250 predicted antagonists. The two sets were merged and the compounds were tested in CCK1 agonist and antagonist cellular assays. An excellent correlation was obtained between predictions and biological results. The effective profiling provided by DVS with active and inactive molecular models, opens new perspectives for finding agonists and antagonists for other class-A GPCR, notably for orphan GPCRs for which no ligands are known.

Medicine counterfeiting is a current problem that the whole pharmaceutical field has to deal with. In 2014, counterfeits entered the legitimate supply chain in Europe. Quick and efficient action had to be taken. The aim of this paper is to explain which analytical strategy was chosen to deal with six of the cases concerned and which criteria have to be considered to provide quick and thorough information about the counterfeits. The evaluation of the packaging was performed in a first step, based on a comparison with genuine samples and evaluation of manipulation signs. Chemical methods were then used, consisting of near infrared and infrared spectroscopy, capillary zone electrophoresis and ultraviolet-visible spectrophotometry, in order to authenticate the samples and provide the chemical composition of the confirmed counterfeits. Among the 20 samples analyzed, 17 were confirmed as counterfeits. The counterfeits were the results of the manipulation of genuine samples, and one contained totally counterfeited parts. Several manipulation signs were asserted, like the addition of glue on the boxes and the vials. Genuine stolen goods had been diluted with water, while for an isolated case, a different active ingredient had been introduced in a vial. The analytical data generated were further investigated from a forensic intelligence perspective. Links could be revealed between the analyzed counterfeits, together with some interesting information about the modus operandi of the counterfeiters. The study was performed on a limited number of cases, and therefore encourages chemical and packaging profiling of counterfeits at a bigger scale. Copyright © 2015 John Wiley & Sons, Ltd.

Off-target effects of drugs on nuclear hormone receptors (NHRs) may result in adverse effects in multiple organs/physiological processes. Reliable assessments of the NHR activities for drug candidates are therefore crucial for drug development. However, the highly permissive structures of NHRs for vastly different ligands make it challenging to predict interactions by examining the chemical structures of the ligands. Here, we report a detailed investigation on the agonistic and antagonistic activities of 615 known drugs or drug candidates against a panel of 6 NHRs: androgen, progesterone, estrogen α/β, and thyroid hormone α/β receptors. Our study revealed that 4.7 and 12.4% compounds have agonistic and antagonistic activities, respectively, against this panel of NHRs. Nonetheless, potent, unintended NHR hits are relatively rare among the known drugs, indicating that such interactions are perhaps not tolerated during drug development. However, we uncovered examples of compounds that unintentionally agonize or antagonize NHRs. In addition, a number of compounds showed multi-NHR activities, suggesting that the cross-talk between multiple NHRs co-operate to elicit in vivo effects. These data highlight the merits of counter screening drug candidate against NHRs during drug discovery/development.