FASN-dependent de novo lipogenesis is required for brain development.

Fate and behavior of neural progenitor cells are tightly regulated during mammalian brain development. Metabolic pathways, such as glycolysis and oxidative phosphorylation, that are required for supplying energy and providing molecular building blocks to generate cells govern progenitor function. However, the role of de novo lipogenesis, which is the conversion of glucose into fatty acids through the multienzyme protein fatty acid synthase (FASN), for brain development remains unknown. Using Emx1Cre-mediated, tissue-specific deletion of Fasn in the mouse embryonic telencephalon, we show that loss of FASN causes severe microcephaly, largely due to altered polarity of apical, radial glia progenitors and reduced progenitor proliferation. Furthermore, genetic deletion and pharmacological inhibition of FASN in human embryonic stem cell-derived forebrain organoids identifies a conserved role of FASN-dependent lipogenesis for radial glia cell polarity in human brain organoids. Thus, our data establish a role of de novo lipogenesis for mouse and human brain development and identify a link between progenitor-cell polarity and lipid metabolism.

A prospective study on tumour response assessment methods after neoadjuvant endocrine therapy in early oestrogen receptor-positive breast cancer.

BACKGROUND: Neoadjuvant endocrine therapy (NET) in oestrogen receptor-positive (ER+) /HER2-negative (HER2-) breast cancer allows real-time evaluation of drug efficacy as well as investigation of the biological and molecular changes that occur after estrogenic deprivation. Clinical and pathological evaluation after NET may be used to obtain prognostic and predictive information of tumour response to decide adjuvant treatment. In this setting, clinical scales developed to evaluate response after neoadjuvant chemotherapy are not useful and there are not validated biomarkers to assess response to NET beyond Ki67 levels and preoperative endocrine prognostic index score (mPEPI). METHODS: In this prospective study, we extensively analysed radiological (by ultrasound scan (USS) and magnetic resonance imaging (MRI)) and pathological tumour response of 104 postmenopausal patients with ER+ /HER2- resectable breast cancer, treated with NET for a mean of 7 months prior to surgery. We defined a new score, tumour cellularity size (TCS), calculated as the product of the residual tumour cellularity in the surgical specimen and the tumour pathological size. RESULTS: Our results show that radiological evaluation of response to NET by both USS and MRI underestimates pathological tumour size (path-TS). Tumour size [mean (range); mm] was: path-TS 20 (0-80); radiological-TS by USS 9 (0-31); by MRI: 12 (0-60). Nevertheless, they support the use of MRI over USS to clinically assess radiological tumour response (rad-TR) due to the statistically significant association of rad-TR by MRI, but not USS, with Ki67 decrease (p = 0.002 and p = 0.3, respectively) and mPEPI score (p = 0.002 and p = 0.6, respectively). In addition, we propose that TCS could become a new tool to standardize response assessment to NET given its simplicity, reproducibility and its good correlation with existing biomarkers (such as ΔKi67, p = 0.001) and potential added value. CONCLUSION: Our findings shed light on the dynamics of tumour response to NET, challenge the paradigm of the ability of NET to decrease surgical volume and point to the utility of the TCS to quantify the scattered tumour response usually produced by endocrine therapy. In the future, these results should be validated in independent cohorts with associated survival data.

European value-based healthcare benchmarking: moving from theory to practice.

BACKGROUND: Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. METHODS: In the VOICE community-a European healthcare centre cluster intending to address VBHC from theory to practice-information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. RESULTS: Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. CONCLUSIONS: To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions.

Validation of the 10-Item Unilateral Vocal Fold Paralysis-Handicap Index quality of life questionnaire.

OBJECTIVES: To validate and test the reliability of the 10-Item Unilateral Vocal Fold Paralysis-Voice Handicap Index (UVFP-HI-10) quality of life (QoL) questionnaire for patients with UVFP. DESIGN: Prospective describe study based on perceptive surveys. PARTICIPANTS: We recruited 61 patients with UVFP and 53 healthy individuals comprised the control group. MAIN OUTCOME MEASURES: Both the patients and controls completed the UVFP-HI-10 questionnaire. A statistical analysis was performed to assess the internal consistency and validity of the survey. In addition, maximum phonation time (MPT) was used to objectively measure patient QoL. RESULTS: Internal consistency was high (α = .914) and the correlation with MPT was significant (rs = -0.722). The estimated marginal mean in the discriminant validity study was around seven times higher in the UVFP group compared to the controls. The UVFP-HI-10 cut-off value was more than 0.9 and the sensitivity and specificity were more than 0.8. CONCLUSIONS: The UVFP-HI-10 is a self-administered patient-reported outcome questionnaire with a high reliability and excellent criterion-based validity. This questionnaire can be used to evaluate specific clinical complaints (e.g., vocalisation, swallowing, and breathing) in terms of their impact on QoL in patients with UVFP. Thus, its use is appropriate as a basic assessment tool as part of a specific UVFP treatment protocol.

Home-hospital care for children with acute illnesses: A 2-year follow-up study.

AIM: Procedures normally performed in the hospital setting are increasingly delivered as part of hospital at home (HAH) programmes. The aim of this study is to describe the procedures and diseases treated during the first 2 years of a new paediatric HAH programme. METHODS: This is a retrospective, observational study conducted in the HAH programme of Niño Jesús Children's Hospital (Spain). We included demographic data, diagnosis and procedures delivered to patients admitted to the HAH programme from November 2018 to November 2020. RESULTS: There were 935 admissions of 833 patients. The median age was 5 years (interquartile range 2.3-9.5). Seventy-five percent of patients were previously healthy. The most frequent illnesses were acute infections (37%) (e.g. complicated appendicitis and ENT, genitourinary, skin and soft tissue infections) and acute respiratory diseases (17.3%) (e.g. asthma, bronchiolitis and pneumonia). Thirty-six percent of admissions underwent nocturnal polysomnography. The median length of stay was 4 days (SD 4.9 days). Eight percent of the episodes studied required care in the emergency department due to condition worsening (55.3%) and problems with devices (36.1%). Hospital readmission was required in 5.6% of cases, 42.4% of which later resumed care in the HAH. The estimated daily cost of HAH is 330.65 euros, while the hospital per-day costs of polysomnography, asthma and endovenous therapy are 1899.24, 1402.5, and 976.26 euros. Ninety percent of families reported a high level of satisfaction. CONCLUSIONS: Paediatric HAH programmes are a feasible, cost-effective alternative to hospital care. Further studies should compare the evolution of patients treated in the traditional hospital setting and those in HAH.

Paternal safety of the use of mycophenolic acid in kidney transplant recipients. Results of the EMVARON study.

BACKGROUND: The use of mycophenolic acid (MPA) in women during pregnancy causes an increase in miscarriages and birth defects with a typical embryopathy profile. Although epidemiological data does not suggest a greater risk among the offspring of male kidney transplant recipients, the European Medicines Agency and The Spanish Agency of Medicines and Medical Devices introduced the recommendation of using contraceptive methods. METHODS: We conducted a national retrospective study in 15 Spanish Kidney Transplant Centers to evaluate the frequency of miscarriages and birth defects between the offspring from male kidney transplants recipients. We included 151 males who had fathered 239 offspring, 225 under MPA and 14 without MPA. RESULTS: The results of our study showed an incidence of miscarriages in the MPA group of 9.8%, and of birth defects of 4%. CONCLUSIONS: We observed an incidence of miscarriages between the offspring fathered by kidney transplant males under MPA lower than the general population. The incidence of birth defects was similar to the incidence described in other studies and the fact that we did not find the typical embryopathy profile makes it difficult to associate them to the use of MPA. Because of that, we urge the European and Spanish Agencies to reconsider their recommendations for males.

What is the radiation before 5G? A correlation study between measurements in situ and in real time and epidemiological indicators in Vallecas, Madrid.

BACKGROUND: Exposure of the general population to electromagnetic radiation emitted by mobile phone base stations is one of the greater concerns of residents affected by the proximity of these structures due to the possible relationship between radiated levels and health indicators. OBJECTIVES: This study aimed to find a possible relationship between some health indicators and electromagnetic radiation measurements. METHODS: A total of 268 surveys, own design, were completed by residents of a Madrid neighborhood surrounded by nine telephone antennas, and 105 measurements of electromagnetic radiation were taken with a spectrum analyzer and an isotropic antenna, in situ and in real - time, both outside and inside the houses. RESULTS: It was shown statistically significant p - values in headaches presence (p = 0.010), nightmares (p = 0.001), headache intensity (p < 0.001), dizziness frequency (p = 0.011), instability episodes frequency (p = 0.026), number of hours that one person sleeps per day (p < 0.001) and three of nine parameters studied from tiredness. Concerning cancer, there are 5.6% of cancer cases in the study population, a percentage 10 times higher than that of the total Spanish population. DISCUSSION: People who are exposed to higher radiation values present more severe headaches, dizziness and nightmares. Moreover, they sleep fewer hours.

Compact Exposimeter Device for the Characterization and Recording of Electromagnetic Fields from 78 MHz to 6 GHz with Several Narrow Bands (300 kHz).

A novel compact device with spectrum analyzer characteristics has been designed, which allows the measuring of the maximum power received in multiple narrow frequency bands of 300 kHz, recording the entire spectrum from 78 MHz to 6 GHz; the device is capable of measuring the entire communications spectrum and detecting multiple sources of electromagnetic fields using the same communications band. The proposed device permits the evaluation of the cross-talk effect that, in conventional exposimeters, generates a mistake estimation of electromagnetic fields. The device was calibrated in an anechoic chamber for far-fields and was validated against a portable spectrum analyzer in a residential area. A strong correlation between the two devices with a confidence higher than 95% was obtained; indicating that the device could be considered as an important tool for electromagnetic field studies.

Evaluation of risk factors associated to detection of Blastocystis sp. in fecal samples in population from Barcelona, Spain: a case-control study.

Blastocystis sp. is the most common intestinal parasite isolated in humans. The aim of the study was to describe the risk factors associated to Blastocystis sp. detection. A case-control retrospective study was carried out at Vall d'Hebron University Hospital (Barcelona, Spain), which receives all fecal samples collected in Barcelona at primary care level. Eligible patients were patients older than 18 years in whom three consecutive stool samples were examined for parasitic diagnosis from January to December 2017. Positive patients for Blastocystis sp. were assigned as cases whereas negative patients were assigned as controls. Overall, 4174 patients were eligible for the study, from whom 724 (17.3%) had Blastocystis sp. detection. From these, 170 cases (Blastocystis sp. positive) and 170 controls (Blastocystis sp. negative) were randomly selected for inclusion. One hundred and twenty-six (37.1%) of them were immigrants, and 171 (50.3%) patients had traveled out of Spain the year before. The majority of individuals had jobs with no direct contact with other people (health personnel, teachers, and caregivers) (85.6%), and 29.4% were in usual contact with animals. Regarding clinical information, 68.2% of patients presented digestive symptoms, 3.5% presented an immunosuppressant condition, and 6.5% were infected by other intestinal parasites. Variables associated to Blastocystis sp. detection were being born in Africa, having traveled abroad, and working in direct contact with other people. Having other intestinal parasitic infections had a protective value. Our study provides new insights into the epidemiology of Blastocystis sp. in industrialized countries.

[Primary Care and oral health promotion: Assessment of an educational intervention in school children]. / Atención Primaria y promoción de la salud bucodental: evaluación de una intervención educativa en población infantil.

OBJECTIVE: To evaluate the short and medium term effectiveness of a Primary Care-driven oral health promotion intervention. DESIGN: A non-randomised community intervention trial. SETTING: Three socio-demographically similar primary schools of a deprived neighborhood in Granada, Spain. PARTICIPANTS: Eighty-two intervention and 109 control students aged 5 to 6, as well as the teachers and the parent's association of the intervention school (IS) participated in the study. INTERVENTION: School-based health promotion activities aimed at students, and regular meetings with the teachers and parents of the IS during 2 consecutive years. MAIN MEASUREMENTS: Students' oral health-related knowledge and behavior, assessed via questionnaires distributed before the intervention, and 6 and 18 months afterwards. RESULTS: Compared to the control groups at 18 months, students belonging to the IS reported enhanced oral health knowledge (OR 3.54; 95% CI 1.46-8.58), and an increased consumption of healthy food at breakfast (OR 2.95; 95% CI 1.26-6.89) and during mid-afternoon snack (OR 3.67; 95% CI 1.49-9.05). A significant decrease was seen in the intake of pastries (OR 4.05; 95% CI 1.68-9.81) and sweetened soft drinks and juices (OR 3.79; 95% CI 1.57-9.12) amongst intervention compared to control students in the medium term (18 months). No significant improvements were observed concerning oral hygiene in the IS. CONCLUSIONS: School-based educational interventions, when developed through an intersectoral and participative approach and considering the socio-economic context, appear to be effective in improving students' diet-related knowledge and behaviors.

Neuronal levels and sequence of tau modulate the power of brain rhythms.

Neural network dysfunction may contribute to functional decline and disease progression in neurodegenerative disorders. Diverse lines of evidence suggest that neuronal accumulation of tau promotes network dysfunction and cognitive decline. The A152T-variant of human tau (hTau-A152T) increases the risk of Alzheimer's disease (AD) and several other tauopathies. When overexpressed in neurons of transgenic mice, it causes age-dependent neuronal loss and cognitive decline, as well as non-convulsive epileptic activity, which is also seen in patients with AD. Using intracranial EEG recordings with electrodes implanted over the parietal cortex, we demonstrate that hTau-A152T increases the power of brain oscillations in the 0.5-6 Hz range more than wildtype human tau in transgenic lines with comparable levels of human tau protein in brain, and that genetic ablation of endogenous tau in Mapt-/- mice decreases the power of these oscillations as compared to wildtype controls. Suppression of hTau-A152T production in doxycycline-regulatable transgenic mice reversed their abnormal network activity. Treatment of hTau-A152T mice with the antiepileptic drug levetiracetam also rapidly and persistently reversed their brain dysrhythmia and network hypersynchrony. These findings suggest that both the level and the sequence of tau modulate the power of specific brain oscillations. The potential of EEG spectral changes as a biomarker deserves to be explored in clinical trials of tau-lowering therapeutics. Our results also suggest that levetiracetam treatment is able to counteract tau-dependent neural network dysfunction. Tau reduction and levetiracetam treatment may be of benefit in AD and other conditions associated with brain dysrhythmias and network hypersynchrony.

Localized conformational changes trigger the pH-induced fibrillogenesis of an amyloidogenic λ light chain protein.

Solvent conditions modulate the expression of the amyloidogenic potential of proteins. In this work the effect of pH on the fibrillogenic behavior and the conformational properties of 6aJL2, a model protein of the highly amyloidogenic variable light chain λ6a gene segment, was examined. Ordered aggregates showing the ultrastructural and spectroscopic properties observed in amyloid fibrils were formed in the 2.0-8.0 pH range. At pH <3.0 a drastic decrease in lag time and an increase in fibril formation rate were found. In the 4.0-8.0 pH range there was no spectroscopic evidence for significant conformational changes in the native state. Likewise, heat capacity measurements showed no evidence for residual structure in the unfolded state. However, at pH <3.0 stability is severely decreased and the protein suffers conformational changes as detected by circular dichroism, tryptophan and ANS fluorescence, as well as by NMR spectroscopy. Molecular dynamics simulations indicate that acid-induced conformational changes involve the exposure of the loop connecting strands E and F. These results are compatible with pH-induced changes in the NMR spectra. Overall, the results indicate that the mechanism involved in the acid-induced increase in the fibrillogenic potential of 6aJL2 is profoundly different to that observed in κ light chains, and is promoted by localized conformational changes in a region of the protein that was previously not known to be involved in acid-induced light chain fibril formation. The identification of this region opens the potential for the design of specific inhibitors.

Risk variation in celiac disease in a population from Southern Spain: evaluating the influence of the DQB1*02:02 allele frequency.

OBJECTIVES: To date, the greatest genetic risk factor known for celiac disease (CD) is the presence of HLA-DQ2 heterodimers, specifically DQ2.5 in state of homozygosis or heterozygosis. DQ2.2 variants are the second most important risk factor when carried trans to DQ2. This study aimed to determine the prevalence and risk genotypes of HLA-DR-DQ. MATERIAL AND METHODS: A total of 196 patients with CD and 206 healthy controls from the Province of Málaga (southern Spain) were included. The corresponding risk gradient in our population was established in accordance with the odds ratios (ORs) found. RESULTS: The heterozygous genotype for DR7-DQ2.2/DR3-DQ2.5 presented the highest risk (OR =6.404, p = .0001) followed by the DR3-DQ2.5 homozygous genotype (OR =4.721, p = .001). An intermediate risk was found for the DQ2.5 heterozygous genotype with no other DQ risk variant (DQ8 or DQ2.2). Similarly, these three genotypes had also an increase in the risk of associated-autoimmune diseases. The DQB1*02:01 allele was the most widely represented among patients with CD respect to the control group (f = 0.479, p = .0001), with the second most common being DQB1*02:02 (f = 0.209, p = .0001). CONCLUSIONS: In addition to the gene dosage effect confirmed in our report, and in contrast with previous studies, we found a raised risk for those patients with DQ2.2 heterodimers in trans configuration to DQ2.5 compared to DQ2.5 homozygous individuals. Therefore, in our population of patients with CD the frequency of DQ2.2 acts as a factor that increases the genetic risk of developing CD.

Bleeding frequency and characteristics among hematologic malignancy inpatient rehabilitation patients with severe thrombocytopenia.

OBJECTIVE: To identify the frequency and characteristics of bleeding complications during acute inpatient rehabilitation of hematologic malignancy patients with severe thrombocytopenia. DESIGN: Retrospective descriptive analysis. SETTING: Comprehensive cancer center acute inpatient rehabilitation unit. PARTICIPANTS: Consecutive hematologic malignancy patients with a platelet count of less than or equal to 20,000/microliter (µL) on the day of acute inpatient rehabilitation admission from 1/1/2005 through 8/31/2016. INTERVENTIONS: Medical records were retrospectively analyzed for demographic, laboratory, and medical data. Patients were rehabilitated using the institutional exercise guidelines for thrombocytopenic patients. MAIN OUTCOME MEASURES: Bleeding events noted in the medical record. RESULTS: Out of 135 acute inpatient rehabilitation admissions, 133 unique patients were analyzed with a total of 851 inpatient rehabilitation days. The mean platelet count was 14,000/µL on the day of admission and 22,000/µL over the course of the rehabilitation admission. There were 252 days of inpatient rehabilitation where patients had less than 10,000/µL platelets. A total of 97 bleeding events were documented in 77/135 (57%) admissions. Of the 97 bleeding events, 72 (74%), 14 (14%), and 11 (11%) were considered to be of low, medium, and high severity, respectively. There were 4/97 (4%) bleeding events that were highly likely attributable to physical activity but only 1/4 was considered high severity. Bleeding rates were .09, .08, .17, and .37 for > 20,000, 15-20,000, 10-15,000, and < 10,000/µL mean platelet counts respectively (p = .003). Forty-four percent of patients were transferred back to the primary acute care service with infection being the most common reason for transfer. CONCLUSIONS: This study is the first to examine exercise-related bleeding complications during acute inpatient rehabilitation in severely thrombocytopenic hematologic cancer patients. Bleeding rates increased with lower platelet counts. However, using the exercise guidelines for severely thrombocytopenic patients, the risk of severe exercise-related bleeding events was low.

Experience With Prophylactic Gentamicin During Penile Prosthesis Surgery: A Retrospective Comparison of Two Different Doses.

BACKGROUND: Gentamicin has been determined to be active against a wide range of bacterial infections and has been commonly used as a preoperative antibiotic for inflatable penile prosthesis (IPP) implantation. However, the best dosing regimen to produce the safest optimal prophylactic effect remains to be determined. AIM: To compare low- and high-dose gentamicin as prophylaxis during IPP implantation. METHODS: We retrospectively analyzed two groups of patients who underwent IPP placement from April 14, 2012 through April 13, 2016. Group 1 was composed of 490 patients who underwent IPP placement from April 14, 2012 through April 13, 2014 and received a low dose of preoperative gentamicin at 80 mg every 8 hours for 1 day. Group 2 was composed of 407 patients who underwent IPP placement from April 14, 2014 through April 13, 2016 and received a single high dose of preoperative gentamicin at 5 mg/kg. We compared the infection rates of IPP and any gentamicin-related toxicities. The same surgeon performed all procedures. All patients received additional vancomycin 1 g before incision and at 12 hours postoperatively. OUTCOME: Demographic data and IPP infection rate were compared and potential toxicities from the higher dose of gentamicin were closely monitored. RESULTS: There were no significant differences in mean age, mean body mass index, and mean interval for IPP placement and IPP infection between the two groups. No toxicity was seen with the higher gentamicin dose. Six cases in group 1 (five de novo cases and one redo case, infection rate = 1.22%) and three cases in group 2 (two de novo cases and one redo case, infection rate = 0.74%) were found to have IPP infection. The infection rate in group 2 appeared to be lower than that in group 1, although a significant statistical difference was not achieved (P = .057). CLINICAL IMPLICATIONS: These findings would help guide urologists in choosing an optimal preoperative gentamicin dose for IPP surgery. STRENGTHS AND LIMITATIONS: This is the first study to report on the usage of high-dose preoperative gentamicin for IPP surgery but with limitations as a retrospective study. CONCLUSIONS: Although not achieving a statistical difference, there was a trend for patients receiving a higher dose of preoperative gentamicin to have a lower IPP infection rate. No toxicity was encountered from the 5-mg/kg gentamicin dose. We recommend following prophylactic high-dose gentamicin guidelines. Xie D, Gheiler V, Lopez I, et al. Experience With Prophylactic Gentamicin During Penile Prosthesis Surgery: A Retrospective Comparison of Two Different Doses. J Sex Med 2017;14:1160-1164.

Needs Perceived by Parents of Preterm Infants: Integrating Care Into the Early Discharge Process.

UNLABELLED: The birth of a preterm infant can have a great emotional impact on the parents when the length of stay is long. Early discharge programs facilitate the transition to the home and have beneficial effects on both the parents and children. However, only a few studies have been conducted to identify the real needs of parents of preterm infants and to determine whether early discharge programs meet such needs. The main objective of this study was to identify the experiences and obstacles, during hospitalization and after discharge, of fathers and mothers of preterm infants who did or did not participate in an early discharge program. METHOD: A qualitative study using semi-structured interviews was performed and included 23 parents of preterm infants. Thematic analysis was performed with the assistance of Atlas.ti 6.2 software. RESULTS: Two main themes were identified: the emotional experience and obstacles to care during hospitalization and the emotional experiences and obstacles at home related to the early discharge program. The results indicated that preterm birth initially has a deep emotional impact on parents. DISCUSSION: There is a remarkable lack of coordination regarding the information provided to parents on their infant's health status. Being first-time parents seems to be an important factor, although further evidence supporting this notion should be provided. CONCLUSION: Parents considered early discharge programs to be very useful in addressing the emotional aspects of hospitalization and the acquisition of neonatal care skills. Parents claim that the coordination and the information provided should be improved.

Obesity/Overweight and the Role of Working Conditions: A Qualitative, Participatory Investigation.

The rising U.S. prevalence of obesity has generated significant concern and demonstrates striking socioeconomic and racial/ethnic disparities. Most interventions target individual behaviors, sometimes in combination with improving the physical environment in the community but rarely involving modifications of the work environment. With 3.6 million workers earning at or below the federal minimum wage, it is imperative to understand the impact of working conditions on health and weight for lower income workers. To investigate this question, a university-community partnership created a participatory research team and conducted eight focus groups, in English and Spanish, with people holding low-wage jobs in various industries. Analysis of transcripts identified four themes: physically demanding work (illnesses, injuries, leisure-time physical activity), psychosocial work stressors (high demands, low control, low social support, poor treatment), food environment at work (available food choices, kitchen equipment), and time pressure (scheduling, having multiple jobs and responsibilities). Physical and psychosocial features of work were identified as important antecedents for overweight. In particular, nontraditional work shifts and inflexible schedules limited participants' ability to adhere to public health recommendations for diet and physical activity. Workplace programs to address obesity in low-wage workers must include the effect of working conditions as a fundamental starting point.

Genotyping of common SIRPB1 copy number variant using Paralogue Ratio Test coupled to MALDI-MS quantification.

Copy number variant (CNV) regions have been proven to have a significant impact on gene expression. Some of them have been also found to be associated to different human diseases. CNV genotyping is often prone to error and cross-validation with independent methods is frequently required. The platform of choice depends on whether it is a genome-wide discovery screening or a candidate CNV study, the cohort size and the number of CNVs included in the assay and, finally, the budget available. Here we illustrate a affordable approach to determine the CNV genotype using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and based on the quantitative determination of single nucleotide duplicated mismatches (SNDM) mapping the CNV region and a paralogue genomic region that is used as a two-copy reference. We have genotyped nsv436327, a common CNV mapping SIRPB1 intron 1 that has been associated to human personality behavior. SIRP cluster region was subjected to several ancestral duplication events what makes SIRPB1 CNV genotyping technically challenging. We designed three sets of primer pairs that amplified paralogue regions inside and outside the CNV, containing three SNDMs. Post-PCR extension analyses of sequencing oligonucleotides mapping immediately upstream each SNDM allowed us to quantify using MALDI-MS the proportion of PCR products derived from the CNV region versus the external reference. In contrast to other approaches, setting up this genotyping method requires an affordable investment.