Identification of reactive Borrelia burgdorferi peptides associated with Lyme disease.

Borrelia burgdorferi, the agent of Lyme disease, is estimated to cause >400,000 annual infections in the United States. Serology is the primary laboratory method to support the diagnosis of Lyme disease, but current methods have intrinsic limitations that require alternative approaches or targets. We used a high-density peptide array that contains >90,000 short overlapping peptides to catalog immunoreactive linear epitopes from >60 primary antigens of B. burgdorferi. We then pursued a machine learning approach to identify immunoreactive peptide panels that provide optimal Lyme disease serodiagnosis and can differentiate antibody responses at various stages of disease. We examined 226 serum samples from the Lyme Biobank and the National Institutes of Health, which included sera from 110 individuals diagnosed with Lyme disease, 31 probable cases from symptomatic individuals, and 85 healthy controls. Cases were grouped based on disease stage and presentation and included individuals with early localized, early disseminated, and late Lyme disease. We identified a peptide panel originating from 14 different epitopes that differentiated cases versus controls, whereas another peptide panel built from 12 unique epitopes differentiated subjects with various disease manifestations. Our method demonstrated an improvement in B. burgdorferi antibody detection over the current two-tiered testing approach and confirmed the key diagnostic role of VlsE and FlaB antigens at all stages of Lyme disease. We also uncovered epitopes that triggered a temporal antibody response that was useful for differentiation of early and late disease. Our findings can be used to streamline serologic targets and improve antibody-based diagnosis of Lyme disease. IMPORTANCE: Serology is the primary method of Lyme disease diagnosis, but this approach has limitations, particularly early in disease. Currently employed antibody detection assays can be improved by the identification of alternative immunodominant epitopes and the selection of optimal diagnostic targets. We employed high-density peptide arrays that enabled precise epitope mapping for a wide range of B. burgdorferi antigens. In combination with machine learning, this approach facilitated the selection of serologic targets early in disease and the identification of serological indicators associated with different manifestations of Lyme disease. This study provides insights into differential antibody responses during infection and outlines a new approach for improved serologic diagnosis of Lyme disease.

Objectively Measured Sleep Duration and Health-Related Quality of Life in Older Adults with Metabolic Syndrome: A One-Year Longitudinal Analysis of the PREDIMED-Plus Cohort.

The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55-75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [ß-coefficient (95% confidence interval) <6 h vs. 7-9 h: -2, 3 (-3.8 to -0.8); p = 0.002. >9 h vs. 7-9 h: -1.1 (-2.0 to -0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [ß-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night.

Thermophysical properties of tetrabutylammonium chloride, paraffin and fatty acids for thermal energy applications.

Investigating the thermophysical properties of substances is crucial for using them as phase change materials (PCMs) and heat transfer fluids (HTFs) in thermal energy applications. In this study, the thermophysical properties of three medium-temperature PCMs (around 338 K) and one ionic liquid, tetrabutylammonium chloride ([N4444 +][Cl-]), were evaluated and compared. The commercial PCMs were two fatty acids (OM65 and stearic acid) and one paraffin (RT64HC). The characterised thermophysical properties were the viscosity, density, phase change temperatures, melting and solidification enthalpies, and thermal conductivity for the solid and liquid phases. The uncertainties for each property were calculated, and two empirical equations were obtained from the correlation of viscosity and thermal conductivity data along isotherms. This paper also compared the thermophysical properties of commercial PCMs and HTFs against the ionic liquid, discussing the potential use of the ionic liquid as a thermal energy storage material and HTFs.

COVID-19 and Cognitive Decline in Older Adults with High-Cardiovascular Risk: A Post Hoc Analysis.

Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m2, harboring ≥ 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (ßadj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.

Characteristics of the phenotypes in prevalent and incident cases of heart failure in primary care: IBERICAN study.

BACKGROUND: The management in primary care (PC) of the patients with Heart Failure (HF) is different from the management hospital, in a special way compared to cardiology departments. OBJECTIVE: To define the characteristics in both phenotypes of HF in prevalent and incident cases of HF in patients recruited in a large PC sample. METHODS: We proposed a and longitudinal analyses, in patients of the IBERICAN cohort, that recruited 8,066 patients in the Spanish primary care system, with 15,488 patients-years of follow-up. Of them, 252 patients (3.1%) had diagnoses of HF. HF was classified according to the 2014 guidelines in two groups: HF with a reduced eject fraction or HFrEF (LVEF < 50%) and HF with preserved eject fraction or HFpEF (LVEF ≥ 50%). Recommended treatment was defined as the patient receiving drug treatment with Renin-Angiotensin-System (RAS) blockers with beta-blockers and, optionally, spironolactone. The incidence of new cases of HF was calculated in the 7,814 patients without HF in the inclusion visit. Finally, we analysed which variables associated the onset new cases and get the hazard ratio (HR) with the confidence interval at 95% ([95%CI]). Clinical trials register: NCT02261441 (02/05/2017). RESULTS: The HFpEF was the most frequent phenotype in prevalent cases (61.1%) and incident cases (73.9%). Patients with HFrEF had a higher prevalence of coronary heart disease (p = 0.008) and PAD (p = 0.028), and no statistically significant differences was observed in the therapeutic groups used between both groups. The incidence of HF was 12.8 cases/1000 inhabitants/year, 35.6% of them was diagnosed in PC. The renin-angiotensin system blockers were more used in PC (60%) and beta-blockers (100%) and spironolactone (60%) in hospital. The female sex showed a protective effect for incident cases (0.51 [0.28-0.92]); and AF (HR [95%CI]: 2.90 [1.51-5.54]), coronary heart disease (HR [95%CI]: 2.18 [1.19-4.00]) and hypertension (HR [95%CI]: 1.91 [1.00-3.64]) increased the risk of developing HF. CONCLUSIONS: HF phenotype more frequent and incident in PC was the HFpEF, but only one third of them are diagnosed in PC level. The female sex showed a protective effect and atrial fibrillation, ischaemic heart disease and hypertension increased the risk of develop HF.

The turnover of ABI5 by scaffold proteins to attenuate ABA signaling.

This article comments on: Li Z, Zhang D, Liang X, Liang J. 2024. Receptor for Activated C Kinase 1 counteracts ABSCISIC ACID INSENSITIVE5-mediated inhibition of seed germination and post-germinative growth in Arabidopsis. Journal of Experimental Botany 75, 3932-3945.

More Adult Women than Men at High Cardiometabolic Risk Reported Worse Lifestyles and Self-Reported Health Status in the COVID-19 Lockdown.

BACKGROUND: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. METHODS: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. RESULTS: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). CONCLUSIONS: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

Environmental impact of the diet of young Portuguese and its relationship with adherence to the Mediterranean Diet.

OBJECTIVE: To estimate, in a cohort of young Portuguese adults, the environmental impact (greenhouse gas (GHG) emissions, land use, energy used, acidification and potential eutrophication) of diet according to adherence to the Mediterranean Diet (MD). METHODS: Data from 1554 participants of the Epidemiologic Health Investigation of Teenagers in Porto (EPITeen) were analysed. Food intake and MD adherence were determined using validated questionnaires. The environmental impact was evaluated with the EAT-Lancet Commission tables, and the link between MD adherence and environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: Higher adherence (high vs. low) to the MD was associated with lower environmental impact in terms of land use (7.8 vs. 8.5 m2, p = 0.002), potential acidification (57.8 vs. 62.4 g SO2-eq, p = 0.001) and eutrophication (21.7 vs. 23.5 g PO4-eq, p < 0.001). Energy use decreased only in the calorie-adjusted model (9689.5 vs. 10,265.9 kJ, p < 0.001), and GHG emissions were reduced only in a complementary model where fish consumption was eliminated (3035.3 vs. 3281.2 g CO2-eq, p < 0.001). Meat products had the greatest environmental impact for all five environmental factors analysed: 35.7% in GHG emissions, 60.9% in energy use, 72.8% in land use, 70% in acidification and 61.8% in eutrophication. CONCLUSIONS: Higher adherence to the MD is associated with lower environmental impact, particularly in terms of acidification, eutrophication, and land use. Reducing meat consumption can contribute to greater environmental sustainability.

Double Z-Rhombic Plasty for Repair of Scalp Defects.

BACKGROUND: The closure of scalp wounds presents with reconstructive challenges due to the poor tissue elasticity. It is not uncommon to require skin grafts for definitive closure, even when large flaps are employed. Herein, we present a novel method for the direct closure of small- to medium-sized wounds defects. It is a modified bilateral rhomboid flap, which enables tension-free closure in many areas of scalp. METHODS: All patients treated with this technique between January 2018 and January 2023 were reviewed. Demographics, complications, and outcomes were reviewed. RESULTS: One hundred forty patients have been operated with this technique. All have been cases of skin tumors. The full flap survival was 97.14%, and they did not present any major local complications, avoiding in all cases the use of skin autografts. Four patients (2.86%) had partial necrosis in the edges of the flap, all managed with topical wound care with good healing and no need of secondary procedures. CONCLUSIONS: This flap is safe and easy to perform when there is skin laxity in the scalp. It can save many skin grafts, simplifying the closure of this area, which can be a first-choice technique on scalp reconstruction.

Association between diet quality and malnutrition: pooled results from two population-based studies in older adults.

BACKGROUND: The role of diet quality on malnutrition in older adults is uncertain, due the paucity of the research conducted and the use of use of screening tools that did not consider phenotypic criteria of malnutrition. OBJECTIVE: To evaluate the association of two indices of diet quality, namely the Mediterranean Diet Adherence Screener (MEDAS) and the Alternative Healthy Eating Index (AHEI-2010), with malnutrition among community-dwelling older adults in Spain. METHODS: Cross-sectional analysis of data from 1921 adults aged ≥ 60 years from the Seniors-ENRICA-1 (SE-1) study, and 2652 adults aged ≥ 65 years from the Seniors-ENRICA-2 (SE-2) study. Habitual food consumption was assessed through a validated diet history. Malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM) phenotypic criteria. Statistical analyses were performed with logistic regression with adjustment for socioeconomic and lifestyle variables as well as for total energy and protein intake. RESULTS: The prevalence of malnutrition in the SE-1 study was 9.5% (95% confidence interval: 8.2 to 10.9) and 11.7% (10.5 to 13.9) in the SE-2. Adherence to the MEDAS score was associated with lower prevalence of malnutrition [pooled odds ratio for high (≥ 9 points) vs. low adherence (< 7 points): 0.64 (0.48-0.84); p-trend < 0.001]. Higher adherence to the AHEI-2010 also showed an inverse association with malnutrition (pooled odds ratio for quartile 4 vs. 1: 0.65 (0.49-0.86); p-trend 0.006). Among the individual components, higher consumption of fish and long-chain n-3 fatty acids in MEDAS and AHEI-2010, and of vegetables and nuts and legumes in AHEI-2010, and lower intake of trans-fat and sugar-sweetened beverages and fruit juice in AHEI-2010 were independently associated with lower odds of malnutrition. CONCLUSION: Adherence to high diet-quality patterns was associated with lower frequency of malnutrition among older adults. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT02804672. June 17, 2016.; ClinicalTrials.gov NCT03541135. May 30, 2018.

Cuidados postoperatorios en el hipospadias. Prácticas habituales y evidencia disponible / Postoperative care in hypospadias: common practices and evidence available

Introducción: Existen numerosas alternativas en lo que respecta alos cuidados postoperatorios en la cirugía de hipospadias. El objetivo deeste estudio es evaluar la situación actual de estos cuidados en nuestromedio y revisar la evidencia existente al respecto para cirujanos pediátricos que realizan este tipo de intervenciones. Material y métodos: Hemos elaborado y distribuido una encuestaque recoge los principales puntos en el cuidado postoperatorio del hipospadias dirigida a cirujanos pediátricos. Se ha realizado revisión dela evidencia actual publicada al respecto en la especialidad.Resultados: Hemos obtenido un total de 46 respuestas. El 100% delos cirujanos dejan algún tipo de sonda o stent y más del 80% están deacuerdo en retirarlo tras 5 o 7 días. El 87,8% de los encuestados utilizael doble pañal, pero solo el 65,2% da alta precoz en el postoperatorio.Un 60,9% pauta profilaxis antibiótica mientras dure el sondaje y un34,8% antibioterapia a dosis plenas. Discusión: Existe consenso general respecto a la tutorización de lauretroplastia y el uso de apósito compresivo entre los cirujanos pediátricos encuestados. Se detectan más discrepancias en el uso de antibioterapia y el alta precoz. La evidencia actual y la práctica a nivel internacional apunta hacia el uso de la sonda a doble pañal con alta precozy la limitación del uso de antibióticos postoperatorios. En ausencia declara evidencia que favorezca un tipo de cuidado u otro, la experienciadel paciente podría ser utilizada para elegir el mejor protocolo postoperatorio individualizado.(AU)

Introduction: There are many alternatives available regarding postoperative care in hypospadias surgery. The objective of this study wasto assess the current care situation in our environment and to review theevidence available for pediatric surgeons who conduct this procedure. Materials and methods. A survey regarding the main aspects ofhypospadias postoperative care was created and distributed to pediatricsurgeons. In addition, the evidence currently published in this field wasreviewed. Results: A total of 46 replies were achieved. 100% of the surgeonsleave in place a probe or stent, and more than 80% remove it after 5 or7 days. 87.8% of the respondents use a double diaper, but only 65.2%discharge patients early in the postoperative period. 60.9% prescribeantibiotic prophylaxis for as long as the probe remains in place, and34.8% use full-dose antibiotic therapy. Discussion: There was a general consensus regarding urethroplastyguiding and the use of compression dressings among the pediatric surgeons surveyed. However, more discrepancies were found in the use ofantibiotic therapy and early discharge. The currently available evidenceand international practice suggest using a probe with double diaperand early discharge, with postoperative antibiotics being limited. Inthe absence of clear evidence for a specific care type, the patient’sexperience could be used to choose the best postoperative protocol onan individual basis.(AU)

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

Reversible S-nitrosylation of bZIP67 by peroxiredoxin IIE activity and nitro-fatty acids regulates the plant lipid profile.

Nitric oxide (NO) is a gasotransmitter required in a broad range of mechanisms controlling plant development and stress conditions. However, little is known about the specific role of this signaling molecule during lipid storage in the seeds. Here, we show that NO is accumulated in developing embryos and regulates the fatty acid profile through the stabilization of the basic/leucine zipper transcription factor bZIP67. NO and nitro-linolenic acid target and accumulate bZIP67 to induce the downstream expression of FAD3 desaturase, which is misregulated in a non-nitrosylable version of the protein. Moreover, the post-translational modification of bZIP67 is reversible by the trans-denitrosylation activity of peroxiredoxin IIE and defines a feedback mechanism for bZIP67 redox regulation. These findings provide a molecular framework to control the seed fatty acid profile caused by NO, and evidence of the in vivo functionality of nitro-fatty acids during plant developmental signaling.

Impact of neurofibromatosis type 1 on quality of life using the Skindex-29 questionnaire quality of life in NF1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common RASopathies predisposing affected patients to melanic lesions and benign tumors. NF1 is associated with considerable esthetic and functional burden negatively affecting the patient's quality of life (QoL). This study aims to assess the clinical features of NF1 patients and evaluate their impact on QoL. We identified NF1 patients from a public health database of a region in Spain. All patients underwent clinical and ophthalmological evaluation for NF1 features. We measured QoL using the Spanish version of the Skindex-29. RESULTS: Forty patients fulfilled the NF1 National Institute of Health criteria when we recruited patients. The median age was 42.00 years (IQR 26.5 -53.75). The median total Skindex-29 score was 12.3 (IQR 5.9-22.4); (emotion: 15.0, IQR 5.0-37.5; symptoms 8.9, IQR 0.0-17.9 and functioning 8.3; IQR 0.5-18.3). Women and NF1 patients with lower educational levels were associated with poorer QoL scores. We identified itching and sleep troubles to influence NF1 patients' QoL negatively. CONCLUSION: NF1 considerably influences the psychological well-being of NF1 patients. We observed that female and low-educated patients scored higher on the emotional dimension of the Skindex-29 and could, therefore, be more at risk of depression. We also pointed out some "minor symptoms" that negatively impact NF1 patients' QoL such, as itching and sleep troubles which doctors could treat if sought by doctors.

Coronavirus disease 2019 is associated with long-term depressive symptoms in Spanish older adults with overweight/obesity and metabolic syndrome.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort. METHODS: Participants (n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology. RESULTS: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted ß = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women (ß = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008). CONCLUSIONS: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62.

NEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identify an NF-κB-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress and are vulnerable to proteostasis challenges. Moreover, a patient with a mutation in the NEMO-encoding IKBKG gene resulting in defective binding of NEMO to linear ubiquitin chains, developed a widespread mixed brain proteinopathy, including α-synuclein, tau and TDP-43 pathology. NEMO amplifies linear ubiquitylation at α-synuclein aggregates and promotes the local concentration of p62 into foci. In vitro, NEMO lowers the threshold concentrations required for ubiquitin-dependent phase transition of p62. In summary, NEMO reshapes the aggregate surface for efficient autophagosomal clearance by providing a mobile phase at the aggregate interphase favoring co-condensation with p62.

Tick-Borne Co-Infections: Challenges in Molecular and Serologic Diagnoses.

Co-infections are a poorly understood aspect of tick-borne diseases. In the United States alone, nineteen different tick-borne pathogens have been identified. The majority of these agents are transmitted by only two tick species, Ixodes scapularis and Amblyomma americanum. Surveillance studies have demonstrated the presence of multiple pathogens in individual ticks suggesting a risk of polymicrobial transmission to humans. However, relatively few studies have explored this relationship and its impact on human disease. One of the key factors for this deficiency are the intrinsic limitations associated with molecular and serologic assays employed for the diagnosis of tick-borne diseases. Limitations in the sensitivity, specificity and most importantly, the capacity for inclusion of multiple agents within a single assay represent the primary challenges for the accurate detection of polymicrobial tick-borne infections. This review will focus on outlining these limitations and discuss potential solutions for the enhanced diagnosis of tick-borne co-infections.

Smoking history and breast cancer risk by pathological subtype: MCC-Spain study.

INTRODUCTION: The role of cigarette smoking on breast cancer risk remains controversial, due to its dual carcinogenic-antiestrogenic action. METHODS: In the population-based multi-case-control study (MCC-Spain), we collected epidemiological and clinical information for 1733 breast cancer cases and 1903 controls, including smoking exposure. The association with breast cancer, overall, by pathological subtype and menopausal status, was assessed using logistic and multinomial regression models. RESULTS: Smokers had higher risk of premenopausal breast cancer, particularly if they had smoked ≥30 years (AOR=1.75; 95% CI: 1.04-2.94), although most estimates did not achieve statistical significance. In contrast, among postmenopausal women, smoking was associated with lower risk of breast cancer, mainly in overweight and obese women. The strongest risk reductions were observed among postmenopausal women who had stopped smoking ≥10 years before cancer diagnosis, particularly for HER2+ tumors (AOR=0.28; 95% CI: 0.11-0.68); p for heterogeneity = 0.040). Also, those who had smoked <10 pack-years (AOR=0.68; 95% CI: 0.47-0.98) or 10-25 pack-years (AOR=0.62; 95% CI: 0.42-0.92) during their lifetime were at a reduced risk of all breast cancer subtypes (p for heterogeneity: 0.405 and 0.475, respectively); however, women who had smoked more than 25 pack-years showed no reduced risk. CONCLUSIONS: Menopausal status plays a key role in the relationship between tobacco and breast cancer for all cancer subtypes. While smoking seems to increase the risk in premenopausal woman, it might be associated to lower risk of breast cancer among postmenopausal women with excess weight.