A nationwide study on immunosenescence biomarkers profile in older adults: ELSI-Brazil.

Immunosenescence is a phenomenon caused by changes in the immune system, and part of these changes involves an increase in circulating immunological biomarkers, a process known as "Inflammaging." Inflammaging can be associated with many diseases related to older people. As the older population continues to grow, understanding changes in the immune system becomes essential. While prior studies assessing these alterations have been conducted in countries with Caucasian populations, this investigation marks a pioneering effort. The object of the study is to describe for the first time that the distribution of cytokines, chemokines, and growth factors serum levels, assessed by Luminex platform, has been examined in a Brazilian population-based study of older adult females and males by age. Blood samples from 2111 participants (≥50 years old) were analyzed at the baseline (2015/2016) of the ELSI-Brazil study. The exploratory variables considered in the study were age, sex, educational level, residence area, geographic region, alcohol and smoking consumption, physical activity, and self-reported medical diagnoses of hypertension, diabetes, asthma, arthritis, and cancer. The association between serum biomarker levels and age was assessed by a quantile regression model adjusted in the total population and stratified by sex. The significance level considered in the analysis was 0.05. The mean age of the participants was 62.9 years, with a slight majority of female (52.7 %). Differences were found between the sexes in the median circulating levels of the CCL11, CXCL10, and FGF biomarkers. Eight biomarkers showed significant associations with age, including the pro-inflammatory CXCL10, TNF-α, IL-6, IL-17, and IL-2; and type 2/regulatory CCL11 and IL-4, showing positive associations, and anti-inflammatory IL-1Ra showing a negative association. The results suggest similar associations between the sexes, revealing an inflammatory profile characterized by types 1 and 2. Remarkably, these findings reinforce the concept of the Inflammaging process in Brazilian population. These findings add novel insights to about the immunosenescence aspects in middle-income countries and help define biomarkers capable of monitoring inflammation in older adults.

A Case of Diltiazem-Induced Pustular Rash in an 83-Year-Old Female.

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute skin eruption characterized by the development of numerous nonfollicular sterile pustules. Most cases are caused by drug reactions, among which Diltiazem has been incriminated. Herein, we present an 83-year-old female who presented for evaluation of generalized skin rash 3 days after initiation of Diltiazem. She was eventually diagnosed with AGEP, Diltiazem was discontinued, and systemic steroids were administered with the resolution of symptoms. This case report has the objective of encouraging clinicians to include AGEP in the differential diagnosis of skin eruption following the initiation of Diltiazem.

Tim-3 Is Differentially Expressed during Cell Activation and Interacts with the LSP-1 Protein in Human Macrophages.

T-cell Immunoglobulin and Mucin Domain 3 (TIM-3) is an immune checkpoint receptor known to regulate T-cell activation and has been targeted for immunotherapy in cancer and other diseases. However, its expression and function in other cell types, such as macrophages, are poorly understood. This study investigated TIM-3 expression in human macrophages polarized to M1 (stimulated with IFN-γ and LPS) and M2 (stimulated with IL-4 and IL-13) phenotypes using an in vitro model. Our results show that M1 macrophages have a lower frequency of TIM-3+ cells compared to M2 macrophages at 48 and 72 hr poststimulation. Additionally, we observed differential levels of soluble ADAM 10, an enzyme responsible for TIM-3 release, in the supernatants of M1 and M2 macrophages at 72 hr. We also found that the TIM-3 intracellular tail might associate with lymphocyte-specific protein 1 (LSP-1), a protein implicated in cell motility and podosome formation. These findings enhance our understanding of TIM-3 function in myeloid cells such as macrophages and may inform the development of immunotherapies with reduced immune-related adverse effects.

Rhythmic profile of memory T and B-cells along childhood and adolescence.

Immunobiography describes the life-long effects of exogenous or endogenous stimuli on remodeling of immune cell biology, including the development of memory T and B-cells. The present study aimed at investigating the rhythms of changes in phenotypic features of memory T and B-cells along childhood and adolescence. A descriptive-observational investigation was conducted including 812 healthy volunteers, clustered into six consecutive age groups (9Mths-1Yr; 2Yrs; 3-4Yrs; 5-7Yrs; 8-10Yrs; 11-18Yrs). Immunophenotypic analysis of memory T-cell (CD4+ and CD8+) and B-cell subsets were performed by flow cytometry. The results pointed out that memory-related biomarkers of T and B-cells displayed a bimodal profile along healthy childhood and adolescence, regardless of sex. The first stage of changes occurs around 2Yrs, with predominance of naive cells, while the second and more prominent wave occurs around the age 8-10Yrs, with the prevalence of memory phenotypes. The neighborhood connectivity profile analysis demonstrated that the number of correlations reaches a peak at 11-18Yrs and lower values along the childhood. Males presented higher and conserved number of correlations when compared to females. Altogether, our results provide new insights into immunobiography and a better understanding of interactions among the cellular subsets studied here during childhood and adolescence.

Comparison of core and process scores on the California Verbal Learning Test-3 for Parkinson's disease and essential tremor patients.

INTRODUCTION: Parkinson's disease (PD) and essential tremor (ET) are two disorders known to lead to executive dysfunction, presumably through distinct pathways to the frontal lobes via the striatum or cerebellum, respectively. Memory functioning in PD and ET patients has been previously suggested to be adversely impacted by executive dysfunction. The aims of this exploratory study were to compare memory performance between and within groups on the California Verbal Learning Test - 3 (CVLT-3) through the analysis of core and process scores and to understand the relationship of these scores with measures of executive functioning. METHOD: Seventy PD and 54 ET patients completed comprehensive neuropsychological testing. Independent sample t-tests or Mann-Whitney tests were used to compare between group core and process scores on the CVLT-3. Within-subjects analyses were conducted via Wilcoxon Signed Rank Test due to nonparametric data. Spearman's correlations were conducted to explore the relationship between memory process scores and measures of executive functioning. RESULTS: The ET and PD samples were similar with regard to age, education, gender, and general cognitive functioning. PD patients made more repetition errors (U = 2391.50, p = .01) than ET patients and Normal Memory PD patients made more repetition errors than Low Memory PD patients (U= 711.00, p= .00). Correlational analyses revealed repetition errors were negatively associated with tests of inhibition, set shifting, and working memory (rs = -.293, -.232). ET patients demonstrated a preference for a serial cluster learning strategy (T = 861.00, p = .005), similar to PD patients (T= 1633.00, p = <.001). CONCLUSIONS: The study revealed presence of higher repetition errors in the PD sample that was demonstrated to have a negative relationship with measures of executive functioning. Implications for investigating process ("qualitative") scores in memory performance to determine extent of executive involvement are discussed.

Specificity of performance validity tests in patients with confirmed epilepsy.

Objective: While assessment of performance validity is essential to neuropsychological evaluations, use of performance validity tests (PVTs) in an epilepsy population has raised concerns due to factors that may result in performance fluctuations. The current study assessed whether specificity was maintained at previously suggested cutoffs in a confirmed epilepsy population on the Warrington Recognition Memory Test (WRMT) - Words and Test of Memory Malingering (TOMM). Method: Eighty-two confirmed epilepsy patients were administered the WRMT-Words and TOMM as part of a standardized neuropsychological evaluation. Frequency tables were utilized to investigate specificity rates on these two PVTs. Results: The suggested WRMT-Words Accuracy Score cutoff of ≤42 was associated with a specificity rate of 90.2%. Five out of the 8 individuals falling below the Accuracy Score cutoff scored 42, suggesting specificity could be further improved by slightly lowering the cutoff. The WRMT-Words Total Time cutoff of ≥207 seconds was associated with 95.1% specificity. A TOMM Trial 1 cutoff of <40 was associated with 93.9% specificity, while the established cutoff of <45 on Trial 2 and the Retention Trial yielded specificity rates of 98.6% and 100.0%, respectively. Conclusions: Our findings demonstrate acceptable performance on two PVTs in a select confirmed epilepsy population without a history of brain surgery, active seizures during testing, and/or low IQ, irrespective of various factors such as seizure type, seizure lateralization/localization, and language lateralization. The possible presence of interictal discharges were not controlled for in the current study, which may have contributed to reduced PVT performances.

Analyses of correct responses and errors on measures of verbal fluency among Parkinson's disease and essential tremor patients.

Objective: Parkinson's disease (PD) and essential tremor (ET) involve neuroanatomical circuitry that impact frontal lobe functioning, via the striatum and cerebellum, respectively. The aim of this exploratory study was to investigate quantitative and qualitative performance between and within these groups on measures of verbal fluency. Method: Sixty-three PD and 53 ET patients completed neuropsychological testing. Linear regression models with robust variance estimation compared verbal fluency performance between groups related to correct responses and errors. Paired t-tests investigated within group error rates. Results: PD patients gave more correct responses for phonological (ß̂ =5.3, p=.01) and category fluency (ß̂ =4.1, p=.01) than ET patients; however, when processing speed was added as a covariate, this attenuated performance on both measures and only phonological fluency remained significant (ß̂ =4.0, p=.04). There were no statistical differences in error scores between groups. Error rates within groups suggested that PD patients had higher error rates in total errors and perseveration errors on phonological fluency (M = 2.6, p=.00; M = 1.6, p=.00) and higher total errors and set-loss error rates on category switching (M = 5.1, p<.001; M = 4.1, p<.001). ET patients had higher error rate with relation to total errors and set-loss errors on phonological fluency (M = 2.5, p=.00; M = 1.5, p=.02) and category switching (M = 3.9, p=,00; M = 3.9, p<.001). Conclusions: PD patients performed better than ET patients on phonological fluency. PD patients appear to make more perseveration errors on phonological fluency, while ET patients made more set-loss errors. Implications for frontal lobe dysfunction and clinical impact are discussed.

The coumarin osthole is a non-electrophilic agonist of TRPA1.

The naturally occurring coumarin osthole has antipruritic properties, and recent reports suggest that this effect is due an inhibition or desensitization of the cation channels TRPV1 and TRPV3. Osthole was also suggested to activate TRPA1, an effect that should rather be pruritic than antipruritic. Here we characterized the effects of osthole on TRPA1 by means of ratiometric calcium imaging and patch clamp electrophysiology. In HEK 293 expressing human (h) TRPA1, osthole induced a concentration-dependent increase in intracellular calcium that was inhibited by the TRPA1-inhibitor A967079. In mouse dorsal root ganglion (DRG) cells, osthole induced a strong calcium-influx that was partly mediated by TRPA1. Osthole evoked fully reversible membrane currents in whole-cell as well as cell-free inside-out recordings on hTRPA1. Osthole failed to activate the mutant hTRPA1-S873V/T874L, a previously described binding site for the non-electrophilic TRPA1-agonists menthol and carvacrol. The combined application of osthole and carvacrol diminished channel activation, suggesting a competitive binding. Finally, osthole failed to activate TRPM8 and TRPV4 but induced a modest activation of hTRPV1 expressed in HEK 293 cells. We conclude that osthole is a potent non-electrophilic agonist of TRPA1. The relevance of this property for the antipruritic effects needs to be further explored.

Cognitive Frailty is Associated With Elevated Proinflammatory Markers and a Higher Risk of Mortality.

BACKGROUND: Cognitive impairment and physical frailty are common among older adults and associated with a higher likelihood of adverse health outcomes. These two conditions frequently coexist in the same individual as cognitive frailty, yet few studies have examined the impact of such comorbidity on clinical outcomes or underlying biological mechanisms. METHODS: A total of 1,340 older adults (age ≥60 years old) from the Bambui Cohort Study of Ageing, with a total follow-up of 10 years, were included in this study. Frailty was defined by the accumulation of deficit framework and cognitive impairment based on scores on the MMSE less than 22. In addition, serum IL-6 levels were measured by cytometric bead array assay. RESULTS: Individuals classified with cognitive frailty had significantly higher serum IL-6 levels compared to the robust, cognitively unimpaired group. Those with cognitive frailty (aOR = 1.97 [1.18-3.27] and prefrailty and cognitive impairment (aOR = 1.83 [1.24-2.69]) had the highest mortality risk over 10 years of follow-up. Higher IL-6 levels were also independently associated with a higher mortality rate (aOR = 1.37 [1.23-1.54]). CONCLUSION: Our study shows that cognitive Frailty indicates a vulnerability state and of increasing mortality risk. Our findings also suggested that proinflammatory abnormalities can be viewed as a central phenomenon underlying common age-related problems (e.g., cognitive impairment and Frailty) and outcomes (e.g., mortality).

Parto gemelar de 310 días de gestación en yegua con resultado de un potro vivo y otro en estado de autolisis / Twin Delivery of 310 Days of Gestation in a Mare Resulting in One Live Foal and One Autolysed Foal

Resumen Las preñeces gemelares son gestaciones de alto riesgo, tanto para la yegua como para ambos fetos. Hoy en día existen diferentes técnicas para evitar el avance de este tipo de eventos, tanto en sus inicios como en gestaciones avanzadas. Aun así, existen múltiples casos de gestaciones dobles que presentan diferentes resultados ya evidenciados. En este caso se reportó una yegua de raza polo argentino de ocho años, que llegó al Centro de Perinatología Equina Foal Care por presentar gestación gemelar de 292 días. Se prolongó la gestación durante dieciocho días más, con ayuda de terapia farmacológica. Finalmente, nació un potro vivo con múltiples complicaciones, incluyendo el hecho de ser un potro prematuro. El segundo potro nació muerto con características de momificación y autolisis. En conclusión, se requirió de un adecuado monitoreo reproductivo por parte del veterinario para prevenir el avance de este tipo de gestación.

Abstract Nowadays, there are different techniques to avoid the progression of this type of events, both in early and advanced gestations. Even so, there are multiple cases of double gestations that present different results already evidenced. In this case, an eight-year-old Argentine polo mare was reported, who arrived at the Foal Care Equine Perinatology Center because she presented a twin gestation of 292 days. The gestation was prolonged for eighteen more days, with the help of pharmacological therapy. Finally, a live foal was born with multiple complications, including being a premature foal. The second foal was stillborn with mummification and autolysis characteristics. In conclusion, adequate reproductive monitoring by the veterinarian was required to prevent the progression of this type of gestation.

[Seroprevalence and factors associated with chronic infections among community-dwelling elderly individuals]. / Soroprevalência e fatores associados a infecções crônicas entre idosos residentes na comunidade.

Chronic infections can contribute to the aging process, but this issue is less studied in Latin America. The aim was to assess the prevalence and factors associated with cytomegalovirus (CMV), Herpes Simplex 1 (HSV-1), Chlamydia pneumoniae and Helicobacter pylori among the elderly. A total of 1,320 individuals participated from the baseline of the Elderly Cohort of Bambuí. IgG antibodies against infections and explanatory variables (sociodemographic factors, health behaviors and health conditions) were evaluated. Poisson regression models with robust variance were used. Seroprevalence rates were 99.4% for CMV, 96.7% for HSV-1, 56% for C. pneumoniae and 70.5% for H. pylori. Elderly men, women, smokers, diabetics, the disabled and those with high levels of IL-6 had a higher prevalence of CMV. HSV-1 was less frequent among women. The prevalence of C. pneumoniae was higher at ages >75 and among diabetics; it was lower among women and individuals with less schooling. H. pylori was less frequent among women and those with detectable levels of IL-1ß, but more common among smokers. The findings show a high prevalence of chronic infection and a different epidemiologic profile for each pathogen, making it possible to detect groups that are vulnerable to these infections.

Infecções crônicas podem contribuir com o processo de envelhecimento, mas isso ainda é pouco explorado na América Latina. O objetivo foi avaliar a prevalência e os fatores associados ao citomegalovírus (CMV), Herpes simples 1 (HSV-1), Chlamydia pneumoniae e Helicobacter pylori entre idosos. Participaram 1.320 indivíduos da linha de base da Coorte de Idosos de Bambuí. Foram avaliados anticorpos (IgG) para as infecções e variáveis exploratórias (sociodemográficas, comportamentos em saúde e condições de saúde). Utilizaram-se modelos de regressão de Poisson com variância robusta. A prevalência foi de 99,4% para CMV, 96,7% para HSV-1, 56,0% para C. pneumoniae e 70,5% para H. pylori. Os mais velhos, mulheres, fumantes, diabéticos, incapazes e com maiores níveis de IL-6 tinham maior prevalência de CMV. HSV-1 foi menos frequente entre as mulheres. Infecção por C. pneumoniae foi maior entre os mais velhos e diabéticos; e menor entre mulheres e os menos escolarizados. H. pylori foi menos frequente entre as mulheres e naqueles com maiores níveis de IL-1ß, mas mais comuns entre os fumantes. Os achados mostram elevada prevalência de infecções crônicas e diferentes perfis epidemiológicos para cada patógeno, permitindo a detecção de grupos vulneráveis a essas infecções.

Chlamydia pneumoniae and Helicobacter pylori infections and immunological profile of community-dwelling older adults.

Chronic bacterial infections are associated with changes in the immunosenescence process and immunological biomarkers can assist in monitoring these changes. The identification of this immunological profile is important because Chlamydia pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori) infections are important factors of morbidity and mortality among the older adults. This study aimed to identify changes in the immunological profile in the presence of C. pneumoniae and H. pylori infections among community-dwelling older adults. This is a cross-sectional study that used data from 1432 participants from the Bambuí Cohort Study of Aging, Minas Gerais, Brazil. The presence of immunoglobulin G (IgG) for C. pneumoniae and H. pylori was considered a dependent variable and assessed in the participants' serum using the enzyme-linked immunosorbent assay (ELISA). In assessing the immunological profile, the following inflammatory markers were considered: CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-1ß, IL-6, IL-10, IL-12, TNF, and CRP. Associations were assessed by logistic regression, estimating odds ratios and confidence intervals (95%) using the Stata® V.13.1 software. The seroprevalence of anti-C. pneumoniae and anti-H. pylori antibodies was 55.9% and 70.3%, respectively. While high levels of anti-C. pneumoniae antibodies were associated with higher concentrations of CXCL10 and IL-10, higher levels of IL-1ß and IL-6 were inversely associated with the titration of anti-H. pylori antibodies. The results characterize immunological profiles associated with these chronic infections and reinforce the potential effects of biomarkers on infections by these bacteria and on the immunosenescence process.

Soroprevalência e fatores associados a infecções crônicas entre idosos residentes na comunidade / Seroprevalence and factors associated with chronic infections among community-dwelling elderly individuals

Resumo Infecções crônicas podem contribuir com o processo de envelhecimento, mas isso ainda é pouco explorado na América Latina. O objetivo foi avaliar a prevalência e os fatores associados ao citomegalovírus (CMV), Herpes simples 1 (HSV-1), Chlamydia pneumoniae e Helicobacter pylori entre idosos. Participaram 1.320 indivíduos da linha de base da Coorte de Idosos de Bambuí. Foram avaliados anticorpos (IgG) para as infecções e variáveis exploratórias (sociodemográficas, comportamentos em saúde e condições de saúde). Utilizaram-se modelos de regressão de Poisson com variância robusta. A prevalência foi de 99,4% para CMV, 96,7% para HSV-1, 56,0% para C. pneumoniae e 70,5% para H. pylori. Os mais velhos, mulheres, fumantes, diabéticos, incapazes e com maiores níveis de IL-6 tinham maior prevalência de CMV. HSV-1 foi menos frequente entre as mulheres. Infecção por C. pneumoniae foi maior entre os mais velhos e diabéticos; e menor entre mulheres e os menos escolarizados. H. pylori foi menos frequente entre as mulheres e naqueles com maiores níveis de IL-1β, mas mais comuns entre os fumantes. Os achados mostram elevada prevalência de infecções crônicas e diferentes perfis epidemiológicos para cada patógeno, permitindo a detecção de grupos vulneráveis a essas infecções.

Abstract Chronic infections can contribute to the aging process, but this issue is less studied in Latin America. The aim was to assess the prevalence and factors associated with cytomegalovirus (CMV), Herpes Simplex 1 (HSV-1), Chlamydia pneumoniae and Helicobacter pylori among the elderly. A total of 1,320 individuals participated from the baseline of the Elderly Cohort of Bambuí. IgG antibodies against infections and explanatory variables (sociodemographic factors, health behaviors and health conditions) were evaluated. Poisson regression models with robust variance were used. Seroprevalence rates were 99.4% for CMV, 96.7% for HSV-1, 56% for C. pneumoniae and 70.5% for H. pylori. Elderly men, women, smokers, diabetics, the disabled and those with high levels of IL-6 had a higher prevalence of CMV. HSV-1 was less frequent among women. The prevalence of C. pneumoniae was higher at ages >75 and among diabetics; it was lower among women and individuals with less schooling. H. pylori was less frequent among women and those with detectable levels of IL-1β, but more common among smokers. The findings show a high prevalence of chronic infection and a different epidemiologic profile for each pathogen, making it possible to detect groups that are vulnerable to these infections.

Complications and treatment to liver wound by gunshot. A retrospective approach.

INTRODUCCIÓN: Un trauma penetrante puede dañar una variedad de órganos. Dado que el hígado es un órgano sólido inelástico, no tiene la tolerancia al estiramiento necesaria para hacer frente a una herida por proyectil de arma de fuego (GSW). MÉTODOS: Este fue un estudio retrospectivo, observacional y descriptivo de 53 registros clínicos de pacientes ingresados en el Departamento de Cirugía por trauma hepático (LT) por un GSW. RESULTADOS: Del total de historias clínicas analizadas, el 89% de los pacientes presentaron una lesión asociada con LT. La lesión orgánica asociada más frecuente fue la torácica, específicamente la lesión pulmonar, en el 58%. El predictor más importante de mortalidad fue una estancia en la unidad de cuidados intensivos (UCI), que aumentó el riesgo unas 21 veces. CONCLUSIÓN: Una estadía en la UCI, seguida de la presencia de fracturas, fue el predictor más importante de mortalidad. Se necesitan nuevas medidas de pronóstico para contrarrestar las variables que ha creado el aumento de GSW, además de disminuir el tiempo de espera desde el evento traumático hasta el tratamiento relevante. INTRODUCTION: A penetrating trauma can damage a variety of organs. Since the liver is an inelastic solid organ, it does not have the necessary stretch tolerance to cope with a gunshot wound (GSW). METHODS: This was a retrospective, observational, and descriptive study of 53 clinical records of patients admitted to the Department of Surgery for liver trauma (LT) by a GSW. RESULTS: Of the total clinical records analyzed, 89% of the patients presented a lesion associated with LT. The most common associated organic lesion was thoracic, specifically lung injury, in 58%. The most important predictor of mortality was a stay in the intensive care unit (ICU), which increased the risk about 21 times. CONCLUSION: A stay in the ICU, followed by the presence of fractures, was the most important predictor of mortality. New prognostic measures are needed to counteract the variables that the increase in GSWs has created, in addition to decreasing the waiting time from the traumatic event to relevant treatment.

Cytomegalovirus and herpes simplex type 1 infections and immunological profile of community-dwelling older adults.

Chronic infections, such as cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1), contribute to the inflammation process among older adults and are associated with the immunosenescence process. The aim was to identify the immunological profile associated with CMV and HSV-1 infections among older adults. This is a cross-sectional study, carried out with 1492 participants from the Bambuí Cohort Study of Aging - Minas Gerais, Brazil. For analysis purposes, we considered the presence of immunoglobulin G (IgG) for CMV and HSV-1 in the participants' serum, assessed by the enzyme-linked immunosorbent assay (ELISA); outcomes were defined by titration above the median (>160 UR/mL for HSV-1 and >399.5 U/mL for CMV). In order to assess the immunological profile, the following biomarkers were considered: IL-1beta, IL-10, IL-12, TNF, CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-6 and CRP; the first four being categorized as detectable levels or not, and the others using the Classification and Regression Tree (CART) method. The analysis was adjusted for sociodemographic variables, health behaviors and health conditions. The seroprevalence of anti CMV and anti HSV-1 antibodies was 99.4% and 97.0%, respectively. Higher concentrations of CXCL8 and CCL5 chemokines were associated with lower antibody titers for CMV, and higher concentrations of CXCL9, IL-6 and CRP were associated with higher levels of antibodies to CMV. Moreover, intermediate levels of CXCL10 were also associated with higher levels of antibodies to CMV. In HSV-1 infection, intermediate levels of CXCL9, CCL5 and IL-6 were less likely to have higher antibody titers for this infection. On the other hand, higher levels of CXCL10 and CRP were positively associated with higher antibody titers for HSV-1. The results describe important immunological changes and reinforce the potential effect of CMV and HSV-1 on the immunosenescence process.

Importance of the lactation period in developmental programming in rodents.

Lactation is a critical period during which maternal nutritional and environmental challenges affect milk composition and, therefore, organ differentiation, structure, and function in offspring during the early postnatal period. Evidence to date shows that lactation is a vulnerable time during which transient insults can have lasting effects, resulting in altered health outcomes in offspring in adult life. Despite the importance of the developmental programming that occurs during this plastic period of neonatal life, there are few comprehensive reviews of the multiple challenges-especially to the dam-during lactation. This review presents milk data from rodent studies involving maternal nutritional challenges and offspring outcome data from studies involving maternal manipulations during lactation. Among the topics addressed are maternal nutritional challenges and the effects of litter size and artificial rearing on offspring metabolism and neural and endocrine outcomes. The lactation period is an opportunity to correct certain functional deficits resulting from prenatal challenges to the fetus, but, if not personalized, can also lead to undesirable outcomes related to catch up-growth and overnutrition.

CXCL9 and CXCL10 display an age-dependent profile in Chagas patients: a cohort study of aging in Bambui, Brazil.

BACKGROUND: Chagas disease is endemic in Latin America and still represents an important public health problem in the region. Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality. The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage, with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response. Although studies have evaluated the role of chemokines in experimental T. cruzi infection, few have addressed their systemic profile, especially for human infection and in aging populations. The present work aimed to use the data from a large population based study of older adults, conducted in an endemic area for Chagas disease, to examine the association between serum levels of cytokines and chemokines, T. cruzi infection and electrocardiogram (ECG) abnormality. METHODS: The present work evaluated serum levels of CCL2, CXCL9, CXCL10, CCL5, CXCL8, IL-1ß, IL-6, TNF, IL-12 and IL-10 by Flow Cytometric Bead Array assay (CBA) and the results expressed in pg/ml. The baseline survey started in January 1st 1997, with 1284 participants of an aged population-based cohort. Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification. RESULTS: Our results demonstrated that Chagas disease patients had higher serum levels of CXCL9, CXCL10 and IL-1ß and lower serum levels of CCL5 than non-infected subjects. Moreover, our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease patients. CONCLUSION: Together, this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.

Inflammatory markers associated with fall recurrence and severity: The Bambuí Cohort Study of Aging.

BACKGROUND: The aim of this study was to analyze the association between inflammatory markers and recurrent and severe falls in 1304 community-dwelling older adults from the Bambuí Cohort Study of Aging. METHODS: Information about falls in the previous 12 months was collected, and classified based on recurrence (two or more falls) and severity (requirement of medical attention). The screened biomarkers included interleukins (IL-1ß, IL-6, IL-10, and IL-12, TNF), chemokines (CXCL8, CXCL9, CXCL10, CCL2, and CCL5), and high-sensitive C-reactive protein (hs-PCR). Potential confounders included sociodemographic, behavioral, and health indicators. Associations were evaluated through logistic regression, using odds ratios (OR) and 95% confidence intervals (95% CI), with Stata 13.1. RESULTS: The prevalence of recurrent and severe falls was 10.7% and 9.0%, respectively. After adjustments, elevated levels of IL-12 (OR: 1.92; 95% CI: 1.09-3.37) and CXCL9 (OR: 1.67; 95% CI: 1.05-2.66) were found to be associated with recurrent falls, while elevated levels of TNF (OR: 1.58; 95% CI: 1.01-2.50), IL-12 (OR: 2.04; 95% CI: 1.13-3.70), CXCL10 (OR: 1.75; 95% CI: 1.04-2.92), and CCL5 (OR: 1.90; 95% CI: 1.18-3.07) were associated with severe falls. CONCLUSIONS: The results highlight a wide range of biomarkers not yet explored in the literature and suggest that inflammation may be an important component of recurrent and severe falls.

Subjective Cognitive Complaints in Concussion.

Studies of symptoms after concussion have been focused heavily on athletic and military populations; generalizability to "civilians" has not recently been demonstrated. We selected cognitive symptoms as an important target to assess because of impact on school and employment. We evaluated cognitive complaints in a highly symptomatic (Rivermead Post-Concussion Symptoms Questionnaire [PCSQ], mean [M] = 29.5) civilian sample (n = 100; age: M = 41.4; 36 male/64 female; days post-injury: range 14-154, M = 51.4) of consecutive referrals to a concussion specialty clinic. The Behavior Rating of Executive Functions-Adult version (BRIEF-A) was used to assess subjective cognitive symptoms. Independent variables were prior neurologic and psychiatric history, current neurological symptoms, objective neuropsychological tests and several measures of depression (Beck Depression Inventory, Second Edition [BDI2]), anxiety (Beck Anxiety Inventory), and stress (Post-Traumatic Stress Checklist-Civilian form). No demographic characteristic, injury measure, or past or current neurological history had any association with cognitive symptoms. Prior psychiatric history (57% of patients) was associated with abnormal BRIEF-A. Cognitive tests were overall in the average range, with only mild and sporadic associations with BRIEF-A elevations. All psychological measures showed significant associations with BRIEF-A elevations. Regression analyses for the BRIEF-A revealed depression was the significant contributor (BDI2, ß = 0.73) with prior psychiatric history (ß = 0.16) and age (ß = 0.14) accounting to a lesser extent. In this civilian cohort, subjective cognitive symptoms appear to be due to psychological distress (in particular, depression) and prior psychiatric history more than actual cognitive impairment or other presenting symptoms. These findings illuminate the importance of early diagnosis and treatment of mood/emotional symptoms after injury.

Sinonasal Myxoma: A Distinct Lesion of Infants.

An 11 month old Caucasian male presented with swelling of the right side of the nose and buccal vestibule of unknown duration. Radiographic images revealed a well-circumscribed, hypodense soft tissue mass with a peripheral hyperdense circumference involving the anterior aspect of the right maxilla. The lesion extended from the inferior aspect of the orbital rim superiorly to the maxillary bone inferiorly without invading any nearby structures. The lesion was completely resected via combined extraoral and intraoral approach. The clinical, radiographic, histologic and immunohistochemical features of a sinonasal myxoma in an infant are discussed.