A role for CD4(+)CD25(+) regulatory T cells (Tregs) in the control of allergic diseases has been postulated. We developed a mouse model in which anaphylaxis is induced in SJL mice by immunization and ...challenge with the fragment of self myelin proteolipid protein (PLP)(139-151), that is not expressed in the thymus, but not with fragment 178-191 of the same protein, that is expressed in the thymus. In this study, we show that resistance to anaphylaxis is associated with naturally occurring CD4(+)CD25(+) Tregs specific for the self peptide expressed in the thymus. These cells increase Foxp3 expression upon Ag stimulation and suppress peptide-induced proliferation of CD4(+)CD25(-) effector T cells. Depletion of Tregs with anti-CD25 in vivo significantly diminished resistance to anaphylaxis to PLP(178-191), suggesting an important role for CD4(+)CD25(+) Tregs in preventing the development of allergic responses to this thymus-expressed peptide. These data indicate that naturally occurring CD4(+)CD25(+) Tregs specific for a peptide expressed under physiological conditions in the thymus are able to suppress the development of a systemic allergic reaction to self.
The purpose of this study was to develop and pilot test nutrition and physical activity educational tools for immigrant Latina women who have type 2 diabetes and low health literacy levels. ...Participants’ ability to use the tools was assessed and a focus group was conducted (n = 26). During two classes, the women were taught diabetes concepts related to nutrition and physical activity and were given a pedometer. The women recorded in a log vegetables consumed and steps taken. Nearly all participants (n = 24) completed the nutrition log, and most used the pedometer (n = 25) and completed the step log for 5 or more days (n = 19). The women reported that the pedometer and logs helped them increase vegetable consumption and physical activity. Interventions for this population should use plain language, tools that are easy to use, and strategies that encourage behavioral change.
Elucidating the mechanisms that protect monkeys previously immunized with attenuated SIV (SIVDeltanef) against challenge infection with pathogenic virus may reveal new strategies for the development ...of an effective HIV vaccine. Here we show that a single atraumatic application of SIVDeltanef to the tonsils of four rhesus macaques conferred protection against SIVmac251 applied intrarectally 26 weeks later. While this protection was not complete, i.e., challenge virus could be isolated from all immunized animals, it was reflected by significantly lower viral loads in the blood (weeks 2-16 after challenge, p < 0.01) and considerably lower loads in lymphoid organs, and more stable peripheral CD4 counts in a proportion of the immunized animals as compared to four non-immunized, SIVmac251-infected control monkeys. SIV-specific humoral as well as systemic and mucosal T cell responses were detected in the immunized animals, but there was no correlation between their magnitude of expression and the level of protection. Analyses of leukocyte subsets in these animals at necropsy (24 weeks after challenge) did not reveal a significantly enhanced proportion of gamma/delta T cells in the tissues of protected monkeys. Therefore, tonsillar application of attenuated SIV induces protection in some animals against a superinfection with wild-type SIV distant at a distant mucosal site.
Este trabajo analiza el desarrollo que Platón hace en el Político del proceso cognitivo necesario para arribar a la definición correcta de un objeto. Tomando como punto de partida los problemas sobre ...la búsqueda de la definición abiertos en el Menón, el análisis muestra que, en el marco de su filosofía tardía, Platón reformuló el proceso que conduce a responder adecuadamente"qué es x". En el Político, "definir" se convierte en un proceso complejo que incluye un acercamiento negativo al objeto. "Decir lo que el objeto no es" constituye uno de los momentos necesarios para arribar a una definición verdadera. Esta perspectiva implica el abandono definitivo de la ignorancia como punto de partida de toda investigación representada, usualmente, en los diálogos platónicos por la intransigencia socrática.This essay analyzes the necessary knowledge process to reach a correct definition of an object, developed by Plato in the Statesman. Starting with the problems found in the search of a definition in the Meno, the paper shows that, in his late philosophy, Plato reshaped the characteristics of the search that leads to answer properly "what is x". In the Statesman, the act of definition becomes a complex process that includes a negative approach to the object. "To say what the object is not" constitutes one of the necessary moments to reach a real definition. This view also implies to move away from the ignorance as a starting point of all kinds of search usually represented in the dialogues by the socratic intransigence.
To determine whether an increased female gender susceptibility to torsades de pointes (TdP) may exist in a clinical model of bradycardia-induced long QT syndrome, we investigated reported cases of ...TdP associated with acquired complete heart block.
Seventy-two cases reported in the medical literature dating from 1941 through 1993 were identified, all describing TdP or "transient ventricular tachycardia/fibrillation" (to include those cases reported prior to the use of TdP terminology) in the setting of acquired complete heart block unassociated with QT prolonging drugs. Expected female prevalence in complete heart block was estimated at 52%, based on projections derived from 206,016 hospital discharges in the National Inpatient Profile (Commission on Professional and Hospital Activities, Ann Arbor, MI), over the years 1985 through 1992. During complete heart block, mean heart rate was 37 beats/min in both sexes (combined n = 43), and absolute QT interval ranged from 0.52 to 0.88 seconds, with a mean of 0.68 seconds (n = 25). Female prevalence among patients with TdP during complete heart block was greater than expected: 72% for all studied cases (P < 0.001); 70% (P < 0.04) and 74% (P < 0.02) among those reported prior to (n = 35) and during or after (n = 37) 1980, respectively; 73% (P < 0.03) among those with documented normokalemia (n = 26); and 68% (P = 0.2) among those with a prolonged QT interval and known polymorphic VT (i.e., unequivocal TdP; n = 25).
Despite inherent limitations of this retrospective study, the data are consistent in suggesting a greater than expected female prevalence among patients with TdP related to complete heart block. This finding lends support to a broadening concept of increased susceptibility of women to the development of TdP in various settings of QT prolongation.
Depression remains a major public health issue for older adults, increasing risk of costly health services utilization. While home-based collaborative care models (CCM) like PEARLS have been shown to ...effectively treat depression in low-income older adults living with multiple chronic conditions, their economic impact is unclear. We conducted a quasi-experimental study to estimate PEARLS effect on health service utilization among low-income older adults. Our secondary data analysis merged de-identified PEARLS program data (
N
= 1106), home and community-based services (HCBS) administrative data (
N
= 16,096), and Medicaid claims and encounters data (
N
= 164) from 2011 to 2016 in Washington State. We used nearest neighbor propensity matching to create a comparison group of social service recipients similar to PEARLS participants on key determinants of utilization guided by Andersen’s Model. Primary outcomes were inpatient hospitalizations, emergency room (ER) visits, and nursing home days; secondary outcomes were long-term supports and services (LTSS), mortality, depression and health. We used an event study difference-in-difference (DID) approach to compare outcomes. Our final dataset included 164 older adults (74% female, 39% people of color, mean PHQ-9 12.2). One-year post-enrollment, PEARLS participants had statistically significant improvements in inpatient hospitalizations (69 fewer hospitalizations per 1000 member months,
p
= 0.02) and 37 fewer nursing home days (
p
< 0.01) than comparison group participants; there were no significant improvements in ER visits. PEARLS participants also experienced lower mortality. This study shows the potential value of home-based CCM for participants, organizations and policymakers. Future research is needed to examine potential cost savings.
A role for CD4 super(+)CD25 super(+) regulatory T cells (Tregs) in the control of allergic diseases has been postulated. We developed a mouse model in which anaphylaxis is induced in SJL mice by ...immunization and challenge with the fragment of self myelin proteolipid protein (PLP) sub(139-151), that is not expressed in the thymus, but not with fragment 178-191 of the same protein, that is expressed in the thymus. In this study, we show that resistance to anaphylaxis is associated with naturally occurring CD4 super(+)CD25 super(+) Tregs specific for the self peptide expressed in the thymus. These cells increase Foxp3 expression upon Ag stimulation and suppress peptide-induced proliferation of CD4 super(+)CD25 super(-) effector T cells. Depletion of Tregs with anti-CD25 in vivo significantly diminished resistance to anaphylaxis to PLP sub(178-191), suggesting an important role for CD4 super(+)CD25 super(+) Tregs in preventing the development of allergic responses to this thymus-expressed peptide. These data indicate that naturally occurring CD4 super(+)CD25 super(+) Tregs specific for a peptide expressed under physiological conditions in the thymus are able to suppress the development of a systemic allergic reaction to self.
Development of a fully effective vaccine against the pre-erythrocytic stage of malaria infection will likely require induction of both humoral and cellular immune responses. Protein based vaccines ...can elicit such broad-based immunity depending on the adjuvant and how the protein is formulated. Here to assess these variables, non human primates (NHP) were immunized three times withPlasmodium falciparum(Pf) circumsporozoite protein (CSP) or CSP cloned into MG38, a monoclonal antibody that targets DEC-205 (αDEC-CSP), an endocytic receptor on dendritic cells (DCs). Both vaccines were administered with or without poly(I:C) as adjuvant. Following three immunizations, the magnitude and quality of cytokine secreting CD4+ T cells were comparable between CSP+poly(I:C) and αDEC-CSP+poly(I:C) groups with both regimens eliciting multi-functional cytokine responses. However, NHP immunized with CSP+poly(I:C) had significantly higher serum titers of CSP-specific IgG antibodies and indirect immunofluorescent antibody (IFA) titers against Pf sporozoites. Furthermore, sera from both CSP or αDEC-CSP+poly(I:C) immunized animals limited sporozoite invasion of a hepatocyte cell line (HC04)in vitro. To determine whether CSP-specific responses could be enhanced, all NHP primed with CSP or αDEC-CSP+poly(I:C) were boosted with a single dose of 150,000 irradiated Pf sporozoites (PfSPZ) intravenously. Remarkably, boosting had no effect on the CSP-specific immunity. Finally, immunization with CSP+poly-ICLC reduced malaria parasite burden in the liver in an experimental mouse model. Taken together, these data showing that poly(I:C) is an effective adjuvant for inducing potent antibody and Th1 immunity with CSP based vaccines offers a potential alternative to the existing protein based pre-erythrocytic vaccines.
Objectives. This study attempted to determine the prevalence and electrocardiographic (ECG) lead distribution of T wave “humps” (T2, after an initial T wave peak, T1) among families with long QT ...syndrome and control subjects.
Background. T wave abnormalities have been suggested as another facet of familial long QT syndrome, in addition to prolongation of the rate-corrected QT interval (QTc), that might aid in the diagnosis of affected subjects.
Methods. The ECGs from 254 members of 13 families with long QT syndrome (each with two to four generations of affected members) and from 2,948 healthy control subjects (age ≥ 16 years, QTc interval 0.39 to 0.46 s) were collected and analyzed. Tracings from familes with long QT syndrome were read without knowledge of QTc interval or family member status (210 blood relatives and 44 spouses).
Results. We found that T2 was present in 53%, 27% and 5% of blood relatives with a “prolonged” (≥ 0.47 s), “borderline” (0.42 to 0.46 s) and “normal” (≤0.41 s) QTc interval, respectively (p < 0.0001), but in only 5% and 0% of spouses with a borderline and normal QTc interval, respectively (p = 0.06 vs. blood relatives). Among blood relatives with T2, the mean ±SD maximal T1T2 interval was 0.10 ± 0.03 s and correlated with the QTc interval (p < 0.01); a completely distinct U wave was seen in 23%. T2 was confined to leads V2and V3in 10%, whereas V4, V5, V6or a limb lead was involved in 90% of blood relatives with T2. Among blood rotatives with a borderline QTc interval, 50% of those with versus 20% of those without major symptoms manifested T2 in at least one left precordial or limb lead (p = 0.05). A T2 amplitude > 1 mm (grade III) was observed, respectively, in 19%, 6% and 0% of blood relatives with a prolonged, borderline and normal QTc interval with T2 in at least one left precordial or limb lead. Among the 2,948 control subjects, 0.6% exhibited T2 confined to leads V2and V3, and 0.9% had T2 involving one or more left precordial lead (but none of the limb leads). Among 37 asymptomatic adult blood relatives with QTc intervals 0.42 to 0.46 s, T2 was found in left precordial or limb leads in 9 (24%; 5 with limb lead involvement) versus only 1.9% of control subjects with a borderline QTc interval (p < 0.0001).
Conclusions. These findings are consistent with the hypothesis that in families with long QT syndrome, T wave humps involving left precordial or (especially) limb leads, even among asymptomatic blood relatives with a borderline QTc interval, suggest the presence of the long QT syndrome trait.
Motion perception was tested by requiring adult subjects to view gratings that remained stationary but reversed in contrast several times per second. Subjects viewed monocularly and judged whether ...the gratings were stationary, or moving in one direction, in successive 3s trials. Subjects who had early-onset strabismus most frequently perceived vertically oriented gratings to be moving nasalward, and horizontally oriented gratings to be moving up or down. Normal subjects and subjects who had late-onset strabismus most frequently perceived the gratings to be stationary. The asymmetries of motion perception in early-onset strabismus imply that the visual motion neurons of cerebral cortex develop properly only if they receive normal binocular input during infancy.
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