Characterizing cognitive deficits and dementia in an aging urban population in India.

Rapid rise in the population of older adults in India will lead to the need for increased health care services related to diagnosis, management, and long-term care for those with dementia and cognitive impairment. A direct approach for service provision through memory clinics can be an effective, successful, and sustaining means of delivering specialized health care services. We have established a memory clinic in Mumbai, India by employing the diverse clinical skills available in Indian academic institutions, diagnostic and research expertise of clinicians and psychologists, and the support of the U.S. National Institutes of Health. Our project involved recruitment of patients, clinical and neuropsychological assessment, and standardized diagnostic procedures, demonstrating the feasibility of using research methods to develop a memory clinic. In this paper, we describe the development of a community-based memory clinic in urban India, including linguistic and cultural factors and present detailed results, including diagnostic characterization, on 194 subjects with various stages of cognitive deficits. Our findings support the feasibility of developing a memory clinic in a public hospital and successful use of research diagnostic criteria to categorize cognitive deficits observed in this population, which may be used to inform the development of other such clinics

α2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment

Slow-onset adaptive changes that arise from sustained antidepressant treatment, such as enhanced adult hippocampal neurogenesis and increased trophic factor expression, play a key role in the behavioral effects of antidepressants. alpha(2)-Adrenoceptors contribute to the modulation of mood and are potential targets for the development of faster acting antidepressants. We investigated the influence of alpha(2)-adrenoceptors on adult hippocampal neurogenesis. Our results indicate that alpha(2)-adrenoceptor agonists, clonidine and guanabenz, decrease adult hippocampal neurogenesis through a selective effect on the proliferation, but not the survival or differentiation, of progenitors. These effects persist in dopamine beta-hydroxylase knock-out (Dbh(-/-)) mice lacking norepinephrine, supporting a role for alpha(2)-heteroceptors on progenitor cells, rather than alpha(2)-autoreceptors on noradrenergic neurons that inhibit norepinephrine release. Adult hippocampal progenitors in vitro express all the alpha(2)-adrenoceptor subtypes, and decreased neurosphere frequency and BrdU incorporation indicate direct effects of alpha(2)-adrenoceptor stimulation on progenitors. Furthermore, coadministration of the alpha(2)-adrenoceptor antagonist yohimbine with the antidepressant imipramine significantly accelerates effects on hippocampal progenitor proliferation, the morphological maturation of newborn neurons, and the increase in expression of brain derived neurotrophic factor and vascular endothelial growth factor implicated in the neurogenic and behavioral effects of antidepressants. Finally, short-duration (7 d) yohimbine and imipramine treatment results in robust behavioral responses in the novelty suppressed feeding test, which normally requires 3 weeks of treatment with classical antidepressants. Our results demonstrate that alpha(2)-adrenoceptors, expressed by progenitor cells, decrease adult hippocampal neurogenesis, while their blockade speeds up antidepressant action, highlighting their importance as targets for faster acting antidepressants

Phenomenological Consequences of Singlet Neutrinos

In this paper, we study the phenomenology of right-handed neutrino isosinglets. We consider the general situation where the neutrino masses are not necessarily given by $m_D^2/M$, where $m_D$ and $M$ are the Dirac and Majorana mass terms respectively. The consequent mixing between the light and heavy neutrinos is then not suppressed, and we treat it as an independent parameter in the analysis. It turns out that $\mu-e$ conversion is an important experiment in placing limits on the heavy mass scale ($M$) and the mixing. Mixings among light neutrinos are constrained by neutrinoless double beta decay, as well as by solar and atmospheric neutrino experiments. Detailed one-loop calculations for lepton number violating vertices are provided.Comment: Revtex file,TRI-PP-94-1,VPI-IHEP-94-1, 23 pages, a compressed for 8 figures is appende

Constraints on a Massive Dirac Neutrino Model

We examine constraints on a simple neutrino model in which there are three massless and three massive Dirac neutrinos and in which the left handed neutrinos are linear combinations of doublet and singlet neutrinos. We examine constraints from direct decays into heavy neutrinos, indirect effects on electroweak parameters, and flavor changing processes. We combine these constraints to examine the allowed mass range for the heavy neutrinos of each of the three generations.Comment: latex, 29 pages, 7 figures (not included), MIT-CTP-221

Flavor Violating Higgs Decays

We study a class of nonstandard interactions of the newly discovered 125 GeV Higgs-like resonance that are especially interesting probes of new physics: flavor violating Higgs couplings to leptons and quarks. These interaction can arise in many frameworks of new physics at the electroweak scale such as two Higgs doublet models, extra dimensions, or models of compositeness. We rederive constraints on flavor violating Higgs couplings using data on rare decays, electric and magnetic dipole moments, and meson oscillations. We confirm that flavor violating Higgs boson decays to leptons can be sizeable with, e.g., h -> tau mu and h -> tau e branching ratios of order 10% perfectly allowed by low energy constraints. We estimate the current LHC limits on h -> tau mu and h -> tau e decays by recasting existing searches for the SM Higgs in the tau-tau channel and find that these bounds are already stronger than those from rare tau decays. We also show that these limits can be improved significantly with dedicated searches and we outline a possible search strategy. Flavor violating Higgs decays therefore present an opportunity for discovery of new physics which in some cases may be easier to access experimentally than flavor conserving deviations from the Standard Model Higgs framework.Comment: 39 pages, 12 figures, 3 tables; v2: Improved referencing, updated mu -> 3e bounds to include large loop contributions, corrected single top constraints; conclusions unchanged; matches version to be published in JHEP; v3: included 2-loop contributions in mu -> e conversion, improved discussion of tau -> 3 mu and of EDM constraints on FV top-Higgs couplings; conclusions unchange

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

CP Violation in τ→3πντ\tau\rightarrow 3\pi\nu_\tau

We consider CP violating effects in the decays $\tau\rightarrow (3\pi)\nu_\tau$ where both the ${\rm J}^{\rm P}=1^+$ resonance, $a_1$, and ${\rm J}^{\rm P}=0^-$ resonance, $\pi^\prime$, can contribute. The interference between the $a_1$ and $\pi^\prime$ resonances can lead to enhanced CP-violating asymmetries whose magnitudes depend crucially on the $\pi^\prime$ decay constant, $f_{\pi^\prime}$. We make an estimate of $f_{\pi^\prime}$ with a simplified chiral Lagrangian coupled to a massive pseudoscalar field, and we compare the estimates from the non-relativistic quark model and from the QCD sum rule with the estimate from the `mock' meson model. We then estimate quantitatively the size of CP-violating effects in a multi-Higgs-doublet model and scalar-leptoquark models. We find that, while CP-violating effects in the scalar-leptoquark models may require more than $10^{10}$ $\tau$ leptons, CP-violating effects from the multi-Higgs-doublet model can be seen at the $2\sigma$ level with about $10^7$ $\tau$ leptons using the chiral Lagrangian estimate of $f_{\pi^\prime}=(1\sim 5)\times 10^{-3}$ GeV.Comment: Latex, 30 pages, 2 figures (not included). Three compressed postscript files of the paper available at ftp://ftp.kek.jp/kek/preprints/TH/TH-419/kekth419.ps.gz, Tau1.ps.gz, Tau2.ps.g

Systemic IL-12 Administration Alters Hepatic Dendritic Cell Stimulation Capabilities

The liver is an immunologically unique organ containing tolerogenic dendritic cells (DC) that maintain an immunosuppressive microenvironment. Although systemic IL-12 administration can improve responses to tumors, the effects of IL-12-based treatments on DC, in particular hepatic DC, remain incompletely understood. In this study, we demonstrate systemic IL-12 administration induces a 2–3 fold increase in conventional, but not plasmacytoid, DC subsets in the liver. Following IL-12 administration, hepatic DC became more phenotypically and functionally mature, resembling the function of splenic DC, but differed as compared to their splenic counterparts in the production of IL-12 following co-stimulation with toll-like receptor (TLR) agonists. Hepatic DCs from IL-12 treated mice acquired enhanced T cell proliferative capabilities similar to levels observed using splenic DCs. Furthermore, IL-12 administration preferentially increased hepatic T cell activation and IFNγ expression in the RENCA mouse model of renal cell carcinoma. Collectively, the data shows systemic IL-12 administration enables hepatic DCs to overcome at least some aspects of the inherently suppressive milieu of the hepatic environment that could have important implications for the design of IL-12-based immunotherapeutic strategies targeting hepatic malignancies and infections