Defeating diabetes in the desert: A community-based mHealth diabetes screening intervention in Jodhpur Rajasthan.

Background: There is a paucity of demonstrated models for mHealth-based diabetes screening and coordinated care in India, especially in western Rajasthan, which is the part of Thar desert.

Materials And Methods: JSPH collaboratively developed and implemented an easy-to-use, noninvasive, mobile phone-based screening interview, to identify adults at high risk for diabetes. The high risk for diabetes was defined using multiple clinical and epidemiologic criteria, all based on the evidence for India and globally.

Burden of sickle cell disease in tribal students in institutions in southern Rajasthan - A pilot study.

Background & Objectives: Sickle cell disease (SCD), an inherited disorder of erythrocytes, is highly prevalent in the tribal population of India. The tribal population of India is approximately 100 million and it is necessary to identify the magnitude of this problem. Furthermore, the prevalence of the disease is unknown among the five million tribal people of southern provinces of Rajasthan.

Effectiveness and feasibility of methanol extracted latex of Calotropis procera as larvicide against dengue vectors of western Rajasthan, India.

Background & Objectives: Identification of novel effective larvicide from natural resources is essential to combat developing resistances, environmental concerns, residue problems and high cost of synthetic insecticides. Results of earlier laboratory findings have shown that Calotropis procera extracts showed larvicidal, ovicidal and refractory properties towards ovipositioning of dengue vectors; further, latex extracted with methanol was found to be more effective compared to crude latex. For testing efficacy and feasibility of extracted latex in field, the present study was undertaken in different settings of Jodhpur City, India against dengue vectors.

Oxidized Ca(2+)/calmodulin-dependent protein kinase II triggers atrial fibrillation.

Background: Atrial fibrillation (AF) is a growing public health problem without adequate therapies. Angiotensin II and reactive oxygen species are validated risk factors for AF in patients, but the molecular pathways connecting reactive oxygen species and AF are unknown. The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has recently emerged as a reactive oxygen species-activated proarrhythmic signal, so we hypothesized that oxidized CaMKIIδ could contribute to AF.

Genetic inhibition of Na+-Ca2+ exchanger current disables fight or flight sinoatrial node activity without affecting resting heart rate.

Rationale: The sodium-calcium exchanger 1 (NCX1) is predominantly expressed in the heart and is implicated in controlling automaticity in isolated sinoatrial node (SAN) pacemaker cells, but the potential role of NCX1 in determining heart rate in vivo is unknown.

Objective: To determine the role of Ncx1 in heart rate.

Methods And Results: We used global myocardial and SAN-targeted conditional Ncx1 knockout (Ncx1(-/-)) mice to measure the effect of the NCX current on pacemaking activity in vivo, ex vivo, and in isolated SAN cells.

Calmodulin-dependent protein kinase II: linking heart failure and arrhythmias.

Understanding relationships between heart failure and arrhythmias, important causes of suffering and sudden death, remains an unmet goal for biomedical researchers and physicians. Evidence assembled over the past decade supports a view that activation of the multifunctional Ca(2+) and calmodulin-dependent protein kinase II (CaMKII) favors myocardial dysfunction and cell membrane electrical instability. CaMKII activation follows increases in intracellular Ca(2+) or oxidation, upstream signals with the capacity to transition CaMKII into a Ca(2+) and calmodulin-independent constitutively active enzyme.

Oxidized CaMKII causes cardiac sinus node dysfunction in mice.

Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress.

Proarrhythmic defects in Timothy syndrome require calmodulin kinase II.

Background: Timothy syndrome (TS) is a disease of excessive cellular Ca(2+) entry and life-threatening arrhythmias caused by a mutation in the primary cardiac L-type Ca(2+) channel (Ca(V)1.2). The TS mutation causes loss of normal voltage-dependent inactivation of Ca(V)1.

Entomological studies for surveillance and prevention of dengue in arid and semi-arid districts of Rajasthan, India.

Background & Objectives: Rajasthan is one of the dengue endemic states of India. Very few studies have been published on entomological aspects of dengue in this state. Owing to water scarcity, inhabitants in desert areas overstore domestic water which leads to the persistence of dengue vectors within the domestic premises.

Importance of socioeconomic status and tree holes in distribution of Aedes mosquitoes (Diptera: Culicidae) in Jodhpur, Rajasthan, India.

Immature Aedes mosquitoes were found in domestic, peridomestic, and tree hole habitats within three socioeconomic strata of Jodhpur, a city within an arid area of Rajasthan, India, endemic for dengue. Peridomestic habitats served as a persistent source of Aedes vectors, especially those used for watering cows for religious reasons that were located within high socioeconomic areas. Domestic (indoor) containers within low socioeconomic strata showed a higher container index (27.

Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.

Rationale: In order to determine the possible relationship between antipsychotic drug properties and inverse agonist activity at h5HT6 and h5HT7 receptors, constitutively activated forms of these receptors were created by site-specific mutagenesis. Typical and atypical antipsychotic drugs were assayed for their potencies as inverse agonists at these mutated receptors.

Objectives: Stable cell lines expressing constitutively activated forms of the h5HT6 and h5HT7 receptors were created.

Arylguanidine and arylbiguanide binding at 5-HT3 serotonin receptors: a QSAR study.

For a series of monosubstituted arylguanidines, 5-HT3 receptor affinity was found generally related to the electron withdrawing nature of the substituent at the aryl 3-position and the lipophilicity of the 4-position substituent. A broader examination of 35 arylguanidines and arylbiguanides revealed that affinity could be described by molecular polarizability, a Chi index term (8chiP), and the sum of all (-Cl) E-State values (SsCl) in the molecule.

Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors.

On the basis of an earlier finding that 5-methyl-5H-1,2,3,4-tetrahydropyrido[4,3-b]indole (5-methyl-1,2,3,4-tetrahydro-gamma-carboline; 1) binds at murine 5-HT(5A) receptors, preliminary structure-affinity studies were conducted. The present investigation extends these structure-affinity studies using human 5-HT(5A) receptors and examined additional analogues of 1. It was found (a) that there is little interspecies difference for the affinities of these compounds, (b) that an intact 1,2,3,4-tetrahydro-gamma-carboline ring system seems optimal and an N(2)-(3-(substituted-phenoxy)propyl) moiety results in high affinity, (c) that structurally related 1,2,3,4-tetrahydro-beta-carbolines also bind at 5-HT(5A) receptors, and (d) that all examined derivatives also possess affinity for 5-HT(2A) receptors.

Conformationally-restricted analogues and partition coefficients of the 5-HT3 serotonin receptor ligands meta-chlorophenylbiguanide (mCPBG) and meta-chlorophenylguanidine (mCPG).

The present investigation examined two features of arylbiguanide and arylguanidine 5-HT(3) ligands: conformation and partition coefficients. Several conformationally-constrained analogues of mCPBG (2) and mCPG (11; K(i)=32 nM) were prepared and of these only 2-amino-5-chloro-3,4-dihydroquinazoline (14; K(i)=34 nM) retained high affinity. The partition coefficient of compound 11 (LogP(app)=-0.

gamma-Carbolines: binding at 5-HT5A serotonin receptors.

Screening of various agents resulted in the identification of 5-methyl-1,2,3,4-tetrahydro-gamma-carboline (1; K(i)=5,300 nM) as a compound with modest affinity for mouse 5-HT(5A) receptors. Structure-affinity studies were conducted resulting in 5-methyl-2-[3-(4-fluorophenoxy)propyl]-1,2,3,4-tetrahydro-gamma-carboline (17; K(i)=13 nM). Although 17 also binds at 5-HT(2) receptors, it serves as a novel lead for the further development of 5-HT(5A) ligands.

Creation, expression, and characterization of a constitutively active mutant of the human serotonin 5-HT6 receptor.

The serotonin 5-HT(6) receptor, a G-protein-coupled receptor, displays high affinity for antipsychotic, antidepressant, and psychotropic drugs. We created a constitutively active form of the human 5-HT(6) receptor in order to probe the molecular domains of receptor activation and to determine if inverse agonist activities of antipsychotic drugs contribute to their clinical profile. Previous studies from our laboratory support a critical role for the c-terminal region of the third intracellular loop (il3) in the activation of G(q)-coupled serotonin receptors.

Constitutive activity of G-protein coupled receptors: emphasis on serotonin receptors.

Several lines of evidence indicate that G-protein coupled receptors (GPCR) may exist in a state that allows a tonic level of stimulation in vivo (constitutive activity). Several native forms of GPCR, when expressed in recombinant cell lines, display significant signal transduction stimulation in the absence of activating ligand. Many GPCR, including three serotonin receptors, display robust constitutive activation upon the mutation of a single amino acid, indicating mutations producing inappropriate constitutive activation may be etiological factors in diseases.