The rationale was to utilize a bioinformatics approach to identify miRNA binding sites in genes with single nucleotide mutations (SNPs) to discover pathways in heart failure (HF).
The objective was to focus on the genes containing miRNA binding sites with miRNAs that were significantly altered in end-stage HF and in response to a left ventricular assist device (LVAD).
Methods and Results
BEDTools v2.14.3 was used to discriminate SNPs within predicted 3′UTR miRNA binding sites. A member of the miR-15/107 family, miR-16, was decreased in the circulation of end-stage HF patients and increased in response to a LVAD (p<0.001). MiR-16 decreased Vacuolar Protein Sorting 4a (VPS4a) expression in HEK 293T cells (p<0.01). The SNP rs16958754 was identified in the miR-15/107 family binding site of VPS4a which abolished direct binding of miR-16 to the 3′UTR of VPS4a (p<0.05). VPS4a was increased in the circulation of end-stage HF patients (p<0.001), and led to a decrease in the number of HEK 293T cells in vitro (p<0.001).
We provide evidence that miR-16 decreases in the circulation of end-stage HF patients and increases with a LVAD. Modeling studies suggest that miR-16 binds to and decreases expression of VPS4a. Overexpression of VPS4a decreases cell number. Together, these experiments suggest that miR-16 and VPS4a expression are altered in end-stage HF and in response to unloading with a LVAD. This signaling pathway may lead to reduced circulating cell number in HF.
Castleman's disease is a rare autoimmune disorder with varied clinical presentations. Castleman's commonly involves mediastinum and hence it is thoracic in most of the reported cases. Paraneoplastic pemphigus (PNP) and myasthenia gravis can be associated with multicentric Castleman's disease. Its association with HIV, Kaposi sarcoma, and lymphoma is also well known. We report a rare combination of unicentric, extrathoracic Castleman's disease with PNP and myasthenia gravis.
Autoimmune; Castleman's disease; myasthenia gravis; pemphigus
We performed a genome-wide association study in non-Hispanic white subjects with fibrotic idiopathic interstitial pneumonias (N=1616) and controls (N=4683); replication was assessed in 876 cases and 1890 controls. We confirmed association with TERT and MUC5B on chromosomes 5p15 and 11p15, respectively, the chromosome 3q26 region near TERC, and identified 7 novel loci (PMeta = 2.4×10−8 to PMeta = 1.1×10−19). The novel loci include FAM13A (4q22), DSP (6p24), OBFC1 (10q24), ATP11A (13q34), DPP9 (19p13), and chromosomal regions 7q22 and 15q14-15. Our results demonstrate that genes involved in host defense, cell-cell adhesion, and DNA repair contribute to the risk of fibrotic IIP.
Vitamin D is known for maintaining calcium homeostasis and bone structure, and may also decrease susceptibility to chronic and infectious diseases. However, data on vitamin D status and its predictors among Southeast Asian populations is limited. We evaluated the distribution and determinants (genetic and environmental) of serum 25-hydroxyvitamin D (25(OH)D) concentrations among 504 middle-aged and elderly participants (aged 45–74 years) in the Singapore Chinese Health Study. Data on dietary and other lifestyle factors were collected by trained interviewers. Serum 25(OH)D concentrations and genetic polymorphisms in vitamin D metabolism pathway enzymes [cytochrome P450 (CYP) 2R1, 3A4, 27B1, 24A1; vitamin D binding protein (GC); and vitamin D receptor (VDR)] were measured using stored biospecimens. Mean 25(OH)D concentration was 68.8 nmol/L. Serum 25(OH)D concentrations were positively associated with dietary vitamin D intake, and inversely associated with hours sitting at work. BMI was not associated with 25(OH)D concentrations. CYP2R1 rs10741657, rs12794714, rs1993116; CYP3A4 rs2242480; and GC rs4588, rs7041, rs16847015, rs2298849 were statistically significantly associated with 25(OH)D concentrations. Individuals with the Gc2-2 haplotype (rs4588AA/rs7041TT) had statistically significantly lower 25(OH)D concentrations compared to all other Gc haplotypes (p-trend<0.001). The majority of participants (86%) had 25(OH)D concentrations ≥50 nmol/L, which is consistent with the 2011 Institute of Medicine (United States) recommendation for bone health, and 32% had concentrations of ≥75 nmol/L that are thought to be required for broader health effects. Dietary vitamin D intake, hours spent indoors at work, and genetic variation in CYP2R1, CYP3A4 and GC are significant predictors of 25(OH)D concentrations among Singapore Chinese.
25-hydroxyvitamin D; CYP2R1; CYP3A4; GC
Human Immunodeficiency Virusinfected women account for almost half the number of cases of HIV worldwide. Despite reduction in HIV prevalence among the population, the percentage of Indian women contracting the disease seems to have increased. The social implications are also different in females.
Materials and Methods:
This prospective observational study was conducted from September 2009 to July 2011 at tertiary care hospitals attached to the Kasturba Medical College Mangalore, on a group of 200 HIV-positive patients. Patients above 18 years of age diagnosed with HIV as per National AIDS Control Organisation guidelines were included in the study. Clinical profile among women and men was compared with respect to clinical presentation, disease detection, CD4 count and response of family and society.
Clinical presentation was similar among both men and women. Eighty-one percent men had promiscual sexual exposure, 19% of women had so. Males were identified to be HIV-positive earlier than their spouse (tested later), time lag being 27.6 weeks. After detection of positivity 77% of females felt being less cared for by the in-laws. CD4 count less than 50 was detected in more number of females as compared to men (11% females and 1% males). Death of spouse was seen more often in females (among 35% of women and 11% of men).
Most of the females were likely to acquire infection from their spouse. Females tend to seek and get medical attention at the late stage of disease as compared to men. HIV in females has different social implications which includes discrimination within the family.
CD4 count; females; HIV/AIDS; social
The asymmetric unit of the title compound, C9H11N3O2, contains two molecules (A and B), which exist in Z conformations with respect to their C=N double bond. The dihedral angles between the benzene ring and the pendant hydroxycarbamimidoyl and acetamide groups are 28.58 (7) and 1.30 (5)°, respectively, in molecule A and 25.04 (7) and 27.85 (9)°, respectively, in molecule B. An intramolecular N—H⋯N hydrogen bond generates an S(6) ring in both molecules. Molecule A also features an intramolecular C—H⋯O interaction, which closes an S(6) ring. In the crystal, the molecules are linked by N—H⋯O, N—H⋯N, O—H⋯O, O—H⋯N, C—H⋯O and C—H⋯N hydrogen bonds and C—H⋯π interactions, generating a three-dimensional network.
In the cation of the title compound, C9H12NO2
+·Cl−, the dihedral angle between the 2-oxoethanaminium N—C—C(=O)– plane [maximum deviation = 0.0148 (12) Å] and the benzene ring is 7.98 (8)°. The methoxy group is approximately in-plane with the benzene ring, with a C—O—C—C torsion angle of −2.91 (18)°. In the crystal, the cations and chloride anions are connected by N—H⋯Cl and C—H⋯Cl hydrogen bonds, forming a layer parallel to the bc plane. A C—H⋯π interaction further links the layers.
Fight against human immunodeficiency virus (HIV) is incomplete without addressing problems associated with difficult diagnosis of tuberculosis in HIV-Tuberculosis coinfected patients. Chest X-ray is a primary tool to evaluate tuberculosis in HIV.
To assess and compare various radiological patterns of pulmonary tuberculosis in HIV patients and compare these patterns in relation to CD4 counts.
Materials and Methods:
Prospective cohort study was conducted in a tertiary hospital in South India from September 2009 to July 2011 with 200 HIV positive patients. WHO guidelines were used for diagnosis of HIV and tuberculosis.
27% of the patients had sputum positive pulmonary tuberculosis, with higher incidence (33%) among CD4 less than 200 as compared to CD4 more than 200 (14%). Infiltration (39%) followed by consolidation (30%), cavity (11%), and lymphadenopathy (9%) seen with CD4 less than 200. Infiltration (37.5%) followed by cavity (25%) and miliary (25%) with CD4 above 200. Bilateral (68.5%) and mid and lower zones or all zone involvement more commonly seen.
In patients with CD4 lower than 200 noncavitory infiltration and consolidation predominated. Involvement of lungs was atypical; diffuse or mid and lower zone involvement than classical upper lobe involvement. A high index of suspicion is necessary for the accurate and timely diagnosis of tuberculosis in HIV positive patients.
CD4; HIV/AIDS; tuberculosis
In the title compound, C15H9Cl2N3O, an intramolecular C—H⋯O interaction generates an S(7) ring motif. The cyclopenta-1,3-diene ring forms dihedral angles of 1.93 (6) and 2.78 (6)° with its attached benzene rings. In the crystal, molecules are linked by C—H⋯N and C—H⋯O hydrogen bonds, thereby forming layers lying parallel to the ac plane. The crystal also features a π–π interaction with a centroid–centroid distance of 3.5612 (6) Å.
In the crystal of the title molecular salt, 2C6H7FN+·SO4
2−, the cations and anions are linked by N—H⋯O and C—H⋯O hydrogen bonds into sheets parallel to the ab plane. The crystal studied was found to be a racemic twin with a 0.50 (10):0.50 (10) domain ratio.
In the title compound, C10H13NO, the C—C—C—C torsion angle formed between the benzene ring and the butan-2-one oxime unit is 73.7 (2)°, with the latter lying above the plane through the benzene ring. In the crystal, intermolecular O—H⋯N hydrogen bonds link pairs of molecules into dimers, forming R
2(6) ring motifs which are stacked along the a axis.
In the title compound, C15H17N3O, the 1H-imidazo[4,5-c]quinoline ring system is approximately planar, with a maximum deviation of 0.036 (1) Å. The C—N—C—C torsion angles formed between this ring system and the isobutyl unit are −99.77 (16) and 79.71 (17)°. In the crystal, intermolecular C—H⋯O hydrogen bonds link the molecules into chains along the c axis.