MIR204 n.37C>T variant as a cause of chorioretinal dystrophy variably associated with iris coloboma,early-onset cataracts and congenital glaucoma

Four members of a three-generation Czech family with early-onset chorioretinal dystrophy were shown to be heterozygous carriers of the n.37C>T in MIR204. The identification of this previously reported pathogenic variant confirms the existence of a distinct clinical entity caused by a sequence change in MIR204. Chorioretinal dystrophy was variably associated with iris coloboma, congenital glaucoma, and premature cataracts extending the phenotypic range of the condition. In silico analysis of the n.37C>T variant revealed 713 novel targets. Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants. Haplotype analysis excluded relatedness with the original family reported to harbour the n.37C>T variant in MIR204. Identification of a second independent family confirms the existence of a distinct MIR204-associated clinical entity and suggests that the phenotype may also involve congenital glaucoma.     

Increase in the effectiveness of somatodendritic 5-HT-1A receptors in a rat model of tardive dyskinesia

The present study concerns responsiveness of pre- and postsynaptic 5-hydroxytryptamine (5-HT)-1A receptors in a rat model of tardive dyskinesia (TD). Vacuous chewing movements (VCMs) in rats are widely accepted as an animal model of TD. Results show that haloperidol injected at a dose of 1 mg/kg twice a day for 5 weeks elicited VCMs, which increased in a time dependent manner following the drug administration for 3-5 weeks. Tolerance was produced in motor coordination during the potentiation of VCMs. Exploratory activity in an open field and in an activity box decreased in haloperidol treated animals. The effects of 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT; 0.5 mg/kg) were monitored 48-h after withdrawal from repeated administration of haloperidol. 8-OH-DPAT-induced locomotion was greater in haloperidol treated rats. 5-HT synthesis increased in haloperidol treated animals, while 8-OH-DPAT-induced decreases of 5-HT synthesis were greater in repeated haloperidol than repeated saline injected animals. The results suggest that an increase in the effectiveness of somatodendritic 5-HT-1A receptors may decrease the inhibitory influence of 5-HT on the activity of dopaminergic neurons to precipitate VCMs. The 5-HT-1A agonist may help to alleviate neuroleptic-induced TD.     

Unsymmetrical 1,3-disubstituted urea derivatives as α-chymotrypsin inhibitors

The objective of this study was to synthesize potent and/or novel inhibitors for α-chymotrypsin activity. Eighteen derivatives of N-methylphenyl-N′-(alkyl/aryl) urea (1–18) were synthesized, and their inhibitory effects on α-chymotrypsin enzyme were evaluated. Two compounds exhibited potent inhibitory activities. The most potent, N-(2-methylphenyl)-2-oxo-1-pyrrolidinecarboxamide (15) having a methyl group at ortho position was the most active inhibitor with an IC₅₀ value of 8.10 ± 0.14 μM, which was comparable to standard chymostatin (IC₅₀ = 8.24 ± 0.11 μM). A slightly less potent, N-(2-acetylphenyl)-N′-(3-methylphenyl) urea (10), exhibited an IC₅₀ of 13.6 ± 0.23 μM. Compounds 3, 4, 7, 11, and 13 exhibited moderate activities. The results demonstrated that α-chymotrypsin inhibition is related to the position of the methyl group and the presence of substituent at the nitrogen of the urea bridge. The inhibitory trend suggests that α-chymotrypsin inhibitory activity declines with ortho > meta > para substitution order. In conclusion, our data suggest that the compound 15 may serve as a lead compound for further designing of other potent or novel α-chymotrypsin inhibitors.     

Population genetic data of 30 insertion–deletion markers in Punjabi population of Pakistan

Insertion–deletion polymorphism (Indels) is valuable diallelic markers for forensic as well as parentage analysis. The Investigator DIPplex Kit (Qiagen) contains thirty autosomal Indels markers along with amelogenin. These thirty markers were tested in the Pakistani Punjabi Population but no significant deviations were observed from Hardy–Weinberg equilibrium rule expectations (Bonferroni corrected) except HLD58, HLD56, HLD99, and HLD40. The mean expected and observed heterozygosity was found 0.4701 and 0.4667 respectively; combined matching probability was computed as 7.31867 × 10−13. However, the use of the 30 Indels markers proved to be a good supplementary tool in forensic casework, particularly when evidence sample is highly degraded. The significant genetic differences were also observed between the Punjabi and other populations of the world.     

Effectiveness of School-Based Intervention Programs in Reducing Prevalence of Overweight

Objectives:

To assess the effectiveness of school-based interventions program in reducing the prevalence of overweight or obesity among schoolchildren.

Data source:

Ovid Medline (1950-December 2012), Embase (1980-2012), CINAHL (1982-2012), secondary references, review articles, and expert in the field.

Study selection:

All published clinical trials were eligible for study if were randomized, methodologically strong-based on a validity assessment, aimed to evaluate a school-based intervention for childhood overweight or obesity, and measured outcome in term of prevalence/incidence difference in overweight and obesity among both groups. Studies involved in cost-effective analysis of school-based intervention have been excluded. Data from eligible studies abstracted and pooled for relative risk.

Results:

Five trials with 3,904 schoolchildren were included. Mean age of the students (boys and girls) ranges 8.6-12.6 years. Meta-analysis showed a statistical significance beneficial effect of school-based intervention programs on obesity status of schoolchildren (risk ratio (RR) 0.58, 95% confidence interval (CI) 0.43-0.78) and suggested 42% reduction in prevalence of obesity among schoolchildren through school-based intervention programs. Individual studies also showed effectiveness of these school-based interventions.

Conclusion:

School-based intervention programs are effective in prevention of childhood overweight and obesity problem and our results quantitatively supported this argument.     

Recent updates on the bioactive compounds of the marine-derived genus Aspergillus

The genus Aspergillus is widely distributed in terrestrial and marine environments. In the marine environment, several Aspergillus species have proved their potential to produce a plethora of secondary metabolites including polyketides, sterols, fatty acids, peptides, alkaloids, terpenoids and miscellaneous compounds, displaying a variety of pharmacological activities such as antimicrobial, cytotoxicity, anti-inflammatory and antioxidant activity. From the beginning of 2015 until December 2020, about 361 secondary metabolites were identified from different marine Aspergillus species. In our review, we highlight secondary metabolites from various marine-derived Aspergillus species reported between January 2015 and December 2020 along with their biological potential and structural aspects whenever applicable.

The genus Aspergillus is widely distributed in terrestrial and marine environments.     

Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review

This review examines the association between the apolipoprotein (apo) var epsilon gene polymorphism (or its protein product (apo E)), metabolic regulation of cholesterol, and cardiovascular disease. The apo var epsilon gene is located at chromosome 19q13.2. Among the variants of this gene, alleles (*) epsilon2, (*) epsilon3, and (*) epsilon4 constitute the common polymorphism found in most populations. Of these variants, apo (*) epsilon3 is the most frequent (>60%) in all populations studied. The polymorphism has functional effects on lipoprotein metabolism mediated through the hepatic binding, uptake, and catabolism of chylomicrons, chylomicron remnants, very low density lipoprotein (VLDL), and high density lipoprotein subspecies. Apo E is the primary ligand for two receptors, the low density lipoprotein (LDL) receptor (also known as the B/E receptor) found on the liver and other tissues and an apo E-specific receptor found on the liver. The coordinate interaction of these lipoprotein complexes with their receptors forms the basis for the metabolic regulation of cholesterol. Allelic variation in apo var epsilon is consistently associated with plasma concentrations of total cholesterol, LDL cholesterol, and apo B (the major protein of LDL, VLDL, and chylomicrons). Apo var epsilon has been studied in disorders associated with elevated cholesterol levels or lipid derangements (i.e., hyperlipoproteinemia type III, coronary heart disease, strokes, peripheral artery disease, and diabetes mellitus). The apo var epsilon genotype yields poor predictive values when screening for clinically defined atherosclerosis despite positive, but modest associations with plaque and coronary heart disease outcomes. In addition to genotype-phenotype associations with vascular disease, the alleles and isoforms of apo var epsilon have been related to dementias, most commonly Alzheimer's disease.     

Effect of gestational age on cord blood plasma copper,zinc, magnesium and albumin

BACKGROUND: The transport of essential trace elements from mother to fetus varies throughout gestation, and the role of transport proteins in the neonate and the mother may change during pregnancy. Magnesium, often used as tocolytic agent, may reach the fetus and appear in cord blood at higher than normal concentrations. AIMS: To determine cord blood plasma zinc, copper and magnesium concentrations, as well as plasma albumin in premature and full-term newborns, and correlate these values with those of maternal blood plasma at birth. Also, to examine whether cord blood plasma concentration of these elements varies with gestational age. SUBJECTS: The 35 mother-infant pairs included: 11 in the 38-42-week gestational age (GA), 9 in the 34-37-week GA, 11 in the 29-33-week GA group and 4 in the 24-28-week GA. Magnesium for tocolysis was given to five of the mothers in the 29-33-week GA cohort and two of the women giving birth at 24-28-week GA. RESULTS: Trend analysis showed that while cord plasma zinc decreased with GA at birth, the reverse was observed for copper. There were no differences with GA either in maternal plasma zinc or copper. However, maternal ceruloplasmin tended to decrease with GA (P=0.0174). Maternal and cord blood plasma magnesium exhibited a strong correlation (r=0.942, P<0.001), as well as between cord plasma magnesium and zinc (r=0.448, P<0.01). CONCLUSIONS: While the vigorous mother-to-fetus uphill zinc transfer is clear throughout the last trimester, copper remains in cord blood plasma at much lower concentrations than in the mother, suggesting that prematurity may place the newborn infant at a greater risk than the term infant to copper deficiency. This situation, together with a reduced synthesis in the fetus of the transport protein ceruloplasmin, creates another potential challenge in the nutritional support of the premature infant.