Fine mapping by genetic association implicates the chromosome 1q23.3 gene UHMK1, encoding a serine/threonine protein kinase, as a novel schizophrenia susceptibility gene.

BACKGROUND: Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects. RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers. CONCLUSIONS: These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia.     

Oral contraceptive pills induced hemichorea in an adolescent female with polycystic ovarian disease

Chorea is a neurological adverse effect of oral contraceptive pills (OCPs). The onset of chorea following OCPs usage varies widely from few weeks to several years. We report a rare case of chorea which developed within a week of starting OCPs in an adolescent girl with polycystic ovarian disease.KEY WORDS: Chorea, oral contraceptive pills, polycystic ovarian disease     

Eco-friendly microbial route to synthesize cobalt nanoparticles using Bacillus thuringiensis against malaria and dengue vectors

The developments of resistance and persistence to chemical insecticides and concerns about the non-target effects have prompted the development of eco-friendly mosquito control agents. The aim of this study was to investigate the larvicidal activities of synthesized cobalt nanoparticles (Co NPs) using bio control agent, Bacillus thuringiensis against malaria vector, Anopheles subpictus and dengue vector, Aedes aegypti (Diptera: Culicidae). The synthesized Co NPs were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), Field-emission scanning electron microscopy (FESEM) with energy dispersive X-ray spectroscopy, and Transmission electron microscopy (TEM). XRD analysis showed three distinct diffraction peaks at 27.03°, 31.00°, and 45.58° indexed to the planes 102, 122, and 024, respectively on the face-centered cubic cobalt acetate with an average size of 85.3 nm. FTIR spectra implicated role of the peak at 3,436 cm^?1 for O–H hydroxyl group, 2924 cm^?1 for methylene C–H stretch in the formation of Co NPs. FESEM analysis showed the topological and morphological appearance of NPs which were found to be spherical and oval in shape. TEM analysis showed polydispersed and clustered NPs with an average size of 84.81 nm. The maximum larvicidal mortality was observed in the cobalt acetate solution, B. thuringiensis formulation, and synthesized Co NPs against fourth instar larvae of A. subpictus and A. aegypti with LC₅₀ values of 29.16, 8.12, 3.59 mg/L; 34.61, 6.94, and 2.87 mg/L; r ² values of 0.986, 0.933, 0.942; 0.962, 0.957, and 0.922, respectively.     

Multiscale photonic imaging of the native and implanted cochlea

The cochlea of our auditory system is an intricate structure deeply embedded in the temporal bone. Compared with other sensory organs such as the eye, the cochlea has remained poorly accessible for investigation, for example, by imaging. This limitation also concerns the further development of technology for restoring hearing in the case of cochlear dysfunction, which requires quantitative information on spatial dimensions and the sensorineural status of the cochlea. Here, we employed X-ray phase-contrast tomography and light-sheet fluorescence microscopy and their combination for multiscale and multimodal imaging of cochlear morphology in species that serve as established animal models for auditory research. We provide a systematic reference for morphological parameters relevant for cochlear implant development for rodent and nonhuman primate models. We simulate the spread of light from the emitters of the optical implants within the reconstructed nonhuman primate cochlea, which indicates a spatially narrow optogenetic excitation of spiral ganglion neurons.

In the case of profound sensorineural hearing impairment, cochlear implants (CIs) partially restore hearing by providing auditory information to the brain via electrical stimulation of the spiral ganglion neurons (SGNs). CIs enable speech understanding in the majority of the ∼700,000 users worldwide. However, current clinical CIs are limited by their wide current spread (1) resulting in poor coding of spectral information (2). Recently, cochlear optogenetics was proposed for stimulating the auditory nerve by light (3–10). As light can be better confined in space, the spread of excitation in the cochlea is lower (3, 9–11) and, hence, future optical CIs (oCIs) promise improved speech comprehension—especially in noisy background—as well as greater music appreciation.For the technical development of oCIs toward a future medical device, major efforts are currently being undertaken to devise multichannel optical stimulators for the cochlea (10, 12–17). As is the case for the electrodes of current CIs, future oCIs will place multiple stimulation channels, here microscale emitters, along the tonotopic axis of the cochlea. Further development of the oCIs requires precise estimates of parameters such as scala tympani size, optimal probe stiffness, and bending radius. Moreover, cochlear optogenetics employs gene transfer to the SGNs for which adeno-associated viruses (AAVs) seem promising candidate vectors (3–5, 8). AAV delivery has used injection of virus suspension via the round window (4, 8) or directly into Rosenthal’s canal (5, 9, 10). Therefore, the volumes of Rosenthal’s canal and the scalae tympani, vestibuli and media needed to be evaluated in order to estimate the required virus load for injection. Finally, the sensorineural status of the cochlea is highly relevant for future gene therapy and CI stimulation, and hence, quantitative imaging of sensory cells and neurons is an important objective.Here, we employed multiscale X-ray phase-contrast tomography (XPCT) and light-sheet fluorescence microscopy (LSFM) and provide an analysis of cochlear morphology for mice, rats, gerbils, guinea pigs, and marmosets. Each of these animal models offers unique advantages for auditory research. The mouse is readily available for genetic manipulation (e.g., ref. 18). Channelrhodopsin-expressing transgenic lines are available also for rats (19, 20) that offer a larger cochlea and can carry heavier implants than mice (21–24). Similarly, gerbils and guinea pigs are established rodent models for auditory research with larger-sized cochleae. Moreover, gerbils, which have low-frequency hearing more similar to humans, have already been employed for cochlear optogenetics (5, 9, 10, 24). Finally, we analyzed the cochlea of the common marmoset, as an established nonhuman primate model for auditory research (e.g., refs. 25, 26). Marmosets possess a rich vocalization repertoire and share a pitch perception mechanism with humans (27). Therefore, we compared cochlear insertion of newly designed oCIs with electrical cochlear implants (eCI) and modeled the optical spread of excitation in the marmoset cochlea.     

Unusual Complication of Toxic Megacolon in Typhoid Colitis

Colitis is a rare manifestation of enteric fever in children. Toxic megacolon complicating typhoid colitis is even rarer and requires early recognition and aggressive management due to the high mortality associated with this condition. The authors report a rare case of Toxic megacolon secondary to typhoid colitis in a seven-year-old girl.     

Green synthesis of titanium dioxide nanoparticles using Psidium guajava extract and its antibacterial and antioxidant properties

Objective:To determine the efficacies of antibacterial and antioxidant activities of aqueous leaf extract of Psidium guajava mediated biosynthesis of titanium dioxide nanoparticles(TiO_2,NPs).Methods:Synthesized TiO_2 NPs were tested by disc diffusion method against against human pathogenic bacteria.The total antioxidant activity and phenolic content(Folin—Ciocalteau method) of synthesized TiO_2 NTs and aqueous plant extract were determined.The scavenging radicals were estimated hv DPPH method.The synthesized TiO_2 NPs were characterized by XRD,FTIR.FESEM and EDX,Results:FTIR spectra of synthesized TiO_2 NPs exhibited prominent peaks at 3410 cm~(-1)(alkynes),1 578 cm~(-1).1 451 cm~(-1)(alkanes),and 1 123 cm~(-1)(C-O absorption).The morphological characterization of synthesized TiO_2 NPs was analysed by FESEM which showed spherical shape and clusters with an average size of 32.58 nm.The maximum zone of inhibition was observed in the synthesized TiO_2 NPs(20 μg/mL) against Staphylococcus aureus(25 mm) and Escherichia coli(23 mm).The synthesized TiO_2 NPs showed more antibacterial activity than the standard antibiotic disk,tetracycline which drastically reduces the chances for the development of antibiotics resistance of bacterial species.The plant aqueous extract and synthesized TiO_2NPs were found to possess maximum antioxidant activity when compared with ascorbic acid.The content of phenolic compounds(mg/g) in Leaf aqueous extract and synthesized TiO_2 NPs were found to be 85.4 and 18.3 mgTA/g,respectively.Conclusions:Green synthesized TiO_2 NPs provides a promising approach can satisfy the requirement of large-scale industrial production hearing the advantage of low—cost,eco—friendly and reproducible.     

Effect of dietary selenite on N-nitrosodiethylamine-induced and phenobarbital promoted multistage hepatocarcinogenesis in rat: reflection in some minerals.

Selenium (Se), a dietary micronutrient, plays a vital role in cancer chemotherapy in many organs including the liver. We have studied the relationship between some minerals, which are essential in normal functioning of cells and anticancer effect of Se in N-nitrosodiethylamine (DEN) induced and phenobarbital (PB) promoted multistage hepatocarcinogenesis. Se (4 ppm through drinking water; as sodium selenite) was given to animals throughout the study, before initiation and during promotion phase of hepatocarcinogenesis, in a defined experimental protocol. Se, sodium, potassium, calcium and iron were measured either in hepatoma, or surrounding liver tissue or whole liver tissue and serum of experimental animals. DEN and PB treatment significantly (P < 0.001) increased potassium, calcium and iron levels in serum, while it decreased (P < 0.001) the Se and sodium levels when compared with control rats. We have also observed significantly increased (P < 0.001) sodium, calcium and iron levels in hepatoma and surrounding liver tissue, whereas, Se, and potassium level was found to be decreased (P < 0.001) when compared with control rats. Supplementation of selenite throughout the study, before initiation and during promotion stage significantly alters the above mineral content. Results showed that the most significant beneficial effect of selenium during hepatocarcinogenesis was exerted potentially in long-term continuous and/or before the initiation phase of carcinogenicity, rather than in the promotion phase. The present and previous results from our laboratory suggest that sub-optimal intake of a single trace mineral can have broad effects on chemotherapy, providing a framework for understanding the multiple beneficial effects of selenium in cancer chemoprevention.     

Associations between Dietary Patterns and Cardiometabolic Risk Factors—A Longitudinal Analysis among High-Risk Individuals for Diabetes in Kerala,India

The association between dietary patterns and cardiometabolic risk factors is not well understood among adults in India, particularly among those at high risk for diabetes. For this study, we analyzed the data of 1007 participants (age 30–60 years) from baseline and year one and two follow-ups from the Kerala Diabetes Prevention Program using multi-level mixed effects modelling. Dietary intake was measured using a quantitative food frequency questionnaire, and dietary patterns were identified using principal component analysis. Two dietary patterns were identified: a “snack-fruit” pattern (highly loaded with fats and oils, snacks, and fruits) and a “rice-meat-refined wheat” pattern (highly loaded with meat, rice, and refined wheat). The “snack-fruit” pattern was associated with increased triglycerides (mg/dL) (β = 6.76, 95% CI 2.63–10.89), while the “rice-meat-refined wheat” pattern was associated with elevated Hb1Ac (percentage) (β = 0.04, 95% CI 0.01, 0.07) and central obesity (OR 1.16, 95% CI 1.01, 1.34). These findings may help inform designing dietary interventions for the prevention of diabetes and improving cardiometabolic risk factors in high-diabetes-risk individuals in the Indian setting.