Chronic pain is highly prevalent in the United States, impacting 28.4% of the adult population, or 69.6 million people, as of 2016. Chronic pain is often associated with anxiety, depression, and restrictions in mobility and daily activities, substantially reducing quality of life. Analgesics, especially opioids, are one of the primary pharmaceutical treatment methods for chronic pain. However, prescription opioid misuse and abuse has become increasingly prevalent and concerning, prompting the need for research into alternative treatment methods which avoid the side effects of traditional treatments. Chronic pain is, in part, thought to be the result of oxidative stress and inflammation, and clinical research has indicated links between these conditions and diet. Thus, dietary interventions are a particularly promising therapeutic treatment for chronic pain, with numerous studies suggesting that diet has a noticeable effect on pain as far down as the cellular level. In this review article, data from a number of clinical trials assessing the effect of three diets-antioxidant-rich, low-carbohydrate, and Mediterranean-on oxidative stress and inflammation is compiled and discussed in the context of chronic pain. Clinical data suggests that low-carbohydrate diets and Mediterranean diets both are especially promising dietary interventions.
Nodal-related protein (ndr2) is a member of the transforming growth factor type β superfamily of factors and is required for ventral midline patterning of the embryonic central nervous system in zebrafish. In humans, mutations in the gene encoding nodal cause holoprosencephaly and heterotaxy. Mutations in the zebrafish, Danio rerio, ndr2 gene lead to similar phenotypes, including loss of medial floor plate, severe deficits in ventral forebrain development, and cyclopia. Alleles of the ndr2 gene have been useful in studying patterning of ventral structures of the central nervous system. Fifteen different ndr2 alleles have been reported in zebrafish, eight of which are from chemical mutagenesis, four are radiationinduced, and the remaining alleles were obtained by random insertion, gene targeting (TALEN) or unknown. Therefore, most mutation sites were random and could not be predicted a priori. Using the CRISPR-Cas9 system from Streptococcus pyogenes, we targeted distinct regions in all three exons of ndr2 and observed cyclopia in the injected (G0) embryos. We show that the use of sgRNA-Cas9 ribonucleoprotein (RNP) complexes can cause penetrant cyclopic phenotypes in injected (G0) embryos. Targeted PCR amplicon analysis using Sanger sequencing showed that most of the alleles have small indels resulting in frameshifts. The sequence information correlates with the loss of ndr2 activity. In this study, we validate multiple CRISPR targets using an in vitro nuclease assay and in vivo analysis using embryos. We describe one specific mutant allele in detail that results in the loss of the conserved terminal cysteine coding sequences. This study is another demonstration of the utility of CRISPR-Cas9 system in generating domain-specific mutations and provides further insights into structure-function of ndr2 gene.
Nodal-related protein (ndr2) is a member of the transforming growth factor type β superfamily of factors and is required for ventral midline patterning of the embryonic central nervous system in zebrafish. In humans, mutations in the gene encoding nodal cause holoprosencephaly and heterotaxy. Mutations in the ndr2 gene in the zebrafish (Danio rerio) lead to similar phenotypes, including loss of the medial floor plate, severe deficits in ventral forebrain development, and cyclopia. Alleles of the ndr2 gene have been useful in studying patterning of ventral structures of the central nervous system. Fifteen different ndr2 alleles have been reported in zebrafish, of which eight were generated using chemical mutagenesis, four were radiation-induced, and the remaining alleles were obtained via random insertion, gene targeting (TALEN), or unknown methods. Therefore, most mutation sites were random and could not be predicted a priori. Using the CRISPR-Cas9 system from Streptococcus pyogenes, we targeted distinct regions in all three exons of zebrafish ndr2 and observed cyclopia in the injected (G0) embryos. We show that the use of sgRNA-Cas9 ribonucleoprotein (RNP) complexes can cause penetrant cyclopic phenotypes in injected (G0) embryos. Targeted PCR amplicon analysis using Sanger sequencing showed that most of the alleles had small indels resulting in frameshifts. The sequence information correlates with the loss of ndr2 activity. In this study, we validate multiple CRISPR targets using an in vitro nuclease assay and in vivo analysis using embryos. We describe one specific mutant allele resulting in loss of conserved terminal cysteine-coding sequences. This study is another demonstration of the utility of the CRISPR-Cas9 system in generating domainspecific mutations and provides further insights into the structure-function of the ndr2 gene..
Cladding is widely used in manufacturing industries for the production of pressure vessel by depositing thick layer of filler material for providing corrosion resistant-surface. The use of metal cored wire in gas metal arc welding (GMAW) process is popular due to its higher deposition rate and productivity. This work investigates the effect of process parameters on the deposition of cladding layer with ER 309L metal core wire (as filler material) on a corrosion resistant material (IS 2062). The welding parameters viz., wire feed rate (WFR), voltage (V), welding speed (S) and nozzle to plate distance (NTD) are employed as process parameters while penetration (P), bead width (W), reinforcement (R), weld penetration shape factor (WPSF) and weld reinforcement form factor (WRFF) as welding responses. The predictive model developed for P, W, R, WPSF, and WRFF using the response surface methodology (RSM) approach is found adequate at 95% confidence interval. The validation results for the developed model results in a model accuracy (MA) of 92.82%, 96.34%, 91.47% 88.98% and 87.75% for model P, W, R, WPSF, and WRFF respectively and it shows higher predictability and accuracy. The process parameters are optimized simultaneously with integrated optimization approach using RSM with Jaya algorithm and obtain optimal solution in less than 20 number of iterations. The minimum fitness value obtained as 1.3008 at an optimal parameter setting of WFR = 12 m min−1, V = 26 V, S = 280 mm min−1, NTD = 10 mm. The validation result at the optimal parameter setting results in an improvement of 6.45%, 11.29%, 13.58%, 16.07%, 15.38% is noted for P, W, R, WPSF, and WRFF respectively.
State have every right over its natural resources, they have the right to exploit and preserve their natural resources. Under International Law states have permanent sovereignty over their natural resources. The natural resources located within the territorial jurisdiction of sovereign state belong to the community i.e. the people themselves. Never the less the principle has received the renewed emphasis offer the initiation of the ages of decolonization. The principle of the permanent sovereignty over natural resources has been develop and reiterated in number of pertinent initiatives taken by the international organizations. There are number of provisions relating to permanent sovereignty over natural resources are embodied in the resolutions of the United Nations General Assembly while other are contained in international contentious or treaties. This paper will be analyzing the concept of sovereignty of the state over the natural resources. The right of state over its natural resources has been an inherent right of every nation. Paper will be analyzing the various initiatives taken by the international organization for the protection of this concept of sovereignty of states over natural resources. This entitlement of the rights to the state will ensure the Human Rights to its nationals.
BACKGROUNDThe frequency of abdominal disorders in HIV/ AIDS patients is second only to pulmonary diseases. The degree of immunodeficiency is related to the level of CD4+ counts, which is a good index for monitoring the disease progression. It is expected that as the immune status decreases, susceptibility to infection and consequently abnormal sonographic findings should increase.The aim of the study was to perform abdominal ultrasonography in adult HIV-infected patients and correlate these findings with CD4 counts of these patients. MATERIALS AND METHODS100 adult HIV infected patients were scanned with abdominal ultrasonography and the findings were documented and correlated with their CD4+ counts. Statistical Analysis Used-Data analysis was done using SPSS 21.0. Two-tailed 'p' values < 0.05 were considered significant. Settings and Design-This was a prospective cross-sectional study using sample size of 100 HIV infected patients, conducted at the Department of Radiodiagnosis and Imaging, Gandhi Medical College and Hamidia Hospital, Bhopal from March 2015 to September 2016. RESULTSSplenomegaly, splenic granuloma, focal hypoechoic liver lesions, renomegaly, lymphadenopathy and ascites showed significant correlation with CD4 counts. Incidence of increased renal echogenicity, bowel thickening and hepatomegaly was higher in low CD4 classes, but no statistically significant correlation was found. CONCLUSIONAbdominal ultrasonography is an excellent and sensitive modality for routine screening of HIV infected patients and focussed assessment in lower CD4 classes and help in early detection of both infective and neoplastic aetiologies. It can also help in guided FNAC/ Biopsies in suspected cases of neoplasms.
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