Estimate of CRP and TNF-alpha level before and after periodontal therapy in cardiovascular disease patients

Introduction: Epidemiological studies show that individuals with periodontitis have a radically amplified threat to develop cardiovascular disease. CRP& TNF-α, are acute phase proteins monitored as a marker of inflammatory status, which have been identified as a major risk factor for atherosclerotic complications. Elevated CRP & TNF-α level in periodontitis patients have been reported by several groups. The present study was performed to determine whether presence of periodontitis and periodontal therapy could influence the serum levels of CRP & TNF-α in cardiovascular disease patients. Methods: Forty cardiovascular disease subjects participated in the study. They were classified into two groups. Group A (Control) where no periodontal treatment was given, Group B (Test) where periodontal treatment (scaling & root planing) was performed. Periodontal clinical parameters like OHI-S, probing pocket depth, were evaluated together with serum CRP, TNF-α, at baseline and reassessed after 8 weeks for all the subjects in both the groups. Results: The CRP & TNF-α levels in both the groups decreased but the decrease in the Group A was minimal and was not statistically significant (P>0.05); whereas in Group B where periodontal therapy was performed, there was statistically significant decrease. Conclusion: It can be concluded from the study that there can be a possible causal relationship between pathogenesis of periodontal disease and CVD as inferred from the statistical significant outcome in the form of decreased inflammatory biomarkers after the periodontal treatment.Key words: CVD, CRP, TNF-alpha, lipopolysaccharide, periodontiti

Rate of Freeze Impacts the Survival and Immune Responses Post Cryoablation of Melanoma.

The emergence of ablative therapies has revolutionized the treatment of inoperable solid tumors. Cryoablation stands out for its uniqueness of operation based on hypothermia, and for its ability to unleash the native tumor antigens, resulting in the generation of anti-tumor immune responses. It is not clearly understood how alterations in the rate of freeze impact the immune response outcomes. In this study, we tested fast freeze and slow freeze rates for their locoregional effectiveness and their ability to elicit immune responses in a B16F10 mouse model of melanoma. Tumor bearing mice treated with fast freeze protocol survived better than the ones treated with slow freeze protocol. Fast freeze resulted in a higher magnitude of CD4 <sup>+</sup> and CD8 <sup>+</sup> T-cell responses, and a significantly extended survival post re-challenge. Thus, fast freeze rate should be applied in any future studies employing cryoablation as an in vivo vaccination tool in conjunction with targeted immunotherapies

Stencil Printing-A Novel Manufacturing Platform for Orodispersible Discs

Stencil printing is a commonly used printing method, but it has not previously been used for production of pharmaceuticals. The aim of this study was to explore whether stencil printing of drug containing polymer inks could be used to manufacture flexible dosage forms with acceptable mass and content uniformity. Formulation development was supported by physicochemical characterization of the inks and final dosage forms. The printing of haloperidol (HAL) discs was performed using a prototype stencil printer. Ink development comprised of investigations of ink rheology in combination with printability assessment. The results show that stencil printing can be used to manufacture HAL doses in the therapeutic treatment range for 6-17 year-old children. The therapeutic HAL dose was achieved for the discs consisting of 16% of hydroxypropyl methylcellulose (HPMC) and 1% of lactic acid (LA). The formulation pH remained above pH 4 and the results imply that the drug was amorphous. Linear dose escalation was achieved by an increase in aperture area of the print pattern, while keeping the stencil thickness fixed. Disintegration times of the orodispersible discs printed with 250 and 500 mu m thick stencils were below 30 s. In conclusion, stencil printing shows potential as a manufacturing method of pharmaceuticals

A low-cost paper-based platform for fast and reliable screening of cellular interactions with materials

A paper-based platform was developed and tested for studies on basic cell culture, material biocompatibility, and activity of pharmaceuticals in order to provide a reliable, robust and low-cost cell study platform. It is based upon a paper or paperboard support, with a nanostructured Latex coating to provide an enhanced cell growth and sufficient barrier properties. Wetting is Limited to regions of interest using a flexographically printed hydrophobic polydimethylsiloxane Layer with circular non-print areas. The nanostructured coating can be substituted for another coating of interest, or the regions of interest functionalized with a material to be studied. The platform is fully up-scalable, being produced with roll-to-roll rod coating, flexographic and inkjet printing methods. Results show that the platform efficiency is comparable to multi-well plates in colorimetric assays in three separate studies: a cell culture study, a biocompatibility study, and a drug screening study. The color intensity is quantified by using a common office scanner or an imaging device and the data is analyzed by a custom computer software without the need for expensive screening or analysis equipment

Barley <i>SIX-ROWED SPIKE3</i> encodes a putative Jumonji C-type H3K9me2/me3 demethylase that represses lateral spikelet fertility

The VRS genes of barley control the fertility of the lateral spikelets on the barley inflorescence. Here, Bull et al. show that VRS3 encodes a putative Jumonji C-type histone demethylase that regulates expression of other VRS genes, and genes involved in stress, hormone and sugar metabolism

HOMEOBOX2, the paralog of SIX-ROWED SPIKE1/HOMEOBOX1, is dispensable for barley spikelet development

The HD-ZIP class I transcription factor Homeobox 1 (HvHOX1), also known as Vulgare Row-type Spike 1 (VRS1) or Six-rowed Spike 1, regulates lateral spikelet fertility in barley (Hordeum vulgare L.). It was shown that HvHOX1 has a high expression only in lateral spikelets, while its paralog HvHOX2 was found to be expressed in different plant organs. Yet, the mechanistic functions of HvHOX1 and HvHOX2 during spikelet development are still fragmentary. Here, we show that compared with HvHOX1, HvHOX2 is more highly conserved across different barley genotypes and Hordeum species, hinting at a possibly vital but still unclarified biological role. Using bimolecular fluorescence complementation, DNA-binding, and transactivation assays, we validate that HvHOX1 and HvHOX2 are bona fide transcriptional activators that may potentially heterodimerize. Accordingly, both genes exhibit similar spatiotemporal expression patterns during spike development and growth, albeit their mRNA levels differ quantitatively. We show that HvHOX1 delays the lateral spikelet meristem differentiation and affects fertility by aborting the reproductive organs. Interestingly, the ancestral relationship of the two genes inferred from their co-expressed gene networks suggested that HvHOX1 and HvHOX2 might play a similar role during barley spikelet development. However, CRISPR-derived mutants of HvHOX1 and HvHOX2 demonstrated the suppressive role of HvHOX1 on lateral spikelets, while the loss of HvHOX2 does not influence spikelet development. Collectively, our study shows that through the suppression of reproductive organs, lateral spikelet fertility is regulated by HvHOX1, whereas HvHOX2 is dispensable for spikelet development in barley

Genetic dissection of drought tolerance in chickpea (Cicer arietinum L.)

Chickpea (Cicer arietinum L.) is the second most important grain legume cultivated by resource poor farmers in the arid and semi-arid regions of the world. Drought is one of the major constraints leading up to 50 % production losses in chickpea. In order to dissect the complex nature of drought tolerance and to use genomics tools for enhancing yield of chickpea under drought conditions, two mapping populations—ICCRIL03 (ICC 4958 × ICC 1882) and ICCRIL04 (ICC 283 × ICC 8261) segregating for drought tolerance-related root traits were phenotyped for a total of 20 drought component traits in 1–7 seasons at 1–5 locations in India. Individual genetic maps comprising 241 loci and 168 loci for ICCRIL03 and ICCRIL04, respectively, and a consensus genetic map comprising 352 loci were constructed (http://cmap.icrisat.ac.in/cmap/sm/cp/varshney/). Analysis of extensive genotypic and precise phenotypic data revealed 45 robust main-effect QTLs (M-QTLs) explaining up to 58.20 % phenotypic variation and 973 epistatic QTLs (E-QTLs) explaining up to 92.19 % phenotypic variation for several target traits. Nine QTL clusters containing QTLs for several drought tolerance traits have been identified that can be targeted for molecular breeding. Among these clusters, one cluster harboring 48 % robust M-QTLs for 12 traits and explaining about 58.20 % phenotypic variation present on CaLG04 has been referred as “QTL-hotspot”. This genomic region contains seven SSR markers (ICCM0249, NCPGR127, TAA170, NCPGR21, TR11, GA24 and STMS11). Introgression of this region into elite cultivars is expected to enhance drought tolerance in chickpea

The genetic basis of composite spike form in barley and &quot;Miracle-Wheat&quot;

Inflorescences of the tribe Triticeae, which includes wheat (Triticum sp. L.) and barley (Hordeum vulgare L.) are characterized by sessile spikelets directly borne on the main axis, thus forming a branchless spike. "Compositum-Barley" and tetraploid "Miracle-Wheat" (T. turgidum convar. compositum (L.f.) Filat.) display non-canonical spike-branching in which spikelets are replaced by lateral branch-like structures resembling small-sized secondary spikes. As a result of this branch formation "Miracle-Wheat" produces significantly more grains per spike, leading to higher spike yield. In this study, we first isolated the gene underlying spike-branching in "Compositum-Barley", i.e. compositum 2 (com2). Moreover, we found that COM2 is orthologous to the branched head(t) (bh(t)) locus regulating spike-branching in tetraploid "Miracle-Wheat". Both genes possess orthologs with similar functions in maize BRANCHED SILKLESS 1 (BD1) and rice FRIZZY PANICLE/BRANCHED FLORETLESS 1 (FZP/BFL1) encoding AP2/ERF transcription factors. Sequence analysis of the bh(t) locus in a collection of mutant and wild type tetraploid wheat accessions revealed that a single amino acid substitution in the DNA-binding domain gave rise to the domestication of "Miracle-Wheat". mRNA in situ hybridization, microarray experiments, and independent qRT-PCR validation analyses revealed that the branch repression pathway in barley is governed through the spike architecture gene Six-rowed spike 4 regulating COM2 expression, while HvIDS1 (barley ortholog of maize INDETERMINATE SPIKELET 1) is a putative down-stream target of COM2. These findings presented here provide new insights into the genetic basis of spike architecture in Triticeae, and have disclosed new targets for genetic manipulations aiming at boosting wheat's yield potential

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years