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Advanced stage is linked to prolonged patient and diagnostic interval for gastrointestinal (GI) cancers. However, objective evidence of this fact is not so forthcoming. Our aim was to study the effect of these intervals on the risk of advanced stage for GI cancers. We performed this retrospective cohort study to analyse the effect of patient and diagnostic intervals on final stage in seven types of GI cancers, during 2013 and 2022. Two groups of stage: early (TNM- 0, I, II) and advanced (TNM- III, IV), were formed. Outcome studied was interdependence between patient and diagnostic intervals and incidence of advanced stage. Binary logistic regression was applied to calculate odds ratio of having an advanced versus early stage as a function of duration of these delays, in the whole cohort. We used restricted cubic splines with five knots to study flexible and non-monotonic pattern of association between these delays and stage. In whole cohort of 1859 patients, median patient and diagnostic intervals of early and advanced cancers were 21 and 26 days and 120 and 45 days, respectively. There was a positive association between patient interval and advanced stage (odds ratio [OR], 1.04, confidence interval [CI], 1.035 to 1.045; P < 0.001) and negative association between diagnostic interval and advanced stage (odds ratio, 0.98, CI, 0.976 to 0.998; P-0.017), among all gastrointestinal cancers combined. Increased risk of advanced stage started from day one of patient interval and for diagnostic interval there was an initial decrease followed by subsequent increase in the risk of advanced stage beyond 26 days of diagnostic interval. Longer patient and diagnostic intervals increase the risk of advanced stage in gastrointestinal cancers. •Risk of advance stage in GI cancers is related to long patient and diagnostic intervals.•Lack of evidence on risk of advance stage with such intervals for many GI cancers.•Positive association in advance stage and patient interval in most GI cancers.•Bimodal link in diagnostic interval and advance stage: high risk after initial decline.

Psyllium and lactitol have been reported to increase fecal volume, moisture content and bowel movement frequency (BMF). However, the benefits of their combined use on constipation has not been examined. The aim of this study was to evaluate the effects of a 4-week intervention with lactitol and/or psyllium on bowel function in constipated volunteers. Adults (N = 172) who were diagnosed with functional constipation per Rome III criteria were randomized to four treatment groups: 10 g lactitol, 3.5 g psyllium, a combination of 10 g lactitol and 3.5 g psyllium, or placebo. The primary endpoint was change in BMF from Day 0 to 28 as compared to placebo. Secondary endpoints were assessed by inventories, including stool consistency, patient assessment of constipation symptoms and quality of life, relief of constipation, 24-h food recall, physical activity, product satisfaction and adverse events (AE). BMF increased by 3.0 BMs with lactitol, by 2.9 with psyllium, and by 3.1 with the combination, but was not different from placebo (3.7 BMs). Other clinical endpoints were similar between treatments. No serious AEs were reported. In conclusion, this study showed a similar effect on relief of constipation in all treatment groups. The treatments that were administered to the volunteers were well tolerated.

Free radicals have been implicated in cerebral ischemia reperfusion (IR) injury. Massive production of nitric oxide and superoxide results in continuous formation of peroxynitrite even several hours after IR insult. This can produce DNA strand nicks, hydroxylation and/or nitration of cytosolic components of neuron, leading to neuronal death. Peroxynitrite decomposition catalysts 5,10,15,20‐tetrakis(N‐methyl‐4′‐pyridyl)porphyrinato iron (III) (FeTMPyP) and 5,10,15,20‐tetrakis(4‐sulfonatophenyl)porphyrinato iron (III) (FeTPPS) have been demonstrated to protect neurons in in vitro cultures; however, their neuroprotective efficacy in cerebral IR injury has not been explored. In the present study, we investigated the efficacy and the therapeutic time window of FeTMPyP and FeTPPS in focal cerebral ischemia (FCI). FCI was induced according to the middle cerebral artery occlusion (MCAO) method. After 2 h of MCAO and 70 h of reperfusion, the extent of neurological deficits, infarct and edema volume were measured in Sprague–Dawley rats. FeTMPyP and FeTPPS were administered at different time points 2, 6, 9 and 12 h post MCAO. FeTMPyP and FeTPPS (3 mg kg−1, i.v.) treatment at 2 and 6 h post MCAO produced significant reduction in infarct volume, edema volume and neurological deficits. However, treatment at latter time points did not produce significant neuroprotection. Significant reduction of peroxynitrite in blood and nitrotyrosine in brain sections was observed on FeTMPyP and FeTPPS treatment. As delayed treatment of FeTMPyP and FeTPPS produced neuroprotection, we tested whether treatment had any influence over the apoptotic neuronal death. DNA fragmentation and in situ nick end‐labeling assays showed that FeTMPyP and FeTPPS treatment reduced IR injury‐induced DNA fragmentation. In conclusion, peroxynitrite decomposition catalysts (FeTMPyP and FeTPPS) produced prominent neuroprotection even if administered 6 h post MCAO and the neuroprotective effect is at least in part due to the reduction of peroxynitrite and apoptosis. British Journal of Pharmacology (2004) 142, 899–911. doi:10.1038/sj.bjp.0705811

Key messageA key genomic region was identified for resistance to FSR at 168 Mb on chromosome 6 in GWAS and haplotype regression analysis, which was validated by QTL mapping in two populations.Fusarium stalk rot (FSR) of maize is an economically important post-flowering stalk rot (PFSR) disease caused by Fusarium verticillioides. The pathogen invades the plant individually, or in combination with other stalk rot pathogens or secondary colonizers, thereby making it difficult to make accurate selection for resistance. For identification and validation of genomic regions associated with FSR resistance, a genome-wide association study (GWAS) was conducted with 342 maize lines. The panel was screened for FSR in three environments using standard artificial inoculation methodology. GWAS using the mixed linear model corrected for population structure and kinship was done, in which 290,626 SNPs from genotyping-by-sequencing were used. A total of 7 SNPs, five on chromosome 6 showing strong LD at 168 Mb, were identified to be associated with FSR. Haplotype regression analysis identified 32 haplotypes with a significant effect on the trait. In a QTL mapping experiment in two populations for validating the identified variants, QTLs were identified with confidence intervals having overlapped physical coordinates in both the populations on chromosome 6, which was closely located to the GWAS-identified variants on chromosome 6. It makes this genomic region a crucial one to further investigate the possibility of developing trait markers for deployment in breeding pipelines. It was noted that previously reported QTLs for other stalk rots in maize mapped within the same physical intervals of several haplotypes identified for FSR resistance in this study. The possibility of QTLs controlling broad-spectrum resistance for PFSR in general requires further investigation.

Pepper leaf curl virus (PepLCV) disease spread by Begomovirus and infected by whiteflies, is the most destructive disease of pepper worldwide. The genetic basis of resistance to PepLCV was studied in F 1 and F 2 generations developed from Punjab Lal (P 1 ) x Kashi Anmol (P 2 ) and back cross population (B 1 and B 2 ) for segregation analysis following a mixed inheritance model. Analysis of the segregation data revealed that PepLCV resistance in Punjab Lal is controlled by pooled additive genes and additive × additive polygenes. Whereas, the F 2 Mendelian population was segregated into 1:3 genetic ratio and showed monogenic recessive gene action. A total of 132 F 2:3 families were evaluated for PepLCV resistance in two separate trials identified eight QTLs on five linkage groups (LG1, LG3, LG5, LG7 and LG8). Out of eight QTLs, six were stable in both the trials except QPlcv.teri.1.1 and QPlcv.teri.8.4. The six QTLs identified in both seasons together explained 69.36% (F3/1st trial) and 58.69% (F 3 /2nd trial) of the total phenotypic variation. Three major QTLs were observed on LG8 QPlcv.teri.8.1 , QPlcv.teri.8.2 and QPlcv.teri.8.3 explained 7.82, 34.23 and 14.27 in F 3 /1st trial whereas 5.86, 28.99 and 12.02 in F 3 /2nd trial, respectively.

Given the dioecious nature of date palms, selecting an effective pollinizer bearing a substantial quantity of high-quality pollen is imperative. In this study, we investigated the effects of 11 male date palm cultivars from Tunisia on the production of female trees, fruit sets, and the characteristics of 'Deglet Nour' cultivar dates. The comparison of pollen germination rates showed that ABD1 and P169 pollens exhibited outstanding viability, with 98.7% and 98.3%, respectively. On the other hand, P169 pollen had the highest germination rate, at 86.3%. The most remarkable fruit set (90.7%) and retention rate (69.7%) were observed in response to P13 pollen. In response to the P165 pollinator, the fruit stood out among the resulting fruits for their notable weight, averaging 11.6 g. In addition, pollination with P90 increased total soluble solids (measured at 74.4°Brix in the Tamr stage), whereas P7-pollinated fruits recorded the highest levels of reducing sugars, reaching 41%. Notably, the highest acidity levels were found in P7-pollinated fruits (0.29%), and pollen sources significantly influenced the fruits' mineral content. Moreover, regarding pomological characteristics, fruits pollinated with P4 attained maximum size, measuring 4.10 cm. Conversely, P7-pollinated fruits had a notable width of 2.02 cm. These findings illustrate the possibility of the selective application of high-value pollinizers and emphasize the direct influence of pollen sources on fruit quantity and quality.

Objective To study the correlation of objective parameters for diagnosing shock viz., perfusion index (PI), plethysmography variability index (PVI) and serum lactate (SL) with invasive blood pressure in late preterm and term infants with shock. Methods Prospective observational study (diagnostic test) conducted at the neonatal intensive care unit of Kanchi Kamakoti CHILDS Trust Hospital, Chennai between June, 2018 and May, 2020. Term and late preterm neonates with shock were included in the study. PI, PVI, SL, SpO2 and heart rate were monitored. PI, PVI and SLL were recorded at 0,12, 24 and 72 hours of onset of shock. All the babies were followed up till discharge or death. Results Total 78 neonates were enrolled in the study. At 0 hour, SL and PVI had negative correlation ( P =0.002 and P =0.003) while PI had a weak-to-moderate positive correlation ( P =0.002) with invasive blood pressure. SL ≥4.65 had a sensitivity of 75% and specificity of 75.8%, and PI <0.455 had a sensitivity of 65%, and specificity of 58.6% for predicting invasive hypotension. PVI ≥23.5 had a sensitivity of 90% and specificity of 63.8% in predicting invasive hypotension. Conclusion PI has moderate positive correlation while SL and PVI have moderate negative correlation with invasive blood pressure. The cutoff values of SL ≥4.65, PI <0.45 and PVI ≥23.5 can predict invasive hypotension with good sensitivity and negative predictive value.

Cytoplasmic male sterility is an important trait in hybrid seed production. Restorer lines are required for production of F1 hybrid seed using cytoplasmic male sterile line. Restorer lines have been identified and characterized only in hot chili varieties of Capsicum annuum. In this study, we screened Bhut Jolokia genotypes for their ability to restore male fertility of a cytoplasmic male sterile line, CCA 4261. Data on fruit set, visual pollen score, pollen viability and anther sections in F1 hybrids of CCA 4261 and Bhut Jolokia showed that a functional restorer of fertility (Rf) gene was present in Bhut Jolokia genotype CC 215 but absent in other genotypes. The inheritance of this Rf gene conformed well with the incomplete dominance model for a single gene. However, the Rf linked marker, CRF-SCAR, known to be linked to Rf locus in C. annuum did not produce any amplicon in CC 215. Identification of restorer in Bhut Jolokia will help in developing high yielding F1 hybrids in this segment of super-hot peppers and increase farm income.