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7-62.5) had first consulted a primary healthcare physician, and a third n = 287, 35.8 %, 95 % CI = 32.6-39.3) had consulted an appropriate specialist first. Presentation interval among those who visited an Ayurvedic physician first was significantly longer than other pathways (p < 0.0001). Diagnosis interval for those who consulted an appropriate consultant was significantly shorter than other pathways (p < 0.0001).

Women take up numerous care paths following self-detection of a breast lesion. Empowering women on appropriate care pathways and expanding dedicated breast clinics where women to be first seen by an appropriate specialist are likely to improve timely breast cancer care in Sri Lanka.

Women take up numerous care paths following self-detection of a breast lesion. Empowering women on appropriate care pathways and expanding dedicated breast clinics where women to be first seen by an appropriate specialist are likely to improve timely breast cancer care in Sri Lanka.

The incidence of metastatic spine disease (MSD) is increasing among cancer patients. Given the poor outcomes and high rates of morbidity associated with MSD, it is important to determine demographic factors that could impact interventions and outcomes for this patient population. The objectives of this study were to compare in-hospital mortality and complication rates, clinical presentation, and interventions between female and male patients diagnosed with MSD.

Patient data were collected from the United States National Inpatient Sample (NIS) database from the years 2012-2014. learn more Descriptive statistics were used to compare data from 51,800 cases; subsequently, multivariable logistic regression analyses were conducted to assess the effect of gender on outcomes.

Males had significantly higher rates of in-hospital mortality (OR 1.30; 95 % CI 1.09-1.56, p = 0.004) and were more likely to have received surgical intervention than females (OR 1.34; 95 % CI 1.16-1.55, p < 0.001). Additionally, female patients were more likely to present with vertebral compression fracture (p < 0.001), while metastatic spinal cord compression (MSCC) and paralysis were more common in male patients (p < 0.001). There was no significant difference in rates of in-hospital complications between female and male patients.

Given the significant differences in mortality, disease course, treatment, and in-hospital complications between female and male patients diagnosed with MSD, additional prospective studies are necessary to understand how to meaningfully incorporate these differences into clinical care and prognostication going forward.

Given the significant differences in mortality, disease course, treatment, and in-hospital complications between female and male patients diagnosed with MSD, additional prospective studies are necessary to understand how to meaningfully incorporate these differences into clinical care and prognostication going forward.The macronutrient potassium (K) has vital physiological functions in plants and its availability can strongly impact quality of crops like tomato. The impact of K nutrition on conventional tomato fruit quality parameters has been described several times, but detailed investigations on the effect of K supply on the fruit metabolite profile are still rare. To fill this gap, we investigated the influence of K fertilization on the metabolite profile of tomato fruits. For this purpose, an outdoor pot experiment with three different cocktail tomato cultivars was performed. A fertilization regimen with five K levels was applied, ranging from deficiency to sufficient supply. Fruit samples were analyzed by untargeted GC×GC-MS to cover the primary metabolite profile as well as some secondary metabolites. As verified using ICP-OES, fruit K content was highly proportional to the supplied amount of K. At the metabolite profile level, the most prominent and cultivar-independent effect of increased K fertilization was the rise of tricarboxylic acid (TCA) cycle intermediates. Further effects were more cultivar-specific, for example an increase of the mobile nitrogen pool (e.g. amines like putrescine and amides like asparagine), changes in the profile of minor sugars (especially disaccharides) as well as higher levels of some secondary metabolites. Pronounced response patterns were mainly observed in the cultivars Primavera and Yellow Submarine that were recently characterized as higher yielding, demanding a stronger consideration of cultivar differences in future studies.Canonical correlation analysis (CCA) serves to identify statistical dependencies between pairs of multivariate data. However, its application to high-dimensional data is limited due to considerable computational complexity. As an alternative to the conventional CCA approach that requires polynomial computational time, we propose an algorithm that approximates CCA using quantum-inspired computations with computational time proportional to the logarithm of the input dimensionality. The computational efficiency and performance of the proposed quantum-inspired CCA (qiCCA) algorithm are experimentally evaluated on synthetic and real datasets. Furthermore, the fast computation provided by qiCCA allows directly applying CCA even after nonlinearly mapping raw input data into high-dimensional spaces. The conducted experiments demonstrate that, as a result of mapping raw input data into the high-dimensional spaces with the use of second-order monomials, qiCCA extracts more correlations compared with the linear CCA and achieves comparable performance with state-of-the-art nonlinear variants of CCA on several datasets. These results confirm the appropriateness of the proposed qiCCA and the high potential of quantum-inspired computations in analyzing high-dimensional data.Cytochrome P450 (CYP) 3A-related drug-drug interaction (DDI) studies are needed during drug development to determine clinical interaction effects. We aimed to evaluate DDI between sildenafil and two CYP3A inhibitors, clarithromycin and itraconazole, regarding the changes in pharmacokinetics and endogenous markers. An open-label, one-sequence, one-period, two-treatment parallel study was conducted in 32 healthy Korean subjects. Each of 16 subjects were randomly assigned to the clarithromycin and itraconazole groups. Both groups received a single dose of sildenafil 25 mg as a control, and either clarithromycin 250 mg or itraconazole 100 mg was administered four times to inhibit CYP3A activity. Pharmacokinetics of sildenafil showed the similar magnitude of inhibitory effects of the two inhibitors on total CYP3A activity; both inhibitors similarly increased systemic exposure of sildenafil by 2-fold. Urinary 6β-OH-cortisone/cortisone and plasma 4β-OH-cholesterol were significantly decreased after clarithromycin administration but not after itraconazole. A significant correlation between sildenafil CL/F and metabolic markers of CYP3A activity was observed after clarithromycin administration. We confirmed that sildenafil has moderate pharmacokinetic interaction with clarithromycin and itraconazole. Endogenous markers well reflected the CYP3A inhibition of clarithromycin, suggesting possible utility in DDI study with moderate to strong CYP3A inhibition; however, there are limitations in predicting intestinal CYP3A mediated DDI.Intestinal cytochrome P450 3A (CYP3A) plays an important role in oral drug metabolism, but only endogenous metabolic markers for measuring hepatic CYP3A activity were identified. Our study evaluated whether hepatic CYP3A markers reflected intestinal CYP3A activity. An open-label, three-period, six-treatment, one-sequence clinical trial was performed in 16 healthy Korean males. In the control phase, all subjects received a single dose of intravenous (IV) and oral midazolam (1 mg and 5 mg, respectively). Clarithromycin (500 mg) was administered twice daily for 4 days to inhibit hepatic and intestinal CYP3A, and 500 mL of grapefruit juice was given to inhibit intestinal CYP3A. Clarithromycin significantly inhibited total CYP3A activity, and the clearance of IV and apparent clearance of oral midazolam decreased by 0.15- and 0.32-fold, respectively. Grapefruit juice only reduced the apparent clearance of oral midazolam by 0.84-fold, which indicates a slight inhibition of intestinal CYP3A activity. Urinary markers, including 6β-OH-cortisol/cortisol and 6β-OH-cortisone/cortisone, were significantly decreased 0.5-fold after clarithromycin administration but not after grapefruit juice. The fold changes in 6β-OH-cortisol/cortisol and 6β-OH-cortisone/cortisone did not correlate to changes in intestinal availability but did correlate to hepatic availability. In conclusion, endogenous metabolic markers are only useful to measure hepatic, but not intestinal, CYP3A activity.Quantification of human cells may be performed using quantitative polymerase chain reaction (qPCR). In preclinical studies, the human Alu sequence is widely used as biomarker for human DNA. However, because the Alu gene is shared by primates, its use is limited to non-primate studies. The biodistribution of human cells in primates is also necessary for translational studies. Therefore, we aimed to design a novel, human-specific primer/probe that enables the quantification of human cells in primates and other animal models. A novel primer/probe set was successfully designed based on highly repetitive LINE1 sequences. qPCR efficiency (94.95-99.21%) and linearity of calibration curves (r2 = 0.996-0.999) were confirmed in tissue homogenates of cynomolgus monkey. The lower limit of detection was 10 cells per 15-mg tissue sample, a sensitivity that is equivalent to existing Alu primers/probes. The set was also effective in other animal models such as mice, rabbits, pigs, and common marmosets. To our knowledge, this is the first study describing the successful design of a human-specific qPCR primer/probe for human cell quantification in various animals, including non-human primates, using LINE1 sequence. The excellent selectivity, sensitivity, and versatility of the LINE1 primers/probes make it a promising quantification tool in preclinical biodistribution studies.The effective application of cisplatin in the clinic as an antitumor treatment has stimulated widespread interest in inorganic metal drugs. In particular, complexes containing the transition metals platinum and gold have attracted considerable attention due to their antitumor effects. The Pt(II) and Au(III) Schiff-base complexes are potential antitumor agents because of their remarkable biological activities and good stability, lipophilicity, and electroluminescent properties. These complexes act via various antitumor mechanisms that are unlike those of the classic platinum drugs, providing a feasible solution for improving the serious side effects caused by metal chemotherapy. In this review, promising antitumor agents based on Pt(II) and Au(III) complexes containing Schiff-base ligands, and their biological targets, including G-quadruplex DNA and thioredoxin reductase, are comprehensively summarized.The last 30 years of gadolinium-based "static" MRI contrast agents motivated to investigate bioresponsive agents with endogenous paramagnets. Iron(III) chelated by N,O-aminophenol skeleton of high versatility, and tuning potential was studied. The two-step convenient route of the ligand is characterized by high selectivity and allows for building a tunable chelate system. Functionalization with galactose endows a bioresponsive character sensitive to the enzyme activity. Direct relaxometric measurements of the resulting complexes revealed extremely high relaxivity of 5.62 mmol/dm3·s-1 comparable to classic gadolinium complexes. Enzymatic hydrolysis leads to relaxivity change by over 80%. Phantom MRI studies prove the bioresponsive character by contras percentage change within the range 40-275%. Cytotoxicity studies showed 70-90% viability of HeLa cells of the iron complexes. Proposed iron-based chelates with galactosidase-sensitive fragment express unequivocal relaxivity and MRI contras change and good biocompatibility.