Involving Older Adults During COVID-19 Restrictions in Developing an Ecosystem Supporting Active Aging: Overview of Alternative Elicitation Methods and Common Requirements From Five European Countries.

Background: Information and communication technology solutions have the potential to support active and healthy aging and improve monitoring and treatment outcomes. To make such solutions acceptable, all stakeholders must be involved in the requirements elicitation process. Due to the COVID-19 situation, alternative approaches to commonly used face-to-face methods must often be used. One aim of the current article is to share a unique experience from the Pharaon project where due to the COVID-19 outbreak alternative elicitation methods were used. In addition, an overview of common functional, quality, and emotional goals identified by six pilot sites is presented to complement the knowledge about the needs of older adults. Methods: Originally planned face-to-face co-creation seminars were impossible to carry out, and all pilot sites chose alternative requirements elicitation methods that were most suitable in their situation. The elicited requirements were presented in the form of goal models. In one summary goal model, we provide an overview of common functional, quality, and emotional goals. Results: Different elicitation methods were combined based on the digital literacy of the target group and their access to digital tools. Methods applied without digital technologies were phone interviews, reviews of literature and previous projects, while by means of digital technologies online interviews, online questionnaires, and (semi-)virtual co-creation seminars were conducted. The combination of the methods allowed to involve all planned stakeholders. Virtual and semi-virtual co-creation seminars created collaborative environment comparable to face-to-face situations, while online participation helped to save the time of the participants. The most prevalent functional goals elicited were "Monitor health," "Receive advice," "Receive information." "Easy to use/comfortable," "personalized/tailored," "automatic/smart" were identified as most prevalent quality goals. Most frequently occurring emotional goals were "involved," "empowered," and "informed." Conclusion: There are alternative methods to face-to-face co-creation seminars, which effectively involve older adults and other stakeholders in the requirements elicitation process. Despite the used elicitation method, the requirements can be easily transformed into goal models to present the results in a uniform way. The common requirements across different pilots provided a strong foundation for representing detailed requirements and input for further software development processes.

Review-Insights into Off-Label therapeutic strategies against mild and severe COVID-19 infection.

Currently, prevention and control of the coronavirus disease pneumonia epidemic situation are grim globally. To cope with total sheer carriers and patients of COVID-19 requires intensive medical support and adjunctive therapies to overcome the disease. The epidemic can be controlled with the help of both, disease suppression via community health measures and adjunctive therapies for patients suffering from infection. Till date, we do not have any proper anti-COVID-19 therapy. In order to achieve the overall realization of this pandemic, there is a need to identify treatments depending upon their direct or indirect targets; like inhibition of polyprotein synthesis, transmembrane serine protease, inhibition of viral entry and endocytosis. This could be possible by turning the focus in the direction towards the development of numerous tentative drugs, particularly in the severe to badly ill. Though, majority of these off-label adjunctive medicines are being inspected in a lot of clinical trials at different stages, scientific organizations have endeavored to elucidate the situation where these adjunctive drugs might be practiced as off-label, open- label or compassionate. Our review compiles the adjunctive therapies adopted in COVID-19 infected patients according to clinical severity in conjugation with practicing recommendations from existing guidance rules issued by global professional bodies in healthcare.

Determination of Arylamine N-Acetyltransferase 2 Acetylation Genotype by PCR and Phenotyping Using Dapsone Through High-Pressure Liquid Chromatography Assay: A Gender Wise Study.

The main aim of the study was to establish the acetylation status of local population of Pakistan by N-acetyltransferase 2 (NAT2) enzyme and to find out the concordance between phenotypic and genotypic methods for the determination of NAT2 acetylation. Gender-wise comparison of selected healthy male and female volunteers aged greater than 18 years was also conducted to see the effect of sex on NAT2 acetylation. Phenotypically, the rate of acetylation was determined by high-pressure liquid chromatography with dapsone (DDS) probe drug, while genotypically, NAT2 acetylation was determined by using specific primers for NAT2 variant alleles (M1, M2, and M3) amplified in separate polymerase chain reactions. High-pressure liquid chromatography results indicated 64% of the male volunteers to be fast acetylators while 36% were slow acetylators, while ratio of fast and slow acetylators for female was found to be 66% and 34%, respectively. Genotypically, the ratio of fast and slow for male was 60% and 40% and for female was 66% and 34%, respectively. The distribution of 3 NAT2 variant alleles was found in invariable number. For male volunteers, the highest frequency distribution showed by M2 allele was 56%, while for M1 and M3 the frequency was 32% and 12%, respectively, and for female volunteers highest frequency (51%) was shown by the M2 variant allele while lowest frequency (18%) was shown by M3 allele. There was the 94% concordance between the DDS phenotype and genotype. Gender effect on the acetylation was found to be nonsignificant (P > .05). Therefore, it is concluded that NAT2 acetylation rate can be used to check in vivo acetylation status with dapsone as probe drug. It is concluded that NAT2 acetylation rate was unaffected by gender and can be used to check in vivo acetylation status with dapsone as probe drug, which is inexpensive and less time-consuming.

Effect of UDP-Glucuronosyltransferase (UGT) 1A Polymorphism (rs8330 and rs10929303) on Glucuronidation Status of Acetaminophen.

Interindividual variability in polymorphic uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) ascribed to genetic diversity is associated with relative glucuronidation level among individuals. The present research was aimed to study the effect of 2 important single nucleotide polymorphisms (SNPs; rs8330 and rs10929303) of UGT1A1 gene on glucuronidation status of acetaminophen in healthy volunteers (n = 109). Among enrolled volunteers, 54.13% were male (n = 59) and 45.87% were female (n = 50). The in vivo activity of UGT1A1 was investigated by high-performance liquid chromatography-based analysis of glucuronidation status (ie, acetaminophen and acetaminophen glucuronide) in human volunteers after oral intake of a single dose (1000 mg) of acetaminophen. The TaqMan SNP genotyping assay was used for UGT1A1 genotyping. The wild-type genotype (C/C) was observed the most frequent one for both SNPs (rs8330 and rs10929303) and associated with fast glucuronidator phenotypes. The distribution of variant genotype (G/G) for SNP rs8330 was observed in 5% of male and 8% of the female population; however, for SNP rs10929303, the G/G genotype was found in 8% of both genders. A trimodal distribution (fast, intermediate, and slow) based on phenotypes was observed. Among the male participants, the glucuronidation phenotypes were observed as 7% slow, 37% intermediate, and 56% fast glucuronidators; however, these findings for the females were slightly different as 8%, 32%, and 60% respectively. The k-statistics revealed a compelling evidence for good concordance between phenotype and genotype with a k value of 1.00 for SNP rs8330 and 0.966 for SNP rs10929303 in our population.

An expedient reverse-phase high-performance chromatography (RP-HPLC) based method for high-throughput analysis of deferoxamine and ferrioxamine in urine.

The present study was planned to optimize and validate an expedient reverse-phase high chromatography (RP-HPLC) based protocol for the analysis of deferoxamine (DFO) and ferrioxamine (FO) in urinary execration of patients suffering ß-thalassemia major. The optimized RP-HPLC method was found to be linear over the wide range of DFO and FO concentration (1-90 µg/mL) with appreciable recovery rates (79.64-97.30%) of quality controls at improved detection and quantitation limits and acceptable inter and intraday variability. Real-time analysis of DFO and FO in the urine of thalassemic patients (male and female) at different intervals of Desferal®(Novartis Pharmaceuticals Corporation) injection revealed DFO and FO excretion at significantly (p < 0) different rates. The maximum concentrations of DFO (76.7 ± 3.06 µg/mL) and FO (74.2 ± 3.25 µg/mL) were found in urine samples, collected after 6 h of drug infusion while the minimum levels of DFO (1.10 ± 0.12 µg/mL) and FO (2.97 ± 0.13 µg/mL) were excreted by patients after 24 h. The present paper offers balanced conditions for an expedient, reliable and quick determination of DFO and FO in urine samples.

Genetic polymorphism of UDP-glucuronosyltransferase (UGT2B15) and glucuronidation of paracetamol in healthy population.

Inter individual variability in polymorphic UDP-glucuronosyltransferase (UGT2B15) has been associated with varied glucuronidation level. The present project was designed to determine the genetic polymorphism of UDP-glucuronosyltransferase (UGT2B15) and glucuronidation of paracetamol in healthy (male=59 and female=50) population. The association between genotype (UGT2B15) and phenotype (paracetamol glucuronidation) has been evaluated. According to trimodal model, genotypes and phenotypes were categorized as fast, intermediate and slow glucuronidators. Presence of wild type allele illustrated a UGT2B15 genotype as fast glucuronidator. The glucuronidation status was investigated by HPLC analysis of paracetamol. Ratio of paracetamol glucuronide to paracetamol was determined with two antimodes at glucuronidation ratio of 0.3 and 1.8. In our study, 7% and 12% of population was distributed as slow glucuronidators by phenotype and genotype, respectively and association between phenotype and genotype was good for analysis of glucuronidation status as displayed by kappa value (0.792).

Quantitative determination of deferiprone in human plasma by reverse phase high performance liquid chromatography and its application to pharmacokinetic study.

Deferiprone (1, 2 dimethyl-3-hydroxypyrid-4-one) is considered to be the standard iron chelator. Pharmacokinetic studies of generic formulations are required in local condition before placed on the market. High performance liquid chromatographic (HPLC) method was used for quantification of deferiprone in human plasma using UV/VIS detector. Chromatographic separation was carried out on C(18) column, with a mobile phase of methanol-buffer (18:82, v/v), pH 3.5, and caffeine was used as an internal standard. The calibration curve was linear over the range 0.25-10 µg/mL in human plasma (R(2) = 0.9994). After oral administration of deferiprone (500 mg) to human, the plasma concentration-time curve of deferiprone was conformed to two-compartment open model. The deferiprone plasma concentration showed a rapid absorption and average area under the plasma concentration-time curve (AUC) of deferiprone was 17.0 ± 1.23 h.µg/ml. Average absorption and elimination half-life values of deferiprone of 24 volunteers were 0.62 ± 0.12 and 2.65 ± 0.43 hours. This study confirms the rapid absorption of deferiprone in humans. AUC was similar to that previously reported but C(max) was slightly lower than that stated in the literature.

Determination of in vitro antidiabetic effects of Zingiber officinale Roscoe

Aqueous extracts of Zingiber officinale rhizomes were studied to evaluate their antidiabetic effects on protein glycation and on the diffusion of glucose in vitro in the present study. Zingiber officinale rhizome aqueous extract were examined at concentrations of 5, 10, 20 and 40 g/L. The antidiabetic effects were found to be dose-dependent. Antidiabetic potential of Zingiber officinale was mainly through inhibition of the glucose diffusion and to a limited extent by reducing the glycation. However, further studies are needed to determine in vitro effects of therapeutic potential by restraining postprandial glucose absorptions and plasma protein glycations in diabetic subjects.

Extratos aquosos de rizomas Zingiber officinale foram estudados para avaliar os seus efeitos antidiabéticos em glicação de proteínas e sobre a difusão de glicose in vitro, no presente estudo. Extratos aquosos de Zingiber officinale foram examinados nas concentrações de 5, 10, 20 e 40 g extrato de planta/L. Os efeitos antidiabéticos observados eram dependentes da dose. O potencial antidiabético de Zingiber officinale se verificou, principalmente, através da inibição da difusão de glicose e, em menor extensão, através da redução da glicação. Estudos adicionais são necessários para elucidar se efeitos in vitro representam potencial terapêutico, restringindo a absorção de glicose pós-prandial e a glicação de proteínas plasmáticas em indivíduos diabéticos.

Physical and chemical modification of distillery sludge for Pb(II) biosorption.

The waste distillery sludge from sugar-cane industry was pretreated physically (boiled, heated and autoclaved) as well as chemically (HCl, H(2)SO(4), H(3)PO(4), NaOH, Ca(OH)(2), Al(OH)(3), C(6)H(6), HCHO, CH(3)OH and C1(2)H(25)OSO(3)Na (sodium dodecyl sulphate (SDS)) for assessing the comparative sorption capacity of untreated and modified distillery sludge for Pb(II) biosorption from aqueous solutions. Experiments were conducted in shake flasks on a batch basis to access the effect of different experimental parameters such as pH, biosorbent dosage, biosorbent size, initial Pb(II) concentration and contact time. The uptake capacity 'q' (mg/g) of untreated and pretreated distillery sludge was in following order: NaOH (51.29+/-1.21)>HCl (49.82+/-1.22)>HCHO (49.56+/-1.14)>H(2)SO(4) (47.71+/-1.20)>HgCl(2) (45.32+/-1.06)>Ca(OH)(2) (44.01+/-1.18)>MeOH (43.73+/-1.23)>C(6)H(6) (42.72+/-1.19)>H(3)PO(4) (42.01+/-1.17)>SDS (40.87+/-1.27)>autoclaved (40.23+/-1.24)>Boiled (39.95+/-1.19)>heated (38.87+/-1.32)>Al (OH)(3) (38.30+/-1.14)>untreated (37.76+/-1.21). In further parameter studies, the optimized biosorbent size was 0.250 mm at pH 5 and best dose was 0.05 g of biosorbent. The applicability of the Langmuir and Freundlich models for sorption process was tested and best fitted model was Langmuir with the coefficient of determination (R(2)) value, 0.97, the process followed second order kinetic mechanism.

Determination of Rhodamine 123 in cell lysate by HPLC with visible wavelength detection.

Rhodamine 123 (R123) is widely used to quantify P-glycoprotein (P-GP) functional efflux activity in vitro. We developed a rapid and specific high-performance liquid chromatography (HPLC) method to quantify Rhodamine 123 for use in experimental cell culture studies. The R123 standards (2.5-250 ng/mL) and quality controls (QCs) (5, 75, 200 ng/mL) were prepared in cell lysis buffer consisting of 0.75% Triton 100X and 0.2% sodium chloride. The mobile phase consisted of acetonitrile, 1.5 mM tetrabutyl ammonium bromide in 20mM sodium acetate buffer (pH 4.0) (50:20:30) delivered at a rate of 1.0 mL/min. Samples (50 microl) were injected onto a C(18) reversed-phase HPLC column with detection at 500 nm. Analyte retention times were 1.4 and 4.3 min for R123 and internal standard (R6G), respectively. Intra- and inter-day coefficients of variation were < or = 4.2%. Samples were stable for at least three freeze-thaw cycles at room temperature for 24 and 48 h. This method was used to evaluate the functional activity of P-glycoprotein in renal tubule cell models including human kidney (HK-2), Madin-Darby canine kidney (MDCK) and multi-drug resistance gene-transfected MDCK cells (MDR1-MDCK).

Validation of a simplified method for determination of cimetidine in human plasma and urine by liquid chromatography with ultraviolet detection.

A HPLC method was developed for determination of cimetidine in human plasma and urine. Plasma samples were alkalinized followed by liquid extraction with water-saturated ethyl acetate then evaporated under nitrogen. The extracts were reconstituted in mobile phase and injected onto a C(18) reversed-phase column; UV detection was set at 228 nm. Urine samples were diluted with an internal standard/mobile phase mixture (1:9) prior to injection. The lower limit of quantification in plasma and urine were 100 ng/ml and 10 microg/ml, respectively; intra- and inter-day coefficients of variation were