Exposure Assessment of Essential and Potentially Toxic Metals in Wheat-Based Sweets for Human Consumption: Multivariate Analysis and Risk Evaluation Studies.

In recent years, there has been a growing concern about the negative impact of unforeseen contaminants such as metals in commonly consumed food items, which pose a threat to human well-being. Therefore, it is of utmost importance to evaluate the levels of these contaminants to guarantee the safe consumption of these food items. The goal of the current research is to determine the levels of essential (EMs: Mg, Ca, Mn, Fe, Co, Cu, and Zn) and potentially toxic metals (PTMs: Al, Cr, Ni, As, Cd, and Pb) in various brands of wheat-based sweets. One hundred samples were collected and analysed via flame atomic absorption spectrometry (FAAS) and inductively coupled plasma-optical emission spectrometry (ICP-OES). Also, the current study was to investigate the distribution, correlation, and multivariate analysis of 13 metals (Mg, Ca, Mn, Fe, Co, Cu, Zn, Al, Cr, Ni, As, Cd, and Pb). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used to interpret the metals' association. The concentration (mg/kg) ranges of EMs were, in order, Mg (12.70-65.67), Ca (24.02-209.12), Mn (1.32-9.61), Fe (4.55-111.23), Co (0.32-8.94), Cu (2.12-8.61), and Zn (2.60-19.36), while the concentration (mg/kg) ranges of PTMs were, in order, Al (0.32-0.87), Cr (0.17-5.74), Ni (0.36-1.54), Cd (0.16-0.56), and Pb (0.14-0.92), and As was not detected in any sample under investigation. The HCA data revealed that Co, Al, and Ni form clusters with other metals. Sweets are prepared at high temperatures, and the elevated temperatures can increase the likelihood of Ni and Al leaching from stainless steel. Tolerable dietary intake (TDI) values for Ni were higher than the values established by the European Food Safety Authority (EFSA). The CR value found for the Ni and Cr was at the threshold level of cancer risk, if an amount of 25 g were to be used over a lifetime. In a nutshell, this study highlights the monitoring of EM and PTM levels in wheat-based sweets, and from a food safety perspective, the study is important for consumers of wheat-based sweets.

Molecular identification and characterization of measles virus genotypes circulating in Afghanistan, 2008-2018.

The measles virus (MV) remains a leading cause of morbidity and mortality in children under 5 years of age. Molecular identification of circulating wild-type MV) strains is a vital component of the measles elimination program. We received 159 oral swab samples from Afghanistan during 2008-2018. Viral RNA was extracted, followed by one-step RT-PCR and positive amplicons were subject to sequencing for genotype identification. Out of 159 total samples, 52% (83/159) were detected positive by RT-PCR. Genotype D4 was identified from 2.4% (2/83), genotype H1, 4.8% (4/83), and genotype B3, 92.7% (77/83) cases, respectively.

Relationship between Lipoprotein(a) and cardiovascular risk factors-data from 4602 participants of the ELITE study.

Lipoprotein(a) (Lp(a)) is becoming increasingly important as an independent risk factor for cardiovascular disease. Since no effective therapy currently exists other than lipid apheresis, the recommendation remains to optimally adjust all other cardiovascular risk factors (CVRF). In a Northwest German population study, the frequency of elevated Lp(a) levels and all other CVRF was investigated. The aim was to investigate whether individuals with elevated Lp(a) levels were also more likely to have other CVRFs. To date, 4602 individuals have been enrolled in the study, and blood pressure, weight, lipids, diabetes, medications, and pre-existing conditions were recorded in addition to Lp(a). In addition, questionnaires assessed physical activity, psychological stress, depression, and brain dysfunction. All participants received detailed individual recommendation about their CVRF and its treatment. In the further follow-up of 5 years, it will be examined how persons with elevated Lp(a) implemented these recommendations in comparison with participants without elevated Lp(a). The first group Lp(a) <75 nmol/L consisted of 3550 (80.2%), the Lp(a) 75-120 nmol/L group of 341 (7.4%) and the Lp(a) >120 nmol/L of 538 (11.7%). 81.6% of all participants had one or more CVRF. Age, sex, and prevalence of hypertension, diabetes, smoking, obesity, and exercise did not differ among the 3 groups. As expected, LDL-Cholesterol was significantly elevated in the Lp(a) >120 nmol/L group despite significantly more frequent use of statins. Significantly more often hypertensive patients were found in the Lp(a) >120 nmol/L group who were inadequately controlled by medication and significantly less often persons without further CVRF. No differences existed in the frequency of psychological stress, depression, and mild cognitive impairment. CVRF occur with comparable frequency in individuals with elevated Lp(a) levels. However, individuals with Lp(a) above 120 nmol/L were more likely to have poorly controlled blood pressure, elevated LDL-C, and less likely to have no other risk factors. This underlines that in case of Lp(a) elevation all further CVRF should be intensively adjusted, especially in case of strongly elevated values >120 nmol/L. However, these recommendations have not been adequately implemented in clinical care in this population to date.

Efficacy and Safety of Use of the Fasting Algorithm for Singaporeans With Type 2 Diabetes (FAST) During Ramadan: A Prospective, Multicenter, Randomized Controlled Trial.

PURPOSE: We aimed to evaluate the efficacy and safety of use of the Fasting Algorithm for Singaporeans with Type 2 Diabetes (FAST) during Ramadan. METHODS: We performed a prospective, multicenter, randomized controlled trial. The inclusion criteria were age ≥21 years, baseline glycated hemoglobin (HbA1c) level ≤9.5%, and intention to fast for ≥10 days during Ramadan. Exclusion criteria included baseline estimated glomerular filtration rate <30 mL/min, diabetes-related hospitalization, and short-term corticosteroid therapy. Participants were randomized to intervention (use of FAST) or control (usual care without FAST) groups. Efficacy outcomes were HbA1c level and fasting blood glucose and postprandial glucose changes, and the safety outcome was incidence of major or minor hypoglycemia during the Ramadan period. Glycemic variability and diabetes distress were also investigated. Linear mixed models were constructed to assess changes. RESULTS: A total of 97 participants were randomized (intervention: n = 46, control: n = 51). The HbA1c improvement during Ramadan was 4 times greater in the intervention group (-0.4%) than in the control group (-0.1%) (P = .049). The mean fasting blood glucose level decreased in the intervention group (-3.6 mg/dL) and increased in the control group (+20.9 mg/dL) (P = .034). The mean postprandial glucose level showed greater improvement in the intervention group (-16.4 mg/dL) compared to the control group (-2.3 mg/dL). There were more minor hypoglycemic events based on self-monitered blood glucose readings in the control group (intervention: 4, control: 6; P = .744). Glycemic variability was not significantly different between the 2 groups (P = .284). No between-group differences in diabetes distress were observed (P = .479). CONCLUSIONS: Our findings emphasize the importance of efficacious, safe, and culturally tailored epistemic tools for diabetes management.

Towards Portable Nanophotonic Sensors.

A range of nanophotonic sensors composed of different materials and device configurations have been developed over the past two decades. These sensors have achieved high performance in terms of sensitivity and detection limit. The size of onchip nanophotonic sensors is also small and they are regarded as a strong candidate to provide the next generation sensors for a range of applications including chemical and biosensing for point-of-care diagnostics. However, the apparatus used to perform measurements of nanophotonic sensor chips is bulky, expensive and requires experts to operate them. Thus, although integrated nanophotonic sensors have shown high performance and are compact themselves their practical applications are limited by the lack of a compact readout system required for their measurements. To achieve the aim of using nanophotonic sensors in daily life it is important to develop nanophotonic sensors which are not only themselves small, but their readout system is also portable, compact and easy to operate. Recognizing the need to develop compact readout systems for onchip nanophotonic sensors, different groups around the globe have started to put efforts in this direction. This review article discusses different works carried out to develop integrated nanophotonic sensors with compact readout systems, which are divided into two categories; onchip nanophotonic sensors with monolithically integrated readout and onchip nanophotonic sensors with separate but compact readout systems.

Biological activities of three medicinal plants from district Mirpur, AJK, Pakistan.

Present research work was aimed to investigate the biological activities i.e. antibacterial, antifungal, antioxidant, cytotoxic and antitumor activities of crude methanolic extract of Anagallis arvensis L., Butea monosperma (Lam.) Kuntze and Coronopus didymus (L.) Pers. against Gram positive strains (Bacillus subtilis, Staphylococcus aureus) and gram negative strains (Vibrio cholera, Enterobacter aerogenes, Klebsiella pneumonia, Agrobacterium tumefaciens, Escherichia coli) were screened. Best activity was observed against K. pneumonia and S. aureus by A. arvensis compared with other strains. Butea monosperma exhibited considerable activity against S. aureus, V. cholera, E. aerogenes and K. pneumonia compared with other strains. Methanolic extract of A. arvensis L. inhibited fungal growth against A. niger up to 30.2%. B. monosperma inhibited the growth of A. niger up to 43.5% and against A. fumigatus 27.3%. C. didymus inhibited the A. fumigates up to 27.3% and against A. niger, it inhibited 48%. Brine shrimps lethality bioassay was used to evaluate the cytotoxic activity and LD50 value was calculated by using probit analysis. Potato disc bioassay was designed to screen antitumor activity and data was analyzed by one way ANOVA.

Controlled release matrix tablets of glipizide: Influence of different grades of ethocel and Co-excipient on drug release.

The aim of the current study was to formulate and evaluate glipizide controlled release matrix tablets by means of different grades of polymer Ethoceland different co-excipients in order to evaluate their effect on drug release profiles during in vitro dissolution studies. Type II diabetes mellitus is usually treated with Glipizide. Glipizide belongs to sulfonylurea group. Gastric disturbance and severe hypoglycemia has been observed after taking glipizide orally. To overcome these problems, controlled release matrices were developed using different grades of ethyl cellulose polymer with a drug-polymer ratio of 1:3by the direct compression method. The effect on drug release of partial replacement of lactose by different co-excipients, HPMC K100M, starch and CMC, were also studied. Diameter, thickness, hardness, friability, weight variations, drug contents of formulations were tested, these properties were within prescribed limits. Co-excipients and polymer containing formulations were compared to the without co-excipients and polymer containing formulations with respect to their release profile. After a 24-hour release study, ethyl cellulose polymer containing formulation exhibited prolonged release for 5-16 hours; however the polymer Ethocel (R) standard FP 7 Premium without co-excipient containing formulation exhibited controlled release for 24 hours. Incompatibility was investigated between drugs, co-excipient DSC and polymer study was performed and any type of interaction was not found. Different kinetic models were used to study the release mechanism. An enhanced release rate was observed in case of excipients containing formulations.

Truncation of the E3 ubiquitin ligase component FBXO31 causes non-syndromic autosomal recessive intellectual disability in a Pakistani family.

In this study, we have performed autozygosity mapping on a large consanguineous Pakistani family segregating with intellectual disability. We identified two large regions of homozygosity-by-descent (HBD) on 16q12.2-q21 and 16q24.1-q24.3. Whole exome sequencing (WES) was performed on an affected individual from the family, but initially, no obvious mutation was detected. However, three genes within the HBD regions that were not fully captured during the WES were Sanger sequenced and we identified a five base pair deletion (actually six base pairs deleted plus one base pair inserted) in exon 7 of the gene FBXO31. The variant segregated completely in the family, in recessive fashion giving a LOD score of 3.95. This variant leads to a frameshift and a premature stop codon and truncation of the FBXO31 protein, p.(Cys283Asnfs*81). Quantification of mRNA and protein expression suggests that nonsense-mediated mRNA decay also contributes to the loss of FBXO31 protein in affected individuals. FBXO31 functions as a centrosomal E3 ubiquitin ligase, in association with SKP1 and Cullin-1, involved in ubiquitination of proteins targeted for degradation. The FBXO31/SKP1/Cullin1 complex is important for neuronal morphogenesis and axonal identity. FBXO31 also plays a role in dendrite growth and neuronal migration in developing cerebellar cortex. Our finding adds further evidence of the involvement of disruption of the protein ubiquitination pathway in intellectual disability.

Compact 1D-silicon photonic crystal electro-optic modulator operating with ultra-low switching voltage and energy.

We demonstrate a small foot print (600 nm wide) 1D silicon photonic crystal electro-optic modulator operating with only a 50 mV swing voltage and 0.1 fJ/bit switching energy at GHz speeds, which are the lowest values ever reported for a silicon electro-optic modulator. A 3 dB extinction ratio is demonstrated with an ultra-low 50 mV swing voltage with a total device energy consumption of 42.8 fJ/bit, which is dominated by the state holding energy. The total energy consumption is reduced to 14.65 fJ/bit for a 300 mV swing voltage while still keeping the switching energy at less than 2 fJ/bit. Under optimum voltage conditions, the device operates with a maximum speed of 3 Gbps with 8 dB extinction ratio, which rises to 11 dB for a 1 Gbps modulation speed.

Genetic analysis of post-weaning growth traits of Thalli sheep under tropical conditions.

Present investigation was carried out to study the influence of genetic and non-genetic factors affecting post-weaning performance traits in Thalli sheep. Data on post-weaning growth of Thalli sheep maintained at Livestock Experiment Station, Rakh Ghulaman, District Bhakkar-Punjab, Pakistan during 1977-2003 were subjected to genetic analysis. The average values for weight at 180 and 270 days of age, yearling weight and post-weaning average daily gain were 22.37 ± 4.21, 25.96 ± 4.90 and 28.93 ± 5.20 kg and 28 ± 0.01 g/day, respectively. Weight at 180, 270 and 365 days of age and post-weaning average daily gain were significantly affected by year of birth, sex, type of birth and weaning weight (covariable) whereas season of birth was a significant source of variation for 180 and 270 days of age. The heritability estimates for 180 and 270 days, yearling weight and post-weaning average daily gain were 0.07 ± 0.02, 0.08 ± 0.02, 0.07 ± 0.02 and 0.07 ± 0.02, respectively.

Novel benzimidazole derivatives as effective inhibitors of prolyl oligopeptidase: synthesis, in vitro and in silico analysis.

Background: This research aims to discover novel derivatives having potential therapeutic applications in treating conditions related to prolyl oligopeptidase (POP) dysfunction. Method: Novel benzimidazole derivatives have been synthesized, characterized and screened for their in vitro POP inhibition. Results: All these derivatives showed excellent-to-good inhibitory activities in the range of IC50 values of 3.61 ± 0.15 to 43.72 ± 1.18 µM, when compared with standard Z-prolyl-prolinal. The docking analysis revealed the strong interactions between our compounds and the target enzyme, providing critical insights into their binding affinities and potential implications for drug development. Conclusion: The significance of these compounds in targeting POP enzyme offers promising prospects for future research in the field of neuropharmacology.

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment.

A library of novel bis-Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC50 = 0.10 ± 0.05 µM), and 9 (IC50 = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC50 = 0.27 ± 0.04 µM). Similarly, derivatives (5, 6, 7, 10 and 4) showed significant to good inhibitory activity in the range of IC50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.

Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide-hydrazone derivatives of 3,4-dihydroxyphenylacetic acid.

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.

The different risk of new-onset, chronic, worsening, and advanced heart failure: A systematic review and meta-regression analysis.

AIMS: Heart failure (HF) is a chronic and progressive syndrome associated with a poor prognosis. While it may seem intuitive that the risk of adverse outcomes varies across the different stages of HF, an overview of these risks is lacking. This study aims to determine the risk of all-cause mortality and HF hospitalizations associated with new-onset HF, chronic HF (CHF), worsening HF (WHF), and advanced HF. METHODS AND RESULTS: We performed a systematic review of observational studies from 2012 to 2022 using five different databases. The primary outcomes were 30-day and 1-year all-cause mortality, as well as 1-year HF hospitalization. Studies were pooled using random effects meta-analysis, and mixed-effects meta-regression was used to compare the different HF groups. Among the 15 759 studies screened, 66 were included representing 862 046 HF patients. Pooled 30-day mortality rates did not reveal a significant distinction between hospital-admitted patients, with rates of 10.13% for new-onset HF and 8.11% for WHF (p = 0.10). However, the 1-year mortality risk differed and increased stepwise from CHF to advanced HF, with a rate of 8.47% (95% confidence interval [CI] 7.24-9.89) for CHF, 21.15% (95% CI 17.78-24.95) for new-onset HF, 26.84% (95% CI 23.74-30.19) for WHF, and 29.74% (95% CI 24.15-36.10) for advanced HF. Readmission rates for HF at 1 year followed a similar trend. CONCLUSIONS: Our meta-analysis of observational studies confirms the different risk for adverse outcomes across the distinct HF stages. Moreover, it emphasizes the negative prognostic value of WHF as the first progressive stage from CHF towards advanced HF.

The environmental sustainable development goals and economic growth: an empirical investigation of selected SAARC countries.

Environmental SDGs, or Sustainable Development Goals, are a set of targets outlined by the United Nations to address the most pressing environmental issues of our time. These goals aim to promote sustainable development by addressing issues such as climate change, biodiversity loss, and pollution. By achieving these goals, we can safeguard the planet's resources for future generations while improving the quality of life for people around the world. This research investigates the effect of environmental SDGs on economic growth (GDPGRO) at the disaggregated level, with two dimensions: economic and social goals. Using panel data from selected SAARC countries between 2000 and 2020, we employ a panel ARDL (PMG) technique. The finding of this study shows that increasing access to SDG 7 (affordable and clean energy), SDG 13 (climate action), and SSDGs (social Sustainable Development Goals) is negatively associated with potential decreases in economic growth which can occur in several ways, such as increased government spending and taxes, redistributive policies, and regulations that increase costs for businesses. Promoting SDG 11 (sustainable cities and communities) and SDG 12 (responsible consumption and production) can lead to long-term economic growth. SDG 15 (life below water) and ESDGs (economic Sustainable Development Goals) have a positive relationship with economic growth by conserving and sustainably using terrestrial ecosystems that can contribute to economic growth in the long term. ESDGs lead to increased income, improved living standards, and reduced poverty and inequality. Policies should prioritize disaster risk mitigation, align climate change goals with sustainable development goals, and promote sustainable production and consumption. This can be achieved by incentivizing cleaner energy sources and sustainable cities. To balance economic growth with sustainability, policies should encourage responsible business practices and sustainable industries.

Impact of subsectors of agriculture and economic growth on CO2 emissions in Pakistan: evidence from Environmental Kuznets Curve.

Modernization produces carbon dioxide (CO2) emissions but is also able to achieve sustainable agriculture growth by introducing the concept of renewable energy into the agriculture sector, and through this process reduce the CO2 emissions in the country. The main objective of this research is to check the environmental Kuznets curve hypothesis with CO2 emissions and economic development in renewable energy and agriculture subsectors such as fisheries and crop production in Pakistan. This study covers the time period 1984 to 2020. We have applied the autoregressive distribution lag (ARDL) bound test. The results indicate the existence of long-term association among all variables in the model. The result of co-integration in the short run shows a negative relationship between CO2 emissions and crop production in the current time period, and it shows a positive correlation with the first lag of CO2 emission, which means that current crop production reduces the CO2 emissions by 32% during a year, while in the lag period, it will increase in the short run. In the long run, a 1% increase in crop production will reduce the CO2 emission by 86%. Renewable energy shows a negative relation with CO2 emissions in the short run; a 1% increase in renewable energy will reduced the CO2 by 0.017%. Our results support the existence of the EKC hypothesis for Pakistan. In light of the findings, it is suggested that policy makers should focus more on renewable energy to decrease the level of CO2 as much as possible. Moreover, the government must provide subsidies for machines used for cropping and give special attention to subsectors such as livestock and fisheries.

The impact of pandemic-related social distancing regulations on exercise performance-Objective data and training recommendations to mitigate losses in physical fitness.

Introduction: In the context of the COVID-19 pandemic in Germany, governmental restrictions led to the closure of sports facilities for several months. To date, only subjective and fitness-tracking related data on physical activity during the pandemic are available. Using data of a chip-controlled fitness circuit, training data as a measure of physical performance before and after the lockdown during the first wave of the COVID-19 pandemic will show the impact of the training interruption on exercise performance in middle-aged and older adults. The re-training data are analyzed, to extract practical recommendations. Methods: Objective training data of 17,450 participants [11,097 middle-aged (45-64 yrs), 6,353 older (≥65 yrs)] were exported from chip-controlled milon® fitness circuit systems before and after the first COVID-19 related lockdown in Germany. The change in the product of training weight (sum of lifting and lowering the training weight) and repetitions on the leg extension resistance exercise device (leg score) between the last three training sessions before the lockdown and the first ten training sessions after individual training resumption as well as the last training session before the second lockdown in October 2020 was analyzed. Results: Participants who trained with high intensity before the lockdown, experienced deleterious effects of the training interruption (middle-aged group: -218 kg, older group: ~-230.8 kg; p < 0.001 for change in leg score from to post-lockdown) with no age effect. Participants training with a leg score of more than 3,000 kg did not resume their leg score until the second lockdown. Conclusion: The interruption of training in a fitness circuit with combined resistance and endurance training due to the lockdown affected mainly those participants who trained at high intensity. Apparently, high-intensity training could not be compensated by home-based training or outdoor activities. Concepts for high-intensity resistance training during closure of sports facilities are needed to be prepared for future periods of high incidence rates of infectious diseases, while especially vulnerable people feel uncomfortable to visit sports facilities. Trial registration: Identifier, DRKS00022433.

Novel flurbiprofen clubbed oxadiazole derivatives as potential urease inhibitors and their molecular docking study.

In this study, twenty eight novel oxadiazole derivatives (5-32) of the marketed available non-steroidal anti-inflammatory drug (NSAID), (S)-flurbiprofen (1), were synthesized via I2 mediated cyclo-addition reaction in better yields. The synthesized hydrazone-Schiff bases were cyclized with iodine by using potassium hydroxide as a base in DMSO solvent to obtain oxadiazole derivatives (5-32). Structures of the synthesized products were confirmed with HR-ESI-MS, 1H-NMR spectroscopy and CHN analysis. After structure confirmations all analogs were evaluated for urease (in vitro) inhibitory activity. Amongst the series, fourteen compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 were found to be excellent inhibitors of urease enzyme, having IC50 values of 12 ± 0.9 to 20 ± 0.5 µM, better than the standard thiourea (IC50 = 22 ± 2.2 µM), whereas the remaining fourteen derivatives displayed good to moderate activity. The in silico study was executed to analyse the interaction between the active site of the enzyme (urease) and the produced compounds. The docking study revealed that compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 had lower docking scores than the standard compound thiourea and revealed better interactions with the urease enzyme.

Heavy metals mitigation and growth promoting effect of endophytic Agrococcus terreus (MW 979614) in maize plants under zinc and nickel contaminated soil.

Introduction: Heavy metals such as iron, copper, manganese, cobalt, silver, zinc, nickel, and arsenic have accumulated in soils for a long time due to the dumping of industrial waste and sewage. Various techniques have been adapted to overcome metal toxicity in agricultural land but utilizing a biological application using potential microorganisms in heavy metals contaminated soil may be a successful approach to decontaminate heavy metals soil. Therefore, the current study aimed to isolate endophytic bacteria from a medicinal plant (Viburnum grandiflorum) and to investigate the growth-promoting and heavy metal detoxification potential of the isolated endophytic bacteria Agrococus tereus (GenBank accession number MW 979614) under nickel and zinc contamination. Methods: Zinc sulfate and nickel sulfate solutions were prepared at the rate of 100 mg/kg and 50 mg/kg in sterilized distilled water. The experiment was conducted using a completely random design (CRD) with three replicates for each treatment. Results and Discussion: Inoculation of seeds with A. tereus significantly increased the plant growth, nutrient uptake, and defense system. Treatment T4 (inoculated seeds), T5 (inoculated seeds + Zn100 mg/kg), and T6 (inoculated seeds + Ni 100 mg/kg) were effective, but T5 (inoculated seeds + Zn100 mg/kg) was the most pronounced and increased shoot length, root length, leaf width, plant height, fresh weight, moisture content, and proline by 49%, 38%, 89%, 31%, 113%, and 146%, respectively. Moreover the antioxidant enzymes peroxidase and super oxidase dismutase were accelerated by 211 and 68% in contaminated soil when plants were inoculated by A. tereus respectively. Similarly the inoculation of A. tereus also enhanced maize plants' absorption of Cu, Mn, Ni, Na, Cr, Fe, Ca, Mg, and K significantly. Results of the findings concluded that 100 mg/kg of Zn and Ni were toxic to maize growth, but seed inoculation with A. tereus helped the plants significantly in reducing zinc and nickel stress. The A. tereus strain may be employed as a potential strain for the detoxification of heavy metals.

Regional management of worsening heart failure: rationale and design of the CHAIN-HF registry.

AIMS: Heart failure (HF) is a progressive disease in which periods of clinical stability are interrupted by episodes of clinical deterioration known as worsening heart failure (WHF). Patients who develop WHF are at high risk of subsequent death, rehospitalization, and excessive healthcare costs. As such, WHF could be seen as a separate disease stage and precursor of advanced HF. Whether WHF has a substantial health, societal, and economic impact evidence regarding its multifactorial nature and the specific barriers in treatment, including advanced HF therapies, remains scarce. The CHAIN-HF registry aims to describe the incidence, characteristics, current treatment, and outcomes of WHF. Additionally, it will promote structured regional collaboration and educate on increasing awareness for WHF and describe the implementation of guideline directed medical therapy and utilization of advanced HF therapies in a collaborative network. METHODS AND RESULTS: The CHAIN-HF registry is a prospective, observational, and multicentre study from the collaborating hospitals (Rijnmond HF Network) in the Rotterdam area. Unselected and consecutive patients (irrespective of ejection fraction) with a WHF event will be included. Comprehensive data including demographics, co-morbidities, treatment, and in-hospital and post-discharge outcomes will be collected. Notably, data on socio-economic status, treatment decisions, and referral for advanced HF therapies will be included. CONCLUSIONS: CHAIN-HF will be the first prospective, dedicated WHF registry in a collaborative network of hospitals that will provide robust real-world evidence on the incidence, characteristics, and outcomes of WHF. Moreover, it will provide information on of the value of regional collaboration to improve awareness and outcomes of WHF.