Synthesis and Photophysical, Electrochemical, and DFT Studies of Piperidyl and Pyrrolidinyl Chalcones.

Small organic molecules with interesting optical and electrochemical properties find applications as organic luminescent materials. In this work, we report the synthesis of novel chalcones with D-A-D and D-A-D-A architecture, followed by their optical, electrochemical, and computational studies. The absorption band of these compounds occurs at 360-480 nm with emission maxima appearing around 513-552 nm. The large Stokes shifts (Δλ) for all compounds (90-132 nm) suggest intramolecular charge transfer (ICT) in the excited states. The molar absorptivity and fluorescence quantum yields were found to be in the range of 1.7-4.26 × 104 M-1 cm-1 and 0.29-0.39, respectively. The electrochemical parameters were determined by using cyclic voltammetry (CV). Density functional theory (DFT) calculations of all compounds were made by using B3LYP/G (d,p) functionals in chloroform and were found to have a good correlation with experimental results. Preliminary studies of absorption, photoluminescence, CV, and their theoretical correlation suggest that these compounds may be optimized for their applications in optoelectronics, sensing, and bioimaging.

Secoisolariciresinol diglucoside and anethole ameliorate lipid abnormalities, oxidative injury, hypercholesterolemia, heart, and liver conditions.

Fennel seeds and flaxseed have been traditionally used against many medical ailments due to their medicinal characteristics. The aim of the study was to investigate the health properties of secoisolariciresinol diglucoside (SDG) and anethole from flaxseed and fennel seeds in rats fed with high-fat diet. Histopathological changes in the heart and liver were also examined. Sixty rats were divided into two main groups. Group I (10 rats) was used as a negative control group and fed on the basal diet only. Group II (50 rats) was fed a hypercholesterolemic diet but not given any drugs during the trial for 2 weeks. This group was further divided into five subgroups (10 rats each). One of them was fed on the basal diet and used as a positive control group. However, the other four subgroups were fed on basal diets and anethole (20 mg/kg/day, orally), SDG (20 mg/kg/day, orally), a mixture of anethole + SDG (10 + 10 mg/kg/day, orally), and atorvastatin (10 mg/kg/day, orally) for 6 weeks. Compared to control, treatment with a combination of anethole + SDG showed a significant (p ≤ .05) improvement in serum levels of triglyceride (TG) (137.88 ± 1.61 mg/dL), total cholesterol-(TC) (180.12 ± 8.99 mg/dL), LDL-C (46.40 ± 6.67 mg/dL), VLDL-C (11.81 ± 1.07 mg/dL), aspartate aminotransferase (AST) (75.97 ± 6.92 U/L), alanine aminotransferase (ALT) (34.83 ± 2.17 U/L), alkaline phosphatase (ALP) (130.65 ± 1.05 U/L), and malondialdehyde (MDA) (30.12 ± 1.89 mmol/g), and improved activities of catalase (70.99 ± 3.29 U/g) and superoxide dismutase (SOD) (35.13 ± 2.53 U/dL) enzymes while SDG and anethole group had relatively less impact. Atorvastatin also improved serum levels of triglyceride, total cholesterol, LDL-C, and VLDL-C significantly and rose serum high-density lipoprotein cholesterol (HDL-C) levels considerably meanwhile it had a minor but negative impact on AST, ALT, and ALP, and negligible impact on activities of MDA, CAT, and SOD enzymes compared to the positive control group. The study revealed that combining anethole and SDG may improve dyslipidemia, improve lipid profile, decrease risks of chronic heart diseases, increase HDL-C, and enhance antioxidant enzymes' activities.

Mapping of familial hypercholesterolemia and dyslipidemias basic management infrastructure in Pakistan: a cross-sectional study.

Background: Familial hypercholesterolemia (FH) is an autosomal inherited disorder characterised by elevated low-density lipoprotein cholesterol and premature cardiovascular events. Despite being declared as a public health priority, FH remains highly underdiagnosed, generally due to the lack of awareness and shortcomings in the available infrastructure, particularly in lower income countries. Methods: To map the existing infrastructure for the management of FH, a survey was conducted among 128 physicians (cardiologists, paediatricians, endocrinologists, and internal medicine specialists) from different regions of Pakistan. Findings: The respondents encountered a limited number of adults or children with diagnosed FH. A very small proportion of the population had access to free cholesterol and genetic testing even when indicated by a physician. In general, cascade screening of the relatives was not performed. Uniform diagnostic criteria for FH had not been established even within the same institution or province. The use of statins and ezetimibe in addition to lifestyle changes were the most common recommended treatment option for FH patients. The respondents considered lack of financial resources as a major barrier for the management of FH and stressed on taking relevant measures for a uniform FH screening programs around the country. Interpretation: National FH screening programmes are not in place worldwide hence FH is commonly undiagnosed, and many individuals are at a high risk for cardiovascular diseases. Timely screening of population for FH requires knowledge about FH among the clinicians and the availability of fundamental infrastructure coupled with sufficient financial resources. Funding: The authors confirm independence from the sponsor. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. FS received funding from Higher Education Commission, Pakistan (Grant 20-15760) and UG received grants from Slovenian Research Agency (J3-2536, P3-0343).

Preventive role of propolis against hyperglycemia and hyperlipidemia in Sprague dawley rats (Rattus norvegicus) animal modelling system.

Human diets with functional ingredients showed promising role in management of diseases of modern age like hyperglycemia and hyperlipidemia and even cancer. The study designed to elucidate role of honeybee propolis for management of hyperglycemia and hyperlipidemia states through animal modeling system. Hydroalcoholic extract of propolis was used for development of functional drink with standard recipe and addition of specified dose of extracts (400mg/500mL). Animals were grouped into three studies including study-I fed on regular diet, study-II fed on sucrose enrich diet and study-III fed on diet enriched with cholesterol and monitored to evaluate the results. Various parameters like feed consumption, liquid intake of animals measured regularly whereas body weight recorded at the end of each week of study. At the end of the study animals were analyzed for different blood indicators like blood lipid indices (cholesterol, LDL, HDL concentration and triglyceride contents)), glucose concentration and insulin contents as well. The maximum feed and drink intake were examined in animals, fed with control diet whereas a non substantial mode of intake was recorded in rest of two groups of animals. The consumption of honeybee propolis based drink reduced cholesterol (6.63% to 10.25%) and LDL (9.96% to 11.23%), whilst a sharp increase in HDL level was ranged as 4.12 to 4.49% among animal groups fed with high cholesterol and high sucrose diet. Blood glucose level was decreased by 10.25% and 6.98% however 6.99% and 4.51% increase were observed in plasma insulin level in both studies, study-II and study-III correspondingly. The overall findings of the study showed that drinks prepared using propolis of propolis found effective for management of hyperglycemia and hypercholesterolemia in present animal modelling system.

Population demographic history and population structure for Pakistani Nili-Ravi breeding bulls based on SNP genotyping to identify genomic regions associated with male effects for milk yield and body weight.

The domestic Nili-Ravi water buffalo (Bubalus bubalis) is the best dairy animal contributing 68% to total milk production in Pakistan. In this study, we identified genome-wide single nucleotide polymorphisms (SNPs) to estimate various population genetic parameters such as diversity, pairwise population differentiation, linkage disequilibrium (LD) distribution and for genome-wide association study for milk yield and body weight traits in the Nili-Ravi dairy bulls that they may pass on to their daughters who are retained for milking purposes. The genotyping by sequencing approach revealed 13,039 reference genome-anchored SNPs with minor allele frequency of 0.05 among 167 buffalos. Population structure analysis revealed that the bulls were grouped into two clusters (K = 2), which indicates the presence of two different lineages in the Pakistani Nili-Ravi water buffalo population, and we showed the extent of admixture of these two lineages in our bull collection. LD analysis revealed 4169 significant SNP associations, with an average LD decay of 90 kb for these buffalo genome. Genome-wide association study involved a multi-locus mixed linear model for milk yield and body weight to identify genome-wide male effects. Our study further illustrates the utility of the genotyping by sequencing approach for identifying genomic regions to uncover additional demographic complexity and to improve the complex dairy traits of the Pakistani Nili-Ravi water buffalo population that would provide the lot of economic benefits to dairy industry.

Effects of galacto-oligosaccharide prebiotics in blood profile of severely acute malnourished children.

This study assessed the effects of galacto-oligosaccharides (Oligomate) on hematocrit, serum enzymes, total bilirubin levels, and serum electrolytes in controls and severely malnourished infants, with emphasis on gastrointestinal symptoms. Oligomate doses and phases did not affect stools frequency per day, indicating that prebiotic effect on stool may be due to the prebiotic type. The number of vomits per day during phases 2 and 3 were significantly reduced (p<0.05) in response to prebiotics, despite the prebiotic dose effect was not significant (p>0.05). Moreover, prebiotics administration during phases 2 and 3 markedly improved hemoglobin levels (p<0.05), but not the dose. Similarly, hematocrit levels and white blood cells were significantly improved during the last 2 phases, but dose have no effects on blood hematocrit levels. Erythrocyte sedimentation rate significantly decreased (p<0.05) in phases 2 and 3 compared to phase 1. No dose-related effect was stated on erythrocytes sedimentation rate. Regarding the serum enzymes, SGPT significantly decreased (p<0.05) in phases 2 and 3 compared to phase 1, whereas SGOT significantly decreased only in phase 3. Total bilirubin levels increased significantly (p<0.05) in phase 3 when compared to phases 1 or 2. Prebiotics significantly decreased (p<0.05) sodium levels in the treated group, while potassium levels did not change in all groups, excepting during phase 2, where it increased significantly. Thus, our results confirm the hypothesis that prebiotic supplementation improves blood parameters and health status, consequently decreasing the infection risk and number of vomit per day in infants.

Bio-therapeutics effects of probiotic strain on the gastrointestinal health of severely acute malnourished children.

The core objective was to evaluate the effect of probiotic fortification at three phases of formula milk administration in malnourished children. A dose related effect was determined in 30 severely acute malnourished children (6-59 months) in a double-blind, randomized design. According to the results, serum albumin levels, treatment T2 (6 billion cfu) has significantly increased albumin levels (3.7g/dL) and the effect of phase-III (Plumpy'nut) was found to be better. Results regarding sodium levels showing probiotic-dose have significant effect (P≤0.05) in phases as well. Moreover, the effect of T1 i.e. 3 billion cfu of probiotics has significantly reduced sodium levels (141.8mmol/L) vs. others and the effect of phase-II was better on reducing sodium levels. which is further confirmed in terms of reduced erythrocyte sedimentation rate levels at phase-III (29.566 vs. phase-II, 41.3 and phase-I, 46.533 mm/h). Conclusively, the effect of 6 billion cfu at phase-III was more effective on blood parameters.

Single tube multiplex PCR assay for the identification of banned meat species.

Food adulteration has a direct impact on public health, religious faith, fair-trades, and wildlife. In the present study, a reliable and sensitive assay has been developed for verifying meat adulteration in food chain. The multiplex PCR system was optimised for identification of chicken, cow/buffalo, sheep/goat, horse/donkey, pork, and dog DNAs in a single reaction mixture simultaneously. The primers were designed using 12 S rRNA gene sequences with fragment size in the range of 113 bp to 800 bp, which can be easily visualised on agarose gel electrophoresis making the technique economical. After validation of accuracy, specificity, and sensitivity, commercially available meat products (n = 190) were screened, comprising both raw and cooked meat samples. The results demonstrated a high rate of adulteration (54.5%) in meat products. The technique developed here can be easily used for screening of different meat products for export and import purposes as well as for food inspection and livestock diagnostic laboratories.

A decoupled circuital model methodology for calculating DC currents in AC grids induced by HVDC grounding current.

Large currents are injected into the earth from grounding poles of HVDC systems under monopole ground return mode. The currents change the earth surface potential and result in DC currents in AC systems. This paper proposes a computationally efficient decoupled circuital calculation method for assessing the unwanted DC currents in AC grids. Firstly, the earth resistive network is acquired by simulating the DC grounding current distribution using Finite Element Method (FEM). Secondly, the earth resistive network and AC grid are combined to develop a decoupled circuital model of the overall system. The acquired model is used to calculate the DC currents in AC grids by solving a set of linear equations. The proposed method is computationally more efficient as compared to field-circuit coupled methods. In addition, its accuracy is proved by showing a close agreement between our results and field-circuit coupled model as well as the actual measurements. Finally, in Shanghai area power grid the DC currents are calculated using the proposed technique. Based on these calculations, remedial measures for reducing the DC currents in AC grid are suggested. Our research results indicate that DC currents in AC systems can be reduced by operating the two HVDC projects with opposite polarities.

Determination of liver and muscle aflatoxin B1 residues and select serum chemistry variables during chronic aflatoxicosis in broiler chickens.

BACKGROUND: Aflatoxins are secondary metabolites of the fungus Aspergillus sp. The presence of aflatoxin in poultry feeds results in direct toxicity and economic losses, and human health hazards after consumption of contaminated liver and meat. OBJECTIVES: The study was conducted to assess tissue residues of aflatoxin B1 (AFB1), and alterations in select clinical chemistry variables in serum during chronic aflatoxicosis in broiler chicks fed different dietary levels of AFB1. MATERIALS AND METHODS: Six groups of broiler chickens were fed diets containing between 0 and 800 ppb of AFB1 for 28 days. Groups of birds were terminated on days 0, 5, 13, 15, 20, and 28, and AFB1 levels were determined by HPLC in liver and muscle. Serum activities of ALT and ALP, and total protein and albumin concentrations were determined. RESULTS: No AFB1 residues were detected in liver after 50 ppb AFB1, and muscle after 50 and 100 ppb AFB1 feeding. Residues above the permissible threshold (> 2.0 ng/g) were only detected in liver tissues of groups fed 400 ppb and 800 ppb AFB1 in feed. The ALT and ALP activities in treated groups were significantly higher, and total protein and albumin concentrations were significantly lower in all treated groups compared to controls. CONCLUSIONS: Continuous feeding of AFB1 to broiler chicken at levels of 50 and 100 ppb for 28 days did not reveal measurable AFB1 residues in muscle tissues. Serum values of ALT, ALP, total protein, and albumin may serve as markers for chronic aflatoxicosis in affected poultry.

Biological screening of Elaeagnus umbellata Thunb.

The bark and fruit extracts of Elaeagnus umbellata have been investigated for their antibacterial, anti-fungal, insecticidal and phytotoxic activities. The petroleum ether extracts of the plant showed significant activity against E. faecalis. The activity of dichloromethane extract was also determined significant against S. aureus. The chloroform extract indicated low activity against E. coli, K. pneumoniae, B. subtilis and S. flexenari. The ethyl acetate fraction demonstrated significant activity against K. pneumoniae while methanolic extract exhibited significant activity against E. coli. All extracts showed low phytotoxic activity. The dichloromethane extract exhibited moderate insecticidal activity while other extract indicated low activity.

Truncated Type II isopentenyl diphosphate isomerase from hyperthermophilic Achaeon Thermococcus kodakaraensis implicates the necessity of its N-terminal amino acid residues in protein thermostability.

The enzyme isopentenyl diphosphate isomerase (IDI, EC 5.3.3.2) interconverts isopentenyl diphosphate and dimethylallyl diphosphate. We had previously cloned Tk-idi gene encoding the thermostable Tk-IDI enzyme from Thermococcus kodakaraensis KOD1. Four putative start codons were found on Tk-idi gene at 123, 213, 297 and 321 positions downstream of the first start codon. In the present work four mutants were obtained by deleting 123, 213, 297 and 321 nucleotides from the 5'-end of Tk-idi gene to obtain Tk-idim, Tk-idim1, Tk-idim2, and Tk-idim3, respectively. When we tried to express these truncated genes in Escherichia coli only Tk-idim was expressed in the active form. The product, Tk-IDIM, was purified and characterized. The molecular mass of the enzyme, estimated by gel filtration chromatography, was 300 kDa which indicated that the truncated enzyme retained the octameric form. The removal of 41 N-terminal amino acids did not exhibit a significant effect on the enzyme activity however, the thermostability of the enzyme decreased. The decrease in thermostability of Tk-IDIM correlated well with the results of circular dichroism (CD) analysis and structural modeling.

Comparison of plasma viscosity and fibrinogen concentration in hypertensive and normotensive diabetics.

BACKGROUND: Body weight, body mass index, fibrinogen concentration and relative plasma viscosity can contribute to the development of hypertension in diabetics. This study compares body weight, body mass index, fibrinogen concentration and relative plasma viscosity between hypertensive diabetics, normotensive diabetics and healthy controls. METHODS: The present study was carried out on normotensive and hypertensive diabetics taken from medical OPD of Saidu group of teaching hospitals, Swat. A group of healthy male subjects between 30-60 years of age from the staff members of Saidu Medical College, Swat was also included. Each group comprised of 35 subjects. Systolic and diastolic blood pressures, body weight, height, body mass index, fibrinogen concentration and relative plasma viscosity were measured and compared. RESULTS: Body weight, body mass index, fibrinogen concentration and relative plasma viscosity were all significantly more in hypertensive diabetics than normotensive diabetics and healthy control subjects. CONCLUSION: The onset of the complications is different in the two groups of diabetics (hypertensive and normotensive), earlier in hypertensive diabetics and delayed in normotensive diabetics.

Perioperative management of diabetic patients.

Diabetes mellitus is the most common metabolic disease. New classifications have recently been proposed by the American Diabetes Association (ADA) and the World Health Organization (WHO). Type 1 (formerly insulin-dependent diabetes mellitus IDDM) is immune-mediated and leads to absolute insulin deficiency. Type 2 diabetes (formerly non-insulin-dependent diabetes mellitus [NIDDM]) is a disease of adult onset and is associated with insulin resistance. Type 3 corresponds to a wide range of specific types of diabetes, including various genetic defects of beta-cell function and insulin action, diseases of exocrine pancreas, endocrinopathies, and drug-induced diabetes. Type 4 is gestational diabetes (Table 1). Diabetics undergoing surgery have increased mortality, and type 1 diabetics are particularly at risk of postoperative complications. Wound complications are increased in diabetics, and healing is severely impaired when glycemic control is poor. However, with the use of modern management plans, the major outcome measures of surgery are comparable in diabetic and nondiabetic patients. Successful management of surgery in diabetic patients requires simple and safe protocols, which are fully understood by all staff and a close liaison among the surgeons, diabetes care team, and anesthetists. There is no consensus on the optimal metabolic management of the diabetic patient during surgery. Several surveys have highlighted the inconsistency with which surgical problems are managed in diabetic patients. The aim of this article is to provide protocols to achieve sensible and practical glycemic control in diabetic patients undergoing surgery.