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• Rebar inspection & progress monitoring smart system. • Interpretation of point cloud models for quantitative rebar monitoring parameters. • Comparison of smart system outcomes with ground truth dimensions of rebar grid. Current rebar inspection practices in construction projects are manual in nature; hence, they are time-consuming. Rebar drawings are technical; therefore, the accuracy of inspection outcomes depends on the inspector's (supervisor or engineer) experience. In contrast, with the emergence of the fourth industrial revolution, the construction industry has also adopted a few technological solutions for rebar progress monitoring. However, most of the available solutions are detecting qualitative aspects, and quantitative aspects are not much covered. Moreover, available studies have focused on specific rebar monitoring parameters and have not given a complete solution. This study aims to develop an automated smart rebar evaluation model (SREM) giving a complete solution for evaluating on-site rebar quality (rebar spacing, rebar diameter) and quantity (number of rebars, rebar length). The devised system will be able to interpret the 3D point cloud model generated via photogrammetry for rebar quality and quantity parameters easily accessible by project stakeholders. The SREM has the capability to evaluate on-site rebar with the help of images with an accuracy of more than 99% for rebar length and the number of rebars, 97% for rebar spacing, and an accuracy of more than 90% for rebar diameter. The SREM offers an economical, effective, and efficient solution with minimum human involvement. It provides site safety, especially for high-rise buildings, remote progress monitoring to far projects, and minimizes CO 2 emission by controlling unnecessary site visits. Most importantly, it is an IoT-supported model. [ABSTRACT FROM AUTHOR]

In order to explore effective acetyl and butyrylcholinesterase enzyme inhibitors, a library of fifteen synthetic 1,2,4-substituted triazoles (5–19) was established and characterized using IR and NMR spectroscopic techniques. Compounds 9 and 16 were found to be the most potent AChE (IC50 = 38.91 ± 0.52 µM) and BChE (IC50 = 42.74 ± 0.42 µM) inhibitors, against the standard eserine (IC50 = 39.19 ± 0.05 µM for AChE and 46.62 ± 0.08 µM for BChE). In addition, binding interactions of potent inhibitors of AChE and BChE were studied using molecular docking. Compounds 9 and 16 were identified as promising dual inhibitors for AChE and BChE that may further be investigated to serve as lead molecules against Alzheimer's disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • SMS-IV-20 and SMS-IV-40 potently induce apoptosis in MCF-7 and MCF-7-CR cells. • The compounds chemo-sensitize MCF-7 and MCF-7-CR cells expressing MOAP-1, Bax, and RASSF1a. • When combine with ABT-737, both compounds enhance apoptotic cell death in MCF-7-CR cells. • The compounds down-regulate the expression of BCl-2, BCL-XL, or both in MCF-7-CR cells. Chemo-resistant cancer cells acquire robust growth potential through cell signaling mechanisms such as the down-regulation of tumor suppressors and the up-regulation of pro-survival proteins, respectively. To overcome chemo-resistance of cancer, small molecule drugs that interact with the cell signaling proteins to enhance sensitization of cancer cells toward cancer therapies are likely to be effective for the treatment of chemo-drug resistant cancer. To identify high potency small molecules, a series of ten novel phenylquinazoline derivatives were synthesized to determine their cellular effects in MCF-7 and MCF-7- cisplatin-resistant (CR) human breast cancer cells which led to the identification of two bioactive compounds, SMS-IV-20 and SMS-IV-40, that exhibited an elevated level of cytotoxicity against the human breast cancer cells and spheroid cells. In addition, both compounds enhanced chemo-sensitization of the human breast cancer cells that were genetically engineered to express the tumor suppressor and pro-apoptotic proteins, MOAP-1, Bax, and RASSF1a (MBR), suggesting that the compounds interact with the MBR signaling pathway. Furthermore, when MCF-7-CR cells were treated with SMS-IV-20 and SMS-IV-40 in the presence of ABT-737, a BCL-XL and BCL-2 inhibitor, enhanced chemo-sensitization was observed, suggesting SMS-IV-20 and SMS-IV-40 exert antagonistic activity to regulate the functional activity of BCL-2 and BCL-XL. Western blot analysis showed that both SMS-IV-20 and SMS-IV-40 induced down-regulation of BCL-2 or both BCl-2 and BCL-XL expression, respectively while promoting the release of mitochondrial Cytochrome C. Taken together, the data showed that SMS-IV-20 and SMS-IV-40 are potent activators of apoptosis that enhance chemo-sensitization through their antagonistic actions on the pro-survival activity of the BCl-2 family in human cancer cells. [ABSTRACT FROM AUTHOR]

• Thorium fulelled ADSR can be an alternative to uranium enrichment. • Reactor MYRRHA can be envisaged as an efficient transmutation system. • Minor actinide production is decreased when using thorium in place of uranium based fuels. Neutronics calculations have been performed of the MYRRHA ADS Reactor with a thorium-based fuel mixture, using the simulation programs MCNPX (Waters, 2002) and Geant4 (Agostinelli, 2003). Thorium is often considered for ADS systems, and this is the first evaluation of the possibilities for thorium based fuels using a reactor design which has been developed in detail. It also extends the application of the widely-used Geant4 program to the geometry of MYRRHA and to thorium. An asymptotic 232Th/233U mixture is considered, together with the standard MOX fuel and a possible 232Th/MOX starter. Neutron fluxes and spectra are calculated at several regions in the core: fuel cells, IPS cells and the two (Mo and Ac) isotope production cells. These are then used for simple calculations of the fuel evolution and of the potential for the incineration of minor actinide waste. Results from the two programs agree and support each other and show that the thorium fuel is viable, and has good evolution/breeding properties, and that minor actinide incineration, though it will not take place on a significant scale, will be demonstrable. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is one of the leading causes of death, which is often neglected due to lack of knowledge and resources. The objective of this study was to determine the effects of home-based exercise on physical functioning, quality of life and fatigue assessment for patients on hemodialysis. A randomized control trial was conducted, with participants divided into two groups. Twenty-six (26) participants were enrolled, and were assigned equally to each group. The control group received hospital-based care, and the intervention group received a home exercise program. Both groups received three sessions per week, for six weeks. Outcome measures included six-minute walk test, standing balance, 4-metre gait speed, chair stand, fatigue assessment scale and quality of life. Significant improvement in sixminute walk test, fatigue assessment scale, 4 meter gait speed, chair stand test and standing balance was noted in the intervention group as compared with control group. This study concluded that aerobic and resistance exercises are more effective in improving the functional outcomes of patients on hemodialysis as compared to routine physical therapy. [ABSTRACT FROM AUTHOR]

We report one-pot synthesis of a series of new 3-aryl-8-methylquinazolin-4(3 H)-ones (QNZ) and their antimicrobial activity against Acanthamoeba castellanii belonging to T4 genotype. A library of fifteen synthetic derivatives of QNZs was synthesized, and their structural elucidation was performed by using nuclear magnetic resonance (NMR) spectroscopy and electron impact mass spectrometry (EI-MS). Elemental analyses and high-resolution mass spectrometry data of all derivatives were found to be in agreeable range. Amoebicidal assays performed at concentrations ranging from 50 to 100 μg/mL revealed that all derivatives of QNZ significantly decreased the viability of A. castellanii and QNZ 2 , 5 , 8 , and 13 were found to have efficient antiamoebic effects. Field emission scanning electron microscopy (FESEM) imaging of amoeba treated with compounds 5 and 15 showed that these compounds cause structural alterations on the walls of A. castellanii. Furthermore, several QNZs inhibited the encystation and excystationas as well as abolished A. castellanii -mediated host cells cytopathogenicity in human cells. Whereas, these QNZs showed negligible cytotoxicity when tested against human cells in vitro. Hence, this study identified potential lead molecules having promising properties for drug development against A. castellanii. A brief structure-activity relationship is also developed to optimize the hit of most potent compounds from the library. To the best of our knowledge, it is first of its kind medicinal chemistry approach on a single class of compounds i.e., quinazolinone against keratitis and brain infection causing free-living amoeba, A. castellanii. Image 1 • Acanthamoeba is an opportunistic parasite that can cause keratitis and encephalitis. • Quinazolinones hold promise in the drug development against infectious diseases. • 3-aryl-8-methylquinazolin-4(3 H)-ones were synthesized by varying aniline derivatives. • A series of fifteen new quinazolinone derivatives have been tested against A. castellanii for the first time. • These quinazolinone derivatives exhibited potent anti -acanthamoebic activity. [ABSTRACT FROM AUTHOR]

2-Indolcarbohydrazones 1 – 28 were synthesized and evaluated for their α -glucosidase inhibitory potential. A varying degree of inhibitory potential with IC 50 values in the range of 2.3 ± 0.11–226.4 ± 6.8 μM was observed while comparing these outcomes with the standard acarbose (IC 50 = 906.0 ± 6.3 μM). The stereochemistry of ten ( 10 ) randomly selected compounds ( 1 , 3 , 6 , 8 , 12 , 18 , 19 , 23 , 25 and 28 ) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of ν C O , ν N C and ν CH (CH in N CH -R). It was observed that except compound 18 , all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds. [ABSTRACT FROM AUTHOR]

Oxadiazole derivatives ( 6 – 28 ) having hydrazone linkage, were synthesized through condensation reaction between benzohydrazide 5 with various benzaldehydes. The oxadiazoles derivatives ( 6 – 28 ) were evaluated for their α-glucosidase inhibitory activity. The IC 50 values for inhibition activity vary in the range between 2.64 ± 0.05 and 460.14 ± 3.25 μM. The IC 50 values were being compared to the standard acarbose (IC 50 = 856.45 ± 5.60 μM) and it was found that compounds 6 – 9 , 12 , 13 , 16 , 18 , 20 , 22 – 28 were found to be more active than acarbose, while other compounds showed no activity. Structure–activity relationship (SAR) studies suggest that oxadiazole benzohydrazones ( 6 – 28 ) inhibitory potential is dependent on substitution of the N -benzylidene part. Compound 18 (IC 50 = 2.64 ± 0.05 μM), which has trihydroxy substitution at C-2′, C-4′, and C-5′ on N -benzylidene moiety, recorded the highest inhibition activity that is three-hundred times more active than the standard drug, acarbose (IC 50 = 856.45 ± 5.60 μM). Compound 23 (IC 50 = 34.64 ± 0.35 μM) was found to be the most active among compounds having single hydroxyl substitution. Shifting hydroxyl from C-2′ to C-4′ ( 6 ) and C-3′ ( 7 ) reduces inhibitory activity significantly. Compounds with chlorine substituent (compounds 16 , 28 , and 27 ) showed potent activities but lower as compared to hydroxyl analogs. Substituent like nitro or methyl groups at any position suppresses enzyme inhibition activity. This reveals the important presence of hydroxyl and halo groups to have enzyme inhibitory potential. [ABSTRACT FROM AUTHOR]

• Quinazolinones inhibited the viability of Acanthamoeba castellanii. • NADPH-cytochrome c reductase is altered by these quinazolinones. • Quinazolinone compounds showed strong binding ability with AcCYP51. • Quinazolinone compounds exhibited wound healing in HaCaT cells. Acanthamoeba spp. are free living amoebae which can give rise to Acanthamoeba keratitis and granulomatous amoebic encephalitis. The surface of Acanthamoeba contains ergosterol which is an important target for drug development against eukaryotic microorganisms. A library of ten functionally diverse quinazolinone derivatives (Q1 – Q10) were synthesised to assess their activity against Acanthamoeba castellanii T4. The in-vitro effectiveness of these quinazolinones were investigated against Acanthamoeba castellanii by amoebicidal, excystation, host cell cytopathogenicity, and NADPH-cytochrome c reductase assays. Furthermore, wound healing capability was assessed at different time durations. Maximum inhibition at 50 μg/mL was recorded for compounds Q5, Q6 and Q8 , while the compound Q3 did not exhibit amoebicidal effects at tested concentrations. Moreover, LDH assay was conducted to assess the cytotoxicity of quinazolinones against HaCaT cell line. The results of wound healing assay revealed that all compounds are not cytotoxic and are likely to promote wound healing at 10 μg/mL. The excystation assays revealed that these compounds significantly inhibit the morphological transformation of A. castellanii. Compound Q3, Q7 and Q8 elevated the level of NADPH-cytochrome c reductase up to five folds. Sterol 14alpha-demethylase (CYP51) a reference enzyme in ergosterol pathway was used as a potential target for anti-amoebic drugs. In this study using i-Tasser, the protein structure of Acanthamoeba castellanii (AcCYP51) was developed in comparison with Naegleria fowleri protein (NfCYP51) structure. The sequence alignment of both proteins has shown 42.72% identity. Compounds Q1 - Q10 were then molecularly docked with the predicted AcCYP51. Out of ten quinazolinones, three compounds (Q3, Q7 and Q8) showed good binding activity within 3 Å of TYR 114. The in-silico study confirmed that these compounds are the inhibitor of CYP51 target site. This report presents several potential lead compounds belonging to quinazolinone derivatives for drug discovery against Acanthamoeba infections. [Display omitted] [ABSTRACT FROM AUTHOR]

A series of Schiff base triazoles 1 – 25 was synthesized and evaluated for their nucleotide pyrophosphatase/phosphodiesterase-1 inhibitory activities. Among twenty-five compounds, three compounds 10 (IC 50 = 132.20 ± 2.89 μM), 13 (IC 50 = 152.83 ± 2.39 μM), and 22 (IC 50 = 251.0 ± 6.64 μM) were identified as potent inhibitors with superior activities than the standard EDTA (IC 50 = 277.69 ± 2.52 μM). The newly identified inhibitors may open a new avenue for the development of treatment of phosphodiesterase-I related disorders. These compounds were also evaluated for carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase inhibitory potential and were found to be inactive. The compounds showed non-toxic effect towards PC3 cell lines. [ABSTRACT FROM AUTHOR]

Oxadiazoles and thiadiazoles 1 – 37 were synthesized and evaluated for the first time for their α-glucosidase inhibitory activities. As a result, fifteen of them 1 , 4 , 5 , 7 , 8 , 13 , 17 , 23 , 25 , 30 , 32 , 33 , 35 , 36 and 37 were identified as potent inhibitors of the enzyme. Kinetic studies of the most active compounds (oxadiazoles 1 , 23 and 25 , and thiadiazoles 35 and 37 ) were carried out to determine their mode of inhibition and dissociation constants K i . The most potent compound of the oxadiazole series (compound 23 ) was found to be a non-competitive inhibitor ( K i = 4.36 ± 0.017 μM), while most potent thiadiazole 35 was identified as a competitive inhibitor ( K i = 6.0 ± 0.059 μM). The selectivity and toxicity of these compounds were also studied by evaluating their potential against other enzymes, such as carbonic anhydrase-II and phosphodiesterase-I. Cytotoxicity was evaluated against rat fibroblast 3T3 cell line. Interestingly, these compounds were found to be inactive against other enzymes, exhibiting their selectivity towards α-glucosidase. Inhibition of α-glucosidase is an effective strategy for controlling post-prandial hyperglycemia in diabetic patients. α-Glucosidase inhibitors can also be used as anti-obesity and anti-viral drugs. Our study identifies two novel series of potent α-glucosidase inhibitors for further investigation. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a significant cause of morbidity and mortality, especially in low and lower-middle income countries. Data from the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) were used to evaluate the organization of structures and services for the provision of AKI care in world countries and ISN regions. An international survey of key stakeholders (clinicians, policymakers, and patient advocates) from countries affiliated with the ISN was conducted from July to September 2022 to assess structures and services for AKI care across countries. Main findings of the study show that overall, 167 countries or jurisdictions participated in the survey, representing 97.4% of the world's population. Only 4% of countries had an AKI detection program based on national policy or guideline, and 50% of these countries used a reactive approach for AKI identification (i.e., cases managed as identified through clinical practice). Only 19% of national governments recognized AKI as a healthcare priority. Almost all countries (98% of the countries surveyed) reported capacity to provide acute hemodialysis (HD) for AKI, but in 31% of countries, peritoneal dialysis (PD) was unavailable for AKI. About half of all countries (44% of countries surveyed) provided acute dialysis (HD or PD) via public funding, but funding availability varied across ISN regions, including less than a quarter of countries in Oceania and South East Asia (17%) and Africa (24%) and highest availability in Western Europe (91%). Availability increased with the increasing country income level. Initiatives have been developed to propose and promote optimal care for AKI (including the ISN 0-by-25 initiative), but capacity for optimal AKI care remains low, particularly in low- and lower-middle-income countries. Concerted efforts by the global community are required to close these gaps, to improve AKI outcomes across the world., Competing Interests: JAN reports personal fees from Baxter Healthcare, personal fees from AcelRx Pharmaceuticals, outside the submitted work. SA reports personal fees from The International Society of Nephrology, outside the submitted work. SD reports personal fees from The International Society of Nephrology, outside the submitted work. JD reports personal fees from The International Society of Nephrology, outside the submitted work. VJ reports personal fees from GSK, Astra Zeneca, Baxter Healthcare, Visterra, Biocryst, Chinook, Vera, and Bayer, paid to his institution, outside the submitted work. MN reports grants and personal fees from KyowaKirin, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Torii, JT, Mitsubishi Tanabe, grants from Takeda and Bayer, and personal fees from Astellas, Akebia, AstraZeneca, and GSK, outside the submitted work. AKB reports other (consultancy and honoraria) from AMGEN Incorporated and Otsuka, other (consultancy) from Bayer and GSK, and grants from Canadian Institute of Health Research and Heart and Stroke Foundation of Canada, outside the submitted work; He is also Associate Editor of the Canadian Journal of Kidney Health and Disease and Co-chair of the ISN-Global Kidney Health Atlas. DWJ reports consultancy fees, research grants, speaker’s honoraria and travel sponsorships from Baxter Healthcare and Fresenius Medical Care, consultancy fees from Astra Zeneca, Bayer, and AWAK, speaker’s honoraria from ONO and Boehringer Ingelheim & Lilly, and travel sponsorships from Ono and Amgen, outside the submitted work. He is also a current recipient of an Australian National Health and Medical Research Council Leadership Investigator Grant, outside the submitted work. All other authors have nothing to declare., (Copyright: © 2024 Wainstein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To assess changes in key measures of kidney care using data reported in 2019 and 2023., Design: Cross sectional survey in 148 countries., Setting: Surveys from International Society of Nephrology Global Kidney Health Atlas between 2019 and 2023 that included participants from countries in Africa (n=36), Eastern and Central Europe (n=16), Latin America (n=18), the Middle East (n=11), Newly Independent States and Russia (n=10), North America and the Caribbean (n=8), North and East Asia (n=6), Oceania and South East Asia (n=15), South Asia (n=7), and Western Europe (n=21)., Participants: Countries that participated in both surveys (2019 and 2023)., Main Outcome Measures: Comparison of 2019 and 2023 data for availability of kidney replacement treatment services, access, health financing, workforce, registries, and policies for kidney care. Data for countries that participated in both surveys (2019 and 2023) were included in our analysis. Country data were aggregated by International Society of Nephrology regions and World Bank income levels. Proportionate changes in the status of these measures across both periods were reported., Results: Data for 148 countries that participated in both surveys were available for analysis. The proportions of countries that provided public funding (free at point of delivery) increased from 27% in 2019 to 28% in 2023 for haemodialysis, 23% to 28% for peritoneal dialysis, and 31% to 36% for kidney transplantation services. Centres for these treatments increased from 4.4 per million population (pmp) to 4.8 pmp (P<0.001) for haemodialysis, 1.4 pmp to 1.6 pmp for peritoneal dialysis, and 0.43 pmp to 0.46 pmp for kidney transplantation services. Overall, access to haemodialysis and peritoneal dialysis improved, however, access to kidney transplantation decreased from 30 pmp to 29 pmp. The global median prevalence of nephrologists increased from 9.5 pmp to 12.4 pmp (P<0.001). Changes in the availability of kidney registries and in national policies and strategies for kidney care were variable across regions and country income levels. The reporting of specific barriers to optimal kidney care by countries increased from 55% to 59% for geographical factors, 58% to 68% (P=0.043) for availability of nephrologists, and 46% to 52% for political factors., Conclusions: Important changes in key areas of kidney care delivery were noted across both periods globally. These changes effected the availability of, and access to, kidney transplantation services. Countries and regions need to enact enabling strategies for preserving access to kidney care services, particularly kidney transplantation., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: funding support for this project from the International Society of Nephrology (grant RES0033080 to the University of Alberta); ST reports fellowship grants from the International Society of Nephrology-Salmasi Family and the Kidney Foundation of Thailand, outside the submitted work. SA reports personal fees from The International Society of Nephrology, outside the submitted work. SD reports personal fees from The International Society of Nephrology, outside the submitted work. JD reports personal fees from The International Society of Nephrology, outside the submitted work. VJ reports personal fees from GSK, Astra Zeneca, Baxter Healthcare, Visterra, Biocryst, Chinook, Vera, and Bayer, paid to his institution, outside the submitted work. VAL reports royalties from Elsevier, consulting fees from the World Health Organization, travel support from the European Renal Association and International Society of Nephrology, and leadership role in Advocacy Working Group of the International Society of Nephrology, outside the submitted work. MN reports grants and personal fees from KyowaKirin, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Torii, Japan Tobacco, Mitsubishi Tanabe, grants from Takeda and Bayer, and personal fees from Astellas, Akebia, AstraZeneca, and GSK, outside the submitted work. AKB reports other (consultancy and honoraria) from AMGEN Incorporated and Otsuka, other (consultancy) from Bayer and GSK, and grants from Canadian Institute of Health Research and Heart and Stroke Foundation of Canada, outside the submitted work; he is also Associate Editor of the Canadian Journal of Kidney Health and Disease and Co-chair of the ISN-Global Kidney Health Atlas. DWJ reports consultancy fees, research grants, speaker’s honoraria and travel sponsorships from Baxter Healthcare and Fresenius Medical Care, consultancy fees from Astra Zeneca, Bayer, and AWAK, speaker’s honoraria from ONO and Boehringer Ingelheim & Lilly, and travel sponsorships from ONO and Amgen, outside the submitted work. He is also a current recipient of an Australian National Health and Medical Research Council Leadership Investigator Grant, outside the submitted work. All other authors have nothing to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale & Objective: Established therapeutic interventions effectively mitigate the risk and progression of chronic kidney disease (CKD). Countries and regions have a compelling need for organizational structures that enable early identification of people with CKD who can benefit from these proven interventions. We report the current global status of CKD detection programs., Study Design: A multinational cross-sectional survey., Setting & Participants: Stakeholders, including nephrologist leaders, policymakers, and patient advocates from 167 countries, participating in the International Society of Nephrology (ISN) survey from June to September 2022., Outcome: Structures for the detection and monitoring of CKD, including CKD surveillance systems in the form of registries, community-based detection programs, case-finding practices, and availability of measurement tools for risk identification., Analytical Approach: Descriptive statistics., Results: Of all participating countries, 19% (n=31) reported CKD registries, and 25% (n=40) reported implementing CKD detection programs as part of their national policies. There were variations in CKD detection program, with 50% (n=20) using a reactive approach (managing cases as identified) and 50% (n=20) actively pursuing case-finding in at-risk populations. Routine case-finding for CKD in high-risk populations was widespread, particularly for diabetes (n=152; 91%) and hypertension (n=148; 89%). Access to diagnostic tools, estimated glomerular filtration rate (eGFR), and urine albumin-creatinine ratio (UACR) was limited, especially in low-income (LICs) and lower-middle-income (LMICs) countries, at primary (eGFR: LICs 22%, LMICs 39%, UACR: LICs 28%, LMICs 39%) and secondary/tertiary health care levels (eGFR: LICs 39%, LMICs 73%, UACR: LICs 44%, LMICs 70%), potentially hindering CKD detection., Limitations: A lack of detailed data prevented an in-depth analysis., Conclusions: This comprehensive survey highlights a global heterogeneity in the organization and structures (surveillance systems and detection programs and tools) for early identification of CKD. Ongoing efforts should be geared toward bridging such disparities to optimally prevent the onset and progression of CKD and its complications., Plain-Language Summary: Early detection and management of chronic kidney disease (CKD) is crucial to prevent progression to kidney failure. A multinational survey across 167 countries revealed disparities in CKD detection programs. Only 19% reported CKD registries, and 25% implemented detection programs as part of their national policy. Half used a reactive approach while others actively pursued case-finding in at-risk populations. Routine case-finding was common for individuals with diabetes and hypertension. However, limited access to gold standard tools such as estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR), especially in low-income and lower-middle income countries, may hinder CKD detection. A global effort to bridge these disparities is needed to optimally prevent the onset and progression of CKD and its complications., (Copyright © 2024 National Kidney Foundation, Inc. All rights reserved.)

Vitamin D is a lipid-soluble compound that plays a key role in bone mineral metabolism. The commercial current kits and several published assay methods (High-performance liquid chromatography (HPLC) and Immunoassay) are complicated due to the use of multiple reagents, larger sample volume, high backpressure, longer extraction time, evaporation under nitrogen after extraction, significant interference and antibody cross-reactivity. Here we report a new HPLC method for the determination of 25-hydroxyvitamin D2 (25-OHD2) and 25-hydroxyvitamin D3 (25-OHD3) that is simple (no evaporation), rapid (10-minute run time) and robust. Serum sample (300 μl) is mixed with 300 μl acetonitrile containing lauraphenone as internal standard. After vortexing and centrifugation, the supernatant was loaded into C18 extraction cartridges, washed with 70% methanol and then eluted with 200 μl of a mixture of 70% ethanol and 30% isopropyl alcohol (IPA). The eluent was mixed with 50 μl of water and injected into the HPLC-UV system for analysis. The method proved to be linear in the range of 10-750 nmol/L of 25-OHD2 and 25-OHD3. The intra- and inter-assay precision was less than 10 for both compounds at four different concentrations. The method was compared with (LC-MS/MS) and the correlation coefficients (R2) were 0.9454 and 0.9673 for 25-OHD2 and 25-OHD3 respectively. The proposed HPLC method is simple, rapid, robust and free from the most common problems encountered with commercial kits. It can be used in a high-volume laboratory that uses the HPLC method for the simultaneous determination of 25-OHD2 and 25-OHD3 in serum samples., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Kidney failure treated with hemodialysis (HD), or peritoneal dialysis (PD) is a major global health problem that is associated with increased risks of death and hospitalization. This study aimed to compare the incidence and causes of death and hospitalization during the first year of HD or PD among countries., Methods: The third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) was conducted between June and September 2022. For this analysis, data were obtained from the cross-sectional survey of key stakeholders from ISN-affiliated countries., Results: A total of 167 countries participated in the survey (response rate 87.4%). In 48% and 58% of countries, 1% to 10% of people treated with HD and PD died within the first year, respectively, with cardiovascular disease being the main cause. Access-related infections or treatment withdrawal owing to cost were important causes of death in low-income countries (LICs). In most countries, <30% and <20% of patients with HD and PD, respectively, required hospitalization during the first year. A greater proportion of patients with HD and PD in LICs were hospitalized in the first year than those in high-income countries (HICs). Access-related infection and cardiovascular disease were the commonest causes of hospitalization among patients with HD, whereas PD-related infection was the commonest cause in patients with PD., Conclusion: There is significant heterogeneity in the incidence and causes of death and hospitalization in patients with kidney failure treated with dialysis. These findings highlight opportunities to improve care, especially in LICs where infectious and social factors are strong contributors to adverse outcomes., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background: There is a lack of contemporary data describing global variations in vascular access for hemodialysis (HD). We used the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to highlight differences in funding and availability of hemodialysis accesses used for initiating HD across world regions., Methods: Survey questions were directed at understanding the funding modules for obtaining vascular access and types of accesses used to initiate dialysis. An electronic survey was sent to national and regional key stakeholders affiliated with the ISN between June and September 2022. Countries that participated in the survey were categorized based on World Bank Income Classification (low-, lower-middle, upper-middle, and high-income) and by their regional affiliation with the ISN., Results: Data on types of vascular access were available from 160 countries. Respondents from 35 countries (22% of surveyed countries) reported that > 50% of patients started HD with an arteriovenous fistula or graft (AVF or AVG). These rates were higher in Western Europe (n = 14; 64%), North & East Asia (n = 4; 67%), and among high-income countries (n = 24; 38%). The rates of > 50% of patients starting HD with a tunneled dialysis catheter were highest in North America & Caribbean region (n = 7; 58%) and lowest in South Asia and Newly Independent States and Russia (n = 0 in both regions). Respondents from 50% (n = 9) of low-income countries reported that > 75% of patients started HD using a temporary catheter, with the highest rates in Africa (n = 30; 75%) and Latin America (n = 14; 67%). Funding for the creation of vascular access was often through public funding and free at the point of delivery in high-income countries (n = 42; 67% for AVF/AVG, n = 44; 70% for central venous catheters). In low-income countries, private and out of pocket funding was reported as being more common (n = 8; 40% for AVF/AVG, n = 5; 25% for central venous catheters)., Conclusions: High income countries exhibit variation in the use of AVF/AVG and tunneled catheters. In low-income countries, there is a higher use of temporary dialysis catheters and private funding models for access creation., (© 2024. The Author(s).)

The International Society of Nephrology Global Kidney Health Atlas charts the availability and capacity of kidney care globally. In the North America and the Caribbean region, the Atlas can identify opportunities for kidney care improvement, particularly in Caribbean countries where structures for systematic data collection are lacking. In this third iteration, respondents from 12 of 18 countries from the region reported a 2-fold higher than global median prevalence of dialysis and transplantation, and a 3-fold higher than global median prevalence of dialysis centers. The peritoneal dialysis prevalence was lower than the global median, and transplantation data were missing from 6 of the 10 Caribbean countries. Government-funded payments predominated for dialysis modalities, with greater heterogeneity in transplantation payor mix. Services for chronic kidney disease, such as monitoring of anemia and blood pressure, and diagnostic capability relying on serum creatinine and urinalyses were universally available. Notable exceptions in Caribbean countries included non-calcium-based phosphate binders and kidney biopsy services. Personnel shortages were reported across the region. Kidney failure was identified as a governmental priority more commonly than was chronic kidney disease or acute kidney injury. In this generally affluent region, patients have better access to kidney replacement therapy and chronic kidney disease-related services than in much of the world. Yet clear heterogeneity exists, especially among the Caribbean countries struggling with dialysis and personnel capacity. Important steps to improve kidney care in the region include increased emphasis on preventive care, a focus on home-based modalities and transplantation, and solutions to train and retain specialized allied health professionals., (© 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Diagnosis of Biotinidase deficiency (BTD) is extremely important to avoid several neurodevelopmental problems in early childhood. Colorimetric and fluorometric methods lack specificity and selectivity due to several interferences resulting in a high number of false positive results. We developed an HPLC method for BTD activity in serum with fluorescent detection. In colorimetric assays, biotinidase attacks the amide linkage of the artificial substrate biotinidyl-4-aminobenzoic acid (B-PABA) and releases p -aminobenzoic acid (PABA), which is converted to a purple dye by diazotization reaction. The newly developed method injects the reaction mixture directly into the HPLC column and quantifies using a six-point calibration curve without coupling and diazotization reaction. The method is linear over the 5-1000 μmol/L range. The detection and quantitation limits were 2.5 μmol/L and 5.0 μmol/L, respectively. When compared with colorimetric assay, the correlation coefficient (R 2 ) was 0.9963. The within-assay and between-assay precision was <10.0% for four levels of quality control samples. No significant variation in BTD activity was detected due to hemolysis, icteric, and lipemic samples. The newly developed method eliminates the potential interference due to the presence of aromatic amines and significantly reduces the false positive results observed with the colorimetric method. It is simple, specific, sensitive, faster in sample preparation, and requires a small sample volume. The newly developed HPLC method was used in our laboratory as a secondary tier test for initial positive BTD samples from newborn screening programs. To our knowledge, no similar HPLC method has been reported to date., Competing Interests: None., (© 2023 The Authors. Published by Elsevier Inc.)

National strategies for addressing chronic kidney disease (CKD) are crucial to improving kidney health. We sought to describe country-level variations in non-communicable disease (NCD) strategies and CKD-specific policies across different regions and income levels worldwide. The International Society of Nephrology Global Kidney Health Atlas (GKHA) was a multinational cross-sectional survey conducted between July and October 2018. Responses from key opinion leaders in each country regarding national NCD strategies, the presence and scope of CKD-specific policies, and government recognition of CKD as a health priority were described overall and according to region and income level. 160 countries participated in the GKHA survey, comprising 97.8% of the world's population. Seventy-four (47%) countries had an established national NCD strategy, and 53 (34%) countries reported the existence of CKD-specific policies, with substantial variation across regions and income levels. Where CKD-specific policies existed, non-dialysis CKD care was variably addressed. 79 (51%) countries identified government recognition of CKD as a health priority. Low- and low-middle income countries were less likely to have strategies and policies for addressing CKD and have governments which recognise it as a health priority. The existence of CKD-specific policies, and a national NCD strategy more broadly, varied substantially across different regions around the world but was overall suboptimal, with major discrepancies between the burden of CKD in many countries and governmental recognition of CKD as a health priority. Greater recognition of CKD within national health policy is critical to improving kidney healthcare globally., Competing Interests: Outside the submitted work, BLN has received fees for advisory boards, scientific presentations, steering committee roles and travel support from AstraZeneca, Bayer, Boehringer and Ingelheim, and Janssen with all honoraria paid to his institution; AL and serves as a scientific advisor to Boehringer Ingelheim, AstraZeneca, and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); is on the data safety and monitoring board for the NIDDK, Kidney Precision Medicine, University of Washington Kidney Research Institute Scientific Advisory Committee; is funded by the Canadian Institute of Health Research and Kidney Foundation of Canada; PH reports grants from Chiesi Pharmaceuticals; VJ has research grants from Baxter, GSK and reports Consultancy and Advisory Board honoraria from Baxter Healthcare, and AstraZeneca; KK-Z has received honoraria and/or support from Abbott, Abbvie, ACI Clinical (Cara Therapeutics), Akebia, Alexion, Amgen, Ardelyx, ASN (American Society of Nephrology), Astra-Zeneca, Aveo, BBraun, Chugai, Cytokinetics, Daiichi, DaVita, Fresenius, Genentech, GSK, Haymarket Media, Hofstra Medical School, IFKF (International Federation of Kidney Foundations), ISH (International Society of Hemodialysis), International Society of Renal Nutrition & Metabolism (ISRNM), JSDT (Japanese Society of Dialysis Therapy), Hospira, Kabi, Keryx, Kissei, Novartis, Novo-Nordisk, OPKO, NIH (National Institutes of Health), NKF (National Kidney Foundations), Pfizer, Regulus, Relypsa, Resverlogix, Dr Schaer, Sandoz, Sanofi, Shire, VA (Veterans’ Affairs), Takeda, Vifor, UpToDate, ZS-Pharma; PGK reports conference attendance support from Amgen Australia and honorarium from Bayer Australia; SK is Director of the Real World Evidence Consortium that conducts investigator initiated industry funded projects (Allergan, Purdue, GSK, CSL, Lundbeck, NovoNordisk, Jansen, Bayer); CPK has received consulting fees from Abbott, Akebia, Astra-Zeneca, Bayer, Cara Therapeutics, CSL Behring, Rockwell and Vifor; JP reports grants and personal fees from Baxter Healthcare, Fresenius Medical Care, and Davita Healthcare partner; RTK reports personal fees from Baxter; AY-MW reports grants from Sanofi and Otsuka; MHZ has been a consultant or advisory committee member for GSK, AstraZeneca, Roche, and Bayer; KJJ reports personal fees from Fresenius Medical Care; VP has received fees for advisory boards, steering committee roles, or scientific presentations from AbbVie, Astellas, AstraZeneca, Bayer, Baxter, BMS, Boehringer Ingelheim, Dimerix, Durect, Eli Lilly, Gilead, GSK, Janssen, Merck, Mitsubishi Tanabe, Mundipharma, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relypsa, Retrophin, Sanofi, Servier, Tricida, and Vifor. MT reports grants from the Canadian Institutes for Health Research during conduct of the study; DWJ has received consultancy fees, research grants, speaker’s honoraria and travel sponsorships from Baxter Healthcare and Fresenius Medical Care, consultancy fees from Astra Zeneca, Bayer, and AWAK, speaker’s honoraria from ONO and BI & Lilly, and travel sponsorships from Ono and Amgen. He is a current recipient of an Australian National Health and Medical Research Council Leadership Investigator Grant., (Copyright: © 2023 Neuen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hyperuricemia is associated with several disease conditions, such as atherosclerosis, arthritis, kidney stones, and many others. Xanthine oxidase (XO) is an enzyme that catalyzes the conversion of xanthine to uric acid. Hence, XO is a major therapeutic drug target in the treatment of hyperuricemia and associated disorders., Objectives: The current study aimed to identify XO inhibitors based on quinazoline derivatives, with the potential to be used against gout and other hyperuricemia-associated diseases., Methods: In the current study, eighteen quinazoline derivatives 2-19 were synthesized and assessed for their in vitro xanthine Oxidase (XO) inhibitory activity. Furthermore, the most active compounds, 5 and 17, were subjected to kinetics studies, followed by computational docking. Human BJ fibroblast cells were used to measure the cytotoxicity of active compounds., Results: Compounds 4-6, 8, 10, 13, 15-17, and 19 were found active against XO, with an IC 50 values between 33.688 to 362.173μM. The obtained results showed that compounds 5 and 17 possess a significant xanthine oxidase inhibitory activity. The kinetics and molecular docking studies suggested that compounds 5 (IC 50 = 39.904 ± 0.21 μM) and 17 (IC 50 = 33.688 ± 0.30 μM) bind in the allosteric site of XO and exhibit a non-competitive type of inhibition. The molecular docking studies also predicted that the NH group of the pyrimidine ring binds with Ser344 residues of XO. Furthermore, all active compounds were non-cytotoxic on the human BJ fibroblasts cell line., Conclusion: This study identifies a series of quinazoline compounds as xanthine oxidase inhibitors, with the potential to be further investigated., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To describe the use of electronic health (eHealth) in support of health coverage for kidney care across International Society of Nephrology (ISN) regions., Design: Secondary analysis of WHO survey on eHealth as well as use of data from the World Bank, and Internet World Stats on global eHealth services., Setting: A web-based survey on the use of eHealth in support of universal health coverage., Participants: 125 WHO member states provided response., Primary Outcome Measures: Availability of eHealth services (eg, electronic health records, telehealth, etc) and governance frameworks (policies) for kidney care across ISN regions., Results: The survey conducted by the WHO received responses from 125 (64.4%) member states, representing 4.4 billion people globally. The number of mobile cellular subscriptions was <100% of the population in Africa, South Asia, North America and North East Asia; the percentage of internet users increased from 2015 to 2020 in all regions. Western Europe had the highest percentage of internet users in all the periods: 2015 (82.0%), 2019 (90.7%) and 2020 (93.9%); Africa had the least: 9.8%, 21.8% and 31.4%, respectively. The North East Asia region had the highest availability of national electronic health record system (75%) and electronic learning access in medical schools (100%), with the lowest in Africa (27% and 39%, respectively). Policies concerning governance aspects of eHealth (eg, privacy, liability, data sharing) were more widely available in high-income countries (55%-93%) than in low-income countries (0%-47%), while access to mobile health for treatment adherence was more available in low-income countries (21%) than in high-income countries (7%)., Conclusion: The penetration of eHealth services across ISN regions is suboptimal, particularly in low-income countries. Increasing utilisation of internet communication technologies provides an opportunity to improve access to kidney education and care globally, especially in low-income countries., Competing Interests: Competing interests: DJ has received consultancy fees, research grants, speaker’s honoraria and travel sponsorships from Baxter Healthcare and Fresenius Medical Care, consultancy fees from AstraZeneca and AWAK, speaker’s honoraria and travel sponsorships from ONO, and travel sponsorships from Amgen. He is a current recipient of an Australian National Health and Medical Research Council Leadership Investigator Grant. VJ has received grants, speaker's honoraria or consultancy fees from GlaxoSmithKline, Biocon, Baxter, Janssen, Medtronic and NephroPlus. He has a policy of all funds being paid to his employer. AKB has received consultancy fees from Janssen. The remaining authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The Global Kidney Health Atlas (GKHA) is a multinational, cross-sectional survey designed to assess the current capacity for kidney care across all world regions. The 2017 GKHA involved 125 countries and identified significant gaps in oversight, funding and infrastructure to support care for patients with kidney disease, especially in lower-middle-income countries. Here, we report results from the survey for the second iteration of the GKHA conducted in 2018, which included specific questions about health financing and oversight of end-stage kidney disease (ESKD) care worldwide., Setting: A cross-sectional global survey., Participants: Key stakeholders from 182 countries were invited to participate. Of those, stakeholders from 160 countries participated and were included., Primary Outcomes: Primary outcomes included cost of kidney replacement therapy (KRT), funding for dialysis and transplantation, funding for conservative kidney management, extent of universal health coverage, out-of-pocket costs for KRT, within-country variability in ESKD care delivery and oversight systems for ESKD care. Outcomes were determined from a combination of desk research and input from key stakeholders in participating countries., Results: 160 countries (covering 98% of the world's population) responded to the survey. Economic factors were identified as the top barrier to optimal ESKD care in 99 countries (64%). Full public funding for KRT was more common than for conservative kidney management (43% vs 28%). Among countries that provided at least some public coverage for KRT, 75% covered all citizens. Within-country variation in ESKD care delivery was reported in 40% of countries. Oversight of ESKD care was present in all high-income countries but was absent in 13% of low-income, 3% of lower-middle-income, and 10% of upper-middle-income countries., Conclusion: Significant gaps and variability exist in the public funding and oversight of ESKD care in many countries, particularly for those in low-income and lower-middle-income countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The International Society of Nephrology established the Global Kidney Health Atlas project to define the global capacity for kidney replacement therapy and conservative kidney care, and this second iteration was to describe the availability, accessibility, quality, and affordability of kidney failure (KF) care worldwide. This report presents results for the International Society of Nephrology North America and the Caribbean region. Relative to other regions, the North America and Caribbean region had better infrastructure and funding for health care and more health care workers relative to the population. Various essential medicines were also more available and accessible. There was substantial variation in the prevalence of treated KF in the region, ranging from 137.4 per million population (pmp) in Jamaica to 2196 pmp in the United States. A mix of public and private funding systems cover costs for nondialysis chronic kidney disease care in 60% of countries and for dialysis in 70% of countries. Although the median number of nephrologists is 18.1 (interquartile range, 15.3-29.5) pmp, which is approximately twice the global median of 9.9 (interquartile range, 1.2-22.7) pmp, some countries reported shortages of other health care workers. Dialysis was available in all countries, but peritoneal dialysis was underutilized and unavailable in Barbados, Cayman Islands, and Turks and Caicos. Kidney transplantation was primarily available in Canada and the United States. Economic factors were the major barriers to optimal KF care in the Caribbean countries, and few countries in the region have chronic kidney disease-specific national health care policies. To address regional gaps in KF care delivery, efforts should be directed toward augmenting the workforce, improving the monitoring and reporting of kidney replacement therapy indicators, and implementing noncommunicable disease and chronic kidney disease-specific policies in all countries., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Approximately 11% of people with kidney failure worldwide are treated with peritoneal dialysis (PD). This study examined PD use and practice patterns across the globe., Study Design: A cross-sectional survey., Setting & Participants: Stakeholders including clinicians, policy makers, and patient representatives in 182 countries convened by the International Society of Nephrology between July and September 2018., Outcomes: PD use, availability, accessibility, affordability, delivery, and reporting of quality outcome measures., Analytical Approach: Descriptive statistics., Results: Responses were received from 88% (n=160) of countries and there were 313 participants (257 nephrologists [82%], 22 non-nephrologist physicians [7%], 6 other health professionals [2%], 17 administrators/policy makers/civil servants [5%], and 11 others [4%]). 85% (n=156) of countries responded to questions about PD. Median PD use was 38.1 per million population. PD was not available in 30 of the 156 (19%) countries responding to PD-related questions, particularly in countries in Africa (20/41) and low-income countries (15/22). In 69% of countries, PD was the initial dialysis modality for≤10% of patients with newly diagnosed kidney failure. Patients receiving PD were expected to pay 1% to 25% of treatment costs, and higher (>75%) copayments (out-of-pocket expenses incurred by patients) were more common in South Asia and low-income countries. Average exchange volumes were adequate (defined as 3-4 exchanges per day or the equivalent for automated PD) in 72% of countries. PD quality outcome monitoring and reporting were variable. Most countries did not measure patient-reported PD outcomes., Limitations: Low responses from policy makers; limited ability to provide more in-depth explanations underpinning outcomes from each country due to lack of granular data; lack of objective data., Conclusions: Large inter- and intraregional disparities exist in PD availability, accessibility, affordability, delivery, and reporting of quality outcome measures around the world, with the greatest gaps observed in Africa and South Asia., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Niemann-Pick type C1 (NPC1) disease is a lysosomal lipid storage disorder caused by mutations of the NPC1 gene. More than 300 disease-associated mutations are reported in patients, resulting in abnormal accumulation of unesterified cholesterol, glycosphingolipids, and other lipids in late endosomes and lysosomes (LE/Ly) of many cell types. Previously, we showed that treatment of many different NPC1 mutant fibroblasts with histone deacetylase inhibitors resulted in reduction of cholesterol storage, and we found that this was associated with enhanced exit of the NPC1 protein from the endoplasmic reticulum and delivery to LE/Ly. This suggested that histone deacetylase inhibitors may work through changes in protein chaperones to enhance the folding of NPC1 mutants, allowing them to be delivered to LE/Ly. In this study, we evaluated the effect of several HSP90 inhibitors on NPC1 I1061T skin fibroblasts. We found that HSP90 inhibition resulted in clearance of cholesterol from LE/Ly, and this was associated with enhanced delivery of the mutant NPC1 I1061T protein to LE/Ly. We also observed that inhibition of HSP90 increased the expression of HSP70, and overexpression of HSP70 also reduced cholesterol storage in NPC1 I1061T fibroblasts. However, we did not see correction of cholesterol storage by arimoclomol, a drug that is reported to increase HSP70 expression, at doses up to 0.5 mM. The increase in other chaperones as a consequence of HSP90 improves folding of NPC1 protein and relieves cholesterol accumulation in NPC1 mutant fibroblasts., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

4-Arylamino-6-nitroquinazolines (2-25) were synthesized and evaluated for their leishmanicidal activities against Leishmania major promastigotes in vitro with IC50 values = 1.87-61.48 μM. Among the twenty four synthetic derivatives, 4-[4'-(methylsulfanyl)phenyl]amino-6-nitroquinazoline (21), and 4-(2'-methoxyphenyl)amino-6-nitroquinazoline (8) showed excellent antileishmanial activities with IC50 values 1.87 ± 0.31 and 4.37 ± 0.02 μM, respectively, more active than the standard drug, pentamidine (IC50 = 5.09 ± 0.09 μM). Compound 16 (IC50 = 6.53 ± 0.21 μM) displayed an activity comparable to the standard. Compounds 15 (IC50 = 9.04 ± 0.03 μM), 18 (IC50 = 12.28 ± 0.18 μM), 14 (IC50 = 19.87 ± 0.22 μM), and 5 (IC50 = 24.03 ± 2.71 μM) also showed good activities., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Twenty-five derivatives of 2-arylquinazolin-4(3H)-ones (1-25) were evaluated for their yeast (Saccharomyces cerevisiae) α-glucosidase inhibitory activities. All synthetic compounds, except 1 and 6, were found to be several hundred fold more active (IC50 values in the range of 0.3±0.01-117.9±1.76μM), than the standard drug, acarbose (IC50=840±1.73μM). The enzyme kinetic studies on the most active compounds 12, 4, 19, and 13 were performed for the determination of their modes of inhibition and dissociation constants Ki. Study of the modes of inhibition of compounds 12, and 4 were also performed using molecular modeling techniques. In brief, current study identifies a novel class of α-glucosidase inhibitors which can be further studied for the treatment of hyperglycemia and obesity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In the title mol-ecule, C16H14N4O4, the quinazoline ring is substanti-ally planar (r.m.s. deviation = 0.0129 Å) and forms a dihedral angle of 2.73 (8)° with the benzene ring. The conformation of the mol-ecule is stabilized by an intra-molecular C-H⋯N hydrogen bond. In the crystal, mol-ecules are linked into chains running parallel to the b axis by C-H⋯O hydrogen bonds. In addition, π-π stacking is observed between dimethoxy-substituted and nitro-substituted benzene rings, with centroid-centroid distances in the range 3.6438 (10)-3.7148 (10) Å.

The title mol-ecule, C10H10N4O2, is almost planar and adopts an E configuration of the azomethine [C=N = 1.298 (2) Å] double bond. The benzene ring is attached to an essentially planar (r.m.s. deviation = 0.0226 Å) amidine moiety (N=CN/Me2), the dihedral angle between the two mean planes being 18.42 (11)°. The cyano group lies in the plane of the benzene ring [the C and N atoms deviating by 0.030 (3) and 0.040 (3) Å, respectively], while the nitro group makes a dihedral angle 5.8 (3)° with the benzene ring. There are two distinct inter-molecular hydrogen bonds, C-H⋯O and C-H⋯N, that stabilize the crystal structure; the former inter-actions result in centrosymmetric dimers about inversion centers resulting in ten-membered rings, while the later give rise to chains of mol-ecules running parallel to the b axis.

The mol-ecule of the title compound, C14H11ClN2O2 adopts an E conformation of the azomethine double bond and the dihedral angle between the benzene rings is 38.96 (13)°. In the crystal, mol-ecules are linked by N-H⋯O and O-H⋯O (with the ketone O atom as acceptor) and C-H⋯O (with the hy-droxy O atom as acceptor) hydrogen bonds, forming a three-dimensional network.

Objective: To assess students' perceptions regarding merits and demerits of selecting medicine as a profession., Method: A cross sectional survey based on convenience sampling was done, where 300 students of both sexes were included, 150 from a medical profession and 150 from a non-medical profession. They were asked to fill a structured, pretested questionnaire, and the results were analyzed by SPSS 16.0., Results: All medical students mentioned that they selected the medical profession because of personal interest. In addition to this 95% students believed this profession offers services to humanity. However, 87% students felt that their family had an influence in their career selection. Interestingly gender consideration, financial reward and overseas consideration ranked low in order. There was a statistically significant difference between the preclinical and clinical groups in their decision of reselecting medicine, if they were given a second chance (p = 0.001). Of those who did not opt for a medical career, 78% students mentioned that medical training is difficult and prolonged, 75% students felt that there is too much competition while 62% students expressed that doctors have excessive working hours., Conclusion: Our study concluded that reasons for joining medical profession are primarily based on personal interest, respect and honor, family influence and service to humanity. Financial gain is not a major consideration of many students in choosing medicine as a profession, however, long working hours and prolonged training discourages many students.