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BACKGROUND: Governance, health financing, and service delivery are critical elements of health systems for provision of robust and sustainable chronic disease care. We leveraged the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to evaluate oversight and financing for kidney care worldwide. METHODS: A survey was administered to stakeholders from countries affiliated with the ISN from July to September 2022. We evaluated funding models utilized for reimbursement of medications, services for the management of chronic kidney disease, and provision of kidney replacement therapy (KRT). We also assessed oversight structures for the delivery of kidney care. RESULTS: Overall, 167 of the 192 countries and territories contacted responded to the survey, representing 97.4% of the global population. High-income countries tended to use public funding to reimburse all categories of kidney care in comparison with low-income countries (LICs) and lower-middle income countries (LMICs). In countries where public funding for KRT was available, 78% provided universal health coverage. The proportion of countries that used public funding to fully reimburse care varied for non-dialysis chronic kidney disease (27%), dialysis for acute kidney injury (either hemodialysis or peritoneal dialysis) (44%), chronic hemodialysis (45%), chronic peritoneal dialysis (42%), and kidney transplant medications (36%). Oversight for kidney care was provided at a national level in 63% of countries, and at a state/provincial level in 28% of countries. CONCLUSION: This study demonstrated significant gaps in universal care coverage, and in oversight and financing structures for kidney care, particularly in in LICs and LMICs.

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BACKGROUND: Kidney transplantation (KT) is the preferred modality of kidney replacement therapy with better patient outcomes and quality of life compared with dialytic therapies. This study aims to evaluate the epidemiology, accessibility and availability of KT services in countries and regions around the world. METHODS: This study relied on data from an international survey of relevant stakeholders (clinicians, policymakers and patient advocates) from countries affiliated with the International Society of Nephrology that was conducted from July to September 2022. Survey questions related to the availability, access, donor type and cost of KT. RESULTS: In total, 167 countries responded to the survey. KT services were available in 70% of all countries, including 86% of high-income countries, but only 21% of low-income countries. In 80% of countries, access to KT was greater in adults than in children. The median global prevalence of KT was 279.0 [interquartile range (IQR) 58.0-492.0] per million people (pmp) and the median global incidence was 12.2 (IQR 3.0-27.8) pmp. Pre-emptive KT remained exclusive to high- and upper-middle-income countries, and living donor KT was the only available modality for KT in low-income countries. The median cost of the first year of KT was $26 903 USD and varied 1000-fold between the most and least expensive countries. CONCLUSION: The availability, access and affordability of KT services, especially in low-income countries, remain limited. There is an exigent need to identify strategies to ensure equitable access to KT services for people with kidney failure worldwide, especially in the low-income countries.

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BACKGROUND: Data monitoring and surveillance systems are the cornerstone for governance and regulation, planning, and policy development for chronic disease care. Our study aims to evaluate health systems capacity for data monitoring and surveillance for kidney care. METHODS: We leveraged data from the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA), an international survey of stakeholders (clinicians, policymakers and patient advocates) from 167 countries conducted between July and September 2022. ISN-GKHA contains data on availability and types of kidney registries, the spectrum of their coverage, as well as data on national policies for kidney disease identification. RESULTS: Overall, 167 countries responded to the survey, representing 97.4% of the global population. Information systems in forms of registries for dialysis care were available in 63% (n = 102/162) of countries, followed by kidney transplant registries (58%; n = 94/162), and registries for non-dialysis chronic kidney disease (19%; n = 31/162) and acute kidney injury (9%; n = 14/162). Participation in dialysis registries was mandatory in 57% (n = 58) of countries; however, in more than half of countries in Africa (58%; n = 7), Eastern and Central Europe (67%; n = 10), and South Asia (100%; n = 2), participation was voluntary. The least-reported performance measures in dialysis registries were hospitalization (36%; n = 37) and quality of life (24%; n = 24). CONCLUSIONS: The variability of health information systems and early identification systems for kidney disease across countries and world regions warrants a global framework for prioritizing the development of these systems.

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BACKGROUND: An adequate workforce is needed to guarantee optimal kidney care. We used the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to provide an assessment of the global kidney care workforce. METHODS: We conducted a multinational cross-sectional survey to evaluate the global capacity of kidney care and assessed data on the number of adult and paediatric nephrologists, the number of trainees in nephrology and shortages of various cadres of the workforce for kidney care. Data are presented according to the ISN region and World Bank income categories. RESULTS: Overall, stakeholders from 167 countries responded to the survey. The median global prevalence of nephrologists was 11.75 per million population (pmp) (interquartile range [IQR] 1.78-24.76). Four regions had median nephrologist prevalences below the global median: Africa (1.12 pmp), South Asia (1.81 pmp), Oceania and Southeast Asia (3.18 pmp) and newly independent states and Russia (9.78 pmp). The overall prevalence of paediatric nephrologists was 0.69 pmp (IQR 0.03-1.78), while overall nephrology trainee prevalence was 1.15 pmp (IQR 0.18-3.81), with significant variations across both regions and World Bank income groups. More than half of the countries reported shortages of transplant surgeons (65%), nephrologists (64%), vascular access coordinators (59%), dialysis nurses (58%) and interventional radiologists (54%), with severe shortages reported in low- and lower-middle-income countries. CONCLUSIONS: There are significant limitations in the available kidney care workforce in large parts of the world. To ensure the delivery of optimal kidney care worldwide, it is essential to develop national and international strategies and training capacity to address workforce shortages.

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BACKGROUND: Worldwide, the uptake of peritoneal dialysis (PD) compared with hemodialysis remains limited. This study assessed organizational structures, availability, accessibility, affordability and quality of PD worldwide. METHODS: This cross-sectional study relied on data from kidney registries as well as survey data from stakeholders (clinicians, policymakers and advocates for people living with kidney disease) from countries affiliated with the International Society of Nephrology (ISN) from July to September 2022. RESULTS: Overall, 167 countries participated in the survey. PD was available in 79% of countries with a median global prevalence of 21.0 [interquartile range (IQR) 1.5-62.4] per million population (pmp). High-income countries (HICs) had an 80-fold higher prevalence of PD than low-income countries (LICs) (56.2 pmp vs 0.7 pmp). In 53% of countries, adults had greater PD access than children. Only 29% of countries used public funding (and free) reimbursement for PD with Oceania and South East Asia (6%), Africa (10%) and South Asia (14%) having the lowest proportions of countries in this category. Overall, the annual median cost of PD was US$18 959.2 (IQR US$10 891.4-US$31 013.8) with full private out-of-pocket payment in 4% of countries and the highest median cost in LICs (US$30 064.4) compared with other country income levels (e.g. HICs US$27 206.0). CONCLUSIONS: Ongoing large gaps and variability in the availability, access and affordability of PD across countries and world regions were observed. Of note, there is significant inequity in access to PD by children and for people in LICs.

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BACKGROUND: Hemodialysis (HD) is the most commonly utilized modality for kidney replacement therapy worldwide. This study assesses the organizational structures, availability, accessibility, affordability and quality of HD care worldwide. METHODS: This cross-sectional study relied on desk research data as well as survey data from stakeholders (clinicians, policymakers and patient advocates) from countries affiliated with the International Society of Nephrology from July to September 2022. RESULTS: Overall, 167 countries or jurisdictions participated in the survey. In-center HD was available in 98% of countries with a median global prevalence of 322.7 [interquartile range (IQR) 76.3-648.8] per million population (pmp), ranging from 12.2 (IQR 3.9-103.0) pmp in Africa to 1575 (IQR 282.2-2106.8) pmp in North and East Asia. Overall, home HD was available in 30% of countries, mostly in countries of Western Europe (82%). In 74% of countries, more than half of people with kidney failure were able to access HD. HD centers increased with increasing country income levels from 0.31 pmp in low-income countries to 9.31 pmp in high-income countries. Overall, the annual cost of in-center HD was US$19 380.3 (IQR 11 817.6-38 005.4), and was highest in North America and the Caribbean (US$39 825.9) and lowest in South Asia (US$4310.2). In 19% of countries, HD services could not be accessed by children. CONCLUSIONS: This study shows significant variations that have remained consistent over the years in availability, access and affordability of HD across countries with severe limitations in lower-resourced countries.

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BACKGROUND: Conservative kidney management (CKM) describes supportive care for people living with kidney failure who choose not to receive or are unable to access kidney replacement therapy (KRT). This study captured the global availability of CKM services and funding. METHODS: Data came from the International Society of Nephrology Global Kidney Health survey conducted between June and September 2022. Availability of CKM, infrastructure, guidelines, medications and training were evaluated. RESULTS: CKM was available in some form in 61% of the 165 responding countries. CKM chosen through shared decision-making was available in 53%. Choice-restricted CKM-for those unable to access KRT-was available in 39%. Infrastructure to provide CKM chosen through shared decision-making was associated with national income level, reported as being "generally available" in most healthcare settings for 71% of high-income countries, 50% of upper-middle-income countries, 33% of lower-middle-income countries and 42% of low-income countries. For choice-restricted CKM, these figures were 29%, 50%, 67% and 58%, respectively. Essential medications for pain and palliative care were available in just over half of the countries, highly dependent upon income setting. Training for caregivers in symptom management in CKM was available in approximately a third of countries. CONCLUSIONS: Most countries report some capacity for CKM. However, there is considerable variability in terms of how CKM is defined, as well as what and how much care is provided. Poor access to CKM perpetuates unmet palliative care needs, and must be addressed, particularly in low-resource settings where death from untreated kidney failure is common.

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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.

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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.

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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.

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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.

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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.

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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 (R2) 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.

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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.

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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 IC50 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 (IC50 = 39.904 ± 0.21 µM) and 17 (IC50 = 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.

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The construction industry is moving toward digitalization, and technologies support various construction processes. In the automated construction progress monitoring domain, several modern progress measurement techniques have been introduced. However, a hesitant attitude has been observed toward its adoption. Researchers have highlighted lack of theoretical understanding of effectual implementation is one of the significant reasons. This study aims to analyze general technological parameters related to automated monitoring technologies and devise a theoretical-based conceptual framework explaining the aspects affecting the adequate operation of automated monitoring. The study has been executed by following a systematic inline process for the identification of effective parameters, which include a structured literature review, semi-structured interviews, pilot survey, questionnaire survey, and structural equation modeling (SEM)-based mathematical model. A refined conceptual framework has been devised with 21 effective parameters under five significant categories, i.e., "Target Object," "Technical," "External Interference," "Occlusions," and "Sensing." A knowledge framework has been established by adopting the SEM technique, which is designed on the characteristics-based theme. This conceptual framework provides the theoretical base for practitioners toward the conceptual understanding of automated monitoring processes related to technological parameters that affect the outcomes. This study is unique as it focused on the general criteria or parameters that affect the performance or outcomes of the digital monitoring process and is easily understandable by the user or operator.

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BACKGROUND: Objective of this study was to compare Reverse Tenzel flap and Cutler Beard flap for upper eyelid defects. METHODS: This interventional study was carried out at occuloplasty department of LRBT (Layton Rahamatullah Benevoloent Trust), Karachi. Patients diagnosed with upper eye lid defect between 50 and 75 years were included after ethical approval from institutional ethical review committee and briefing patients about study dynamics. The patients were randomly divided in two groups, group A in whom reverse tanzel flap was done, while in group B Cutler beard procedure was done. Main outcome measure was eyelid contour, complete lid closure and surgical procedure time. SPSS version 25.0 was used for data analysis. RESULTS: Reverse Tenzel flap mean age 64.00±6.17 years, mean duration of surgery 33±5.78 minutes, and mean healing time 2.2±0.41 weeks. Cutler Beard flap mean age 59.60±6.26 years, mean duration of surgery 32±5.78 minutes, and mean healing time 5.7±0.8 in 3 weeks. 60% of patients were female. 30 (50%) patients each underwent Reverse Tenzel flap and Cutler Beard flap. In Reverse Tenzel flap, no complications were observed. In Cutler Beard flap, 06 (20%) patients reported mild entropion, 04 (13.3%) retraction of flap and 02 (6.7%) were found to have mild incomplete lid closure. CONCLUSIONS: Reverse Tenzel flap was superior to Cutler Beard flap as it reported no complications, being single stage surgery with early healing. Cutler-Beard flap reported mild entropion and retraction of flaps which required second surgery and delayed healing.

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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.

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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.

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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.

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