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Over the last few decades, cancer has been regarded as an independent and self sustaining progression. The earliest hallmarks of cancer comprise of sustaining proliferative signalling, avoiding growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Nonetheless, two emerging hallmarks are being described: aberrant metabolic pathways and evasion of immune destruction. Changes in tumour cell metabolism are not restricted to tumour cells alone; the products of the altered metabolism have a direct impact on the activity of immune cells inside the tumour microenvironment, particularly tumour-associated macrophages (TAMs). The complicated process of cancer growth is orchestrated by metabolic changes dictating the tight mutual connection between these cells. Here, we discuss approaches to exploit the interaction of cancer cells' abnormal metabolic activity and TAMs. We also describe ways to exploit it by reprogramming fatty acid metabolism via TAMs., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest regarding the publication of this paper., (© the Author(s).)

Lisinopril is an antihypertensive drug with poor intestinal permeability. Enhancement of intestinal absorption depends on a clear understanding of the permeation pathways and absorption mechanisms. Unfortunately, these are not fully elucidated for lisinopril. Accordingly, the aim was to determine lisinopril permeation pathways and obstacles limiting membrane transport with subsequent nomination of appropriate permeation enhancers. This employed an in situ rabbit intestinal perfusion technique, which revealed site-dependent absorptive clearance (PeA/L) from a lisinopril simple solution (5 μg/ml), with paracellular absorption playing a role. Regional drug permeability ranked as colon> duodenum> jejunum> ileum opposing intestinal expression rank of P-glycoprotein (P-gp) efflux transporters. Duodenal and jejunal perfusion of a higher lisinopril concentration (50 μg/ml) reflected saturable absorption, suggesting carrier-mediated transport. The effect of piperine and verapamil as P-gp inhibitors on intestinal absorption of lisinopril was investigated. Coperfusion with either piperine or verapamil significantly enhanced lisinopril absorption, with enhancement being dominant in the ileum segment. This supported the contribution of P-gp transporters to poor lisinopril permeability. On the other hand, coperfusion of lisinopril with zinc acetate dihydrate significantly multiplied lisinopril PeA/L by 2.3- and 6.6-fold in duodenum and ileum segments, respectively, through magnifying intestinal water flux. The study explored the barriers limiting lisinopril intestinal absorption. Moreover, the study exposed clinically relevant lisinopril interactions with common coadministered cargos that should be considered for an appropriate lisinopril regimen. However, this requires further in vivo verification., (© 2022 John Wiley & Sons Ltd.)

Peritoneal dialysis (PD) is an important home-based treatment for kidney failure and accounts for 11% of all dialysis and 9% of all kidney replacement therapy globally. Although PD is available in 81% of countries, this provision ranges from 96% in high-income countries to 32% in low-income countries. Compared with haemodialysis, PD has numerous potential advantages, including a simpler technique, greater feasibility of use in remote communities, generally lower cost, lesser need for trained staff, fewer management challenges during natural disasters, possibly better survival in the first few years, greater ability to travel, fewer dietary restrictions, better preservation of residual kidney function, greater treatment satisfaction, better quality of life, better outcomes following subsequent kidney transplantation, delayed need for vascular access (especially in small children), reduced need for erythropoiesis-stimulating agents, and lower risk of blood-borne virus infections and of SARS-CoV-2 infection. PD outcomes have been improving over time but with great variability, driven by individual and system-level inequities and by centre effects; this variation is exacerbated by a lack of standardized outcome definitions. Potential strategies for outcome improvement include enhanced standardization, monitoring and reporting of PD outcomes, and the implementation of continuous quality improvement programmes and of PD-specific interventions, such as incremental PD, the use of biocompatible PD solutions and remote PD monitoring., (© 2022. Springer Nature Limited.)

In this study, we developed and characterized various open-cell composite scaffolds for bone regeneration. These scaffolds were made from Polylactic acid (PLA) as the scaffold matrix biopolymeric phase, and chitosan (CS) and chitosan-grafted-PLA (CS-g-PLA) copolymer as the dispersed biopolymeric phase. As a first step, successful grafting of PLA onto CS backbone was executed and confirmed by both FTIR and XPS. Mechanical characterization confirmed that adding CS or CS-g-PLA to the intrinsically rigid PLA made their corresponding PLA/CS and PLA/CS-g-PLA composite scaffolds more flexible under compression. This flexibility was higher for the latter due to the improved compatibility between PLA and CS-g-PLA copolymer. The hydrolytic stability of both PLA/CS and PLA/CS-g-PLA composite scaffolds inside phosphate-buffered saline (PBS) solution, as well as MG-63 osteoblast cell adhesion and proliferation inside both scaffolds, were characterized. The corresponding results revealed that PLA/CS composite scaffolds showed hydrolytic degradation due to the cationic properties of CS. However, modified PLA/CS-g-PLA scaffolds were hydrolytically stable due to the improved interfacial adhesion between the PLA matrix and CS-g-PLA copolymer. Finally, biological characterization was done for both PLA/CS and PLA/CS-g-PLA composite scaffolds. Contrarily to what was observed for uncompatibilized PLA/CS scaffolds, compatibilized PLA/CS-g-PLA scaffolds showed a high MG-63 osteoblast cell proliferation after three and five days of cell culture. Moreover, it was observed that cell proliferation increased with CS-g-PLA content. This suggests that the PLA/CS-g-PLA composite scaffolds could be a potential solution for bone regeneration.

[ 18 F]sodium fluoride ([ 18 F]NaF) is recognised to be superior to [ 99 mTc]-methyl diphosphate ([ 99m Tc]Tc-MDP) and 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) in bone imaging. However, there is concern that [ 18 F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [ 18 F]AlF-NOTA-pamidronic acid was prepared, optimised, and tested for its in vitro uptake. NOTA-pamidronic acid was prepared by an N- Hydroxysuccinimide (NHS) ester strategy and validated by liquid chromatography-mass spectrometry analysis (LC-MS/MS). Radiolabeling of [ 18 F]AlF-NOTA-pamidronic acid was optimised, and it was ensured that all quality control analysis requirements for the radiopharmaceuticals were met prior to the in vitro cell uptake studies. NOTA-pamidronic acid was successfully prepared and radiolabeled with 18 F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl 3 ) to NOTA-pamidronic acid and heated at 100 °C for 15 min in the presence of 50% ethanol ( v / v ), which proved to be optimal. The preliminary in vitro results of the binding of the hydroxyapatite showed that [ 18 F]AlF-NOTA-pamidronic acid was as sensitive as [ 18 F]sodium fluoride ([ 18 F]NaF). Normal human osteoblast cell lines (hFOB 1.19) and human osteosarcoma cell lines (Saos-2) were used for the in vitro cellular uptake studies. It was found that [ 18 F]NaF was higher in both cell lines, but [ 18 F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [ 18 F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research.

Tumour heterogeneity refers to the complexity of cell subpopulations coexisting within the tumour microenvironment (TME), such as proliferating tumour cells, tumour stromal cells and infiltrating immune cells. The bidirectional interactions between cancer and the surrounding microenvironment mark the tumour survival and promotion functions, which allow the cancer cells to become invasive and initiate the metastatic cascade. Importantly, these interactions have been closely associated with metabolic reprogramming, which can modulate the differentiation and functions of immune cells and thus initiate the antitumour response. The purpose of this report is to review the CD36 receptor, a prominent cell receptor in metabolic activity specifically in fatty acid (FA) uptake, for the metabolic symbiosis of cancer-macrophage. In this review, we provide an update on metabolic communication between tumour cells and macrophages, as well as how the immunometabolism indirectly orchestrates the tumour metastasis.

The whitefly, Bemisia tabaci , is the main pest for many field and horticultural crops, causing main and significant problems. The efficiency of imidacloprid insecticide as seed treatment and foliar spray at three rates against the whitefly, B. tabaci , was evaluated in tomato plants under field conditions; in addition, insecticide residues were determined in tomato leaves and fruits. The obtained results revealed that the seedlings produced from treated seeds with imidacloprid were the most effective treatment in decreasing whitefly stages. Reduction percentages of whitefly stages in seedlings produced from treated seeds and sprayed with ½, ¾ and 1 field rates of imidacloprid were more than that produced from untreated seeds. Tomato fruit yield in seedlings produced from treated seeds and sprayed with one recommended rate of imidacloprid was more than that of untreated seeds. The residues of imidacloprid in leaves and fruits in seedlings produced from treated seeds and sprayed with field rate were more than that of untreated seeds; additionally, the residues were higher in leaves than in fruits. The residual level in fruits was less than the maximum residual level (MRL = 1 mg kg -1 ) of the Codex Alimentarius Commission. The half-life (t ½) was 6.99 and 6.48 days for leaves and fruits of seedlings produced from treated seeds and 5.59 and 4.59 days for untreated seeds. Residues in tomato fruits were less than the MRL, therefore, imidacloprid is considered an unconventional insecticide appropriate for B. tabaci control that could be safe for the environment.

Objectives: This study aimed to investigate how titanium (Ti) surface with different range roughness created by industrial machining influence the biological response of primary human gingival fibroblasts (HGFB) and keratinocytes (HGKC) in terms of cell proliferation and cytotoxicity., Methods: Four Ti surfaces of different roughness ranges were investigated: smooth (S: 0.08-0.1 µm), minimally rough (MM: 0.3-0.5 µm), moderately rough (MR: 1.2-1.4 µm) and rough (R: 3.3-3.7 µm). Discs topography and surface roughness were evaluated by scanning electron microscopy (SEM) and non-contact profilometer. Both cell lines were cultured, expanded, and maintained according to their supplier's protocols. Cell proliferation and cytotoxicity were evaluated at days 1, 3, 5, and 10 using cell viability and cytotoxicity colorimetric assays. Data were analysed via two-way ANOVA, one-way ANOVA and Tukey's post hoc test (p = 0.05 for all tests)., Results: Both cell lines showed comparable initial proliferation activity of 70-86% for all the investigated roughnesses. HGKC showed better and higher proliferation % with S surface at all time points than all the other investigated surfaces which was significantly higher than MM at day 3 and higher than all the other investigated surfaces at day 5 and 10. On the other hand, HGFB exhibited the best proliferation with both MM and R surfaces with no significant differences from the other two surfaces (S and MR). Different surface roughnesses and exposure times showed significant effect on cell proliferation in both cell lines. Cytotoxicity for both cell lines was generally the highest on day 3, with the following order from highest to lowest: S (19.86%)> R> MR> MM for HGKC and MM (39.48%)> MR> S> R for HGFB. Different exposure times showed a significant effect on cell cytotoxicity in both cell lines and a significant effect of surface roughness in HGFB., Significance: All investigated roughness levels were sufficiently biologically compatible with cells representative of the major population of the soft tissue surrounding dental implants. However, the S surface was most cytotoxic to HGKC, while the MM surface was most cytotoxic to HGFB cells., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Seborrheic keratoses (SKs) are the most common benign epithelial tumors encountered in clinical practice. Complications associated with traditional treatments of SKs urge the scientists to seek alternative treatment modalities. Objective To compare the efficacy and safety of 2940-nm erbium-doped yttrium aluminum garnet (Er:YAG) laser versus 980-nm diode laser both clinically and dermoscopically for the treatment of seborrheic keratosis., Methods: Thirty subjects with multiple SKs were randomized to receive two sessions of either Er:YAG laser (n = 15) or diode laser (n = 15) and were followed up for 2 weeks after each session, and at 3 and 6 months after the second session., Results: Both lasers exhibited significant clearance of SKs with no significant difference in clinical and dermoscopic improvement between the two systems. However, Er:YAG laser showed shorter total downtime but more serious erythema, while scarring and hyperpigmentation were observed in diode laser group. No recurrence was detected in both groups at 6 months follow-up., Conclusion: Er:YAG and diode lasers both are effective, non-invasive and well-tolerated techniques in treatment of SKs., (© 2022 Wiley Periodicals LLC.)

Background And aim: The coronavirus-19 is an ongoing global pandemic resulting in millions of deaths worldwide. For a patient population at higher risk of infection, telemedicine is a promising means of providing safe and alternative care routes while minimizing their risk of exposure. This study gives insight into patients' experiences and satisfaction with telemedicine during this pandemic., Methods: We conducted a cross-sectional study on 297 patients (RR: 85%) at the National Center for Cancer Care and Research (NCCCR), Qatar. Data was collected through electronic medical records of the eligibe patient population, and phone calls were made whereby the physician read a standard introductory script followed by a survey questionnaire. We focused on patients' experience with telemedicine services amid the pandemic. This was done using a six-point Likert scoring system of seven questions that were scaled from 1 to 6., Results: More than 80% of patients somewhat to strongly agreed that telemedicine met their healthcare needs, improved their confidence in their healthcare system, and were generally satisfied with the quality of care provided. Nearly all patients (90%) understood their physicians' recommendations over the phone. In addition, more than half of the patients (89%) felt they could freely communicate their concerns. Patients also showed an inclination towards face-to-face consultations at 68%; however, 90% were willing to participate in future teleconsultations., Conclusion: Our study indicates an overall positive experience among patients towards the use of telemedicine. Telemedicine is a safe, futuristic approach toward patient care management and, thus, provides healthcare professionals a platform to implement further patient and physician education. Even though our data also showed that patients liked in-person visits to some degree, this needs to be looked into more in future studies., Competing Interests: The authors declare no conflict of interest. Note: Abdulqadir J. Nashwan is an Editorial Board member of Health Science Reports and co‐authorco‐author of this article. He is excluded from editorial decision‐making related to the acceptance of this article for publication in the journal., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Objectives: This study aimed to investigate the response of human gingival fibroblasts (HGFB) and human gingival keratinocytes (HGKC) towards different dental implant abutment materials. Methods: Five materials were investigated: (1) titanium (Ti), (2) titanium nitride (TiN), (3) cobalt-chromium (CoCr), (4) zirconia (ZrO2), and (5) modified polyether ether ketone (m-PEEK). Both cell lines were cultured, expanded, and seeded in accordance with the protocol of their supplier. Cell proliferation and cytotoxicity were evaluated at days 1, 3, 5, and 10 using colourimetric viability and cytotoxicity assays. Data were analysed via two-way ANOVA, one-way ANOVA, and Tukey’s post hoc test (p < 0.05 for all tests). Results: There was a statistically significant difference in cell proliferation of HGKC and HGFB cells in contact with different abutment materials at different time points, with no significant interaction between different materials. There was a significant effect on cell proliferation and cytotoxicity with different exposure times (p < 0.0001) for each material. Cell proliferation rates were comparable for both cell lines at the beginning of the study, however, HGFB showed higher proliferation rates for all materials at day 10 with better proliferation activities with ZrO and m-PEEK (40.27%) and (48.38%) respectively. HGKC showed significant interactions (p < 0.0001) in cytotoxicity between different materials. Conclusion: The present in vitro assessment investigated the biocompatibility of different abutment materials with soft tissue cells (HGFB and HGKC). The findings suggest that m-PEEK and TiN are biologically compatible materials with human cells that represent the soft tissue and can be considered as alternative implant abutment materials to Ti and ZrO2, especially when the aesthetic is of concern.

Climate variables play a critical role in COVID-19's spread. Therefore, this research aims to analyze the effect of average temperature and relative humidity on the propagation of COVID-19 in Africa's first four affected countries (South Africa, Morocco, Tunisia, and Ethiopia). As a result, policymakers should develop effective COVID-19 spread control strategies. For each country, using daily data of confirmed cases and weather variables from May 1, 2020, to April 30, 2021, generalized linear models (Poisson regression) and general linear models were estimated. According to the findings, the rising average temperature causes COVID-19 daily new cases to increase in South Africa and Ethiopia while decreasing in Morocco and Tunisia. However, in Tunisia, the relative humidity and daily new cases of COVID-19 are positively correlated, while in the other three countries, they are negatively associated., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Objectives: This study aimed to investigate human osteoblasts (HOB) response towards different dental implant abutment materials., Methods: Five dental implant abutment materials were investigated: (1) titanium (Ti), (2) titanium coated nitride (TiN), (3) cobalt chromium (CoCr), (4) zirconia (ZrO₂), and (5) modified polyether ether ketone (m-PEEK). HOBs were cultured, expanded, and seeded according to the supplier's protocol (PromoCell, UK). Cell proliferation and cytotoxicity were evaluated at days 1, 3, 5, and 10 using Alamar Blue (alamarBlue) and lactate dehydrogenase (LDH) colorimetric assays. Data were analysed via two-way ANOVA, one-way ANOVA and Tukey's post hoc test (significance was determined as p < 0.05 for all tests)., Results: All the investigated materials showed high and comparable initial proliferation activities apart from ZrO₂ (46.92%), with P% of 79.91%, 68.77%, 73.20%, and 65.46% for Ti, TiN, CoCr, and m-PEEK, respectively. At day 10, all materials exhibited comparable and lower P% than day 1 apart from TiN (70.90%) with P% of 30.22%, 40.64%, 37.27%, and 50.65% for Ti, CoCr, ZrO₂, and m-PEEK, respectively. The cytotoxic effect of the investigated materials was generally low throughout the whole experiment. At day 10, the cytotoxicity % was 7.63%, 0.21%, 13.30%, 5.32%, 8.60% for Ti, TiN, CoCr, ZrO₂, and m-PEEK. The Two-way ANOVA and Tukey's Multiple Comparison Method highlighted significant material and time effects on cell proliferation and cytotoxicity, and a significant interaction (p < 0.0001) between the tested materials. Notably, TiN and m-PEEK showed improved HOB proliferation activity and cytotoxic levels than the other investigated materials. In addition, a non-significant negative correlation between viability and cytotoxicity was found for all tested materials. Ti (p = 0.07), TiN (p = 0.28), CoCr (p = 0.15), ZrO₂ (p = 0.17), and m-PEEK (p = 0.12)., Significance: All the investigated materials showed excellent biocompatibility properties with more promising results for the newly introduced TiN and m-PEEK as alternatives to the traditionally used dental implant and abutment materials., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate human osteoblast (HOB) responses towards different degrees of titanium (Ti) implant surface roughness. Methods: Four degrees of Ti surface roughness were investigated on a micrometer roughness scale: smooth (S: 0.08−0.1 µm), minimally rough (MM: 0.3−0.5 µm), moderately rough (MR: 1.2−1.4 µm), and rough (R: 3.3−3.7 µm). HOB cells were cultured, expanded, and maintained according to the supplier’s protocol. Cell proliferation and cytotoxicity were assessed at day 1, 3, 5, and 10 using alamarBlue and lactate dehydrogenase colorimetric assays. Data were analyzed with one-way ANOVA, two-way ANOVA, and Tukey’s post hoc test (p = 0.05 for all tests). Results: There was no significant difference in the cell proliferation or cytotoxicity of the HOB cells in contact with the different degrees of Ti surface roughness. There was, however, a significant time effect on cell proliferation (p < 0.0001) with different exposure durations for each roughness degree. Furthermore, a positive correlation (non-significant) between proliferation and cytotoxicity was observed for all investigated degrees of surface roughness. Conclusion: All investigated roughness degrees showed comparable HOB proliferation, with the MR surface presenting the highest percentage, followed by the R, MM, ad S, surfaces, respectively. The S surface showed the highest cytotoxic effect on HOBs; however, it did not reach the cytotoxic level suggested by the ISO for any medical device to be considered cytotoxic.

Purpose: Sofosbuvir, a nucleotide antiviral drug, is a Biopharmaceutics Classification System (BCS) class III prodrug suffering from limited intestinal absorption due to its high hydrophilicity and low intestinal permeability. This research aims to investigate the luminal stability of Sofosbuvir, the influence of anatomical site on its intestinal absorption and the effects of verapamil on such absorption., Method: The study utilized in situ rabbit intestinal perfusion technique to examine absorption of Sofosbuvir from duodenum, jejunum, ileum and ascending colon. This was conducted both with and without verapamil., Results: The luminal stability study showed that Sofosbuvir was subjected to premature degradation with varying fractions degraded from the different intestinal segments. The in situ perfusion data showed incomplete absorption of Sofosbuvir from small and large intestinal segments. The recorded values of the absorptive clearance per unit length (Pe.A/L) of Sofosbuvir were 0.026, 0.0075, 0.0026, & 0.054 ml/min.cm for duodenum, jejunum, ileum, and ascending colon, respectively. The Pe.A/L values were ordered as colon > duodenum > jejunum > ileum. This is the opposite rank of P-gp content in the different intestinal segments. The recorded values of the length required for complete Sofosbuvir absorption (L95%) were 29.58, 128.47, 949.2 and, 13.63 cm for duodenum, jejunum, ileum, and ascending colon, respectively. Co-perfusion with verapamil significantly increased Pe.A/L and reduced the L95% of Sofosbuvir from both jejunum and ileum (P-value < 0.05)., Conclusion: The results indicated that the absorptive clearance of Sofosbuvir was site dependent and associated with the content of P-glycoprotein, in addition to the expected drug interactions that can occur in polymedicated hepatitis C virus (HCV) infected patients., (© 2021. Springer Nature Switzerland AG.)

Haemodialysis (HD) is the commonest form of kidney replacement therapy in the world, accounting for approximately 69% of all kidney replacement therapy and 89% of all dialysis. Over the last six decades since the inception of HD, dialysis technology and patient access to the therapy have advanced considerably, particularly in high-income countries. However, HD availability, accessibility, cost and outcomes vary widely across the world and, overall, the rates of impaired quality of life, morbidity and mortality are high. Cardiovascular disease affects more than two-thirds of people receiving HD, is the major cause of morbidity and accounts for almost 50% of mortality. In addition, patients on HD have high symptom loads and are often under considerable financial strain. Despite the many advances in HD technology and delivery systems that have been achieved since the treatment was first developed, poor outcomes among patients receiving HD remain a major public health concern. Understanding the epidemiology of HD outcomes, why they might vary across different populations and how they might be improved is therefore crucial, although this goal is hampered by the considerable heterogeneity in the monitoring and reporting of these outcomes across settings., (© 2022. Springer Nature Limited.)

Background: Kidney transplantation (KT) is the optimal treatment for kidney failure and is associated with better quality of life and survival relative to dialysis. However, knowledge of the current capacity of countries to deliver KT is limited. This study reports on findings from the 2018 International Society of Nephrology Global Kidney Health Atlas survey, specifically addressing the availability, accessibility, and quality of KT across countries and regions., Methods: Data were collected from published online sources, and a survey was administered online to key stakeholders. All country-level data were analyzed by International Society of Nephrology region and World Bank income classification., Results: Data were collected via a survey in 182 countries, of which 155 answered questions pertaining to KT. Of these, 74% stated that KT was available, with a median incidence of 14 per million population (range: 0.04-70) and median prevalence of 255 per million population (range: 3-693). Accessibility of KT varied widely; even within high-income countries, it was disproportionately lower for ethnic minorities. Universal health coverage of all KT treatment costs was available in 31%, and 57% had a KT registry., Conclusions: There are substantial variations in KT incidence, prevalence, availability, accessibility, and quality worldwide, with the lowest rates evident in low- and lower-middle income countries. Understanding these disparities will inform efforts to increase awareness and the adoption of practices that will ensure high-quality KT care is provided around the world., Competing Interests: D.W.J. has received consultancy fees, research grants, speaker’s honoraria, and travel sponsorships from Baxter Healthcare and Fresenius Medical Care; consultancy fees from Astra Zeneca 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. V.J. has received grants, speaker honoraria, or consultancy fees from GlaxoSmithKline, Biocon, Baxter, Janssen, Medtronic, and NephroPlus. He has a policy of all funds being paid to his employer. A.K.B. has received consultancy fees from Janssen. The International Society of Nephrology provided administrative support for the design and implementation of the study and data collection activities. The authors were responsible for data management, analysis, and interpretation, as well as article preparation, review, and approval and the decision to submit the article for publication. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The Kingdom of Saudi Arabia has undergone a significant transformation in eating habits and the native diets have been replaced with Western diets. The present study investigated the effect of dietary behavior on nutritional status and associated factors of Yemeni students studying in Saudi Arabia. The socioeconomic characteristics, food habits, daily food intake, and anthropometric measurement (BMI) were used to assess the nutrition status of 240 adults (120 males and 120 females) Yemni students with the ages ranging from 18 to 35 years studying at King Saud University, Saudi Arabia. The majority of students were married, had higher education level and reasonable income and eat three meals a day. Higher number of female studnets skipped breakfast compared to male students. Energy intake, i.e., vitamins and minerals was lower than the dietary recommended intake (DRI) for both male and female students. The majority of males were overweight compared to females. Most of the socioeconomic characteristics and food habits had positive or negative correlation with body mass index (BMI). Overall, the results revealed that the majority of Yemeni male students had poor eating habits compared to females, resulting in obesity. High income, number of meals per day, breakfast consumption, restaurant meals, consumption of soft drinks, sweets, and potato chips were identified as factors associated with the nutritional status of male and female students included in the study., Competing Interests: The authors have declared that no competing interests exist.

The focus on managing Alzheimer's disease (AD) is shifting towards prevention through lifestyle modification instead of treatments since the currently available treatment options are only capable of providing symptomatic relief marginally and result in various side effects. Numerous studies have reported that the intake of fermented foods resulted in the successful management of AD. Food fermentation is a biochemical process where the microorganisms metabolize the constituents of raw food materials, giving vastly different organoleptic properties and additional nutritional value, and improved biosafety effects in the final products. The consumption of fermented foods is associated with a wide array of nutraceutical benefits, including anti-oxidative, anti-inflammatory, neuroprotective, anti-apoptotic, anti-cancer, anti-fungal, anti-bacterial, immunomodulatory, and hypocholesterolemic properties. Due to their promising health benefits, fermented food products have a great prospect for commercialization in the food industry. This paper reviews the memory and cognitive enhancement and neuroprotective potential of fermented food products on AD, the recently commercialized fermented food products in the health and food industries, and their limitations. The literature reviewed here demonstrates a growing demand for fermented food products as alternative therapeutic options for the prevention and management of AD.

The management of a vestibular fistula is a challenge for pediatric surgeons. We compared four different operative techniques in terms of postoperative complications, continence, and cosmetic appearance. This prospective, randomized, comparative study included female children with rectovestibular fistulae who were selected from patients with Anorectal Malformations (ARMs) treated between January 2016 and July 2020. The patients were randomly divided into four groups based on the operative technique: Trans-Sphincter Anorectoplasty (TSARP), Posterior Sagittal Anorectoplasty (PSARP), Classic Anterior Sagittal Anorectoplasty (ASARP), and modified ASARP. The incidence of vestibular fistulae among all patients with ARMs was 13.4%. The total number of patients with vestibular fistula was 112, including eighty-four (75%) with rectovestibular fistulae and twenty-eight (25%) with anovestibular fistulae. Associated congenital anomalies were found in nineteen (22.6%) patients. The percentage of parents satisfied with the cosmetic appearance and continence of their children was the highest after TSARP. PSARP had the lowest incidence regarding vaginal wall injuries. TSARP is the best operative technique for handling rectovestibular fistulae and is suitable for infants and children. In the TSARP technique, the external sphincter muscle can be preserved following complete dissection of the rectum without the need for a midline skin incision. A midline skin incision is required in the modified ASARP technique.

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.)

The study assessed the site dependent intestinal absorption of Daclatasvir and investigated the effects of piperine and omeprazole on such absorption utilizing in situ rabbit intestinal perfusion technique. The intestinal absorption of Daclatasvir was assessed in four segments: duodenum, jejunum, ileum, and colon. The effect of co-perfusion with omeprazole was monitored through the tested anatomical sites. The effect of piperine, a P-glycoprotein (P-gp) inhibitor on Daclatasvir absorption from jejunum and ileum was tested. The results showed that Daclatasvir was incompletely absorbed from the rabbit small and large intestine. The absorptive clearance per unit length (PeA/L) was site dependent and was ranked as colon > duodenum > jejunum > ileum. This rank is the opposite of the rank of P-gp intestinal content suggesting possible influence for P-gp. Co-perfusion with omeprazole increased PeA/L and this was evidenced also with reduced the L95% of Daclatasvir from both small and large intestinal segments. Significant enhancement in Daclatasvir absorption through jejunum and ileum was shown in presence of piperine. Daclatasvir showed site dependent intestinal absorption in a manner suggesting its affection by P-gp efflux. This effect was inhibited by piperine. Co-administration of Daclatasvir with omeprazole can enhance intestinal absorption a phenomenon which requires extension to human pharmacokinetic investigation., (© 2022 John Wiley & Sons Ltd.)

Background: Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas., Methods: As part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT)., Results: Out of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups., Conclusions: These findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The chicken gut is the habitat to trillions of microorganisms that affect physiological functions and immune status through metabolic activities and host interaction. Gut microbiota research previously focused on inflammation; however, it is now clear that these microbial communities play an essential role in maintaining normal homeostatic conditions by regulating the immune system. In addition, the microbiota helps reduce and prevent pathogen colonization of the gut via the mechanism of competitive exclusion and the synthesis of bactericidal molecules. Under commercial conditions, newly hatched chicks have access to feed after 36-72 h of hatching due to the hatch window and routine hatchery practices. This delay adversely affects the potential inoculation of the healthy microbiota and impairs the development and maturation of muscle, the immune system, and the gastrointestinal tract (GIT). Modulating the gut microbiota has been proposed as a potential strategy for improving host health and productivity and avoiding undesirable effects on gut health and the immune system. Using early-life programming via in ovo stimulation with probiotics and prebiotics, it may be possible to avoid selected metabolic disorders, poor immunity, and pathogen resistance, which the broiler industry now faces due to commercial hatching and selection pressures imposed by an increasingly demanding market.

Antimicrobial resistance remains one of the most challenging issues that threatens the health of people around the world. Plant-derived natural compounds have received considerable attention for their potential role to mitigate antibiotic resistance. This study was carried out to assess the antimicrobial activity and mode of action of a monoterpene, 1,8-cineol (CN) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Results showed that resazurin microplate assay and time-kill analysis revealed bactericidal effects of CN at 28.83 mg/mL. Zeta potential showed that CN increased the surface charge of bacteria and an increase of outer membrane permeability was also detected. CN was able to cause leakage of proteins and nucleic acids in KPC-KP cells upon exposure to CN and ethidium bromide influx/efflux experiment showed the uptake of ethidium bromide into the cell; this was attributed to membrane damage. CN was also found to induce oxidative stress in CN-treated KPC-KP cells through generation of reactive oxygen species which initiated lipid peroxidation and thus damaging the bacterial cell membrane. Scanning and transmission electron microscopies further confirmed the disruption of bacterial cell membrane and loss of intracellular materials. In this study, we demonstrated that CN induced oxidative stress and membrane damage resulting in KPC-KP cell death., (© 2021. The Author(s).)

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.)

In this study, the combined effect of different packaging materials (transparent PET, transparent glass, glass-PET bottle and tin), some aromatic herbs (thyme, rosemary, sage and olive leaf) and also their essential oils (thyme, rosemary and sage) on fatty acid composition of virgin olive oil was investigated during storage period. The initial amounts of the main fatty acids as oleic, palmitic and linoleic acids were determined as 72.89%, 11.89% and 8.96%, respectively. The addition of aromatic plants and essential oils did not effect the fatty acid profile. Also, packaging materials had a minor influence on fatty acids. In the 6th month of storage, the oleic acid contents of olive oils showed the increase in all of samples. The highest increase was observed in olive oil stored in glass-PET (74.30-75.01%), followed by stored in glass bottle (73.41-74.82%). Generally, during the storage, the differences of fatty acid contents were in minor level. The fatty acid composition of olive oils stored under different essential oil and extract concentrations showed partial differences depending on the extract type and concentration.

Background: Although various treatments are currently available for primary cutaneous amyloidosis (PCA), there is no entirely satisfactory treatment. Recently, fractional ablative lasers are claimed to have therapeutic effects for PCA., Objective: To evaluate the efficacy and safety of fractional Er:YAG laser for the treatment of PCA., Methods and Materials: Ten patients with macular and lichen amyloidosis received 4 treatment sessions with 4-week intervals. The outcome was assessed clinically (degree of pigmentation, rippling, lichenification, and itching) through photographs and histologically (amount of amyloid, melanin, epidermal thickness, and depth of rete ridges) through biopsy specimens stained with hematoxylin-eosin, Congo red, and Fontana-Masson stain. Patients were followed up for 3 months after the final treatment., Results: At 3-month follow-up, fractional Er:YAG laser exhibited a significant clinical and histological improvement. Patient satisfaction concurred with physicians' evaluations. Recurrence was detected in 1 patient., Conclusion: In light of the authors' findings, fractional Er:YAG laser offered a great clinical and histological efficacy with excellent safety profile. Careful laser selection based on making a compromise between efficacies and safeties may improve outcome., (Copyright © 2021 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Sorghum grains were subjected to microwave heating at different power levels 350 and 500 W for application times of 15, 30, and 45 s. The effect of microwave heating on fungal growth, protein content, in vitro digestibility, protein solubility, and functional and antioxidant properties of sorghum grain was investigated. The microwave heating at 350 and 500 W significantly reduced fungal incidence in the grain up to 26.2 and 33.4%. No significant changes were found in the crude protein and digestibility of protein, water holding capacity, and oil holding capacity of sorghum. However, application of microwave energy at 500 W for 30 & 45 s caused a sharp reduction on the protein solubility (8.2-7.6%), foaming capacity (6.47-0.98%), emulsion capacity (0.43-0.32 mL/g) and the emulsion stability (2.2-1.6%) of sorghum grain, respectively. Conversely, a significant increment of grain total phenolic content up to 47.1 and 50.8 mg GAE/g and the antioxidant activity up to 40.9 and 59.1% after microwave heat treatment at 350 and 500 W for 45 s, respectively, was observed. These findings revealed that sorghum grain should be treated with microwave at 350 and 500 W for 45 and 15 s, respectively, in order to maintained and enhanced its functional and nutritional properties. Accordingly, microwave heating, particularly at low power, may be an effective emerging method for improving the physicochemical and nutritional properties of sorghum grain., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Osteosarcoma (OS) is a life-threatening malignant bone tumor associated with poor prognosis among children. The survival rate of the patient is still arguably low even with intensive treatment provided, plus with the inherent side effects from the chemotherapy, which gives more unfavorable outcomes. Hence, the search for potent anti-osteosarcoma agent with promising safety profile is still on going. Natural occurring substance like curcumin has gained a lot of attention due to its splendid safety profile as well as it pharmacological advantages such as anti-metastasis and anti-angiogenesis. However, natural curcumin was widely known for its poor cellular uptake, which undermines all potential that it possesses. This prompted the development of synthetically synthesized curcuminoid analog, known as (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2- en-1-one (DK1). In this present study, in vitro scratch assay, transwell migration/invasion assay, HUVEC tube formation assay, and ex vivo rat aortic ring assays were performed in order to investigate the anti-metastatic and anti-angiogenic potential of DK1. For further comprehension of DK1 mechanism on human osteosarcoma cell lines, microarray gene expression analysis, quantitative polymerase chain reaction (qPCR), and proteome profiler were adopted, providing valuable forecast from the expression of important genes and proteins related to metastasis and angiogenesis. Based on the data gathered from the bioassays, DK1 was able to inhibit the metastasis and angiogenesis of human osteosarcoma cell lines by significantly reducing the cell motility, number of migrated and invaded cells as well as the tube formation and micro-vessels sprouting. Additionally, DK1 also has significantly regulated several cancer pathways involved in OS proliferation, metastasis, and angiogenesis such as PI3K/Akt and NF-κB in both U-2 OS and MG-63. Regulation of PI3K/Akt caused up-regulation of genes related to metastasis inhibition, namely, PTEN, FOXO, PLK3, and GADD45A. Meanwhile, NF-κB pathway was regulated by mitigating the expression of NF-κB activator such as IKBKB and IKBKE in MG-63, whilst up-regulating the expression of NF-κB inhibitors such as NFKBIA and NFKBIE in U-2 OS. Finally, DK1 also has successfully hindered the metastatic and angiogenic capability of OS cell lines by down-regulating the expression of pro-metastatic genes and proteins like MMP3, COL11A1, FGF1, Endoglin, uPA, and IGFBP2 in U-2 OS. Whilst for MG-63, the significantly down-regulated oncogenes were Serpin E1, AKT2, VEGF, uPA, PD-ECGF, and Endoglin. These results suggest that curcumin analog DK1 may serve as a potential new anti-osteosarcoma agent due to its anti-metastatic and anti-angiogenic attributes.

This present research investigated the anti-obesity and hepatoprotective effects of ethanolic Moringa peregrina leaf (MPLE) and bark extracts (MPBE), in the rats fed with a high-fat diet (HFD). Healthy male rats (n = 48) were randomly distributed to six groups (n = 8): control AIN-93 diet; HFD; HFD + MPBE bark extracts ((300 mg/kg); HFD + MPBE (600 mg/kg); HFD + MPLE (300 mg/kg); HFD + MPLE (600 mg/kg). HFD-fed rats in the Moringa peregrina (MP) treatment groups received orally administered MP leaf or bark extract daily for eight weeks. The results revealed that both doses of MP leaf extract significantly reduced HFD-induced increases in their food intake and the gained body weight, fat pad weights (visceral, subcutaneous, and epididymal), glucose and insulin plasma levels, and leptin and resistin serum levels in HFD-fed rats. Concomitantly, MP leaf extract improved glucose levels after oral or intraperitoneal glucose tolerance tests, reduced serum cholesterol, triglycerides, and the low-density lipoprotein LDL concentration, reduced hepatic triglycerides and cholesterol levels, and increased serum high-density lipoproteins HDL levels and triglycerides and cholesterol levels in fecal. Moreover, the administration of MPLE to HFD-fed rats improved liver architecture, reduced fat accumulation, reduced hepatic malondialdehyde, tumor necrosis factor-α, and interleukin-6 levels. Hepatic glutathione peroxidase, superoxide dismutase, and catalase activities were significantly increased. All observed effects were more pronounced in HFD-fed rats treated with a 600 mg/kg MP dose. However, neither dose of MPBE altered the measured markers in the HFD-fed rats. In conclusion, MPLE showed potential anti-obesity and hepatoprotective activity in HFD-induced obese rats, mediated by reduced lipid absorption, anti-hyperlipidemic effects, and hepatic antioxidant effects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Objectives: We sought to investigate the nutritional and hematological status of Sudanese women of childbearing age with sickle cell anemia (SCA). Anthropometry and hematology were used to assess nutritional status and health and disease conditions, respectively., Methods: Women with steady-state (HbSS, n = 39; age = 19.0±2.7) and without (HbAA, n = 36; age, 19.8±2.7) SCA were recruited during a routine visit to the Hematology Clinic, Ibn-Auf Teaching Hospital, Khartoum, Sudan., Results: The two groups of women lived in similar environmental conditions and ate similar diets three times a day. However, despite taking regular meals, the women with sickle anemia were thinner and lighter ( p < 0.001) and shorter ( p = 0.002) compared with those who do not have the disease. Also, they had higher levels of mean corpuscular hemoglobin (Hb) concentration and white cell count ( p < 0.001), mean corpuscular volume ( p = 0.003), and platelet ( p = 0.002) and lower packed cell volume and Hb ( p < 0.001). There was no difference in levels of anthropometric and hematological variables between the hydroxyurea treated and untreated SCA patients ( p > 0.050)., Conclusions: The low anthropometric (height, weight, and body mass index) and abnormal hematological values in the women with SCA in steady-state reflect sustained nutritional insults inflected by the disease and poverty. Tailored nutritional counseling/advice must be an integral part of managing patients with SCA. Such advice is particularly vital for women of childbearing age because of the adverse effects of prepregnancy nutritional deficiency on outcomes., (The OMJ is Published Bimonthly and Copyrighted 2021 by the OMSB.)

Kefir is a fermented beverage with renowned probiotics that coexist in symbiotic association with other microorganisms in kefir grains. This beverage consumption is associated with a wide array of nutraceutical benefits, including anti-inflammatory, anti-oxidative, anti-cancer, anti-microbial, anti-diabetic, anti-hypertensive, and anti-hypercholesterolemic effects. Moreover, kefir can be adapted into different substrates which allow the production of new functional beverages to provide product diversification. Being safe and inexpensive, there is an immense global interest in kefir's nutritional potential. Due to their promising benefits, kefir and kefir-like products have a great prospect for commercialization. This manuscript reviews the therapeutic aspects of kefir to date, and potential applications of kefir products in the health and food industries, along with the limitations. The literature reviewed here demonstrates that there is a growing demand for kefir as a functional food owing to a number of health-promoting properties.

Objective: Apatinib is an oral TKI targeting VEGFR-2. Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated mBC. Oral vinorelbine also holds promise as a treatment of choice in patients with mBC. This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated mBC. In addition, we detected gene variants in ctDNA to explore the therapeutic implications., Methods: This study enrolled patients with HER2-negative mBC who were pretreated with anthracycline/taxanes. Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m 2 on days 1, 8, and 15 of every cycle (3 weeks). The primary endpoint was PFS. The secondary endpoints were ORR, CBR, OS, and safety. Patients eligible for ctDNA detection were evaluated before and during treatment., Results: Forty patients were enrolled. The median PFS was 5.2 months (95% CI, 3.4-7.0 months), and the median OS was 17.4 months (95% CI, 8.0-27.0 months). The ORR was 17.1% (6/35), and the CBR was 45.7% (16/35). The most common AEs included gastrointestinal reaction, myelosuppression, and hypertension. In 20 patients, ctDNA was detected at baseline and during treatment. A significant difference was found in PFS for undetected vs. detected baseline ctDNA (13.9 months vs. 3.6 months, P = 0.018)., Conclusions: All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative mBC, with acceptable and manageable toxicity profiles. Patients with no gene variant detected and lower variant allele frequencies in ctDNA at baseline showed longer PFS., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2021 Cancer Biology & Medicine.)

Background: De-escalating anthracycline is gaining popularity for breast cancer patients. We aim to evaluate the non-inferiority of an anthracycline-free or short-term regimen to the standard anthracycline-based regimen for operable patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer., Methods: It is a prospective, open-label, phase 3, randomized non-inferiority trial from June 1, 2010 to June 1, 2017. Follow-up had been kept until July 2019. This trial was conducted at Fudan University Shanghai Cancer Center. Patients with pT1-3N+ or pT2-3N0 but high-risk (grade II/III, lymphovascular invasion, ≤35 years of age or hormone-receptor negative) HER2-negative operable breast cancer were eligible and stratified by age, pathological tumour stage, pathological node status and hormone-receptor status. Patients were randomized to 6 cycles of docetaxel and cyclophosphamide (TC, n  = 524), 3 cycles of cyclophosphamide/epirubicin/fluorouracil followed by 3 cycles of docetaxel (CEF-T, n  = 523) or epirubicin and cyclophosphamide for 4 cycles followed by paclitaxel for 12 weeks (EC-P, n  = 524) as the intention-to-treat population. Of these patients, 94% completed allocated therapy. Difference in disease-free survival (DFS) compared to EC-P. The prespecified non-inferiority margin was 4.5%, corresponding to the hazard ratio (HR) of 1.44 (one-sided α = 0.05), with an assumed 5-year DFS of 89% for EC-P., Findings: Included in the intention-to-treat population were 1571 patients (median [IQR] age, 50 [45-57] years; 92% estrogen receptor [ER]-positive; 59% pN+). Through a median follow-up of 5.5 years, HR for TC versus EC-P was 1.05 (5-year DFS: 85.0% vs . 85.9%; 90% confidence interval [CI]: 0.79-1.39, non-inferior P  = 0.048) and for CEF-T versus EC-P, 0.99 (5-year DFS: 85.1% vs . 85.9%; 90% CI: 0.75-1.30, non-inferior P  = 0.045). Grade 3 or 4 adverse events for TC included rash (3.9%) and peripheral neuropathy (2.8%) and for CEF-T and EC-P diarrhea and nausea/vomiting were predominant. Results of per-protocol analyses were similar., Interpretation: Both TC and CEF-T are non-inferior adjuvant regimen to EC-P mainly in patients with ER+HER2- breast cancer. TC is a safe regimen that avoids anthracycline-related side effects., Funding: This work was supported by grants from the National Natural Science Foundation of China (Grants 81672600, 81722032, 82072916, and 91959207), the 2018 Shanghai Youth Excellent Academic Leader, the Fudan ZHUOSHI Project, the Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals (grant SHDC12010116), the Cooperation Project of Conquering Major Diseases in the Shanghai Municipality Health System (grant 2013ZYJB0302), the Innovation Team of the Ministry of Education (grant IRT1223), and the Shanghai Key Laboratory of Breast Cancer (grant 12DZ2260100) and the National Cancer Institute (grant P30 CA16058)., Competing Interests: The authors have declared no conflicts of interest., (© 2021 The Author(s). Published by Elsevier Ltd.)

The International Society of Nephrology Global Kidney Health Atlas analyzed the current state of kidney care in Newly Independent States and Russia. Our results demonstrated that the Newly Independent States and Russia region was not an exception and showed the same effect of chronic kidney disease on health and its outcomes, facing many difficulties and challenges in terms of improving kidney care across the countries. This work summarized and presented demographics, health information systems, statistics, and national health policy of the region, as well as characteristics of the burden of chronic kidney disease and kidney failure (KF) of participating countries. Besides significant economic advancement in the region, the collected data revealed existing shortage in KF care providers, essential medications, and health product access for KF care. Moreover, there was low reporting of kidney replacement therapy (dialysis and kidney transplantation) quality indicators and low capacity for long-term hemodialysis, peritoneal dialysis, and kidney transplantation. The financial issues and funding structures for KF care across the region needs strategic support for fundamental changes and further advancement. This article emphasizes the urgent need for further effective regional and international collaborations and partnership for establishment of universal health care systems for KF management., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Kidney failure (KF) is a public health problem in all regions of the world. We aim to provide comprehensive information regarding the disease burden of KF and capacity for providing optimal care in the International Society of Nephrology North and East Asia region based on data from the International Society of Nephrology Global Kidney Health Atlas project. Seven of eight jurisdictions participated, and wide variation was found in terms of KF burden and care capacity. Prevalence of long-term dialysis ranged from 88.4 per million population in mainland China to 3251 per million population in Taiwan. Hemodialysis was the predominant modality of dialysis in all jurisdictions, except for Hong Kong, where peritoneal dialysis (PD) was much more prevalent than hemodialysis. All jurisdictions provided public funding for kidney replacement therapy (dialysis and transplantation). Although the frequency and duration of hemodialysis followed a standard pattern in all investigated jurisdictions, the density of nephrologists and kidney replacement therapy centers varied according to income level. Conservative care, whether medically advised or chosen by patients, was available in most jurisdictions. All jurisdictions had official registries for KF and recognized KF as a health priority. These comprehensive data provide information about the burden of KF and capacity to provide optimal care in North and East Asia, which varied greatly across jurisdictions in the region., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Latin America is a region with a widely variable socioeconomic landscape, facing a surge in noncommunicable diseases, including chronic kidney disease and kidney failure, exposing significant limitations in the delivery of care. Despite region-wide efforts to explore and address these limitations, much uncertainty remains as to the capacity, accessibility, and quality of kidney failure care in Latin America. Through this second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to report on these indicators to provide a comprehensive map of kidney failure care in the region. Survey responses were received from 18 (64.2%) countries, representing 93.8% of the total population in Latin America. The median prevalence and incidence of treated kidney failure in Latin America were 715 and 157 per million population, respectively, the latter being higher than the global median (142 per million population), with Puerto Rico, Mexico, and El Salvador experiencing much of this growing burden. In most countries, public and private systems collectively funded most aspects of kidney replacement therapy (dialysis and transplantation) care, with patients incurring at least 1% to 25% of out-of-pocket costs. In most countries, >90% of dialysis patients able to access kidney replacement therapy received hemodialysis (n = 11; 5 high income and 6 upper-middle income), and only a small minority began with peritoneal dialysis (1%-10% in 67% of countries; n = 12). Few countries had chronic kidney disease registries or targeted detection programs. There is a large variability in the availability, accessibility, and quality of kidney failure care in Latin America, which appears to be subject to individual countries' funding structures, underreliance on cheap kidney replacement therapy, such as peritoneal dialysis, and limited chronic kidney disease surveillance and management initiatives., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Kidney failure is the permanent impairment of kidney function associated with increased morbidity, hospitalization, and requirement for kidney replacement therapy. A total of 11 countries in the Middle East region (84.6%) responded to the survey. The prevalence of chronic kidney disease in the region ranged from 5.2% to 10.6%, whereas prevalence of treated kidney failure ranged from 152 to 826 per million population. Overall, the incidence of kidney transplantation was highest in Iran (30.9 per million population) and lowest in Oman and the United Arab Emirates (2.2 and 3.0 per million population, respectively). Long-term hemodialysis services were available in all countries, long-term peritoneal dialysis services were available in 9 (69.2%) countries, and transplantation services were available in most countries of the region. Public funding covered the costs of nondialysis chronic kidney disease care in two-thirds of countries, and kidney replacement therapy in nearly all countries. More than half of the countries had dialysis registries; however, national noncommunicable disease strategies were lacking in most countries. The Middle East is a region with high burden of kidney disease and needs cost-effective measures through effective health care funding to be available to improve kidney care in the region. Furthermore, well-designed and sustainable health information systems are needed in the region to address current gaps in kidney care in the region., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Provision of adequate kidney care for patients with chronic kidney disease or kidney failure (KF) is costly and requires extensive resources. There is an inequality in the global distribution of wealth and resources needed to provide this care. In this second iteration of the International Society of Nephrology Global Kidney Health Atlas, we present data for countries in Eastern and Central Europe. In the region, the median prevalence of chronic kidney disease was 13.15% and treated KF was 764 per million population, respectively, slightly higher than the global median of 759 per million population. In most countries in the region, over 90% of dialysis patients were on hemodialysis and patients with a functioning graft represented less than one-third of total patients with treated KF. The median annual costs for maintenance hemodialysis were close to the global median, and public funding provided nearly universal coverage of the costs of kidney replacement therapy. Nephrologists were primarily responsible for KF care. All countries had the capacity to provide long-term hemodialysis, and 95% had the capacity to provide peritoneal dialysis. Home hemodialysis was generally not available. Kidney transplantation and conservative care were available across most of the region. Almost all countries had official dialysis and transplantation registries. Eastern and Central Europe is a region with a high burden of chronic kidney disease and variable capacity to deal with it. Insufficient funding and workforce shortages coupled with increasing comorbidities among aging patients and underutilization of cost-effective dialysis therapies such as peritoneal dialysis and kidney transplantation may compromise the quality of care for patients with KF. Some workforce shortages could be addressed by improving the organization of nephrological care in some countries of the region., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Information about disease burden and the available infrastructure and workforce to care for patients with kidney disease was collected for the second edition of the International Society of Nephrology Global Kidney Health Atlas. This paper presents findings for the 8 countries in the South Asia region. The World Bank categorizes Afghanistan and Nepal as low-income; Bangladesh, Bhutan, India, and Pakistan as lower-middle-income; and Sri Lanka and the Maldives as upper-middle-income countries. The prevalence of chronic kidney disease (CKD) in South Asia ranged from 5.01% to 13.24%. Long-term hemodialysis and long-term peritoneal dialysis are available in all countries, but Afghanistan lacks peritoneal dialysis services. Kidney transplantation was available in all countries except Bhutan and Maldives. Hemodialysis was the dominant modality of long-term dialysis, peritoneal dialysis was more expensive than hemodialysis, and kidney transplantation overwhelmingly depended on living donors. Bhutan provided public funding for kidney replacement therapy (dialysis and transplantation); Sri Lanka, India, Pakistan, and Bangladesh had variable funding mechanisms; and Afghanistan relied solely on out-of-pocket expenditure. There were shortages of health care personnel across the entire region. Reporting was variable: Afghanistan and Sri Lanka have dialysis registries but publish no reports, whereas Bangladesh has a transplant registry. South Asia has a large, but poorly documented burden of CKD. Diabetes and hypertension are the major causes of CKD throughout the region with a higher prevalence of infectious causes in Afghanistan and a high burden of CKD of an unknown cause in Sri Lanka and parts of India. The extent and quality of care delivery is suboptimal and variable. Sustainable strategies need to be developed to address the growing burden of CKD in the region., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Populations in the high-income countries of Western Europe are aging due to increased life expectancy. As the prevalence of diabetes and obesity has increased, so has the burden of kidney failure. To determine the global capacity for kidney replacement therapy and conservative kidney management, the International Society of Nephrology conducted multinational, cross-sectional surveys and published the findings in the International Society of Nephrology Global Kidney Health Atlas. In the second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to describe the availability, accessibility, quality, and affordability of kidney failure care in Western Europe. Among the 29 countries in Western Europe, 21 (72.4%) responded, representing 99% of the region's population. The burden of kidney failure prevalence varied widely, ranging from 760 per million population (pmp) in Iceland to 1612 pmp in Portugal. Coverage of kidney replacement therapy from public funding was nearly universal, with the exceptions of Germany and Liechtenstein where part of the costs was covered by mandatory insurance. Fourteen (67%) of 21 countries charged no fees at the point of care delivery, but in 5 countries (24%), patients do pay some out-of-pocket costs. Long-term dialysis services (both hemodialysis and peritoneal dialysis) were available in all countries in the region, and kidney transplantation services were available in 19 (90%) countries. The incidence of kidney transplantation varied widely between countries from 12 pmp in Luxembourg to 70.45 pmp in Spain. Conservative kidney care was available in 18 (90%) of 21 countries. The median number of nephrologists was 22.9 pmp (range: 9.47-55.75 pmp). These data highlight the uniform capacity of Western Europe to provide kidney failure care, but also the scope for improvement in disease prevention and management, as exemplified by the variability in disease burden and transplantation rates., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Oceania and South East Asia (OSEA) is a socioeconomically, culturally, and ethnically diverse region facing a rising epidemic of noncommunicable diseases, including chronic kidney disease (CKD). The second iteration of the International Society of Nephrology Global Kidney Health Atlas aimed to provide a comprehensive evaluation of kidney care in OSEA. Of the 30 countries/territories in OSEA, 15 participated in the survey, representing 98.5% of the region's population. The median prevalence of treated kidney failure in OSEA was 1352 per million population (interquartile range, 966-1673 per million population), higher than the global median of 787 per million population. Although the general availability, access, and quality of kidney replacement therapy (i.e., dialysis and transplantation) was high in OSEA, inequalities in accessibility and affordability of kidney replacement therapy across the region resulted in variability between countries. According to the survey results, in a third of the participating countries (mostly lower-income countries), less than half the patients with kidney failure were able to access dialysis, whereas it was readily available to all with minimal out-of-pocket costs in high-income countries; similar variability in access to transplantation was also recorded. Limitations in workforce and resources vary across the region and were disproportionately worse in lower-income countries. There was little advocacy for kidney disease, moderate use of registries, restricted CKD detection programs, and limited availability of routine CKD testing in some high-risk groups across the region. International collaborations, as seen in OSEA, are important initiatives to help close the gaps in CKD care provision across the region and should continue receiving support from the global nephrology community., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Despite positive economic forecasts, stable democracies, and reduced regional conflicts since the turn of the century, Africa continues to be afflicted by poverty, poor infrastructure, and a massive burden of communicable diseases such as HIV, malaria, tuberculosis, and diarrheal illnesses. With the rising prevalence of chronic kidney disease and kidney failure worldwide, these factors continue to hinder the ability to provide kidney care for millions of people on the continent. The International Society of Nephrology Global Kidney Health Atlas project was established to assess the global burden of kidney disease and measure global capacity for kidney replacement therapy (dialysis and kidney transplantation). The aim of this second iteration of the International Society of Nephrology Global Kidney Health Atlas was to evaluate the availability, accessibility, affordability, and quality of kidney care worldwide. We identified several gaps regarding kidney care in Africa, chief of which are (i) severe workforce limitations, especially in terms of the number of nephrologists; (ii) low government funding for kidney care; (iii) limited availability, accessibility, reporting, and quality of provided kidney replacement therapy; and (iv) weak national strategies and advocacy for kidney disease. We also identified that within Africa, the availability and accessibility to kidney replacement therapy vary significantly, with North African countries faring far better than sub-Sahara African countries. The evidence suggests an urgent need to increase the workforce and government funding for kidney care, collect adequate information on the burden of kidney disease from African countries, and develop and implement strategies to enhance disease prevention and control across the continent., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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.)

Background: Specific language impairment (SLI) diagnosis is inconvenient due to manual procedures and hardware cost. Computer-aided SLI diagnosis has been proposed to counter these inconveniences. This study focuses on evaluating the feasibility of computer systems used to diagnose SLI., Methods: The accuracy of Webgazer.js for software-based gaze tracking is tested under different lighting conditions. Predefined time delays of a prototype diagnosis task automation script are contrasted against with manual delays based on human time estimation to understand how automation influences diagnosis accuracy. SLI diagnosis binary classifier was built and tested based on randomised parameters. The obtained results were cross-compared to Singlims&#95;ES.exe for equality., Results: Webgazer.js achieved an average accuracy of 88.755% under global lighting conditions, 61.379% under low lighting conditions and 52.7% under face-focused lighting conditions. The diagnosis task automation script found to execute with actual time delays with a deviation percentage no more than 0.04%, while manually executing time delays based on human time estimation resulted in a deviation percentage of not more than 3.37%. One-tailed test probability value produced by both the newly built classifier and Singlims&#95;ES were observed to be similar up to three decimal places., Conclusion: The results obtained should serve as a foundation for further evaluation of computer tools to help speech language pathologists diagnose SLI., Competing Interests: Conflict of Interest None., (© Penerbit Universiti Sains Malaysia, 2021.)

Background: Helicobacter pylori pathogenicity and disease severity are determined by the tyrosine phosphorylation motifs of CagA protein. This study is aimed at detecting the presence of H . pylori and identifying the CagA tyrosine phosphorylation motifs in Ghanaian patients. Material and Methods . A total of 94 archival genomic DNA samples from gastric biopsies were used for the study, and H . pylori was detected by amplifying the 16S rRNA gene. The 3'-end variable region of the cagA gene was amplified, and the entire 3'-end was sequenced and translated into amino acids., Results: H . pylori was detected in 53.2% (50/94) of the samples, and all the detected bacteria harboured the cagA gene. Two variants of the bacteria were identified based on the size of the amplified cagA gene: 207 bp and 285 bp. The 207 bp and 285 bp variants accounted for 74% and 22%, respectively, and 4% showed both fragments. Translated amino acid sequence of the cagA gene showed EPIYA-A, EPIYA-B, and EPIYA-C (ABC type) motifs, indicating the Western variant. The CagA protein C-terminal showed insertion of amino acids in the sequence flanking the EPIYA-A motif at the N-terminal and a complete deletion of the EPIYA-CC and EPIYA-CCC motifs together with the flanking sequences., Conclusions: H . pylori identified were Western variant (ABC type) with unique amino acid insertions, suggesting unique variants in Ghanaian patients. Further investigation is however required to understand the role of the molecular diversity of the variant in gastric disease outcome., Competing Interests: The authors declare no conflict of interest for this paper., (Copyright © 2021 Emmanuel A. Tagoe et al.)

This study investigated the effect of solar drying on storability and physiochemical and antioxidant capacities of dried tomatoes. Sliced fruit was dried at 45 ± 2 °C for 24 h under a solar tunnel dryer and stored at ambient temperature for 90 and 180 days. Solar drying treatments significantly ( p < 0.05) reduced the bacterial and mold load, and eliminated Staphylococcus aureus , S. saprophyticus , and Escherichia coli in all samples. Solar drying treatment reduced the water activity of the dried tomato's to 0.31 that remained at the same level during storage period 180 days. Storage of dried tomato slices resulted in the decrease of both color and vitamin C content while it increased the total carotenoid, lycopene, phenolic compound content, and antioxidant activity. Furthermore, the principle component analysis (PCA) revealed that solar drying of tomato slices enhanced its physicochemical properties, antioxidant capacity particularly after storage for 90 and 180 days. Interestingly, the solar drying process enhanced tomato slices storage and physicochemical characteristics, that resulted in extending the shelf life by up to 6 months, indicating the great potential application of low-tech solar in food industry and could become an emerging effective post-harvest preservative method for seasonal perishable vegetable and fruit, particularly in developing countries.

The current experiment was designed to evaluate the effects of dietary supplementations of zinc oxide nanoparticles (ZONPs) on some behavioural, performance, welfare and histopathological changes in broilers exposed to multidrug resistant Staphylococcus aureus (MRSA)-induced footpad dermatitis (FPD). Eighty-four male Indian River (IR) broilers were randomly allotted to six different dietary treatments as follows: C-ve, C+ve, 10, 20, 30 and 40 ppm ZONPs from 7 to 49d of age. At day 28, broilers ( n  = 70) were sub-cutaneously injected with 0.5 ml of saline containing 5.3 × 10 7  CFU/ml of S. aureus (MRSA) in each metatarsal foot pad. Control (non-infected) broilers were given 0.5 ml of saline ( n  = 14). Results clarified that non-infected birds and ZONPs-fed birds had significantly higher standing and feeding activities and lower resting activities in comparison with the infected group. Also, the S. aureus infected group had significantly lower body weight gain (BWG) and higher feed conversion ratio (FCR) than the non-infected group. In addition, the non-infected birds and ZONPs groups had significantly lower object crossing and tonic immobility times (TI) and gait scores (GS) in comparison with the S. aureus group. Only ZONPs 30, 40 ppm and non-infected groups had a significantly higher latency to lie time (LLT) and lower serum cortisol level in comparison with the S. aureus group. Moreover, there were significant changes in the gross lesion score and histopathological lesions between the different groups. In conclusion, the dietary supplementation of ZONPs can reduce S. aureus -induced negative effects of FPD in broilers.