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Nanofertilizers release nutrients slowly and in a controlled manner, matching the plants’ growth needs. By reducing the need for chemical inputs such as fertilizers and pesticides, nanotechnology contributes to more sustainable agricultural practices. The present study used nano-urea with Azotobacter on strawberry cv. ‘Winter Dawn’ under protected cultivation to evaluate its impact on soil fertility status and leaf nutrient content. Formulations as per the treatment requirements were sprayed onto the strawberry plants. The plants provided with nano-urea formulations exhibited enhanced levels of nitrogen (2.49%), phosphorus (0.37%), and potassium (2.60%) compared to the plants treated with conventional urea. Soil nutrient analysis showed enhanced levels of NPK in soil samples from traditional application treatments. A higher concentration of microorganisms in the soil was observed when urea was applied at the nano level. Nano-urea combined with Azotobacter can significantly impact the soil’s NPK levels. This innovative blend enhances nutrient availability in the soil and promotes sustainable agricultural practices. By leveraging the nanotechnology-infused urea alongside the nitrogen-fixing process of Azotobacter bacteria, the soil experiences a synergistic boost in nitrogen, phosphorus, and potassium content. This dynamic duo fosters a conducive environment for plant growth while minimizing nutrient leaching and environmental degradation.

Background: Climate change impacts health and threatens the stability of care delivery systems, while healthcare is mobilizing to reduce its significant environmental impact. Objective: This study aimed to assess knowledge, attitudes, and practices (KAP) about climate change among Canadian kidney care providers. Design, setting, participants, measurements, and methods: An electronic KAP survey, created by the Canadian Society of Nephrology-Sustainable Nephrology Action Planning committee, was distributed to kidney care providers across Canada, from March to April 2023. Results: A total of 516 people responded to the survey. Most respondents (79%) identified as women; 83% were aged 30 to 59 years. Nurses and nephrologists made up 44% and 23% of respondents, respectively. About half of the participants felt informed about climate change to an average degree. Most respondents (71%; 349/495 and 62%; 300/489) were either extremely or very concerned about climate change and waste generated in their kidney care program, respectively. The vast majority of respondents (89%; 441/495) reported taking steps to lower their personal carbon footprint. People who felt more informed about climate change presented higher degrees of concern. Similarly, both those who felt more informed and those who reported higher degrees of concern about climate change were more likely to take steps to reduce their carbon footprint. Over 80% of respondents (314/386) were at least moderately interested in learning sessions about environmentally sustainable initiatives in care. Limitations: This survey is at risk of social acceptability, representative, and subjective bias. Overrepresentation from Quebec and British Columbia, as well as the majority of respondents identifying as women and working in academic centers, may affect generalizability of the findings. Conclusions: Most kidney care providers who responded to this survey are informed and concerned about climate change, and their knowledge is directly associated with attitude and practices. This indicates that educational initiatives to increase awareness and knowledge on climate change will likely lead to practice changes.

Introduction: Curcuma isolates from different agroclimatic zones in Chhattisgarh have been found to possess a varied spectrum of Curcumin, we set out to learn more about their genetic diversity by molecular fingerprinting in the present study. Methods: Using SSR primers, the genetic variability of 25 Curcuma genotypes has been analyzed. These included the fingerprints of Curcuma longa, Curcuma aromatica, and Curcuma caesia. 13 inter simple sequence repeat (ISSR) primers amplified 107 unique fragments across all kinds, whereas 11 simple sequence repeat (SSR) primers amplified 51 unique fragments across all varieties, with 97 % and 86 % showing polymorphism, respectively. Results: A total of 1080 ISSR and 567 SSR loci were amplified across all genotypes; among these, 5 monomorphic and 102 polymorphic alleles were produced in ISSR primers. However, SSR data showed 47 polymorphic and 4 monomorphic alleles. A panel of ISSR and SSR markers calculated DNA fingerprinting, genetic similarity, and distance estimates between Curcuma genotypes. In order to examine the diversity in different Curcuma genotypes, UPGMA data scoring methods were used. Discussion: Curcuma species demonstrate significant genetic variability, which is essential for breeding initiatives focused on creating better cultivars with desirable characteristics such as increased productivity, resistance to diseases, and improved medicinal capabilities.

Background: Kidney transplant recipients with graft failure (KTR-GF) and those with a failing graft are an increasingly prevalent group of patients. Their clinical management is complex, and outcomes are worse than transplant naïve patients on dialysis. In 2023, the Kidney Disease: Improving Global Outcomes (KDIGO) organization reported findings from a controversies conference and identified several clinical practice priorities for KTR-GF. Objective: As an exercise in needs assessment, we aimed to collate and summarize current practices in adult Canadian kidney transplant programs around these KDIGO-identified clinical practice priorities. Design: Environmental scan followed by content analysis. Setting: Canadian adult kidney transplant programs. Measurements: We categorized the themes of our content analysis around 7 clinical practice priorities: (1) determining prognosis and kidney failure trajectory; (2) immunosuppression management; (3) management of medical complications; (4) preparing for return to dialysis; (5) evaluation and listing for re-transplantation; (6) management of psychological effects; and (7) transition to supportive care. Methods: We solicited documents that identified each program’s current care practices for KTR-GF or patients with a failing graft, including policies, procedures, pathways, and protocols. A content analysis of documents and informal correspondence (email or telephone conversations) was done to extract information surrounding the 7 practice priorities. Results: Of the 18 programs contacted, 12 transplant programs participated in this study and a document from a provincial organization (where 2 non-responding programs are located) was procured and included in this analysis. Overall, practice gaps and discrepancies were noted. Many participants highlighted the lack of evidence or consensus to guide the management of KTR-GF as the key reason. Immunosuppression management was the most frequently addressed priority. Six programs and the provincial document recommended a nuanced approach to immunosuppressant management based on clinical factors and re-transplant candidacy. Two programs used the Kidney Failure Risk Equation and eGFR to determine referral trajectories and prepare patients for return to dialysis. Exact processes outlining medical management during the transition were not found except for nephrectomy indications and in 1 program that has a specific transition clinic for KTR-GF. All programs have a formal or informal policy that KTR-GF should be assessed for re-transplantation. Referrals for psychological support and transition to supportive care were made on a case-by-case basis. Limitations: Our environmental scan was at risk of non-response bias and restricted to transplant programs. Kidney clinics and dialysis units may have relevant policies and procedures that were not examined. Conclusion: The findings from our environmental scan suggest gaps in care and potential areas for quality improvement, including a lack of multidisciplinary care, structured dialysis preparation and psychological support. There is also a need to prioritize research that generates evidence to guide the management of KTR-GF and contributes to the aim of developing clinical practice guidelines.

Background: Paediatric neurodevelopmental disorders, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disability (ID), and specific learning disabilities (SLD), present a growing healthcare challenge globally. This study, conducted at a tertiary care hospital in India, aims to explore the utility of neuroimaging techniques in understanding the structural and functional abnormalities associated with these disorders, considering the unique demographic and healthcare landscape of India. Methods: A multidisciplinary team collaborated in a cross-sectional observational study involving paediatric patients diagnosed with neurodevelopmental disorders. State-of-the-art magnetic resonance imaging (MRI) and functional MRI (fMRI) were employed. Participants underwent clinical assessments, and neuroimaging data were analyzed for structural and functional abnormalities. Advanced techniques such as diffusion tensor imaging (DTI) were utilized to explore microstructural changes in white matter tracts. Results: Distinct neuroimaging patterns were observed in different neurodevelopmental disorders. Structural abnormalities were prominent in ASD and ID, with nuanced variations in gray and white matter volumes. Functional connectivity abnormalities in ADHD were highlighted, emphasizing the involvement of attention and executive function networks. DTI revealed microstructural changes in white matter tracts, particularly in the prefrontal-striatal circuitry in ADHD and disruptions in interhemispheric communication in ASD. Conclusion: Our study contributes valuable insights into the neurobiological underpinnings of paediatric neurodevelopmental disorders, emphasizing the importance of neuroimaging for tailored diagnostic and therapeutic approaches.

Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier, coupled with microbial dysbiosis, has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis. In vivo Rab7 knocked down mice (Rab7KD) displayed a compromised mucus layer, increased microbial permeability, and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis. These abnormalities emerged owing to altered mucus composition, as revealed by mucus proteomics, with increased expression of mucin protease chloride channel accessory 1 (CLCA1). Mechanistically, Rab7 maintained optimal CLCA1 levels by controlling its lysosomal degradation, a process that was dysregulated during colitis. Overall, our work establishes a role for Rab7-dependent control of CLCA1 secretion required for maintaining mucosal homeostasis.

Mechanistic understanding of antibiotic persistence is a prerequisite in controlling the emergence of MDR cases in Tuberculosis (TB). We have reported that the cholesterol-induced activation of VapC12 ribonuclease is critical for disease persistence in TB. In this study, we observed that relative to the wild type, mice infected with ΔvapC12 induced a pro-inflammatory response, had a higher pathogen load, and responded better to the anti-TB treatment. In a high-dose infection model, all the mice infected with ΔvapC12 succumbed early to the disease. Finally, we reported that the above phenotype of ΔvapC12 was dependent on the presence of the TLR4 receptor. Overall, the data suggests that failure of a timely resolution of the early inflammation by the ΔvapC12 infected mice led to hyperinflammation, altered T-cell response and high bacterial load. In conclusion, our findings suggest the role of the VapC12 toxin in modulating the innate immune response of the host in ways that favor the long-term survival of the pathogen inside the host.

Abstract Aberrant overexpression or activation of EGFR drives the development of non-small cell lung cancer (NSCLC) and acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) by secondary EGFR mutations or c-MET amplification/activation remains as a major hurdle for NSCLC treatment. We previously identified WDR4 as a substrate adaptor of Cullin 4 ubiquitin ligase and an association of WDR4 high expression with poor prognosis of lung cancer. Here, using an unbiased ubiquitylome analysis, we uncover PTPN23, a component of the ESCRT complex, as a substrate of WDR4-based ubiquitin ligase. WDR4-mediated PTPN23 ubiquitination leads to its proteasomal degradation, thereby suppressing lysosome trafficking and degradation of wild type EGFR, EGFR mutant, and c-MET. Through this mechanism, WDR4 sustains EGFR and c-MET signaling to promote NSCLC proliferation, migration, invasion, stemness, and metastasis. Clinically, PTPN23 is downregulated in lung cancer and its low expression correlates with WDR4 high expression and poor prognosis. Targeting WDR4-mediated PTPN23 ubiquitination by a peptide that competes with PTPN23 for binding WDR4 promotes EGFR and c-MET degradation to block the growth and progression of EGFR TKI-resistant NSCLC. These findings identify a central role of WDR4/PTPN23 axis in EGFR and c-MET trafficking and a potential therapeutic target for treating EGFR TKI-resistant NSCLC.

Anemia induced by chronic kidney disease (CKD) has multiple underlying mechanistic causes and generally worsens as CKD progresses. Erythropoietin (EPO) is a key endogenous protein which increases the number of erythrocyte progenitors that mature into red blood cells that carry hemoglobin (Hb). Recombinant human erythropoietin (rHuEPO) in its native and re-engineered forms is used as a therapeutic to alleviate CKD-induced anemia by stimulating erythropoiesis. However, due to safety risks associated with erythropoiesis-stimulating agents (ESAs), a new class of drugs, prolyl hydroxylase inhibitors (PHIs), has been developed. Instead of administering exogenous EPO, PHIs facilitate the accumulation of HIF-α, which results in the increased production of endogenous EPO. Clinical trials for ESAs and PHIs generally involve balancing decisions related to safety and efficacy by carefully evaluating the criteria for patient selection and adaptive trial design. To enable such decisions, we developed a quantitative systems pharmacology (QSP) model of erythropoiesis which captures key aspects of physiology and its disruption in CKD. Furthermore, CKD virtual populations of varying severities were developed, calibrated, and validated against public data. Such a model can be used to simulate alternative trial protocols while designing phase 3 clinical trials, as well as an asset for reverse translation in understanding emerging clinical data.

Background: Despite of multimodality treatment of Ovarian Cancer (OC), about two-thirds of patients have peritoneal recurrence with 5-year survival of 15–35%. HIPEC (Hyperthermic Intraperitoneal Chemotherapy) delivers cell-cycle non-specific chemotherapeutic agents along with the temperature of 41°C to 43 °C into the peritoneal cavity after achieving complete cytoreduction, improving overall survival around 50% and recurrence-free survival significantly. Cytoreductive surgery (CRS) and HIPEC may be UpfrontOR Primary - when performed primarily, Interval - when performed after 3 to 6 six cycles of Neo-adjuvant chemotherapy(NACT) and Secondary-when performed for patients who have a recurrence after CRS. OC is associated frequently with tumor-infiltrating lymphocytes in OC microenvironment. Here, we sought to study the interaction of HIPEC on FOXp3 and RORɣ T cells in primary, interval and recurrent settings of HIPEC. Methodology: We have seen the expression of FOXp3, RORɣ in tumor tissue and surrounding normal tissue of ovarian cancer patients. We also performed IHC of tumor tissue and qRT-PCR of cDNA, isolated from tumor tissue and adjacent normal tissue for the same expression and compared intra-group and among the groups.We studied the expression of FOXp3,RORɣ, Interleukin-10 (IL-10) and Interleukin-17 (IL-17) in peripheral blood mononuclear cells(PBMC) before and after HIPEC in one week and four weeks and compared the changes of expressions. We included 30 patients with FIGO stage III to IVA advanced Epithelial ovarian cancer patients, with minimum 10 patients in each subgroup i.e.,upfront, interval and secondary. The pilot study was conducted between June 2017 to February 2021 at the premier Institute, India after Ethical approval. Results: Though there was highest expression of FOXp3 mRNA in recurrent group followed by upfront and interval. However, there was no difference in RORɣ T cell mRNA (by qRT-PCR) expression among three subgroups. We found the change in the expression of FOXp3 and RORɣ T cell in Peripheral blood mononuclear cells by flowcytometry, before and after HIPEC (around 1 week and 4 week after HIPEC) to be significant. In the interval group, there was decreased expression of pre-op Foxp3 compared to the upfront (p = 0.0121) and control (p = 0.0187). These findings suggest that neoadjuvant chemotherapy may reverse the immunosuppressive environment in ovarian cancers. In the upfront group, there was a transient increase of FOXp3 in one week post HIPEC (p = 0.005) and then it decreased to below pre-op values in 4 weeks (p = 0.022). There was no difference in pre-op RORγ and IL 17 among the three subgroups.However, RORγ was increased at four weeks post-HIPEC in the upfront group (p = 0.009), interval group (p = 0.032), and the recurrent group. (p = 0.001). Overall these findings suggest that HIPEC can reverse the immunosuppressive mechanism in ovarian tumor microenvironment (TME),thereby improving survival Conclusions: In this study, we could come to a conclusion that there is a complex nature of interaction at a molecular and immunological level in epithelial ovarian cancer patients underwent HIPEC in different settings. There is an urgent need to explore bio-molecular markers to improve treatment outcomes of ovarian cancer patients. This basic research study exploring the role of FOXp3 Tregs and RORγ T-helper cells indicated their potential role as biomarkers in understanding ovarian cancer prognosis and the impact of therapeutic interventions like HIPEC in this study, on outcomes.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) poses a diagnostic and management challenge to the clinician, which further gets heightened when patients present with abdominal complications in a cancer care center. The atypical manifestations of the disease provide a diagnostic conundrum to the radiologist and leave the pathologist in the perils of guiding further management to the clinician. Although previous literature shows gastrointestinal involvement in COVID-19, we present a case series of complicated subjects with clinical imaging as a pictorial essay and relevant pathology. The abdominal manifestations of COVID-19 are complicated in cancer patients where a variety of other differentials such as infiltration by metastatic disease and drug-related chemo toxicity effects must be taken into account, which may be ruled out by clinical workup, adequate imaging, and laboratory tests. This would help achieve better clinical acumen and modify management in these subjects.

Precision medicine can put clinicians in a position where they must act more as resource allocators than their traditional role as patient advocates. In the allocation of transplantable organs and tissues, the use of eplet matching will enhance precision medicine but, in doing so, generate a tension with the present reliance on rule of rescue and justice-based factors for allocations. Matching donor and recipient human leukocyte antigens (HLA) is shown to benefit virtually all types of solid organ transplants yet, until recently, HLA-matching has not been practical and was shown to contribute to ethnic/racial disparities in organ allocation. Recent advances using eplets from the HLA molecule has renewed the promise of such matching for predicting patient outcomes. The rule of rescue in organ allocation reflects a combination of ethical, policy, and legal imperatives. However, the rule of rescue can impede the allocation strategies adopted by professional medical associations and the optimal use of scarce transplant resources. While eplet-matching seeks to improve outcomes, it may potentially frustrate current ethics-motivated initiatives, established patient-practitioner relationships, and functional conventions in the allocation of medical resources such as organ and tissue transplants. Eplet-matching allocation schemes need to be carefully and collaboratively designed with clear, fair and equitable guidelines that complement functional conventions and maintain public trust.

Rationale: Cryptococcal-immune reconstitution inflammatory syndrome (C-IRIS) is a rare but recognized clinical entity in solid organ transplant recipients, though its clinical course and sequelae remain largely poorly described. Presenting Concerns of the Patient: We present the case of a kidney transplant recipient who presented with headache and fever. A cerebrospinal fluid analysis was performed and found to be compatible with cryptococcal meningitis. After down titration of immunosuppression and antifungal initiation, the patient initially improved. Weeks later, they experienced a sudden deterioration in mental status, prompting admission to the intensive care unit (ICU). Diagnosis: This deterioration was attributed to C-IRIS, which developed following rapid de-escalation of immunosuppression in response to the diagnosis of cryptococcal meningitis. Interventions: The initial episode of C-IRIS responded well to high-dose steroids; however, maintenance immunosuppression was not increased. Outcomes: Within 2 months, the patient presented again to the hospital with a pulmonary infiltrate and multifocal ischemic strokes. Novel Findings: We argue this to be a case of relapsing multisystem C-IRIS, thus expanding the known spectrum of manifestations of C-IRIS in renal transplant recipients. We propose that following the diagnosis of C-IRIS, maintenance immunosuppression be escalated to avoid the risk of relapse and inflammatory-mediated organ dysfunction.

BackgroundLiving donor kidney transplantation (LDKT) is the best treatment option for patients with kidney failure and offers significant medical and economic advantages for both patients and health systems. Despite this, rates of LDKT in Canada have stagnated and vary significantly across Canadian provinces, the reasons for which are not well understood. Our prior work has suggested that system-level factors may be contributing to these differences. Identifying these factors can help inform system-level interventions to increase LDKT. ObjectiveOur objective is to generate a systemic interpretation of LDKT delivery across provincial health systems with variable performance. We aim to identify the attributes and processes that facilitate the delivery of LDKT to patients, and those that create barriers and compare these across systems with variable performance. These objectives are contextualized within our broader goal of increasing rates of LDKT in Canada, particularly in lower-performing provinces. MethodsThis research takes the form of a qualitative comparative case study analysis of 3 provincial health systems in Canada that have high, moderate, and low rates of LDKT performance (the percentage of LDKT to all kidney transplantations performed). Our approach is underpinned by an understanding of health systems as complex adaptive systems that are multilevel and interconnected, and involve nonlinear interactions between people and organizations, operating within a loosely bounded network. Data collection will comprise semistructured interviews, document reviews, and focus groups. Individual case studies will be conducted and analyzed using inductive thematic analysis. Following this, our comparative analysis will operationalize resource-based theory to compare case study data and generate explanations for our research question. ResultsThis project was funded from 2020 to 2023. Individual case studies were carried out between November 2020 and August 2022. The comparative case analysis will begin in December 2022 and is expected to conclude in April 2023. Submission of the publication is projected for June 2023. ConclusionsBy investigating health systems as complex adaptive systems and making comparisons across provinces, this study will identify how health systems can improve the delivery of LDKT to patients with kidney failure. Our resource-based theory framework will provide a granular analysis of the attributes and processes that facilitate or create barriers to LDKT delivery across multiple organizations and levels of practice. Our findings will have practice and policy implications and help inform transferrable competencies and system-level interventions conducive to increasing LDKT. International Registered Report Identifier (IRRID)DERR1-10.2196/44172

Background: Patients with kidney failure represent a major public health burden, and living donor kidney transplantation (LDKT) is the best treatment option for these patients. Current work to optimize LDKT delivery to patients has focused on microlevel interventions and has not addressed interdependencies with meso and macro levels of practice. Objective: We aimed to learn from a health system with historically low LDKT performance to identify facilitators and barriers to LDKT. Our specific aims were to understand how LDKT delivery is organized through interacting macro, meso, and micro levels of practice and identify what attributes and processes of this health system facilitate the delivery of LDKT to patients with kidney failure and what creates barriers. Design: We conducted a qualitative case study, applying a complex adaptive systems approach to LDKT delivery, that recognizes health systems as being made up of dynamic, nested, and interconnected levels, with the patient at its core. Setting: The setting for this case study was the province of Quebec, Canada. Participants: Thirty-two key stakeholders from all levels of the health system. This included health care professionals, leaders in LDKT governance, living kidney donors, and kidney recipients. Methods: Semi-structured interviews with 32 key stakeholders and a document review were undertaken between February 2021 and December 2021. Inductive thematic analysis was used to generate themes. Results: Overall, we identified strong links between system attributes and processes and LDKT delivery, and more barriers than facilitators were discerned. Barriers that undermined access to LDKT included fragmented LDKT governance and expertise, disconnected care practices, limited resources, and regional inequities. Some were mitigated to an extent by the intervention of a program launched in 2018 to increase LDKT. Facilitators driven by the program included advocacy for LDKT from individual member(s) of the care team, dedicated resources, increased collaboration, and training opportunities that targeted LDKT delivery at multiple levels of practice. Limitations: Delineating the borders of a “case” is a challenge in case study research, and it is possible that some perspectives may have been missed. Participants may have produced socially desirable answers. Conclusions: Our study systematically investigated real-world practices as they operate throughout a health system. This novel approach has cross-disciplinary methodological relevance, and our findings have policy implications that can help inform multilevel interventions to improve LDKT.

Abstract Background Plasmodium falciparum is the pathogen responsible for the most devastating form of human malaria. As it replicates asexually in the erythrocytes of its human host, the parasite feeds on haemoglobin uptaken from these cells. Heme, a toxic by-product of haemoglobin utilization by the parasite, is neutralized into inert hemozoin in the food vacuole of the parasite. Lipid homeostasis and phospholipid metabolism are crucial for this process, as well as for the parasite’s survival and propagation within the host. P. falciparum harbours a uniquely large family of phospholipases, which are suggested to play key roles in lipid metabolism and utilization. Results Here, we show that one of the parasite phospholipase (P. falciparum lysophospholipase, PfLPL1) plays an essential role in lipid homeostasis linked with the haemoglobin degradation and heme conversion pathway. Fluorescence tagging showed that the PfLPL1 in infected blood cells localizes to dynamic vesicular structures that traffic from the host-parasite interface at the parasite periphery, through the cytosol, to get incorporated into a large vesicular lipid rich body next to the food-vacuole. PfLPL1 is shown to harbour enzymatic activity to catabolize phospholipids, and its transient downregulation in the parasite caused a significant reduction of neutral lipids in the food vacuole-associated lipid bodies. This hindered the conversion of heme, originating from host haemoglobin, into the hemozoin, and disrupted the parasite development cycle and parasite growth. Detailed lipidomic analyses of inducible knock-down parasites deciphered the functional role of PfLPL1 in generation of neutral lipid through recycling of phospholipids. Further, exogenous fatty-acids were able to complement downregulation of PfLPL1 to rescue the parasite growth as well as restore hemozoin levels. Conclusions We found that the transient downregulation of PfLPL1 in the parasite disrupted lipid homeostasis and caused a reduction in neutral lipids essentially required for heme to hemozoin conversion. Our study suggests a crucial link between phospholipid catabolism and generation of neutral lipids (TAGs) with the host haemoglobin degradation pathway.

Some infants develop broadly neutralizing antibodies (bnAbs) to HIV in a shorter time frame than adults, but the reasons aren’t well understood. Here, the authors study a cohort of 51 HIV-1 clade C perinatally infected infants of Indian origin and find that multivariant infection is associated with bnAbs in elite neutralizers.

Abstract Background Lipofuscin deposition is a characteristic manifestation of aging. There is very limited literature in humans and in animals describing these deposits in native kidneys. Overall, it is thought to be non-pathogenic and successful transplants from a donor with lipofuscin deposits have been reported. We present the case of a patient who underwent a kidney transplant and a for-cause biopsy post-transplantation incidentally revealed lipofuscin deposition. Case presentation A 48-year old gentleman with a past medical history of diabetes, hypertension, coronary artery disease, and ischemic and then hemorrhagic cardiovascular accident underwent a successful kidney transplant. His donor was an expanded criteria donor with no major past medical history. Post-transplant course was complicated by delayed graft function requiring one dialysis treatment for hyperkalemia. After that he had an uneventful course and achieved a baseline creatinine of 1.2 mg/dL, with no proteinuria. On a routine 19-month follow-up he was noted to have proteinuria and an antibody against the major-histocompatibility-complex class I-related chain A. A graft biopsy revealed acute antibody-mediated rejection and impressive lipofuscin deposition. He was subsequently treated with an antibody-mediated rejection protocol that included high dose steroids, Rituximab, plasmapheresis, and intravenous immunoglobulin, but responded poorly to this regimen. A 6-month follow up biopsy continued to show lipofuscin deposition, with similar microvascular injury scores and 12-months later his creatinine remained stable but his proteinuria worsened. Patient was struggling with recurrent infectious episodes requiring hospitalizations and thus no further diagnostic or therapeutic treatments were pursued. Conclusions Lipofuscin deposition has been reported in solid organ transplants but the significance and cause are not well understood. Several physiologic and some pathologic causes to these deposits have been reported including age, diabetes, medications and a genetic syndrome. We propose that immunologic causes such as rejection in the presence of other risk factors could potentiate the oxidative stress leading to excessive lipofuscin deposition in kidney transplants. In the case of our patient, we conclude that these deposits were likely recipient-derived, and postulate that the cumulative burden of inflammation from rejection, and underlying medical conditions led to increased lipofuscin deposition. We speculate them to be an innocent bystander.

Rationale: New-onset psychosis in an immunosuppressed patient post-kidney transplantation (KT) is a diagnostic challenge. A broad differential diagnosis merits consideration; however, an approach to this differential diagnosis remains to be outlined in the literature. Also, when and how to modify the maintenance immunosuppressive regimen remains a significant area of controversy. Presenting concerns: A 23-year-old male, known for X-linked Alport syndrome for which he had undergone KT 1 year prior, presented with a 1-week history of disorganized speech, bizarre behavior, religious delusions, and visual hallucinations. Diagnoses: After ruling out infectious, metabolic, autoimmune, and structural causes, immunosuppressant medications were changed from tacrolimus to cyclosporine. The patient did not improve after this change, and a second opinion consultation with a transplant psychiatrist led to a diagnosis of primary first-episode psychosis, later refined to bipolar disorder type I. Interventions: The patient was started on risperidone, which led to a significant improvement in his symptoms. Outcomes: Twelve months after discharge, his mood and behavior had returned to baseline on aripiprazole, bupropion, and citalopram. However, he developed acute allograft rejection, prompting a change from cyclosporine back to tacrolimus, with stability of his mental state and graft function. Teaching points: This report offers learners an extensive and organized differential diagnosis to the work up of psychosis post kidney transplantation. A complete history, with input from collateral sources, and a systematic approach to the differential diagnosis, are crucial and should not be overshadowed by the risk of immunosuppressant-related neurotoxicity. We underscore the importance of multi-disciplinary management and comprehensive psychosocial assessment and re-assessment to refine the diagnosis. We also report the successful re-introduction of tacrolimus once the diagnosis of a primary psychiatric disorder is confirmed. Finally, we offer a simplified approach that can aid in distinguishing between a primary psychiatric diagnosis versus tacrolimus-associated psychosis.

Retinoblastoma (RB) is the most common intraocular childhood malignancy, and it is considered potentially fatal if untreated. The management of RB has undergone a tremendous leap in the past four decades, with a global effort to save life along with eye and vision. Despite the on-going genetic and clinical research, there is a lack of clinical expertise and understanding of optimal management as it is customized and has to be tailored individually depending on various factors. In this review, we explore the management of RB and various chemotherapeutic alternatives using intravenous chemotherapy and the newer modalities such as intra-arterial and intravitreal chemotherapy in combating this deadly but curable disease. The strategy of management is challenging and mainly depends on the stage of the disease and tumor laterality.

The current work presents a novel hybrid approach for motion estimation of various video sequences with a purpose to speed up the entire process without affecting the accuracy. The method integrates the dynamic Zero motion pre-judgment (ZMP) technique with Initial search centers (ISC) along with half way search termination and Small diamond search pattern. Calculation of the initial search centers has been shifted after the process of zero motion pre-judgment unlike most the previous approaches so that the search centers for stationary blocks need not be identified. Proper identification of ISC dismisses the need to use any fast block matching algorithm (BMA) to find the motion vectors (MV), rather a fixed search pattern such as small diamond search pattern is sufficient to use. Half way search termination has also been incorporated into the algorithm which helps in deciding whether the predicted ISC is the actual MV or not which further reduced the number of computations. Simulation results of the complete hybrid approach have been compared to other standard methods in the field. The method presented in the manuscript ensures better video quality with fewer computations.

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.

In recent years, the enhancement in technology has been envisioning for people to complete tasks in an easier way. Every manufacturing industry requires heavy machinery to accomplish tasks in a symmetric and systematic way, which is much easier with the help of advancement in the technology. The technological advancement directly affects human life as a result. It is found that humans are now fully dependent on it. The online game industry is one example of technology breakthrough. It is now a prominent industry to develop online games at world level. In this paper, our main objective is to analyze major factors which encourage mobile games industry to expand. Analyzing the system and symmetric relations inside can be done into two phases. The first phase is through a TAM Model, which is a very efficient way to solve statistical problems, and the second phase is with machine learning (ML) techniques, such as SVM, logistic regression, etc. Both strategies are popular and efficient in analyzing a system while maintaining the symmetry in a better way. Therefore, according to results from both the TAM model and ML approach, it is clear that perceived usefulness, attitude, and symmetric flow are important factors for game industry. The analytics provide a clear insight that perceived usefulness is an important parameter over behavior intention for the online mobile game industry.

Background: Living donor kidney transplantation (LDKT) has several advantages over deceased donor kidney transplantation. Yet rates of living donation are declining in Canada and there exists significant interprovincial variability. Efforts to improve living donation tend to focus on the patient and barriers identified at their level, such as not knowing how to ask for a kidney or lack of education. These efforts favor those who have the means and the support to find living donors. Thus, a Canadian Institutes of Health Research (CIHR)-organized workshop recommended that education efforts to understand and remove barriers should focus on health professionals (HPs). Despite this, little attention has been paid to what they identify as barriers to discussing LDKT with their patients. Objective: Our aim was to explore HP-identified barriers to discuss living donation with patients in 3 provinces of Canada with low (Quebec), moderate (Ontario), and high (British Columbia) rates of LDKT. Design: This study consists of an interpretive descriptive approach as it enables to move beyond description and inform clinical practice. Setting: Purposive criterion and quota sampling were used to recruit HPs from Quebec, Ontario, and British Columbia who are involved in the care of patients with kidney disease and/or with transplant coordination. Patients: Not applicable. Measurements: Semistructured interviews were conducted. The interview guide was developed based on a preliminary analytical framework and a review of the literature. Methods: Thematic analysis was used to analyze the data stemming from the interviews. The coding process comprised of a deductive and inductive approach, and the use of a qualitative analysis software (NVivo 11). Following this, themes were identified and developed. Interviews were conducted until thematic saturation was obtained. In total, we conducted 16 telephone interviews as thematic saturation was attained. Results: Six predominant themes emerged: (1) lack of communication between transplant and dialysis teams, (2) absence of referral guidelines, (3) role perception and lack of multidisciplinary involvement, (4) HP’s lack of information and training, (5) negative attitudes of some HP toward LDKT, (6) patient-level barriers as defined by the HP. HPs did mention patients’ attitudes and some characteristics as the main barriers to discussions about living donation; this was noted in all provinces. HPs from Ontario and British Columbia indicated multiple strategies being implemented to address some of these barriers. Those from Ontario mentioned strategies that center on the core principles of provincial-level standardization, while those from British Columbia center on engaging the entire multidisciplinary team and improved role perception. We noted a dearth of such efforts in Quebec; however, efforts around education and promotion, while tentative, have emerged. Limitations: Social desirability and selection bias. Our analysis might not be applicable to other provinces. Conclusions: HPs involved with the referral and coordination of transplantation play a major role in access to LDKT. We have identified challenges they face when discussing living donation with their patients that warrant further assessment and research to inform policy change.