Kidney Amyloidosis: Updates on Pathogenesis and Therapeutic Frontiers.

BACKGROUND: Amyloidosis includes a diverse group of rare diseases characterized by the misfolding of native or mutant proteins, leading to extracellular accumulation in various organs. While 42 proteins have been identified to date, their distribution differs between systemic and localized forms. SUMMARY: Mass spectrometry analysis of tissue samples in the US show immunoglobulin light chain (AL) amyloidosis as the most prevalent systemic type, followed by transthyretin (ATTR). Heart and kidney involvement are common. Although there are 14 recognized types of kidney-related amyloidosis, clinicopathologic studies in the US have identified 11 types, with AL amyloidosis being the most prevalent cause of kidney involvement.

Pharmacokinetics of tenofovir alafenamide, emtricitabine, and dolutegravir in a patient on peritoneal dialysis.

INTRODUCTION: Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual kidney function. Data on pharmacokinetics (PK) of antiretrovirals in patients on peritoneal dialysis are limited. METHODS: A single-participant study was performed on a 49-year-old gentleman with ESKD on PD and controlled HIV on once daily dolutegravir (DTG) 50 mg + tenofovir alafenamide (TAF) 25 mg / emtricitabine (FTC) 200 mg. He underwent serial blood plasma, peripheral blood mononuclear cell, and urine PK measurements over 24 h after an observed DTG + FTC/TAF dose. RESULTS: Plasma trough (Cmin) concentrations of TAF, tenofovir (TFV), FTC, and DTG were 0.05, 164, 1,006, and 718 ng/mL, respectively. Intracellular trough concentrations of TFV-DP and FTC-TP were 1142 and 11,201 fmol/million cells, respectively. Compared to published mean trough concentrations in PWH with normal kidney function, observed TFV and FTC trough concentrations were 15.5- and 20-fold higher, while intracellular trough concentrations of TFV-DP and FTC-TP were 2.2-fold and 5.4-fold higher, respectively. TFV and FTC urine levels were 20 times lower than in people with normal GFR. CONCLUSIONS: In a single ESKD PWH on PD, daily TAF was associated with plasma TFV and intracellular TFV-DP trough concentrations 15-fold and 2-fold higher than those of people with uncompromised kidney function, potentially contributing to nephrotoxicity. This suggests that TFV accumulates on PD; thus, daily TAF in PD patients may require dose adjustment or regimen change to optimize treatment, minimize toxicity, and preserve residual kidney function.

A very complicated UTI: malakoplakia following E. coli urinary tract infection.

Malakoplakia is a rare inflammatory disorder believed to result from a defect in macrophage phagocytic function triggering a granulomatous reaction. It can present with genitourinary, gastrointestinal, or cutaneous manifestations in immunocompromised or, less commonly, immunocompetent hosts. We describe a case of renal malakoplakia in a young, otherwise healthy patient presenting with nephromegaly and sepsis following an E. coli urinary tract infection. We discuss diagnosis and management, including antibiotic selection and the decision to pursue nephrectomy. This case highlights the potential for kidney recovery with prolonged antibiotic therapy in conjunction with adjunct immunomodulatory therapies and source control.

The mediating role of cardiac patients' perception of nursing care on the relationship between kinesiophobia, anxiety and depression in rural hospitals: a cross-sectional study.

BACKGROUND: Kinesiophobia could act as a significant barrier against physical activity following cardiac procedures worsening cardiovascular health problems and potentially leading to conditions like hospital-acquired anxiety and depression among patients with cardiovascular disease (CVD). Nurses are the vanguard health care team who can aid patients in taking proactive steps to overcome fear of movement following cardiac procedures. AIM: The overarching aim is to investigate the relationship between kinesiophobia, anxiety and depression, and patients' perception of nursing care. METHOD: A descriptive correlational research design in two rural hospitals, conducted at cardiac intensive care units of Kafr Eldawar Hospital and Damanhur Medical National Institute. Data were collected from 265 nurses, using the following patient-reported outcome measures, the Tampa Scale for Kinesiophobia (TSK), the Hospital Anxiety and Depression Scale (HADS), the Person-Centered Critical Care Nursing Questionnaire (PCCNP) and the patients' demographic and clinical profile. RESULT: A significant negative correlation was found between HADS and PCCNP (r: -0.510, p < 0.001) however, Kinesiophobia was significantly and positively correlated (r: 0.271, p < 0.001). A direct effect of PCCNP in the presence of the mediator was found to be not statistically significant (-0.015, CR = 0.302, p = 0.763). Nonetheless, PCCNP indirectly affects kinesiophobia through HADS (p=-0.099). IMPLICATION FOR NURSING PRACTICE: Customizing individualized cardiac rehabilitation (CR) programs based on the emotional experience of cardiac patients will be conducive to rehabilitation and prognosis for patients, thereby lessening the physical burden and improving their quality of life.

The role of Empathy in the relationship between emotional support and caring behavior towards patients among intern nursing students.

BACKGROUND: The empathic relationship between nursing students and patients allows them to understand and address caring behavior for patients. Appropriate emotional support equips them to overcome the complexities and difficulties inherent in patient care. This support cultivates resilience and self-awareness, enabling students to manage their emotions effectively and establish meaningful connections and caring with their patients. OBJECTIVES: To investigate the role of empathy in the association between emotional support and caring behavior toward patients among intern nursing students at Alexandria and Damanhur University. SUBJECTS: The study subjects were 200 intern nursing students in their internship years of 2022-2023, randomly selected from an equal sample size from Alexandria and Damanhur University, Egypt. TOOLS: A questionnaire of social information& academics from students, the Toronto Empathy Questionnaire, the Caring Dimension Inventory, and the Multidimensional Scale of Perceived Social Support are used to collect participants' data. RESULTS: Empathy was associated with caring behavior and emotional support among nursing students (P < 0.001), and higher levels of empathy indicated increased levels of caring behavior and emotional support. The caring behavior significantly increased when intern nursing students received more emotional support and among those who were not working in private hospitals (p < 0.001,&p = 0.023 respectively). Empathy acts as a mediating role in the relationship between emotional support and caring behavior. IMPLICATIONS: Implementing strategies to assist interns in navigating challenges and promoting a culture of support can facilitate the cultivation of caring behaviors. Shedding light on the interconnectedness of empathy, emotional support, and caring behavior can inform the design of interventions to strengthen empathy as a pathway to improving patient outcomes. CONCLUSION: Empathy is a mediating factor in the relationship between emotional support and caring behavior. This suggests that interventions promoting empathy may serve as a pathway to enhancing caring behavior among nursing students and strategies for improving patient care outcomes by strengthening empathy skills among healthcare professionals.

Perceived stress, coping strategies, symptoms severity and function status among carpal tunnel syndrome patients: a nurse-led correlational Study.

BACKGROUND: Carpal tunnel syndrome (CTS) is a prevalent condition characterized by hand pain, tingling, and numbness. The severity of symptoms and functional status in CTS patients may be influenced by perceived stress and how individuals cope with it. However, scarce knowledge exists about the role of coping strategies as moderators in this relationship. Unfolding the role of perceived stress and coping strategies for CTS management will help the nurse to provide comprehensive and tailored nursing care. This will ultimately improve patient comfort, functionality, and quality of life. PURPOSES: This study aimed to examine the role of coping strategies (adaptive and maladaptive) in the relationship between perceived stress and both symptoms severity and function status among those patients. METHOD: We employed a multisite, correlational study design with moderation analysis. The study included 215 patients with CTS from neurosurgery outpatient clinics at three hospitals in Egypt. After obtaining their consent to participate, eligible participants completed anonymous, self-reported measures of perceived stress, the brief COPE inventory, and the Boston Carpal Tunnel Questionnaire. Demographic and biomedical data were also collected. The questionnaire took about 20 min to be completed. The data was collected over six months, starting in February 2023. RESULTS: The results showed that perceived stress, adaptive coping, and maladaptive coping were significant predictors of symptoms severity and functional status. Adaptive coping moderated the relationships between perceived stress and both symptoms severity and function status, while maladaptive coping did not. The interaction between perceived stress and adaptive coping explained a moderate effect on symptoms severity and function status after controlling for the main effects and the covariates. CONCLUSION: This study explored the relationship between perceived stress, coping strategies, and outcomes in patients with CTS. The results indicate that nurses play a vital role in assessing and assisting patients to adopt effective coping strategies to manage perceived stress and alleviate symptoms and functional impairment. Moreover, the findings support the need for psychological interventions that address both perceived stress and coping strategies as a way to enhance the functioning status and quality of life of patients with CTS.

Hooked on technology: examining the co-occurrence of nomophobia and impulsive sensation seeking among nursing students.

BACKGROUND: Nomophobia, the crippling fear of being disconnected from mobile devices, is a burgeoning global concern. Given the critical nature of the profession of nursing students, understanding nomophobia's prevalence and potential impacts on patient care and professional conductors becomes even more crucial. AIM: This study explores the relationship between nomophobia and impulsive sensation-seeking among nursing students in Egypt. DESIGN AND METHODS: A multicenter cross-sectional survey was conducted with 1626 nursing students randomly selected from three universities across Egypt. TOOLS: The Arabic versions of the Nomophobia and Impulsive Sensation Seeking Questionnaires were employed to gather data. RESULTS: Our findings revealed that 40.3% of the surveyed nursing students exhibited severe nomophobia, indicating a substantial dependence on their mobile devices. Notably, this high prevalence was accompanied by a strong tendency towards impulsive sensation-seeking behaviors. Furthermore, a stepwise regression analysis identified several significant predictors of nomophobia (p < 0.001). Impulsive sensation-seeking, year of study, average daily smartphone usage, and age emerged as key factors, explaining 27.5% of the variability in nomophobia scores. CONCLUSION: The prevalence of nomophobia among Egyptian nursing students is undeniable, highlighting their substantial reliance on mobile devices. A significant association with impulsive sensation-seeking behavior further compounds this dependence. Factors such as impulsive sensation seeking, year of study, average daily smartphone usage, and age were identified as significant predictors of nomophobia. Recognizing these factors as key predictors of nomophobia is crucial for designing effective interventions and psychotherapies. Prioritizing such interventions can promote future nurses' well-being and ensure they deliver the highest quality care to their patients.

Climate anxiety, environmental attitude, and job engagement among nursing university colleagues: a multicenter descriptive study.

BACKGROUND: Climate change, a pervasive global phenomenon, exerts discernible impacts on the physical, social, and psychological dimensions of well-being. The apprehension surrounding this complex environmental issue has reached a critical juncture, with over 76,000 individuals across more than thirty nations expressing profound levels of concern, characterizing their anxiety as either "very" or "extremely" pronounced. This surge in awareness regarding the potential consequences of climate change has given rise to an emergent and escalating challenge known as climate anxiety. This distinctive form of anxiety manifests through profound feelings of fear, helplessness, and despair elicited by the impending repercussions of climate change. Notably, the intersection of climate anxiety with occupational domains, particularly within the context of Nursing University Colleagues, suggests a nuanced relationship with job engagement, wherein the psychological responses to climate change may influence professional commitment and involvement. AIM OF THE STUDY: To examine the correlation among Climate Anxiety, Environmental Attitude, and Job Engagement among Nursing University Colleagues comprising eight distinct nursing faculties. DESIGN: A multicenter descriptive, cross-sectional research design study followed. SUBJECT: Three hundred fifty-nine participants from the Centre, Delta, West, Suez Canal, and Upper regions of Egypt using a stratified random cluster sampling technique. MEASUREMENTS: Social and health related to climate data structured questionnaire, climate anxiety scale, environmental attitude inventory, and job engagement scale. RESULTS: The influence of demographics on climate anxiety, environmental attitude, and job involvement was not observed. Nevertheless, geographical variations emerged as a noteworthy factor. A statistically significant inverse correlation was identified between climate anxiety, job engagement dimensions, and the overall score of environmental attitudes. CONCLUSION: Climate anxiety was strongly associated with environmental attitudes and job engagement among nursing university colleagues. Higher climate anxiety is associated with a lower attitude towards the environment and decreased job engagement. Additionally, a higher attitude towards the environment is associated with decreased overall engagement in participants' jobs. IMPLICATIONS: The study's patterns make it clear how important it is to provide targeted psycho-educational interventions to help reduce climate anxiety among the group of nursing university colleagues. The imperative lies not only in alleviating the immediate psychological distress associated with heightened climate anxiety but also in fostering adaptive coping mechanisms. By doing so, these interventions serve as instrumental tools in nurturing resilience, thereby fortifying the mental well-being of nursing professionals amidst the evolving landscape of climate-related concerns.

Exploring the mediating influence of acceptance of change: A study on gerontechnology acceptance, mental well-being, and urban-rural disparities among older adults.

BACKGROUND: The global aging population necessitates leveraging technology for older adults' independence and mental well-being. Gerontechnology, tailored for older users, thrives when accessible and accepted, with the pivotal role of acceptance of change shaping its adoption. AIMS: This study investigates the mediating role of acceptance of change in the relationship between gerontechnology acceptance and mental well-being among older adults and explores disparities in urban and rural settings DESIGN & METHODS: A cross-sectional, correlational design adhering to STROBE guidelines collected data through an interview survey from 802 older adults. Instruments included the Older Adult Structured Survey, Short Version of Senior Technology Acceptance, Acceptance of Change Scale, and the World Health Organization Well-Being Index. RESULTS: The results underscore a significant correlation between technology adoption, adaptability, and mental well-being among 60-year-olds and older. Notably, an individual's openness to change significantly influences the technology-mental well-being relationship, emphasizing its impact on overall health. Urban areas exhibit a stronger positive correlation between technology acceptance and mental well-being, whereas rural regions demonstrate a more pronounced negative correlation. CONCLUSION: This research contributes valuable knowledge for addressing the unique challenges older adults face in diverse geographic settings, paving the way for targeted and effective initiatives. IMPLICATIONS: Nurses should prioritize understanding the nexus between gerontechnology acceptance, change adaptability, and mental wellness, integrating technology education and culturally sensitive interventions to enhance care strategies for older adults in diverse geographic settings. This study lays the groundwork for developing person-centered geriatric nursing care plans, underscoring the importance of harnessing technology for improved mental well-being.

Light-Driven Hydrogen Evolution Reaction Catalyzed by a Molybdenum-Copper Artificial Hydrogenase.

Orange protein (Orp) is a small bacterial metalloprotein of unknown function that harbors a unique molybdenum/copper (Mo/Cu) heterometallic cluster, [S2MoS2CuS2MoS2]3-. In this paper, the performance of Orp as a catalyst for the photocatalytic reduction of protons into H2 has been investigated under visible light irradiation. We report the complete biochemical and spectroscopic characterization of holo-Orp containing the [S2MoS2CuS2MoS2]3- cluster, with docking and molecular dynamics simulations suggesting a positively charged Arg, Lys-containing pocket as the binding site. Holo-Orp exhibits excellent photocatalytic activity, in the presence of ascorbate as the sacrificial electron donor and [Ru(bpy)3]Cl2 as the photosensitizer, for hydrogen evolution with a maximum turnover number of 890 after 4 h irradiation. Density functional theory (DFT) calculations were used to propose a consistent reaction mechanism in which the terminal sulfur atoms are playing a key role in promoting H2 formation. A series of dinuclear [S2MS2M'S2MS2](4n)- clusters, with M = MoVI, WVI and M'(n+) = CuI, FeI, NiI, CoI, ZnII, CdII were assembled in Orp, leading to different M/M'-Orp versions which are shown to display catalytic activity, with the Mo/Fe-Orp catalyst giving a remarkable turnover number (TON) of 1150 after 2.5 h reaction and an initial turnover frequency (TOF°) of 800 h-1 establishing a record among previously reported artificial hydrogenases.

Identification of 2-Methylthio-methylenethio-N6 -(cis-4-hydroxyisopentenyl)adenosine (msms2 io6 A37 ) as a Novel Modification at Adenosine 37 of tRNAs from Salmonella typhimurium.

Post-transcriptional modifications of tRNA nucleotide are important determinants in folding, structure and function. We have successfully identified and characterized a new modified base named 2-methylthio-methylenethio-N6 -(cis-4-hydroxyisopentenyl)adenosine, which is present at position 37 in some tRNAs. We also showed that this new modified adenosine is derived from the known 2-methylthio-methylenethio-N6 -(isopentenyl)adenosine nucleoside by a catalytic cycle of the tRNA-diiron monooxygenase, MiaE, present in Salmonella typhimurium.

Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease.

PURPOSE: Fabry disease (FD) is a rare lysosomal storage disorder caused by pathogenic variants in the GLA gene encoding α-galactosidase (α-Gal)-A. We evaluated long-term safety/efficacy of pegunigalsidase alfa, a novel PEGylated α-Gal-A enzyme replacement therapy (ERT) now approved for FD. METHODS: In a phase-1/2 dose-ranging study, 15 ERT-naive adults with FD completed 12 months of pegunigalsidase alfa and enrolled in this 60-month open-label extension of 1 mg/kg pegunigalsidase alfa infusions every 2 weeks. RESULTS: Fifteen patients enrolled (8 males; 7 females); 10 completed ≥48 months (60 months total treatment), and 2 completed 60 months (72 months total treatment). During treatment, most treatment-emergent adverse events were mild/moderate in severity and all infusion-related reactions were mild/moderate in severity. Four patients were transiently positive for anti-pegunigalsidase alfa IgG. Patients showed continuous reduction in plasma lyso-Gb3 concentrations with mean (standard error) reduction of 76.1 [25.1] ng/mL from baseline to month 24. At 60 months, the estimated glomerular filtration rate slope was comparable to that observed in patients treated with other ERTs. Cardiac function assessments revealed stability; no cardiac fibrosis was observed. CONCLUSION: In this first long-term assessment of pegunigalsidase alfa administration in patients with FD, we found favorable safety/efficacy. Our data suggest long-term continuous benefits of pegunigalsidase alfa treatment in adults with FD.

Updates on HIV and Kidney Disease.

PURPOSE OF REVIEW: With the advent of antiretroviral therapy, HIV infection has become a chronic disease in developed countries. RECENT FINDINGS: Non-HIV-driven risk factors for kidney disease, such as APOL1 risk variants and other genetic and environmental factors, have been discovered and are better described. Consequently, the field of HIV-associated kidney disease has evolved with greater attention given to traditional risk factors of CKD and antiretroviral treatment's nephrotoxicity. In this review, we explore risk factors of HIV-associated kidney disease, diagnostic tools, kidney pathology in HIV-positive individuals, and antiretroviral therapy-associated nephrotoxicity.

The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties.

The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.

Compassion fatigue and stress related to cardiopulmonary resuscitation: a study of critical care nurses' experiences.

BACKGROUND: Cardiopulmonary resuscitation (CPR) is considered one of the most stressful experiences in critical care nursing; it directly and indirectly leads to compassion fatigue and burnout. AIM: Determine the levels of and relationship between postcode stress and compassion fatigue. DESIGN AND METHODS: A descriptive-correlational study using 300 critical care nurses from five intensive care units in two hospitals was conducted. TOOLS: Demographic and work-related data, the Postcode Stress Scale, and the Professional Quality of Life Scale: Compassion Fatigue subscale. RESULTS: Nurses had moderate to high postcode stress and compassion fatigue (67.98 ± 16.39 and 65.40±14.34, respectively). Moreover, there was a significant positive correlation between postcode stress, burnout (r=0.350, p=<0.001), secondary traumatic stress (r=0.518, p=<0.001), and subsequently, compassion fatigue (r=0.449, p=<0.001). In addition, higher levels of postcode stress were associated with higher levels of compassion fatigue with its subscales: burnout and secondary traumatic stress, with a coefficient of determination for compassion fatigue (0.199), burnout subscale (0.121), and secondary traumatic stress (0.266). CONCLUSION: Critical care nurses involved in resuscitation experiences are susceptible to postcode stress, burnout, secondary traumatic stress, and compassion fatigue. There is a significant relationship between these factors, with higher levels of postcode stress contributing to higher levels of compassion fatigue and its subscales: burnout and secondary traumatic stress. These results highlight the importance of addressing and managing the psychological well-being of nurses in resuscitation settings to mitigate the adverse effects of stress and promote their overall resilience and well-being.

Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study.

BACKGROUND: Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI. METHODS: This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients. The primary end point was the proportion of patients who developed AKI determined by serum creatinine by postoperative day 5. Other end points included AKI severity and duration using various prespecified criteria. To inform future clinical development, a composite end point of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25% reduction of estimated glomerular filtration rate was assessed. Both serum creatinine and serum cystatin-C were used for estimated glomerular filtration rate assessments. RESULTS: A total of 360 patients were randomly assigned in 41 centers; 341 dosed patients were 73±7.5 years of age (mean±SD), 72% were men, and median European System for Cardiac Operative Risk Evaluation score was 2.6%. Demographics and surgical parameters were similar between groups. AKI incidence was 37% for teprasiran- versus 50% for placebo-treated patients, a 12.8% absolute risk reduction, P=0.02; odds ratio, 0.58 (95% CI, 0.37-0.92). AKI severity and duration were also improved with teprasiran: 2.5% of teprasiran- versus 6.7% of placebo-treated patients had grade 3 AKI; 7% teprasiran- versus 13% placebo-treated patients had AKI lasting for 5 days. No significant difference was observed for the major adverse kidney events at day 90 composite in the overall population. No safety issues were identified with teprasiran treatment. CONCLUSIONS: The incidence, severity, and duration of early AKI in high-risk patients undergoing cardiac surgery were significantly reduced after teprasiran administration. A phase 3 study with a major adverse kidney event at day 90 primary outcome that has recently completed enrollment was designed on the basis of these findings (NCT03510897). Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02610283.

History of proliferative glomerulonephritis predicts end stage kidney disease in pure membranous lupus nephritis.

OBJECTIVES: Pure membranous (class V) LN is considered a less aggressive phenotype, but tissue fibrosis and chronic kidney disease may still develop. This study aimed to elucidate the prognostic value of a history of class switch in pure membranous LN. METHODS: We included LN patients with at least two clinically indicated kidney biopsies. New onset of end stage kidney disease (ESKD) was defined as estimated glomerular filtration rate <15 ml/min/1.73 m2, initiation of dialysis or kidney transplantation. RESULTS: Among 220 patients (542 biopsies), 199 (90%) were female, and 118 (54%) were African American, 59 (27%) Caucasian, with median age of 28 years at the first kidney biopsy. Patients with pure class V in a first biopsy converted to proliferative LN in 41% of cases. Pure class V in a repeat biopsy was preceded by proliferative LN in 52%. Trajectory analysis of up to four repeat biopsies revealed that ISN class switch may happen at any time, even after multiple biopsies with the same class. New onset ESKD was observed within 2 years in 5/56 (9%) patients with pure class V in a repeat biopsy. All five patients had proliferative LN in the first biopsy (log rank P = 0.024). CONCLUSIONS: The conversion from proliferative to membranous (and vice-versa) is frequent in SLE. It can occur at any time in the course of disease, limiting the prognostic value of the first biopsy. Evidence of prior proliferative LN is key as it is associated with higher risk of ESKD in non-proliferative LN.

High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership.

OBJECTIVE: Delayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1. METHODS: A total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year. RESULTS: At biopsy, 54 patients had UPCR <1 and 221 had UPCR ≥1. Independent of UPCR or biopsy number, a majority (92%) of patients had class III, IV, V or mixed histology. Moreover, patients with UPCR <1 and class III, IV, V, or mixed had a median activity index of 4.5 and chronicity index of 3, yet 39% of these patients had an inactive sediment. Neither anti-dsDNA nor low complement distinguished class I or II from III, IV, V or mixed in patients with UPCR <1. Of 29 patients with baseline UPCR <1 and class III, IV, V or mixed, 23 (79%) had a UPCR <0.5 at 1 year. CONCLUSION: In this prospective study, three-quarters of patients with UPCR <1 had histology showing class III, IV, V or mixed with accompanying activity and chronicity despite an inactive sediment or normal serologies. These data support renal biopsy at thresholds lower than a UPCR of 1.

Structural, biochemical and functional analyses of tRNA-monooxygenase enzyme MiaE from Pseudomonas putida provide insights into tRNA/MiaE interaction.

MiaE (2-methylthio-N6-isopentenyl-adenosine37-tRNA monooxygenase) is a unique non-heme diiron enzyme that catalyzes the O2-dependent post-transcriptional allylic hydroxylation of a hypermodified nucleotide 2-methylthio-N6-isopentenyl-adenosine (ms2i6A37) at position 37 of selected tRNA molecules to produce 2-methylthio-N6-4-hydroxyisopentenyl-adenosine (ms2io6A37). Here, we report the in vivo activity, biochemical, spectroscopic characterization and X-ray crystal structure of MiaE from Pseudomonas putida. The investigation demonstrates that the putative pp-2188 gene encodes a MiaE enzyme. The structure shows that Pp-MiaE consists of a catalytic diiron(III) domain with a four alpha-helix bundle fold. A docking model of Pp-MiaE in complex with tRNA, combined with site directed mutagenesis and in vivo activity shed light on the importance of an additional linker region for substrate tRNA recognition. Finally, krypton-pressurized Pp-MiaE experiments, revealed the presence of defined O2 site along a conserved hydrophobic tunnel leading to the diiron active center.

Adaptive Scheme for Detecting Induction Motor Incipient Broken Bar Faults at Various Load and Inertia Conditions.

This paper introduces a novel online adaptive protection scheme to detect and diagnose broken bar faults (BBFs) in induction motors during steady-state conditions based on an analytical approach. The proposed scheme can detect precisely adjacent and non-adjacent BBFs in their incipient phases under different inertia, variable loading conditions, and noisy environments. The main idea of the proposed scheme is monitoring the variation in the phase angle of the main sideband frequency components by applying Fast Fourier Transform to only one phase of the stator current. The scheme does not need any predetermined settings but only one of the stator current signals during the commissioning phase. The threshold value is calculated adaptively to discriminate between healthy and faulty cases. Besides, an index is proposed to designate the fault severity. The performance of this scheme is verified using two simulated motors with different designs by applying the finite element method in addition to a real experimental dataset. The results show that the proposed scheme can effectively detect half, one, two, or three broken bars in adjacent/non-adjacent versions and also estimate their severity under different operating conditions and in a noisy environment, with accuracy reaching 100% independently from motor parameters.