Spontaneous Remission of Minimal Change Disease in a Colon Cancer Patient: A Case Report.

Introduction: Minimal change disease (MCD) is most often primary but may occur secondary to other systemic diseases such as malignancy. In secondary MCD, spontaneous remission of nephrotic syndrome after the treatment of related diseases without steroid therapy is rare. Case Presentation: A 78-year-old man visited the outpatient clinic with foamy urine and generalized edema that had persisted for 2 months. The patient had nephrotic syndrome. Before a kidney biopsy, he underwent several tests to determine the secondary cause of the nephrotic syndrome. The serum CEA was slightly elevated, and colon cancer was detected in the sigmoid colon. MCD was diagnosed from a kidney biopsy. He immediately underwent surgery for colon cancer. Complete remission of the MCD was achieved within 2 weeks after surgery. Conclusion: Here, we report a rare case of a patient with secondary MCD who successfully achieved spontaneous remission after colon cancer surgery.

New health index derived from oxidative potential and cell toxicity of fine particulate matter to assess its potential health effect.

Toxicological data and exposure levels of fine particulate matters (PM2.5) are necessary to better understand their health effects. Simultaneous measurements of PM2.5 oxidative potential (OP) and cell toxicity in urban areas (Beijing, China and Gwangju, Korea) reveal their dependence on chemical composition. Notably, acids (Polar), benzocarboxylic acids, and Pb were the chemical components that affected both OP and cell toxicity. OP varied more significantly among different locations and seasons (winter and summer) than cell toxicity. Using the measured OP, cell toxicity, and PM2.5 concentration, a health index was developed to better assess the potential health effects of PM2.5. The health index was related to the sources of PM2.5 derived from the measured chemical components. The contributions of secondary organic aerosols and dust to the proposed health index were more significant than their contributions to PM2.5 mass. The developed regression equation was used to predict the health effect of PM2.5 without further toxicity measurements. This new index could be a valuable health metric that provides information beyond just the PM2.5 concentration level.

Successful management of proteinuria in recurrent immunoglobulin A nephropathy after deceased donor kidney transplantation: A case report.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis, and recurrent IgAN is common after kidney transplantation (KT). Owing to the differences in various biopsy protocols and follow-ups in each study, the recurrence rate varies from 9.7% to 46%. Although the relapse rates are high, there is no definitive treatment for IgAN recurrence. METHODS: We present a case of successful management of proteinuria in recurrent IgAN after deceased donor KT. A 60-year-old man diagnosed with IgAN 20 years prior, who progressed to end-stage renal disease, underwent deceased donor KT 5 years prior and was admitted to our hospital with progressively increasing proteinuria. RESULTS: The pathological examination of the kidney biopsy specimen revealed recurrent IgAN. High-dose steroid treatment was initiated, and the patient was discharged while maintaining steroid treatment. However, outpatient follow-up showed that proteinuria did not decrease while steroids were maintained. Therefore, an angiotensin receptor blocker was administered after explaining its benefits to the patient. After the addition of angiotensin receptor blocker, proteinuria continued to decrease. CONCLUSION: This case report highlights the importance of using renin-angiotensin system inhibitors with supportive care in cases of suspected of recurrent IgAN after KT. It also emphasizes the need to prescribe renin-angiotensin system inhibitors when steroid therapy is unsuccessful in cases of recurrent IgAN after KT.

What's inside the Mind of a CEO? The Effects of Discretionary Slack Resources on R&D Investment.

This study investigates the effects of discretionary slack resources on a firm's R&D investment. Specifically, we examine whether and how a CEO's psychological traits play a role in the relationship between discretionary slack and R&D investment. Using a panel sample from U.S. manufacturing firms in 2006-2010, we found that slack resources lead to an increase in R&D intensity. Furthermore, this positive effect is stronger when CEOs have a strong promotion focus and perceive an addressable negative attainment discrepancy. Thus, our findings show how (a) the level of discretionary slack and (b) CEOs' promotion focus and aspiration level jointly shape R&D investment decisions. Considering CEOs' psychological traits contributes to a more comprehensive view of the conditions under which discretionary slack resources matter for a firm's strategic decisions.

24,25-Dihydroxy Vitamin D and Vitamin D Metabolite Ratio as Biomarkers of Vitamin D in Chronic Kidney Disease.

The appropriate management of vitamin D deficiency and hyperparathyroidism is essential to prevent metabolic bone disorder (MBD) and cardiovascular diseases in chronic kidney disease (CKD). Recently, the 24,25-dihydroxyvitamin D [24,25(OH)2D] and vitamin D metabolite ratio (VMR), i.e., the ratio of 24,25(OH)2D to 25-hydroxyvitamin D [25(OH)D], have emerged as biomarkers of vitamin D level. We analyzed the usefulness of vitamin D biomarkers for the evaluation of MBD in patients with CKD. We analyzed blood and urine samples from 208 outpatients with CKD stage G2-G5. 25(OH)D showed a poor correlation with the estimated glomerular filtration rate (eGFR). Conversely, the 24,25(OH)2D level and VMR were significantly correlated with eGFR and the intact parathyroid hormone level. In conclusion, 24,25(OH)2D and VMR have the potential to be vitamin D biomarkers for the detection of MBD in CKD patients.

Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer's disease.

Complex diseases are characterized by spatiotemporal cellular and molecular changes that may be difficult to comprehensively capture. However, understanding the spatiotemporal dynamics underlying pathology can shed light on disease mechanisms and progression. Here we introduce STARmap PLUS, a method that combines high-resolution spatial transcriptomics with protein detection in the same tissue section. As proof of principle, we analyze brain tissues of a mouse model of Alzheimer's disease at 8 and 13 months of age. Our approach provides a comprehensive cellular map of disease progression. It reveals a core-shell structure where disease-associated microglia (DAM) closely contact amyloid-ß plaques, whereas disease-associated astrocyte-like (DAA-like) cells and oligodendrocyte precursor cells (OPCs) are enriched in the outer shells surrounding the plaque-DAM complex. Hyperphosphorylated tau emerges mainly in excitatory neurons in the CA1 region and correlates with the local enrichment of oligodendrocyte subtypes. The STARmap PLUS method bridges single-cell gene expression profiles with tissue histopathology at subcellular resolution, providing a tool to pinpoint the molecular and cellular changes underlying pathology.

Anti-α-synuclein c-terminal antibodies block PFF uptake and accumulation of phospho-synuclein in preclinical models of Parkinson's disease.

Parkinson's disease (PD), a neurodegenerative disease affecting dopaminergic (DA) neurons, is characterized by decline of motor function and cognition. Dopaminergic cell loss is associated with accumulation of toxic alpha synuclein aggregates. As DA neuron death occurs late in the disease, therapeutics that block the spread of alpha synuclein may offer functional benefit and delay disease progression. To test this hypothesis, we generated antibodies to the C terminal region of synuclein with high nanomolar affinity and characterized them in in vitro and in vivo models of spread. Interestingly, we found that only antibodies with high affinity to the distal most portion of the C-terminus robustly reduced uptake of alpha synuclein preformed fibrils (PFF) and accumulation of phospho (S129) alpha synuclein in cell culture. Additionally, the antibody treatment blocked the spread of phospho (S129) alpha synuclein associated-pathology in a mouse model of synucleinopathy. Blockade of neuronal PFF uptake by different antibodies was more predictive of in vivo activity than their binding potency to monomeric or oligomeric forms of alpha synuclein. These data demonstrate that antibodies directed to the C-terminus of the alpha synuclein have differential effects on target engagement and efficacy. Furthermore, our data provides additional support for the development of alpha synuclein antibodies as a therapeutic strategy for PD patients.

Quantitative systems pharmacology model of the amyloid pathway in Alzheimer's disease: Insights into the therapeutic mechanisms of clinical candidates.

Despite considerable investment into potential therapeutic approaches for Alzheimer's disease (AD), currently approved treatment options are limited. Predictive modeling using quantitative systems pharmacology (QSP) can be used to guide the design of clinical trials in AD. This study developed a QSP model representing amyloid beta (Aß) pathophysiology in AD. The model included mechanisms of Aß monomer production and aggregation to form insoluble fibrils and plaques; the transport of soluble species between the compartments of brain, cerebrospinal fluid (CSF), and plasma; and the pharmacokinetics, transport, and binding of monoclonal antibodies to targets in the three compartments. Ordinary differential equations were used to describe these processes quantitatively. The model components were calibrated to data from the literature and internal studies, including quantitative data supporting the underlying AD biology and clinical data from clinical trials for anti-Aß monoclonal antibodies (mAbs) aducanumab, crenezumab, gantenerumab, and solanezumab. The model was developed for an apolipoprotein E (APOE) ɛ4 allele carrier and tested for an APOE ɛ4 noncarrier. Results indicate that the model is consistent with data on clinical Aß accumulation in untreated individuals and those treated with monoclonal antibodies, capturing increases in Aß load accurately. This model may be used to investigate additional AD mechanisms and their impact on biomarkers, as well as predict Aß load at different dose levels for mAbs with known targets and binding affinities. This model may facilitate the design of scientifically enriched and efficient clinical trials by enabling a priori prediction of biomarker dynamics in the brain and CSF.

Disease-associated oligodendrocyte responses across neurodegenerative diseases.

Oligodendrocyte dysfunction has been implicated in the pathogenesis of neurodegenerative diseases, so understanding oligodendrocyte activation states would shed light on disease processes. We identify three distinct activation states of oligodendrocytes from single-cell RNA sequencing (RNA-seq) of mouse models of Alzheimer's disease (AD) and multiple sclerosis (MS): DA1 (disease-associated1, associated with immunogenic genes), DA2 (disease-associated2, associated with genes influencing survival), and IFN (associated with interferon response genes). Spatial analysis of disease-associated oligodendrocytes (DAOs) in the cuprizone model reveals that DA1 and DA2 are established outside of the lesion area during demyelination and that DA1 repopulates the lesion during remyelination. Independent meta-analysis of human single-nucleus RNA-seq datasets reveals that the transcriptional responses of MS oligodendrocytes share features with mouse models. In contrast, the oligodendrocyte activation signature observed in human AD is largely distinct from those observed in mice. This catalog of oligodendrocyte activation states (http://research-pub.gene.com/OligoLandscape/) will be important to understand disease progression and develop therapeutic interventions.

Clinical and histopathological analyses of kidney biopsies in a single center for 7 years.

Kidney biopsy is the most important tool for diagnosing kidney disease and can be helpful in determining treatment and prognosis. Pathological spectra vary by country, region, race, sex, and age. We are the first to investigate the pathological spectrum of biopsy-proven kidney disease in Gyeongnam province of South Korea. We retrospectively analyzed 631 patients who underwent a kidney biopsy between 2013 and 2019 at Gyeongsang National University Hospital. The mean age of the 631 patients was 51.5 ± 18.1 years, and 361 patients (57.2%) were male. The mean estimated glomerular filtration rate by serum creatinine (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) was 68.0 ± 45.7 mL/min/1.73 m2. The mean systolic blood pressure was higher in 2017, 2018, and 2019 than in 2013 (P = .002). Hypertension (47.4%) was the most common comorbid disease, followed by diabetes (18.2%) and dyslipidemia (10.9%). Common clinical syndromes at the time of biopsy were renal insufficiency (42.0%) and nephrotic syndrome (33.9%). The prevalence of primary and secondary glomerular disease and tubulointerstitial disease were 71.4%, 16.9%, and 5.4%, respectively. Immunoglobulin A nephropathy was the most common primary glomerular disease (34.9%). Diabetic nephropathy was the most common secondary glomerular disease, followed by lupus nephritis. Tubulointerstitial disease was underestimated, as in other reports. Our data can be a useful reference for diagnosing kidney disease and understanding the patients in our province.

Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice.

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and progression to chronic kidney disease (CKD). However, no effective therapeutic intervention has been established for ischemic AKI. Endothelial progenitor cells (EPCs) have major roles in the maintenance of vascular integrity and the repair of endothelial damage; they also serve as therapeutic agents in various kidney diseases. Thus, we examined whether EPCs have a renoprotective effect in an IRI mouse model. Mice were assigned to sham, EPC, IRI-only, and EPC-treated IRI groups. EPCs originating from human peripheral blood were cultured. The EPCs were administered 5 min before reperfusion, and all mice were killed 72 h after IRI. Blood urea nitrogen, serum creatinine, and tissue injury were significantly increased in IRI mice; EPCs significantly improved the manifestations of IRI. Apoptotic cell death and oxidative stress were significantly reduced in EPC-treated IRI mice. Administration of EPCs decreased the expression levels of NLRP3, cleaved caspase-1, p-NF-κB, and p-p38. Furthermore, the expression levels of F4/80, ICAM-1, RORγt, and IL-17RA were significantly reduced in EPC-treated IRI mice. Finally, the levels of EMT-associated factors (TGF-ß, α-SMA, Snail, and Twist) were significantly reduced in EPC-treated IRI mice. This study shows that inflammasome-mediated inflammation accompanied by immune modulation and fibrosis is a potential target of EPCs as a treatment for IRI-induced AKI and the prevention of progression to CKD.

Case Report: Acute Kidney Injury Due to Chronic Milk-Alkali Syndrome in a Patient With Colon Cancer.

BACKGROUND: Common causes of hypercalcemia include primary hyperparathyroidism and paraneoplastic syndrome of malignancy. Because of this, physicians can easily miss extrinsic causes of hypercalcemia such as milk-alkali syndrome in patients with cancer. We successfully treated a case of acute kidney injury due to severe hypercalcemia caused by milk-alkali syndrome due to long-term milk drinking in a patient with colon cancer. CASE DESCRIPTION: A 62-year-old man was referred to nephrology for hypercalcemia and azotemia that was found during preoperative evaluation for colon cancer surgery. The patient had experienced several months of dizziness and anorexia. We started hemodialysis because hypercalcemia and azotemia were not improved despite large amounts of hydration and diuretics. We suspected paraneoplastic syndrome because of concomitant colon cancer and low intact parathyroid hormone (PTH). Renal microcalcifications were observed on ultrasonography. Metastatic calcifications of the lung and stomach were present, but no malignant metastasis appeared on bone scans. There was no evidence of metastatic malignant lesions on chest or abdominal enhanced computed tomography. PTH-related peptide was not detected. Thus, other causes of hypercalcemia beyond malignancy were considered. On history-taking, the patient reported consuming 1,000 to 1,200 mL of milk daily for the prior 3 months. Hypercalcemia was due to chronic milk-alkali syndrome. We advised withdrawal of milk and nutritional pills. Hemodialysis was stopped after 2 weeks since azotemia and hypercalcemia were resolving. Acute kidney injury was improved, and mild hypercalcemia remained when he underwent hemicolectomy after 1 month. Thereafter, serum calcium and creatinine remained normal at discharge and follow-up for 1 year in the outpatient clinic. However, lung calcifications still remained on bone scan after 1 year. CONCLUSIONS: Chronic milk-alkali syndrome is a rare condition resulting from excessive calcium and alkali intake through various routes, like milk, nutritional supplements, and medicines for osteoporosis. Therefore, early management for hypercalcemia should include precise history taking including diet, previous diagnoses, and current medications.

TREM2-independent oligodendrocyte, astrocyte, and T cell responses to tau and amyloid pathology in mouse models of Alzheimer disease.

Non-neuronal responses in neurodegenerative disease have received increasing attention as important contributors to disease pathogenesis and progression. Here we utilize single-cell RNA sequencing to broadly profile 13 cell types in three different mouse models of Alzheimer disease (AD), capturing the effects of tau-only, amyloid-only, or combined tau-amyloid pathology. We highlight microglia, oligodendrocyte, astrocyte, and T cell responses and compare them across these models. Notably, we identify two distinct transcriptional states for oligodendrocytes emerging differentially across disease models, and we determine their spatial distribution. Furthermore, we explore the impact of Trem2 deletion in the context of combined pathology. Trem2 knockout mice exhibit severely blunted microglial responses to combined tau and amyloid pathology, but responses from non-microglial cell types (oligodendrocytes, astrocytes, and T cells) are relatively unchanged. These results delineate core transcriptional states that are engaged in response to AD pathology, and how they are influenced by a key AD risk gene, Trem2.

Oral cyclophosphamide-induced posterior reversible encephalopathy syndrome in a patient with ANCA-associated vasculitis: A case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) manifests many neurological symptoms with typical features on neuroimaging studies and has various risk factors. Cyclophosphamide is one of the therapeutic agents for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Cyclophosphamide as the sole cause of PRES has been reported in only a few cases. Herein, we report a unique case of early-onset oral cyclophosphamide-induced PRES in a patient with ANCA-associated vasculitis. CASE SUMMARY: A 73-year-old man was transferred to our hospital for sepsis due to acute cholangitis. He had already received hemodialysis for two weeks due to septic acute kidney injury. His azotemia was not improved after sepsis resolved and perinuclear-ANCA was positive. Kidney biopsy showed crescentic glomerulonephritis. Alveolar hemorrhage was observed on bronchoscopy. He was initially treated with intravenous methylprednisolone and plasma exchange for one week. And then, two days after adding oral cyclophosphamide, the patient developed generalized tonic-clonic seizures. We diagnosed PRES by Brain magnetic resonance imaging (MRI) and electroencephalography. Seizures were controlled with fosphenytoin 750 mg. Cyclophosphamide was suspected to be the cause of PRES and withdrawal. His mentality was recovered after seven days and brain MRI showed normal state after two weeks. CONCLUSION: The present case shows the possibility of PRES induction due to short-term use of oral cyclophosphamide therapy. Physicians should carefully monitor neurologic symptoms after oral cyclophosphamide administration in elderly patients with underlying diseases like sepsis, renal failure and ANCA-associated vasculitis.

Changes in energy consumption according to building use type under COVID-19 pandemic in South Korea.

An unprecedented global lockdown has been implemented for controlling the spread of COVID-19 in many countries. These actions are reducing the number of coronics, but with the prolonged COVID-19 outbreak, the restrictions on the activities of people are having a significant impact on all industries. Accordingly, this study aimed to statistically analyze changes in building energy consumption under the COVID-19 pandemic in South Korea, as well as identify the relationship between COVID-19 and building energy consumption according to the building use type. As a result, the average rate of changes in electricity and gas energy consumption decreased -4.46% and -10.35%, respectively, compared to the previous year. The energy consumption in most facilities has tended to decrease while energy consumption in residential facilities increased during COVID-19. The rate of change in building energy consumption had a significantly positive correlation with COVID-19 related factors in various facilities (e.g., neighborhood, religious, educational, and research facilities). Significant findings of this study that social distancing by the COVID-19 outbreak, has changed energy consumption according to building use type indicates the need for new energy systems to effectively manage the energy demand at the community level in the Post COVID-19 era.

Acute interstitial nephritis associated with ingesting a Momordica charantia extract: A case report.

RATIONALE: Momordica charantia is often used to treat type 2 diabetes mellitus in Korea. Drug-induced acute interstitial nephritis (AIN) accounts for 60% to 70% of AIN cases. However, only 1 case of AIN associated with ingesting M charantia has been reported in the English literature. We report an extremely rare case of AIN that occurred after a patient ingested a pure M charantia extract over 7 months. PATIENT CONCERNS: A 60-year-old Korean woman was admitted to our hospital for a renal biopsy. Her renal function had decreased gradually over the last 9 months without symptoms or signs. DIAGNOSIS: Her blood urea nitrogen and serum creatinine levels were 29.7 mg/dL (range: 8.0-20.0 mg/dL) and 1.45 mg/dL (range: 0.51-0.95 mg/dL) on admission. Renal histology indicated AIN; there was immune cell infiltration into the interstitium, tubulitis, and epithelial casts, although the glomeruli were largely intact. INTERVENTIONS: M charantia was discontinued and prednisolone was prescribed. OUTCOMES: The value of serum creatinine has almost been restored to the baseline level after 3 months. CONCLUSION: s: This is the first case report of AIN associated with the ingestion of a pure M charantia extract. Recognition of the possible adverse effects of these agents by physicians is very important for early diagnosis and appropriate management.

Bilateral Acute Renal Infarction Due to Paradoxical Embolism in a Patient with Eisenmenger Syndrome and a Ventricular Septal Defect.

A 52-year-old man who was diagnosed with Eisenmenger syndrome due to a muscular-type ventricular septal defect 30 years previously, visited our emergency room after experiencing six hours of severe left flank pain and vomiting. On laboratory examination, azotemia and microscopic haematuria were identified. Contrast-enhanced computed tomography also revealed pulmonary embolism (PE) and bilateral acute renal infarction. The flank pain resolved after heparin was administered for anti-coagulation and aspiration thrombectomy was performed. The patient was discharged on warfarin as anticoagulant therapy. In this case, a paradoxical embolism was considered to have been the cause of PE and bilateral acute renal infarction in a patient with Eisenmenger syndrome.

Spontaneous rupture of a renal artery pseudoaneurysm in a hemodialysis patient: A case report.

RATIONALE: Renal artery pseudoaneurysm is a rare vascular lesion usually caused by trauma or percutaneous urological procedures. Spontaneous rupture of pseudoaneurysms without predisposing events, especially in hemodialysis patients, has rarely been reported. PATIENT CONCERNS: A 25-year-old man receiving maintenance hemodialysis visited the emergency room because of sudden severe right flank pain. He had no history of trauma or urological procedures except for a left renal biopsy to diagnose Alport syndrome 10 years prior. DIAGNOSIS: Contrast-enhanced computed tomography revealed a right perirenal hematoma with pseudoaneurysms. INTERVENTIONS: On renal angiography, multiple pseudoaneurysms were observed in the right renal artery branches and embolization was performed. OUTCOMES: Post-angiography showed no pseudoaneurysms. His abdominal pain improved, and he was discharged 2 weeks after embolization. LESSONS: When maintenance dialysis patients complain of severe abdominal pain, spontaneous rupture of a renal pseudoaneurysm should be considered as a differential diagnosis, even if the patient has no history of trauma or previous urological procedures.

Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease.

Tau has become an attractive alternative target for passive immunotherapy efforts for Alzheimer's disease (AD). The anatomical distribution and extent of tau pathology correlate with disease course and severity better than other disease markers to date. We describe here the generation, preclinical characterization, and phase 1 clinical characterization of semorinemab, a humanized anti-tau monoclonal antibody with an immunoglobulin G4 (igG4) isotype backbone. Semorinemab binds all six human tau isoforms and protects neurons against tau oligomer neurotoxicity in cocultures of neurons and microglia. In addition, when administered intraperitoneally once weekly for 13 weeks, murine versions of semorinemab reduced the accumulation of tau pathology in a transgenic mouse model of tauopathy, independent of antibody effector function status. Semorinemab also showed clear evidence of target engagement in vivo, with increases in systemic tau concentrations observed in tau transgenic mice, nonhuman primates, and humans. Higher concentrations of systemic tau were observed after dosing in AD participants compared to healthy control participants. No concerning safety signals were observed in the phase 1 clinical trial at single doses up to 16,800 mg and multiple doses totaling 33,600 mg in a month.

Acute interstitial nephritis associated with ingestion of Achyranthes japonica extract: a case report.

BACKGROUND: The Japanese chaff flower, Achyranthes japonica, is used as complementary medicine to control degenerative arthritis. Although commonly used in South Korea, there has been no report of side effects. We report the first case of acute interstitial nephritis (AIN) that occurred in a woman who ingested A. japonica extract for 4 months. CASE PRESENTATION: A 56-year-old Korean woman was admitted for deterioration of renal function. She had general weakness and nausea for 1 month. Her initial blood urea nitrogen and serum creatinine levels were 26.3 mg/dL and 3.2 mg/dL, respectively. She acknowledged ingesting A. japonica extract for the past 4 months. Renal histology demonstrated AIN represented by immune cell infiltration into the interstitium, tubulitis, and tubular atrophy, but the glomeruli were intact. A. japonica was discontinued immediately and conservative management was started. Renal function was nearly restored to the baseline level without medication after 13 months. CONCLUSION: This is a rare case report of AIN associated with a pure A. japonica extract. In the case of unknown etiology of AIN, physicians should ask about the use of herbal medicines, nutraceuticals, and traditional folk medicines including A. japonica.