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Hematuria is the presence of blood in the urine and is classified as either gross hematuria or microscopic hematuria. There are many causes of hematuria, and the differential diagnosis depends on the presence or absence of comorbidities and whether it is glomerular or non-glomerular. When hematuria in children is symptomatic or persistent, an evaluation of the cause is essential. The causes of hematuria and basic approaches to its diagnosis are discussed in this review.

In response to the increase in the prevalence of chronic kidney disease (CKD) in Korea, the growth of patients requiring renal replacement therapy and the subsequent increase in medical costs, the rapid expansion of patients with end-stage kidney disease (ESKD), and the decrease in patients receiving home therapy, including peritoneal dialysis, the Korean Society of Nephrology has proclaimed the new policy, Kidney Health Plan 2033 (KHP 2033). KHP 2033 would serve as a milestone to bridge the current issues to a future solution by directing the prevention and progression of CKD and ESKD, particularly diabetic kidney disease, and increasing the proportion of home therapy, thereby reducing the socioeconomic burden of kidney disease and improving the quality of life. Here, we provide the background for the necessity of KHP 2033, as well as the contents of KHP 2033, and enlighten the Korean Society of Nephrology’s future goals. Together with patients, healthcare providers, academic societies, and national policymakers, we need to move forward with goal-oriented drive and leadership to achieve these goals.

Proteinuria is an important risk factor for renal and cardiovascular disease. It is associated with a risk for glomerulonephritis, chronic kidney disease, and end-stage renal disease. Therefore, if persistent proteinuria is detected, kidney biopsy is considered to diagnose and treat the underlying disease. Recently, variants in the cubulin (CUBN) gene, which is associated with albuminuria, have been reported. This gene encodes cubilin, a membrane glycoprotein receptor expressed in the renal proximal tubules. Cubilin is a component of the megalin and cubilin-amnionless complex that mediates albumin reabsorption into the proximal tubules through endocytosis. A defect in cubilin leads to a reduction in albumin reuptake, resulting in albumin-dominant proteinuria. Although numerous controversies exist, several reports suggest that cubilin defects lead to proteinuria with a high portion of albuminuria but may not impair renal filtration function. If albuminuria due to reduced cubilin function is confirmed as a benign condition, we can consider using genetic studies to detect CUBN mutations in patients with proteinuria and they may not require any treatment or kidney biopsy. Here, we review recent papers on CUBN mutations and discuss the prognosis and management of individuals with this mutation.

BackgroundWe evaluated the long-term clinical outcomes of nephrocalcinosis (NC) according to etiology and grade in preschool-age children with NC.MethodsWe retrospectively analyzed the clinical outcomes and disease grade of children with NC classified into three groups according to etiology: prematurity, tubular disorders, and others.ResultsOverall, 67 children were diagnosed with NC [median age, 0.76 years; interquartile range (IQR) 0.46–2.14 years]. The etiologies of NC included prematurity (28.4%), tubular disorders (25.4%), and others (46.3%). Moreover, 56 (83.6%) children were asymptomatic and diagnosed accidentally through kidney ultrasonography. Newly diagnosed underlying diseases were greater in the tubular disorders group than in the other two groups (P = 0.001). Significantly more newly diagnosed NCs were grade 3 than grade 1 (P = 0.003). The median estimated glomerular filtration rate (eGFR) changed from 96.1 (IQR 68.8–119.2) ml/min/1.72 m2 at diagnosis to 90.9 (IQR 76.4–106.4) ml/min/1.72 m2 at the last follow-up, without a significant difference (P = 0.096). Changes in the kidney function did not differ according to etiology. However, patients without improvement in NC grade showed a decrease in eGFR from 98.1 (IQR 71.1–132.9) to 87.4 (IQR 74.0–104.1) ml/min/1.73 m2 (P = 0.023), while patients with improved NC grade did not show any change in the kidney function.ConclusionsEarly recognition, especially in NC grade 3, can help uncover further diagnoses, such as tubular disorders. Long-term kidney function depends on whether the NC grade improves.

Genomic medicine, an emerging medical discipline, applies the principles of evolution, developmental biology, functional genomics, and structural genomics within clinical care. Enabling widespread adoption and integration of genomic medicine into clinical practice is key to achieving precision medicine. We delineate a biological framework defining diagnostic utility of genomic testing and map the process of genomic medicine to inform integration into clinical practice. This process leverages collaboration and collective cognition of patients, principal care providers, clinical genomic specialists, laboratory geneticists, and payers. We detail considerations for referral, triage, patient intake, phenotyping, testing eligibility, variant analysis and interpretation, counseling, and management within the utilitarian limitations of health care systems. To reduce barriers for clinician engagement in genomic medicine, we provide several decision-making frameworks and tools and describe the implementation of the proposed workflow in a prototyped electronic platform that facilitates genomic care. Finally, we discuss a vision for the future of genomic medicine and comment on areas for continued efforts.

Interstitial fibrosis and tubular atrophy (IF/TA) after kidney transplantation causes a chronic deterioration of graft function. IF/TA can be diagnosed by means of a graft biopsy, which is a necessity as non-invasive diagnostic methods are unavailable. In this study, we identified IF/TA-related differentially expressed genes (DEGs) through next-generation sequencing using peripheral blood mononuclear cells. Blood samples from kidney transplant recipients undergoing standard immunosuppressive therapy (tacrolimus/mycophenolate mofetil or mycophenolate sodium/steroid) and diagnosed as IF/TA (n = 41) or normal (controls; n = 41) at their one-year protocol biopsy were recruited between January of 2020 and August of 2020. DEGs were derived through mRNA sequencing and validated by means of a quantitative real-time polymerase chain reaction. We identified 34 DEGs related to IF/TA. ADAMTS2, PLIN5, CLDN9, and KCNJ15 demonstrated a log2(fold change) of >1.5 and an area under the receiver operating characteristic curve (AUC) value of >0.6, with ADAMTS2 showing the largest AUC value and expression levels, which were 3.5-fold higher in the IF/TA group relative to that observed in the control group. We identified and validated DEGs related to IF/TA progression at one-year post-transplantation. Specifically, we identified ADAMTS2 as a potential IF/TA biomarker.

Crystallographic observation of structural changes in real time requires that those changes be uniform both spatially and temporally. A primary challenge with time-resolved ligand-mixing diffraction experiments is asynchrony caused by variable factors, such as efficiency of mixing, rate of diffusion, crystal size, and subsequently, conformational heterogeneity. One method of minimizing such variability is use of a photolabile caged ligand, which can fully saturate the crystal environment (spatially), and whose photoactivation can rapidly (temporally) trigger the reaction in a controlled manner. Our recently published results on a ligand-mixing experiment using time-resolved X-ray crystallography (TRX) with an X-ray free electron laser (XFEL) demonstrated that large conformational changes upon ligand binding resulted in a solid-to-solid phase transition (SSPT), while maintaining Bragg diffraction. Here we investigate this SSPT by polarized video microscopy (PVM) after light-triggered release of a photo-caged adenine (pcADE). In general, the mean transition times and transition widths of the SSPT were less dependent on crystal size than what was observed in previous PVM studies with direct ADE mixing. Instead, the photo-induced transition appears to be heavily influenced by the equilibrium between caged and uncaged ADE due to relatively low sample exposure and uncaging efficiency. Nevertheless, we successfully demonstrate a method for the characterization of phase transitions in RNA crystals that are inducible with a photocaged ligand. The transition data for three crystals of different sizes were then applied to kinetic analysis by fitting to the known four-state model associated with ligand-induced conformational changes, revealing an apparent concentration of uncaged ADE in crystal of 0.43–0.46 mM. These results provide further insight into approaches to study time-resolved ligand-induced conformational changes in crystals, and in particular, highlight the feasibility of triggering phase transitions using a light-inducible system. Developing such approaches may be paramount for the rapidly emerging field of time-resolved crystallography.

Summary: Background: Prior studies have revealed remarkable phenotypic heterogeneity in KCNQ2-related disorders, correlated with effects on biophysical features of heterologously expressed channels. Here, we assessed phenotypes and functional properties associated with KCNQ2 missense variants R144W, R144Q, and R144G. We also explored in vitro blockade of channels carrying R144Q mutant subunits by amitriptyline. Methods: Patients were identified using the RIKEE database and through clinical collaborators. Phenotypes were collected by a standardized questionnaire. Functional and pharmacological properties of variant subunits were analyzed by whole-cell patch-clamp recordings. Findings: Detailed clinical information on fifteen patients (14 novel and 1 previously published) was analyzed. All patients had developmental delay with prominent language impairment. R144Q patients were more severely affected than R144W patients. Infantile to childhood onset epilepsy occurred in 40%, while 67% of sleep-EEGs showed sleep-activated epileptiform activity. Ten patients (67%) showed autistic features. Activation gating of homomeric Kv7.2 R144W/Q/G channels was left-shifted, suggesting gain-of-function effects. Amitriptyline blocked channels containing Kv7.2 and Kv7.2 R144Q subunits. Interpretation: Patients carrying KCNQ2 R144 gain-of-function variants have developmental delay with prominent language impairment, autistic features, often accompanied by infantile- to childhood-onset epilepsy and EEG sleep-activated epileptiform activity. The absence of neonatal seizures is a robust and important clinical differentiator between KCNQ2 gain-of-function and loss-of-function variants. The Kv7.2/7.3 channel blocker amitriptyline might represent a targeted treatment. Funding: Supported by FWO, GSKE, KCNQ2-Cure, Jack Pribaz Foundation, European Joint Programme on Rare Disease 2020, the Italian Ministry for University and Research, the Italian Ministry of Health, the European Commission, the University of Antwerp, NINDS, and Chalk Family Foundation.

Summary: Genome-wide sequencing (GWS) is a standard of care for diagnosis of suspected genetic disorders, but the proportion of patients found to have pathogenic or likely pathogenic variants ranges from less than 30% to more than 60% in reported studies. It has been suggested that the diagnostic rate can be improved by interpreting genomic variants in the context of each affected individual’s full clinical picture and by regular follow-up and reinterpretation of GWS laboratory results.Trio exome sequencing was performed in 415 families and trio genome sequencing in 85 families in the CAUSES study. The variants observed were interpreted by a multidisciplinary team including laboratory geneticists, bioinformaticians, clinical geneticists, genetic counselors, pediatric subspecialists, and the referring physician, and independently by a clinical laboratory using standard American College of Medical Genetics and Genomics (ACMG) criteria. Individuals were followed for an average of 5.1 years after testing, with clinical reassessment and reinterpretation of the GWS results as necessary. The multidisciplinary team established a diagnosis of genetic disease in 43.0% of the families at the time of initial GWS interpretation, and longitudinal follow-up and reinterpretation of GWS results produced new diagnoses in 17.2% of families whose initial GWS interpretation was uninformative or uncertain. Reinterpretation also resulted in rescinding a diagnosis in four families (1.9%). Of the families studied, 33.6% had ACMG pathogenic or likely pathogenic variants related to the clinical indication. Close collaboration among clinical geneticists, genetic counselors, laboratory geneticists, bioinformaticians, and individuals’ primary physicians, with ongoing follow-up, reanalysis, and reinterpretation over time, can improve the clinical value of GWS.

Botulinum toxin (BoNT) injection is widely used to improve spasticity. However, after the treatment, the patient may experience pain, inflammation, swelling and redness at the injection site. In this case, we addressed deep vein thrombosis (DVT) after BoNT treatment of the upper limb. A male aged 37 years had spasticity and dystonia in his left upper extremity. BoNT-A 100 U was injected into the left biceps brachii and an equal amount into the brachialis to relieve spasticity. After three days, he developed redness and painful swelling in the left upper arm and the next day, through the upper extremity computed tomography venography, DVT was identified in the left cephalic vein. The thrombus resolved after the anticoagulation therapy with rivaroxaban (Xarelto). We hypothesized the role of mainly three mechanisms in the development of DVT in this case: repetitive strenuous activity, relative stasis due to reduced muscle tone, and possible direct mechanical damage to the vessel wall.

Objective To investigate the differences of spinal curvature, thoracic sagittal mobility, and respiratory strength between patients with chronic neck pain (CNP) and people without cervical pain, and to determine the correlation between respiratory strength and thoracic mobility in CNP patients. Methods A total of 78 participants were finally included in this study, of whom 30 had no cervical pain and 48 had CNP. The Neck Disability Index (NDI), cervical lordotic curvature, thoracic kyphotic curvature, thoracic sagittal range of motion (ROM), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were measured and analyzed. Results In males, thoracic sagittal ROMMEP-MIP and MEP showed a significant difference between the no cervical pain group and the CNP group. In females, thoracic kyphotic curvature, thoracic sagittal ROMMEP-MIP, MIP, and MEP were significantly different between the no cervical pain group and the CNP group. Thoracic kyphotic curvature was significantly correlated with MEP and MIP in all population groups, and significantly correlated with NDI in the female group. Thoracic sagittal ROMMEP-MIP had a significant linear relationship with NDI, MEP, and MIP in all population groups. Conclusion The thoracic mobility during forced respiration was reduced in patients with CNP and was correlated with respiratory strength. Changes in the biomechanics of the cervicothoracic spine and rib cage due to CNP may contribute to impairment of respiratory strength.

Abstract Background In the Brassicaceae, the early stages of compatible pollen-stigma interactions are tightly controlled with early checkpoints regulating pollen adhesion, hydration and germination, and pollen tube entry into the stigmatic surface. However, the early signalling events in the stigma which trigger these compatible interactions remain unknown. Results A set of stigma-expressed pseudokinase genes, termed BRASSIKINs (BKNs), were identified and found to be present in only core Brassicaceae genomes. In Arabidopsis thaliana Col-0, BKN1 displayed stigma-specific expression while the BKN2 gene was expressed in other tissues as well. CRISPR deletion mutations were generated for the two tandemly linked BKNs, and very mild hydration defects were observed for wild-type Col-0 pollen when placed on the bkn1/2 mutant stigmas. In further analyses, the predominant transcript for the stigma-specific BKN1 was found to have a premature stop codon in the Col-0 ecotype, but a survey of the 1001 Arabidopsis genomes uncovered three ecotypes that encoded a full-length BKN1 protein. Furthermore, phylogenetic analyses identified intact BKN1 orthologues in the closely related outcrossing Arabidopsis species, A. lyrata and A. halleri. Finally, the BKN pseudokinases were found to be plasma-membrane localized through the dual lipid modification of myristoylation and palmitoylation, and this localization would be consistent with a role in signaling complexes. Conclusion In this study, we have characterized the novel Brassicaceae-specific family of BKN pseudokinase genes, and examined the function of BKN1 and BKN2 in the context of pollen-stigma interactions in A. thaliana Col-0. Additionally, premature stop codons were identified in the predicted stigma specific BKN1 gene in a number of the 1001 A. thaliana ecotype genomes, and this was in contrast to the out-crossing Arabidopsis species which carried intact copies of BKN1. Thus, understanding the function of BKN1 in other Brassicaceae species will be a key direction for future studies.

The purpose of this study was to evaluate the image quality of compressed-sensing accelerated single-shot fast spin-echo (SSFSECS) sequences acquired within a single breath-hold in comparison with conventional SSFSE (SSFSECONV) and multishot TSE (mTSE). A total of 101 patients who underwent liver MRI at 3 T, including SSFSECONV (acquisition time (TA) = 58–62 s), mTSE (TA = 108 s), and SSFSECS (TA = 18 s), were included in this retrospective study. Two radiologists assessed the three sequences with respect to artifacts, organ sharpness, small structure visibility, overall image quality, and conspicuity of main lesions of liver and pancreas using a five-point evaluation scale system. Descriptive statistics and the Wilcoxon signed-rank test were used for statistical analysis. SSFSECS was significantly better than SSFSECONV and mTSE for artifacts, small structure visibility, overall image quality, and conspicuity of main lesions (p < 0.005). Regarding organ sharpness, mTSE and SSFSECS did not significantly differ (p = 0.554). Conspicuity of liver lesion did not significantly differ between SSFSECONV and mTSE (p = 0.404). SSFSECS showed superior image quality compared with SSFSECONV and mTSE despite a more than three-fold reduction in TA, suggesting a remarkable potential for saving time in liver imaging.

Background Docetaxel is one of the standard treatments for advanced non-small cell lung cancer. Docetaxel is usually administered in a 3-week schedule, but there is significant toxicity. In this phase II clinical study, we investigated the efficacy and safety of a 4-weekly schedule of docetaxel monotherapy, as first-line chemotherapy for advanced squamous cell carcinoma in elderly lung cancer patients. Methods Patients with stage IIIB/ IV lung squamous-cell carcinoma age 70 or older, that had not undergone cytotoxic chemotherapy were enrolled. Patients received docetaxel 25 mg/m2 on days 1, 8, and 15, every 4 weeks. Primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results A total of 19 patients were enrolled. Among 19 patients, 17 were for evaluated efficacy and safety. In the intent-to-treat population, ORR and disease control rate (DCR) were 11.8% and 47.1%, respectively. In the response evaluable population, ORR was 16.7% and DCR was 66.7%. Median PFS and OS were 3.1 months and 3.3 months, respectively. There were three adverse grade 3/4 events. Grade 1 neutropenia was reported in one patient. Conclusion Our data failed to demonstrate efficacy of a 4-weekly docetaxel regimen, in elderly patients with a poor performance status. However, incidence of side effects, including neutropenia, was lower than with a 3-week docetaxel regimen, as previously reported.

Abstract Background The effects of corticosteroid-based therapy in patients with idiopathic nonspecific interstitial pneumonia (iNSIP), and factors affecting treatment outcome, are not fully understood. We aimed to investigate the long-term treatment response and factors affecting the treatment outcome in iNSIP patients from a multi-center study in Korea. Methods The Korean interstitial lung disease (ILD) Study Group surveyed ILD patients from 2003 to 2007. Patients were divided into two groups to compare the treatment response: response group (forced vital capacity (FVC) improves ≥10% after 1 year) and non-response group (FVC

Abstract Background This study aimed to investigate clinical characteristics of Korean PAP patients and to examine the potential risk factors of PAP. Methods We retrospectively reviewed medical records of 78 Korean PAP patients diagnosed between 1993 and 2014. Patients were classified into two groups according to the presence/absence of treatment (lavage). Clinical and laboratory features were compared between the two groups. Results Of the total 78 PAP patients, 60% were male and median age at diagnosis was 47.5 years. Fifty three percent were ever smokers (median 22 pack-years) and 48% had a history of dust exposure (metal 26.5%, stone or sand 20.6%, chemical or paint 17.7%, farming dust 14.7%, diesel 14.7%, textile 2.9%, and wood 2.9%). A history of cigarette smoking or dust exposure was present in 70.5% of the total PAP patients, with 23% having both of them. Patients who underwent lavage (n = 38) presented symptoms more frequently (38/38 [100%] vs. 24/40 [60%], P

The purpose of this study is to identify amino acid derivatives with potent anti-eumelanogenic activity. First, we compared the effects of twenty different amidated amino acids on tyrosinase (TYR)-mediated dopachrome formation in vitro and melanin content in dark-pigmented human melanoma MNT-1 cells. The results showed that only L-cysteinamide inhibited TYR-mediated dopachrome formation in vitro and reduced the melanin content of cells. Next, the antimelanogenic effect of L-cysteinamide was compared to those of other thiol compounds (L-cysteine, N-acetyl L-cysteine, glutathione, L-cysteine ethyl ester, N-acetyl L-cysteinamide, and cysteamine) and positive controls with known antimelanogenic effects (kojic acid and β-arbutin). The results showed the unique properties of L-cysteinamide, which effectively reduces melanin content without causing cytotoxicity. L-Cysteinamide did not affect the mRNA and protein levels of TYR, tyrosinase-related protein 1, and dopachrome tautomerase in MNT-1 cells. L-Cysteinamide exhibited similar properties in normal human epidermal melanocytes (HEMs). Experiments using mushroom TYR suggest that L-cysteinamide at certain concentrations can inhibit eumelanin synthesis through a dual mechanism by inhibiting TYR-catalyzed dopaquinone synthesis and by diverting the synthesized dopaquinone to the formation of DOPA-cysteinamide conjugates rather than dopachrome. Finally, L-cysteinamide was shown to increase pheomelanin content while decreasing eumelanin and total melanin contents in MNT-1 cells. This study suggests that L-cysteinamide has an optimal structure that can effectively and safely inhibit eumelanin synthesis in MNT-1 cells and HEMs, and will be useful in controlling skin hyperpigmentation.

BackgroundPirfenidone is an antifibrotic medication approved for idiopathic pulmonary fibrosis (IPF). Fybro®, a generic version of pirfenidone developed in South Korea, gained approval and is available in 200 mg and in higher-dose formulations of 400 and 600 mg. This real-world prospective cohort study investigated the safety and effectiveness of Fybro®.MethodsA nationwide observational study was conducted in patients with IPF. Patients were followed up for 6 months, with a subset of patients being followed up for 12 months. Data on lung function and adverse events were collected. Patient adherence to fewer-pill (400 and/or 600 mg tablets) and multiple-pill (200 mg tablets) regimens were compared.ResultsOf the 359 enrolled patients, 352 received pirfenidone (Fybro®) at least once and were included in the analysis. The mean age was 69.0 years and 82.4% of patients were male. The median treatment duration was 186.0 days. A total of 253 patients (71.9%) experienced adverse events, with decreased appetite being the most common (16.5%). The adjusted decline rates in lung function were −1.5% and −2.2% predicted per year for forced vital capacity and diffusing capacity, respectively. No significant differences were observed based on the pirfenidone dose. For a daily intake of 1,200 or 1800 mg of pirfenidone, a significantly longer duration of drug administration was observed with the fewer-pill regimen than with multiple-pill regimen.ConclusionThe safety and effectiveness of Fybro® observed in this real-world cohort study are consistent with previous studies. Using higher-strength tablets to reduce pill burden may improve medication adherence.

Pseudohypoaldosteronism type 1 (PHA1) is a rare form of mineralocorticoid resistance characterized in newborns by salt wasting with dehydration, hyperkalemia and failure to thrive. This disease is heterogeneous in etiology and includes autosomal dominant PHA1 owing to mutations of the NR3C2 gene encoding the mineralocorticoid receptor, autosomal recessive PHA1 due to mutations of the epithelial sodium channel (ENaC) gene, and secondary PHA1 associated with urinary tract diseases. Amongst these diseases, autosomal dominant PHA1 shows has manifestations restricted to renal tubules including a mild salt loss during infancy and that shows a gradual improvement with advancing age. Here, we report a neonatal case of PHA1 with a NR3C2 gene mutation (a heterozygous c.2146_2147insG in exon 5), in which the patient showed failure to thrive, hyponatremia, hyperkalemia, and elevated plasma renin and aldosterone levels. This is the first case of pseudohypoaldosteronism type 1 confirmed by genetic analysis in Korea.

Bartter syndrome (BS) is a clinically and genetically heterogeneous inherited renal tube disorder characterized by renal salt wasting, hypokalemic metabolic alkalosis and normotensive hyperreninemic hyperaldosteronism. There have been several case reports of BS complicated by focal segmental glomerulosclerosis (FSGS). Here, we have reported the case of a BS patient who developed FSGS and subsequent end-stage renal disease (ESRD) and provided a brief literature review. The patient presented with classic BS at 3 months of age and developed proteinuria at 7 years. Renal biopsy performed at 11 years of age revealed a FSGS perihilar variant. Hemodialysis was initiated at 11 years of age, and kidney transplantation was performed at 16 years of age. The post-transplantation course has been uneventful for more than 3 years with complete disappearance of BS without the recurrence of FSGS. Genetic study revealed a homozygous p.Trp(TGG)610Stop(TGA) mutation in the CLCNKB gene. In summary, BS may be complicated by secondary FSGS due to the adaptive response to chronic salt-losing nephropathy, and FSGS may progress to ESRD in some patients. Renal transplantation in patients with BS and ESRD results in complete remission of BS.

Bartter syndrome (BS) is an autosomal recessively inherited rare renal tubular disorder characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism with normal to low blood pressure due to a renal loss of sodium. Genetically, BS is classified into 5 subtypes according to the underlying genetic defects, and BS is clinically categorized into antenatal BS and classical BS according to onset age. BS type I is caused by loss-of-function mutations in the SLC12A1 gene and usually manifests as antenatal BS. This report concerns a male patient with compound heterozygous missense mutations on SLC12A1 (p.C436Y and p.L560P) and atypical clinical and laboratory features. The patient had low urinary sodium and chloride levels without definite metabolic alkalosis until the age of 32 months, which led to confusion between BS and nephrogenic diabetes insipidus (NDI). In addition, the clinical onset of the patient was far beyond the neonatal period. Genetic study eventually led to the diagnosis of BS type I. The low urinary sodium and chloride concentrations may be caused by secondary NDI, and the later onset may suggest the existence of a genotype-phenotype correlation.In summary, BS type I may have phenotype variability including low urine sodium and chloride levels and later onset. A definitive diagnosis can be confirmed by genetic testing.

Natural regeneration is an essential component of forest dynamics and the recovery of ecosystem functions. Therefore, understanding regeneration status, and how abiotic and biotic factors affect it, is important for ecological studies. This study discovered different regeneration statuses of tropical forests in response to differences in rainfall in Myanmar, and the environmental and overstory factors that had the most influence on understory regeneration. Study sites were set up in regions with 625 to 2035 mm of annual rainfall, and ecological characteristics were measured. According to the results, natural regeneration increased with rainfall, showing a good regeneration status at all sites. Forests within a range of 1411–2035 mm of annual rainfall had a significantly higher density and species diversity at specific natural regeneration stages than those with 625–1029 mm. Not only abiotic but also overstory structure affected the natural regeneration of forests. However, not all factors influenced natural regeneration status. Overstory size distribution parameters did not show a significant influence on natural regeneration. Average annual rainfall (abiotic), as well as ecosystem complexity, density, species richness, and diversity (overstory), were found to be the most influential factors for the density and diversity of natural regeneration. The results of this study will support silviculture and the management of tropical forests.

An understanding of how species diversity, structural pattern, and species distribution vary across different environmental regions is crucially important for tropical ecology. In this study, we explored how these ecological parameters vary across various rainfall regions in the tropics with annual rainfall levels ranging from 843 to 2035 mm. Diversity, similarity, structure, and forest classification, and their correspondence with rainfall regions were tested. We found that species diversity, site class, and structural complexity increased with rainfall, with differences of 1000 mm having significant effects on diversity. The structure and heterogeneity of forests were higher in the high rainfall regions than the low rainfall regions. The forest structure was significantly correlated with rainfall, and the structure differed substantially where annual rainfall differed among sites by approximately 200 or 400 mm. Forests could be classified into two types according to whether they had high annual rainfall (1411–2035 mm) or low annual rainfall (843–1029 mm). In addition, the dominance of species changed noticeably from high- to low-rainfall regions, with Tectona hamiltoniana and Terminalia oliveri only being abundant in the low rainfall region. Species diversity and richness were significantly correlated with rainfall and average temperature. These findings will provide invaluable information for forest management and ecological phytogeography.

The aim of this study was to explore the relationship between diabetes and depression and investigate the effects of comorbid diabetes and depression on healthcare utilization.The study sample included 10,179 Korean adults aged ≥ 45 years. The presence of diabetes was assessed by asking participants if the participants had ever been diagnosed with diabetes. Depression was measured using the 10-item Center for Epidemiological Studies-Depression scale. Healthcare utilization was assessed by self-report. Multiple logistic regression analyses were performed.Diabetes was positively associated with depression after controlling socioeconomic and health variables. Diabetic patients who had low socioeconomic status, who were obese, who were smokers, and who had higher numbers of chronic diseases had a higher depression risk. Diabetes and depression was associated with increased healthcare utilization. People with both diabetes and depression had significantly increased odds of multiple physician visits, multiple hospital admissions, and prolonged hospitalization compared with individuals with neither diabetes nor depression. Patients with both diabetes and depression had greater odds of multiple hospital admissions than patients with diabetes alone.We found a positive association between diabetes and depression. Depression in persons with diabetes is associated with increased multiple hospital admissions. More research is warranted to clarify an association between co-occurring depression with diabetes and increased healthcare utilization.

Secreted signaling peptides are central regulators of growth, development, and stress responses, but specific steps in the evolution of these peptides and their receptors are not well understood. Also, the molecular mechanisms of peptide-receptor binding are only known for a few examples, primarily owing to the limited availability of protein structural determination capabilities to few laboratories worldwide. Plants have evolved a multitude of secreted signaling peptides and corresponding transmembrane receptors. Stress-responsive SERINE RICH ENDOGENOUS PEPTIDES (SCOOPs) were recently identified. Bioactive SCOOPs are proteolytically processed by subtilases and are perceived by the leucine-rich repeat receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2) in the model plant Arabidopsis thaliana. How SCOOPs and MIK2 have (co)evolved, and how SCOOPs bind to MIK2 are unknown. Using in silico analysis of 350 plant genomes and subsequent functional testing, we revealed the conservation of MIK2 as SCOOP receptor within the plant order Brassicales. We then leveraged AI-based structural modeling and comparative genomics to identify two conserved putative SCOOP-MIK2 binding pockets across Brassicales MIK2 homologues predicted to interact with the "SxS" motif of otherwise sequence-divergent SCOOPs. Mutagenesis of both predicted binding pockets compromised SCOOP binding to MIK2, SCOOP-induced complex formation between MIK2 and its coreceptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1, and SCOOP-induced reactive oxygen species production, thus, confirming our in silico predictions. Collectively, in addition to revealing the elusive SCOOP-MIK2 binding mechanism, our analytic pipeline combining phylogenomics, AI-based structural predictions, and experimental biochemical and physiological validation provides a blueprint for the elucidation of peptide ligand-receptor perception mechanisms. [ABSTRACT FROM AUTHOR]

To be digitally responsible, one should be aware of the current issues in the digital world; therefore, raising awareness on digital responsibility and data privacy is important in the public and private sectors. This study aimed to raise awareness on digital responsibility and help students understand the importance of utilizing the design thinking process for generating creative ideas. The authors facilitated a design thinking workshop where 62 students from different cultural backgrounds (Korean and Swiss) and majors collaboratively explored data privacy issues and presented their novel, creative solutions. The data gathered from observations and interviews were analyzed using qualitative content analysis. These students of the digital age developed remarkable ones, such as keeping data safe from social networking services and protecting voice data from being recorded by a third party. The cross-cultural, interdisciplinary team rapidly implemented their creative and globally applicable solutions with visually feasible, diagrammed prototypes, which is an effective tool of the design thinking process. The article demonstrates how design thinking techniques could be applied in university classes and could inspire teachers to use the five stages of design thinking in their teaching.

The actin-based cytoskeleton is considered a fundamental driving force for cell differentiation and development. Destrin (Dstn), a member of the actin-depolymerizing factor family, regulates actin dynamics by treadmilling actin filaments and increasing globular actin pools. However, the specific developmental roles of dstn have yet to be fully elucidated. Here, we investigated the physiological functions of dstn during early embryonic development using Xenopus laevis as an experimental model organism. dstn is expressed in anterior neural tissue and neural plate during Xenopus embryogenesis. Depleting dstn promoted morphants with short body axes and small heads. Moreover, dstn inhibition extended the neural plate region, impairing cell migration and distribution during neurulation. In addition to the neural plate, dstn knockdown perturbed neural crest cell migration. Our data suggest new insights for understanding the roles of actin dynamics in embryonic neural development, simultaneously presenting a new challenge for studying the complex networks governing cell migration involving actin dynamics. [ABSTRACT FROM AUTHOR]

Central venous catheterization is a preferred method for intensive care patients who require total parenteral nutrition (TPN). TPN can cause tissue damage due to osmotic effects and the presence of ions. We report a case of TPN extravasation into the pleural cavity due to a shift in position of a subclavian central vein catheter. In this report, we discuss the importance of serial follow up of chest X-ray examination in patients with central vein catheterization.

Objective: This study investigated the clinical and laboratory factors associated with the presence of dysmorphic oocytes in intracytoplasmic sperm injection (ICSI) cycles. Methods: The study involved 200 ICSI cycles, performed from 2020 to 2021, that yielded at least one mature oocyte. Clinical characteristics and ovarian stimulation methods were compared between 68 cycles with at least one dysmorphic oocyte (the dysmorphic group) and 132 cycles with normal-form oocytes only (the non-dysmorphic group). Dysmorphic oocytes were characterized by dark cytoplasm, cytoplasmic granularity, cytoplasmic vacuoles, refractile bodies in the cytoplasm, smooth endoplasmic reticulum in the cytoplasm, an oval shape, an abnormal zona pellucida, a large perivitelline space, debris in the perivitelline space, or an abnormal polar body. Results: The ages of the women, indications for in vitro fertilization, serum anti-Müllerian hormone levels, and rates of current ovarian endometrioma were similar between the dysmorphic and non-dysmorphic groups. In both groups, the three ovarian stimulation regimens, two types of pituitary suppression, and total gonadotropin dose were employed similarly. However, the dual-trigger method was used more frequently in the dysmorphic group (67.6% vs. 50%, p=0.024). The dysmorphic group contained significantly more immature oocytes and exhibited significantly lower oocyte maturity (50% vs. 66.7%, p=0.001) than the non-dysmorphic cycles. Within the dysmorphic group, significantly lower oocyte maturity was found in the cycles using a dual-trigger, but not in those with a human chorionic gonadotropin trigger. Conclusion: ICSI cycles with dysmorphic oocytes are closely associated with reduced oocyte maturity. This association was observed exclusively in dual-trigger cycles. [ABSTRACT FROM AUTHOR]

Background: In the porcine industry, Escherichia coli (E. coli) infections have been causing post-weaning diarrhea (PWD) and edema disease (ED) for many years. It is classified into pathotypes and serotypes in animals according to virulence factors. Serotyping is performed for O, K, H, and F antigens, essential for discriminating pathogenicity and epidemiology. Furthermore, E. coli strains that produce F18 fimbriae are major sources of ED and PWD associated with Shiga-toxin producing E. coli (STEC) expressing F18ab and enterotoxigenic E. coli (ETEC) expressing F18ac, respectively. Aim: To investigate the pathogenicity potential and infection characteristics of experimental infection and confirm the pathological features of the Korean STEC/ETEC strains F18ab and F18ac in piglets. Methods: Three-week-old pigs were randomized into three experimental groups: infected G1 (F18ab), infected G2 (F18ac), and G3 (control). General health status was monitored daily, and pathological changes were evaluated. Results: Diarrhea occurred in all infected piglets. Pathological changes were only observed in the small intestine and regional lymph nodes. In G1, mucosal necrosis, inflammatory cell infiltration with hemorrhagic lesions, and apoptotic cell death in the tunica media of arterioles in the small intestine were observed. In contrast, the mucosa and epithelium appeared almost intact, with no abnormal vessel lesions in G2. Conclusion: Both strains, isolated from pigs in Korea, could be infected and did not spread from the alimentary tract to other organs. The pathological features were quite different among the F18 subtypes. The F18ab strain was more virulent than F18ac, and the virulence characteristics of the F18ac strain were more similar to ETEC than STEC. [ABSTRACT FROM AUTHOR]