Impact of the Omicron Strain on Febrile Convulsions Requiring Hospitalization in Children: A Single-Center Observational Study.

BACKGROUND: The emergence of the Omicron strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of December 2021 has drastically increased the number of infected children in Japan, along with the number of children with febrile convulsions, but its clinical impact is unclear. MATERIALS AND METHODS: We compared the frequency of SARS-CoV-2 infection in children hospitalized with febrile convulsions with the frequency of SARS-CoV-2 infection in children with fever and respiratory symptoms without convulsions. RESULTS: In 2021 and 2022, 49 and 58 children required emergency hospitalization for febrile convulsions (FC group) with status epilepticus or cluster spasms, in which 24 and 38 children underwent a Filmarray® respiratory panel test (FA test), respectively, and others received a quantitative antigen test for SARS-CoV-2. In 2022, only six patients tested positive for SARS-CoV-2 (10.3%, 6/58). As a reference group, 655 children aged <10 years who underwent the FA test for fever and respiratory symptoms during the same period were investigated, and 4 (1.8%, 4/223) and 42 (9.7%, 42/432) tested positive for SARS-CoV-2 in 2021 and 2022, respectively. Rhinovirus/enterovirus (RV/EV) was the most frequently detected virus (40.3%, 264/655), followed by respiratory syncytial virus (RSV) (18.9%, 124/655) and parainfluenza virus 3 (PIV3) (7.8%, 51/655). There was no significant difference in the trend of detected viruses between the two groups. CONCLUSIONS: The frequency and severity of febrile convulsions requiring hospitalization associated with SARS-CoV-2 infection of the Omicron strain may be similar to that of other respiratory viruses in children.

Membranous nephropathy in a female patient with X-linked thrombocytopenia.

BACKGROUND: Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia and eczema and is caused by a mutation in the WAS gene. WAS has heterogeneous clinical manifestations, and its clinically milder form is called X-linked thrombocytopenia (XLT). Patients with WAS/XLT sometimes have kidney complications, the most common of which is immunoglobulin (Ig)A nephropathy associated with aberrant glycosylation of IgA. CASE DIAGNOSIS/TREATMENT: The patient was a 6-year-old girl who was diagnosed with female XLT at the age of 4 years; she presented with microscopic hematuria and proteinuria at a school urinalysis. Her father had thrombocytopenia and IgA nephropathy while in his 20 s. The patient and her father had the same WAS gene mutations. A kidney biopsy was performed, and no abnormal findings were observed by light microscopy. Immunofluorescence analysis revealed a granular pattern of IgG staining along the capillary wall. Electron microscopy revealed small electron-dense deposits in subepithelial lesions. Consequently, we diagnosed her with membranous nephropathy (MN). Tissue PLA2R and THSD7A were negative, and she was judged unlikely to have secondary MN on the basis of blood test findings and IgG staining. We started the administration of angiotensin-converting enzyme inhibitors, and her proteinuria gradually decreased. CONCLUSION: To our knowledge, this is the first report of MN in a female WAS/XLT patient. WAS protein expression defects affect all immune system cells; however, the mechanisms underlying the occurrence of autoimmunity are not completely understood. In WAS/XLT patients, MN may develop as a result of increased autoantibody production, similar to other types of immunodeficiency.

CXCL12 promotes CCR7 ligand-mediated breast cancer cell invasion and migration toward lymphatic vessels.

Chemokines are a family of cytokines that mediate leukocyte trafficking and are involved in tumor cell migration, growth, and progression. Although there is emerging evidence that multiple chemokines are expressed in tumor tissues and that each chemokine induces receptor-mediated signaling, their collaboration to regulate tumor invasion and lymph node metastasis has not been fully elucidated. In this study, we examined the effect of CXCL12 on the CCR7-dependent signaling in MDA-MB-231 human breast cancer cells to determine the role of CXCL12 and CCR7 ligand chemokines in breast cancer metastasis to lymph nodes. CXCL12 enhanced the CCR7-dependent in vitro chemotaxis and cell invasion into collagen gels at suboptimal concentrations of CCL21. CXCL12 promoted CCR7 homodimer formation, ligand binding, CCR7 accumulation into membrane ruffles, and cell response at lower concentrations of CCL19. Immunohistochemistry of MDA-MB-231-derived xenograft tumors revealed that CXCL12 is primarily located in the pericellular matrix surrounding tumor cells, whereas the CCR7 ligand, CCL21, mainly associates with LYVE-1+ intratumoral and peritumoral lymphatic vessels. In the three-dimensional tumor invasion model with lymph networks, CXCL12 stimulation facilitates breast cancer cell migration to CCL21-reconstituted lymphatic networks. These results indicate that CXCL12/CXCR4 signaling promotes breast cancer cell migration and invasion toward CCR7 ligand-expressing intratumoral lymphatic vessels and supports CCR7 signaling associated with lymph node metastasis.

An adolescent girl diagnosed with IgA nephropathy following the first dose of the COVID-19 vaccine.

There has been growing interest in reported cases of IgA nephropathy (IgAN) flare-up following administration of the coronavirus disease 2019 (COVID-19) vaccine. Our patient is a previously healthy 17-year-old girl who presented with a 10-year history of microscopic hematuria. Because there were no abnormal findings in blood examination or ultrasonography, we followed her up twice per year as asymptomatic hematuria. Although she never developed gross hematuria when she had upper respiratory infections or received an influenza vaccine, she presented with gross hematuria and proteinuria within a few days after receiving the first dose of the Pfizer vaccine. We performed renal biopsy 2 weeks after the first vaccination. It revealed minor glomerular abnormalities with diffuse mesangial IgA deposits, and we diagnosed her with mild IgAN. Gross hematuria was detected after both the first and second doses, although it changed to microscopic hematuria within 1 week. Additionally, her proteinuria resolved spontaneously approximately 10 days after the second dose of the vaccine. Therefore, we opted to observe her without administering medication. The causation between COVID-19 vaccination and IgAN flare-up remains unclear. Several reports showed IgAN patients presenting gross hematuria following the second dose of the Pfizer or Moderna vaccines. However, our patient developed gross hematuria and proteinuria even after the first dose and without known severe acute respiratory syndrome coronavirus 2 exposure. Nephrologists should inform both patients with IgAN and those with asymptomatic hematuria that this side effect can occur even after the first vaccination.

Obesity and febrile urinary tract infection in young children.

BACKGROUND: Obesity is a risk factor for infectious diseases. However, the relationship between obesity and febrile urinary tract infection (fUTI) is controversial. This study aimed to determine the relationship between obesity and fUTI in young children. METHODS: We analyzed the medical records of children aged <2 years who were admitted to our hospital because of fever between April 2013 to March 2018. The children were categorized into three groups of non-obese, overweight, and obese according to the World Health Organization weight-for-length curves for children aged <2 years. RESULTS: A total of 600 patients were enrolled in this study, of whom 118 were diagnosed with first fUTI. Patients in the fUTI group were younger than those in the control group (patients who were diagnosed with other febrile diseases) (5 ± 5.11 vs 11 ± 6.53 months; P < 0.001). There were no significant differences in the populations of overweight and obese children between the fUTI and control groups. In the fUTI group, the duration of fever, types of pathogen, recurrent rate, the grades of vesicoureteral reflux, and renal scarring were not associated with obesity. The white blood cell count and C-reactive protein levels were not significantly different among the three weight-for-length categories. The same results were obtained when the fUTI group was compared with an age-matched control group (n = 192, 4 ± 2.55 months old; P = 0.261). CONCLUSIONS: Obesity is not a significant risk factor for fUTI in febrile hospitalized young children. Our study suggests that conducting urinalysis for febrile young children without obvious sources, irrespective of obesity, should be considered.

Comparative Impact of Isolated Ultrafiltration and Hemodialysis on Fluid Distribution: A Bioimpedance Study.

INTRODUCTION: Isolated ultrafiltration (IUF) is an alternative treatment for diuretic-resistant patients with fluid retention. Although hemodialysis (HD) predominantly decreases extracellular water (ECW), the impact of IUF on fluid distribution compared with HD remains unclear. METHODS: We compared the effect of HD (n = 22) and IUF (n = 10) sessions on the body fluid status using a bioimpedance analysis device (InBody S10). RESULTS: The total ultrafiltration volume was similar between HD and IUF (HD 2.5 ± 0.3 vs. ICF 2.1 ± 0.3 L/session, p = 0.196). The reduction rate of ECW was significantly higher than that of intracellular water (ICW) after HD (ECW -7.9% ± 0.8% vs. ICW -3.0% ± 0.9%, p < 0.001) and IUF (ECW -5.8% ± 0.9% vs. ICW -3.6% ± 0.8%, p = 0.048). However, the change in the ratio of ECW to total body water in HD was significantly larger than that in IUF (HD -3.2% ± 0.3% vs. ICF -1.1% ± 0.4%, p < 0.001). The reduction rates in serum tonicity (effective osmolality) were higher after HD than after IUF (HD -1.8% ± 0.5% vs. IUF -0.6% ± 0.2%, p = 0.052). Among the components of effective osmolality, the reduction rates of serum K+ and glucose levels after HD were significantly higher than those after IUF (serum K+: HD -30.5% ± 1.6% vs. IUF -0.5% ± 3.8%, p < 0.001; serum glucose: HD -15.4% ± 5.0% vs. IUF 0.7% ± 4.8%, p = 0.026), while the serum Na+ level was slightly and similarly reduced (HD -0.8% ± 0.4% vs. IUF -0.8% ± 0.4%, p = 0.500). The reduction in the osmolal gap value (measured osmolality-calculated osmolarity) was significantly greater after HD sessions than after IUF sessions (HD -12.4 ± 1.4 vs. IUF 2.0 ± 1.0 mOsm/kg, p = 0.001). CONCLUSION: The extracellular fluid reduction effect of HD is stronger than that of IUF. The different changes in effective osmolality and osmolal gap after HD and IUF sessions may be related to the different effects of HD and IUF on fluid distribution.

Exploring factors that motivate nursing students to engage in skills practice in a laboratory setting: A descriptive qualitative design.

OBJECTIVES: The aim of this study was to explore factors that motivate students to engage in skills practice in a laboratory setting, and to identify their motivation types and the regulatory styles. METHODS: Semi-structured interviews were conducted with 23 nursing students from three universities between November 2017 and January 2018. A thematic analysis was used to identify factors associated with students' motivation to engage in skills practice in a laboratory. The types and the regulatory styles of student motivation were identified based on the self-determination theory. RESULTS: Seven motivating factors were identified. These factors included the students' desire "to acquire the skills necessary to work as a nurse", the "desire to improve skills in preparation for clinical practicum", and their felt "obligations to patients as a nurse". Moreover, "the impetus to study arising from the objective evaluation of oneself and others" and "wanting to pass the skills examination" motivated the students to engage in skills practice. A "learning environment that facilitates students' learning" and the "supportive involvement of educators" facilitated their learning. Based on the self-determination theory, the students were found to embrace extrinsic motivation with four regulatory styles of motivation, namely integrated, identified, introjected, and external regulation. CONCLUSIONS: Nurse educators should understand the motivating factors of students, and help students embrace a more internally controlled motivation by helping them envision their future careers as nurses, and by fostering their ethical duty to care for patients.

Association between Immunoglobulin M and Steroid Resistance in Children with Nephrotic Syndrome: A Retrospective Multicenter Study in Japan.

Background: The prognosis of steroid-resistant nephrotic syndrome (SRNS) in children is poorer than steroid-sensitive cases. Diagnosis of SRNS is made after observing the response to the initial 4-week corticosteroid therapy, which might be accompanied by side effects. However, predictive indicators at initial diagnosis remain unknown. We aimed to investigate whether selectivity index (SI) and other indicators at initial diagnosis-for example, serum IgM and total serum protein-albumin ratio (TA ratio, total serum protein level over albumin level)-can predict SRNS. Methods: A total of 80 children were enrolled from seven hospitals in Japan between January 2008 and December 2019 (mean age, 4.7 years; 65% male). Of the children enrolled, 13 (16%, M/F=5:8) had been diagnosed as steroid resistant after initial treatment with steroids. The association between serum IgM (tertile categories: low, 24-133; middle, 134-169; and high, 169.1-510 mg/dl), SI (<0.2 or ≥0.2), and TA ratio (tertile categories: low, 1.8-2.6; middle, 2.62-3.75; and high, 3.8-15.3) at initial diagnosis and steroid resistance was evaluated with logistic regression, adjusting for age and sex. Results: Low levels of serum IgM were significantly associated with steroid resistance (adjusted odds ratio, 6.94; 95% CI, 1.12 to 43.11). TA ratio and SI were not significantly associated with steroid resistance. Conclusions: Low levels of serum IgM at initial diagnosis might predict steroid resistance among Japanese children with idiopathic nephrotic syndrome.

A Multichannel Pattern-Recognition-Based Protein Sensor with a Fluorophore-Conjugated Single-Stranded DNA Set.

Recently, pattern-recognition-based protein sensing has received considerable attention because it offers unique opportunities that complement more conventional antibody-based detection methods. Here, we report a multichannel pattern-recognition-based sensor using a set of fluorophore-conjugated single-stranded DNAs (ssDNAs), which can detect various proteins. Three different fluorophore-conjugated ssDNAs were placed into a single microplate well together with a target protein, and the generated optical response pattern that corresponds to each environment-sensitive fluorophore was read via multiple detection channels. Multivariate analysis of the resulting optical response patterns allowed an accurate detection of eight different proteases, indicating that fluorescence signal acquisition from a single compartment containing a mixture of ssDNAs is an effective strategy for the characterization of the target proteins. Additionally, the sensor could identify proteins, which are potential targets for disease diagnosis, in a protease and inhibitor mixture of different composition ratios. As our sensor benefits from simple construction and measurement procedures, and uses accessible materials, it offers a rapid and simple platform for the detection of proteins.

The extracellular volume status predicts body fluid response to SGLT2 inhibitor dapagliflozin in diabetic kidney disease.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an antihyperglycemic drug with diuretic action. We recently reported that the SGLT2 inhibitor dapagliflozin ameliorates extracellular volume expansion with a mild increase in urine volume. However, the impact of the pretreatment extracellular volume status on the body fluid response to SGLT2 inhibitors remains unclear. METHODS: Thirty-six diabetic kidney disease (DKD) patients were treated with dapagliflozin. The body fluid volume, including intracellular water (ICW), extracellular water (ECW) and total body water (TBW), were measured on baseline and day 7 using a bioimpedance analysis (BIA) device. The ECW/TBW and ECW were used as markers of the extracellular volume status. For a comparison, the extracellular volume status responses to loop diuretic furosemide (n = 16) and vasopressin V2 receptor antagonist tolvaptan (n = 13) were analyzed. RESULTS: The body weight, brain natriuretic peptide and body fluid parameters measured by a BIA (ICW, ECW, TBW, and ECW/TBW) were significantly decreased for 1 week after dapagliflozin administration. The change in the ECW/TBW in the high-ECW/TBW group (over the median value of 0.413) was significantly higher than in the low-ECW/TBW group (- 2.1 ± 0.4 vs. - 0.5 ± 0.4%, p = 0.006). Only with dapagliflozin treatment (not furosemide or tolvaptan treatment) was the baseline ECW/TBW significantly correlated with the changes in the ECW/TBW (r = - 0.590, p < 0.001) and ECW (r = - 0.374, p = 0.025). CONCLUSIONS: The pretreatment extracellular volume status predicts the body fluid response to the SGLT2 inhibitor dapagliflozin in DKD patients. The diminished extracellular fluid reduction effect of dapagliflozin in patients without severe extracellular fluid retention may contribute to maintaining a suitable body fluid status.

Spin glass transition of single-crystalline TmFe2O4- δ.

TmFe2O4 is one kind of multiferroic material in which equivalent amounts of Fe2+ and Fe3+ occupy a two-dimensional triangular lattice, leading to charge and spin frustrations. The spin frustration is expected to be increased as the fraction of Fe2+ (Fe3+) becomes larger than that of Fe3+ (Fe2+). We have grown single-crystalline TmFe2O4-δ with oxygen vacancies by using floating zone melting method and examined its magnetic properties. On cooling the compound, a long-range magnetic ordering develops around ∼240 K. With further cooling, a maximum of zero-field-cooled (ZFC) magnetization is observed at 186.2 K. The ac magnetic susceptibility obtained by ZFC process also manifests a maximum in its temperature dependence, and the variation of spin-freezing temperature with frequency of ac magnetic field is explainable in terms of the dynamic scaling law with the critical component of 8.68(8). This value suggests that the spin glass transition occurs at 186.2 K. The effect of external dc magnetic field on the irreversible transition temperature is coincident with the de Almeida-Thouless (AT) line. Aging-memory and rejuvenation effect is also observed below the spin-freezing temperature. These facts support the idea that TmFe2O4-δ undergoes spin glass transition below the ferrimagnetic transition temperature. In other words, TmFe2O4-δ can be regarded as a reentrance spin glass. It is thought that the oxygen vacancies bring about unequal number of Fe2+ and Fe3+ ions and thereby strengthen the magnetic frustration among the iron ions coupled with antiferromagnetic interactions, leading to the spin glass behavior.

An eight-year-old girl with autoimmune polyglandular syndrome type3A that developed during the course of primary Epstein-Barr virus (EBV) infection: clinical implication of EBV in autoimmune thyroid disease.

An eight-year-old girl was admitted for prolonged fever and general fatigue. Bilateral reddened and swollen tonsils covered with white fur and increased numbers of atypical lymphocytes in blood led to a diagnosis of infectious mononucleosis (IM) due to primary Epstein-Barr virus (EBV) infection, which was confirmed by a positive anti-EBV viral capsid antigen IgM antibody reaction. She had a swollen thyroid gland and glycosuria at admission, which persisted after IM resolved. Undetectable thyroid-stimulating hormone (TSH), increased thyroid hormone and elevated HbA1c levels led to a diagnosis of autoimmune polyglandular syndrome type3A, based on the presence of antibodies for TSH receptor and glutamic acid decarboxylase. The clinical significance of EBV infection in the development of autoimmune endocrine disorders has been discussed.

Students' perceptions of teaching factors that demotivate their learning in lectures and laboratory-based skills practice.

OBJECTIVES: The objective of this paper is to report students' perceptions of factors that demotivated their learning in lectures and laboratory-based skills practice settings. METHODS: A total of 23 students were recruited from the Bachelor of Nursing courses at three Japanese universities, using purposive sampling. A semi-structured interview was conducted with each participant between November 2017 and January 2018 to elicit their perceptions about which aspects of the teaching context demotivated their engagement in learning. The results were analyzed using thematic analysis. RESULTS: Three themes were generated: a restrictive environment, discouraging attitudes and discouraging teaching approaches. CONCLUSIONS: To prevent students from experiencing demotivation, teachers in the nursing faculty need to manage learning resources more effectively, create a quiet and focused atmosphere to allow students to concentrate, and be enthusiastic about teaching. They also need to add value to their classes, help students to follow lectures, and ensure that the workload they give their students is appropriate.

Effect of nonthermal atmospheric discharge on stain removal of tooth.

The purpose of this study was to evaluate the effect of the repeated nonthermal atmospheric discharge (NADC) exposure without peroxide or water on bleaching effect of cycling stained tooth and to evaluate surface roughness and microhardness of the enamel surface exposed by NADC. Specimens with 5×5mm were prepared from extracted bovine teeth. Staining with tea and exposure by NADC were repeated for five times and color was measured at each step. Other specimens were prepared and surface roughness (Ra) and microhardness (Vickers hardness) were measured after exposure by NADC. The repeated NADC exposure without peroxide or water showed bleaching effect for stained bovine teeth. The surface roughness was not changed by NADC exposure. The less microhadness was shown by NADC exposere.

Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on fluid distribution: A comparison study with furosemide and tolvaptan.

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an antihyperglycemic drug with diuretic properties. We recently reported that an SGLT2 inhibitor ameliorated extracellular fluid expansion with a transient increase in urinary Na+ excretion. However, the effects of SGLT2 inhibitors on fluid distribution in comparison to conventional diuretics remain unclear. METHODS: Forty chronic kidney disease patients with fluid retention (average estimated glomerular filtration rate 29.2 ± 3.2 mL/min per 1.73 m2 ) were divided into the SGLT2 inhibitor dapagliflozin (DAPA), loop diuretic furosemide (FR) and vasopressin V2 receptor antagonist tolvaptan (TLV). The body fluid volume was measured on days 0 and 7 using a bioimpedance analysis device. RESULTS: In all three groups, body weight was significantly and similarly decreased, and urine volume numerically increased for 7 days. Bioimpedance analysis showed that the changes in intracellular water were similar, but that there were significant changes in the extracellular water (ECW) (DAPA -8.4 ± 1.7, FR -12.5 ± 1.3, TLV -7.4 ± 1.5%, P = 0.048). As a result, the change in the ratio of ECW to total body water in the DAPA group was significantly smaller than that in the FR group, but numerically larger than that in the TLV group (DAPA -1.5 ± 0.5, FR -3.6 ± 0.5, TLV -0.5 ± 0.4%, P < 0.001). CONCLUSION: Sodium-glucose cotransporter 2 inhibitor DAPA predominantly decreased the ECW with a mild increase in urine volume, but the change in the ECW/total body water was smaller than that in patients treated with FR, and larger than that in patients treated with TLV, suggesting that the effects of SGLT2 inhibitors on fluid distribution may differ from those of conventional diuretics.

Hemolytic Uremic Syndrome: An Increasingly Recognized Public Health Problem.

A 28-year-old man was referred and admitted to our hospital due to Escherichia coli O157-mediated hemorrhagic colitis with severe thrombocytopenia. A systemic workup concluded that the patient had acute pancreatitis as well as hemolytic uremic syndrome. The patient was ultimately discharged, with his platelet count having recovered. Our case serves an illustrative example of potentially serious complications of an increasingly recognized public health problem. Systemic studies on this topic are insufficient, and we strongly recommend the further accumulation of more experiences like ours. Several diagnostic and management concerns that emerged in this case are also discussed.

Valacyclovir Neurotoxicity and Nephrotoxicity in an Elderly Patient Complicated by Hyponatremia.

A 66-year-old women with no history of renal disease was admitted due to a coma and acute kidney injury with a serum creatinine level of 7.44 mg/dL which were ascribed to valacyclovir neurotoxicity and nephrotoxicity, respectively. She had received valacyclovir at a standard dosage for the treatment of herpes zoster and was finally discharged, having fully returned to her normal baseline mental status with a recovered serum creatinine level of 0.68 mg/dL. We feel that awareness of this pathology remains a challenge for physicians and therefore strongly recommend the further accumulation of experiences similar to our own. Our experience underscores the pitfalls of administering valacyclovir to elderly patients who barely appear to have a favorable renal function. Several concerns regarding the therapeutic management, including blood purification strategies, that emerged in this case are also discussed.