Pediatric blood pressure category predicts longitudinal blood pressure change in adolescence and early adulthood.

BACKGROUND: Patterns of blood pressure (BP) change from early adolescence to young adulthood have not been well-described. The objective of this study was to examine the predictive value of pediatric BP classification on BP change and identify subpopulations with large BP increases during adolescence and early adulthood. METHODS: Baseline data were obtained from medical checkups of Japanese adolescents aged 12-13 years in 2009 or 2010 and subsequent BP values were followed for a 9-year period. Mixed-effects models were used to estimate the effects of baseline factors on subsequent BP changes. RESULTS: Hypertensive and elevated BP group consistently had higher BP values than normal BP group throughout the observation period. Multivariate mixed-effects model analyses revealed group-by-time interactions between systolic BP change and BP category in males and uric acid category in females, and between diastolic BP change and white blood cell count in males and obesity and high-density lipoprotein cholesterol in females; however, these factors had limited effects on the rate of BP increase, indicating that they are not suitable as clinical predictors of BP increase. CONCLUSIONS: Pediatric BP category predicted BP values, but there was no factor that identified subpopulations with large BP increases in adolescence and early adulthood. IMPACT: Blood pressure category in the American Academy of Pediatrics clinical practice guideline at age 12-13 years predicted subsequent blood pressure values during adolescence and early adulthood. No baseline factor that identified a subpopulation with large increase in blood pressure during adolescence and early adulthood in clinical practice was found. Our study contributes to the existing literature by demonstrating the usefulness of the American Academy of Pediatrics clinical practice guideline for blood pressure classification in a Japanese population.

Low birth weight is associated with decline in renal function in Japanese male and female adolescents.

BACKGROUND: Low birth weight (LBW) is a risk factor for chronic kidney disease (CKD) in later life and is becoming increasingly common in developed countries, including Japan. Furthermore, a serial decrease in birth weight has been associated with an increasing prevalence of CKD stage 2 in male Japanese adolescents. Sex-specific differences affect CKD susceptibility, and the association between birth weight and CKD in women, has not been elucidated. In this study, we investigated the sex-specific effect of LBW on renal function. METHODS: Annual cross-sectional data of 2417 Japanese adolescents (males 1736; females 681), aged 15-16 years, were evaluated over 8 years (2007-2014). RESULTS: Over the study period, mean birth weights decreased significantly in males (p < 0.01) and females (p < 0.05). Furthermore, both sexes showed significant decrease in estimated glomerular filtration rates corresponding to the birth weight reduction. The prevalence of CKD stage 2 also increased in males (from 26.0 to 32.4%, p < 0.01) and females (from 6.3 to 18.5%, p < 0.05). The incidence of CKD stage 2 was significantly related to history of LBW (males: odds ratio 1.73; 95% confidence interval 1.06-2.80; p < 0.05; females: odds ratio 3.29; 95% confidence interval 1.25-8.02; p < 0.05). CONCLUSIONS: Our data revealed that renal function and birth weight have decreased over time, in healthy Japanese adolescents. In view of the recent declining trend demonstrated by birth weight in Japan, we speculate that the prevalence of CKD might increase in the future.

Temporal trends in renal function and birthweight in Japanese adolescent males (1998-2015).

Background: Low birthweight (LBW) is a worldwide public health problem, demonstrating an increasing incidence in developed countries, including Japan. LBW is also a risk factor for later development of chronic kidney disease (CKD). To date, studies have not evaluated the population impacts of increasing LBW rates on renal function. Methods: Estimated glomerular filtration rate (eGFR) was evaluated in 3737 Japanese adolescent males (15-16 years old) using annual cross-sectional data over an 18-year period (1998-2015). Results: Between the initial (1998-2003) and final (2010-15) periods of the study, the mean birthweight decreased from 3213.4 ± 383.8 to 3116.2 ± 382.3 g and the LBW rate increased from 2.5 to 5.5% (both P ≤ 0.01). Additionally, the mean eGFR decreased from 105.1 ± 15.9 to 97.4 ± 13.8 mL/min/1.73 m2 and the prevalence of mildly reduced renal function (eGFR ≤ 60- <90 mL/min/1.73 m2) increased from 16.4 to 30.0% (both P ≤ 0.01), most evident in the LBW group (from 10.3 to 41.7%, P ≤0.01). The prevalence of proteinuria also increased significantly. Mildly reduced renal function was significantly associated with LBW [odds ratio (LBW 3000-3999 g) 1.51; 95% confidence interval 1.00-2.55; P = 0.047]. Conclusions: In this population of Japanese adolescents, the frequency of mildly reduced renal function increased as the LBW frequency increased. Our findings may have implications for the broader Japanese population as well as for other populations in which the prevalence of LBW is increasing.

High Glucose Stimulates Mineralocorticoid Receptor Transcriptional Activity Through the Protein Kinase C ß Signaling.

Activation of mineralocorticoid receptor (MR) is shown in resistant hypertension including diabetes mellitus. Although protein kinase C (PKC) signaling is involved in the pathogenesis of diabetic complications, an association between PKC and MR is not known. Activation of PKCα and PKCß by TPA (12-O-Tetradecanoylphorbol 13-acetate) increased MR proteins and its transcriptional activities in HEK293-MR cells. In contrast, a high glucose condition resulted in PKCß but not PKCα activation, which is associated with elevation of MR protein levels and MR transcriptional activities. Reduction of endogenous PKCß by siRNA decreased those levels. Interestingly, high glucose did not affect MR mRNA levels, but rather decreased ubiquitination of MR proteins. In db/db mice kidneys, levels of phosphorylated PKCß2, MR and Sgk-1 proteins were elevated, and the administration of PKC inhibitor reversed these changes compared to db/+ mice. These data suggest that high glucose stimulates PKCß signaling, which leads to MR stabilization and its transcriptional activities.

[Cardiovascular and cerebrovascular disease].

Circadian blood pressure (BP) patterns are regulated mainly by autonomic nerve system. Ambulatory blood pressure monitoring (ABPM) reveals that BP has circadian pattern over a 24 h period. The decline in nocturnal BP by 10-20% is considered to be normal (a dipper pattern). Non-dipper, riser, and extreme-dipper circadian patterns are considered to be abnormal because of their association with poor prognosis and end organ damage such as heart failure and cerebral vascular disease (CVD). On the other hand, end organ damage alters circadian BP patterns especially at night and people with CVD or heart failure have a high prevalence of abnormal circadian BP patterns.

Secular trends and age-specific distribution of blood pressure in Japanese adolescents aged 12-18 years in 2000-2019.

Adolescent blood pressure is a predictor of future risk for hypertension and cardiovascular diseases, and therefore its status needs to be accurately determined. However, limited evidence is available regarding the secular trends and distribution of adolescent blood pressure. In the present study, we assessed the secular trends and age-specific distributions of blood pressure in Japanese adolescents aged 12-18 years by using data drawn from 20 years of annual health checkups conducted between 2000 and 2019. Participants underwent health checkups every year for three years at the same school and the data were divided into four 5-year cycles: 2000-2004, 2005-2009, 2010-2014, and 2015-2019. From a total of 124,460 records (33,496 individuals) retrieved, 3000 records (3000 individuals) from each year-cycle were randomly selected to avoid duplicating data from the same individuals. In the study period, in males systolic blood pressure showed a decreasing trend over time, whereas in females diastolic blood pressure showed an increasing trend. Subgroup analyses by school category (junior/senior high school) and by obesity category showed similar blood pressure trends as in the overall analysis. Age-specific blood pressure values in Japanese adolescents increased with age in males but not in females. Thus, different patterns of change in blood pressure values over the past 20 years were observed between males and females. Age-specific blood pressure distributions are also presented. Together, these findings will be useful for understanding blood pressure trends among adolescents.

Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification.

This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. Liquid chromatography-tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295-307. Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus.

Melanogenesis-inhibitory and cytotoxic activities of diarylheptanoids from Acer nikoense bark and their derivatives.

Nine cyclic diarylheptanoids, 1-9, including two new compounds, i.e., 9-oxoacerogenin A (8) and 9-O-ß-D-glucopyranosylacerogenin K (9), along with three acyclic diarylheptanoids, 10-12, and four phenolic compounds, 13-16, were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K (17) and D-glucose. Two of the cyclic diarylheptanoids, acerogenin A (1) and (R)-acerogenin B (5), were converted to their ether and ester derivatives, 18-24 and 27-33, respectively, and to the dehydrated derivatives, 25, 26, 34, and 35. Upon evaluation of compounds 1-16 and 18-35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α-melanocyte-stimulating hormone (α-MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2-4, 6, 9, and 12, and two phenolic glycosides, 15 and 16, exhibited inhibitory activities with 24-61% reduction of melanin content at 100 µM concentration with no or almost no toxicity to the cells (88-106% of cell viability at 100 µM). In addition, when compounds 1-16 and 18-35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11, ten ether and ester derivatives, 18-22 and 27-31, and two dehydrated derivatives, 34 and 35, exhibited potent cytotoxicities against HL60 human leukemia cell line (IC(50) 8.1-19.3 µM), and five compounds, 10, 11, 20, 29, and 30, against CRL1579 human melanoma cell line (IC(50) 10.1-18.4 µM).

Remission of Angiographically Confirmed Minocycline-induced Renal Polyarteritis Nodosa: A Case Report and Literature Review.

A 23-year-old man presented with severe hypertension. Based on his history of minocycline treatment for over three years and clinical symptoms, such as myalgias and renovascular hypertension with multiple intrarenal aneurysms, he was diagnosed with minocycline-induced renal polyarteritis nodosa (PAN). After minocycline treatment cessation and management of the hypertension, his blood pressure, renin-aldosterone levels, and urinary protein levels gradually improved. Seven and a half years later, repeated angiography found that the aneurysms had resolved. This is the first report in English describing a case of minocycline-induced renal PAN that was reversed functionally and morphologically without steroids or immunosuppressive drugs.

Lysine-specific demethylase 1 as a corepressor of mineralocorticoid receptor.

Mineralocorticoid receptor (MR) and its ligand aldosterone play a central role in controlling blood pressure by promoting sodium reabsorption in the kidney. Coregulators are recruited to regulate the activation of steroid hormone receptors. In our previous study, we identified several new candidates for MR coregulators through liquid chromatography-tandem mass spectrometry analysis using a biochemical approach. Lysine-specific demethylase 1 (LSD1) was identified as a candidate. The relationship between LSD1 and salt-sensitive hypertension has been reported; however, the role of MR in this condition is largely unknown. Here, we investigated the functions of LSD1 as a coregulator of MR. First, a coimmunoprecipitation assay using HEK293F cells showed specific interactions between MR and LSD1. A chromatin immunoprecipitation study demonstrated LSD1 recruitment to the gene promoter of epithelial Na+ channel (ENaC), a target gene of MR. Reduced LSD1 expression by treatment with shRNA potentiated the hormonal activation of ENaC and serum/glucocorticoid-regulated kinase 1, another target gene of MR, indicating that LSD1 is a corepressor of MR. In an animal study, mice with kidney-specific LSD1 knockout (LSD1flox/floxKSP-Cre mice) developed hypertension after a high-salt diet without elevation of aldosterone levels, which was counteracted by cotreatment with spironolactone, an MR antagonist. In conclusion, our in vitro and in vivo studies demonstrated that LSD1 is a newly identified corepressor of MR.

NF-YC functions as a corepressor of agonist-bound mineralocorticoid receptor.

The role of aldosterone has been implicated in the metabolic syndrome and cardiovascular diseases. The biological actions of aldosterone are mediated through mineralocorticoid receptor (MR). Nuclear receptor-mediated gene expression is regulated by dynamic and coordinated recruitment of coactivators and corepressors. To identify new coregulators of the MR, full-length MR was used as bait in yeast two-hybrid screening. We isolated NF-YC, one of the subunits of heterotrimeric transcription factor NF-Y. Specific interaction between MR and NF-YC was confirmed by yeast two-hybrid, mammalian two-hybrid, coimmunoprecipitation assays, and fluorescence subcellular imaging. Transient transfection experiments in COS-7 cells demonstrated that NF-YC repressed MR transactivation in a hormone-sensitive manner. Moreover, reduction of NF-YC protein levels by small interfering RNA potentiated hormonal activation of endogenous target genes in stably MR-expressing cells, indicating that NF-YC functions as an agonist-dependent MR corepressor. The corepressor function of NF-YC is selective for MR, because overexpression of NF-YC did not affect transcriptional activity mediated by androgen, progesterone, or glucocorticoid receptors. Chromatin immunoprecipitation experiments showed that endogenous MR and steroid receptor coactivator-1 were recruited to an endogenous ENaC gene promoter in a largely aldosterone-dependent manner, and endogenous NF-YC was sequentially recruited to the same element. Immunohistochemistry showed that endogenous MR and NF-YC were colocalized within the mouse kidney. Although aldosterone induces interaction of the N and C termini of MR, NF-YC inhibited the N/C interaction. These findings indicate that NF-YC functions as a new corepressor of agonist-bound MR via alteration of aldosterone-induced MR conformation.

CASZ1b is a novel transcriptional corepressor of mineralocorticoid receptor.

Aldosterone is a biological ligand for mineralocorticoid receptor (MR) that elevates blood pressure by promoting sodium reabsorption in the kidneys. However, the molecular mechanisms of aldosterone-MR-mediated transcription and the role of this transcription in hypertension remain largely unknown. In this study, we aimed to identify novel MR coregulators and elucidate one of the molecular mechanisms of hypertension. We purified MR-interacting factors from HEK293F cells stably expressing FLAG-MR through a biochemical approach and identified the zinc finger protein castor homolog 1 isoform b (CASZ1b) as a candidate novel MR coregulator via liquid chromatography-tandem mass spectrometry analysis. The CASZ1 gene has been implicated in hypertension in genome-wide single-nucleotide polymorphism studies, but its role in the development of hypertension remains unclear. We found that CASZ1b colocalized with MR in the kidneys and interacted with MR in an aldosterone-dependent manner. In luciferase assays using HEK293F cells, overexpression of CASZ1b reduced aldosterone-dependent MR transcriptional activity by ~50%. In contrast, knockdown of CASZ1b via RNA interference increased the expression levels of the aldosterone-induced MR target genes epithelial Na+ channel-α (ENaCα) and serum/glucocorticoid regulated kinase 1 (SGK1) by approximately twofold and 2.3-fold, respectively. Upon aldosterone-MR binding, CASZ1b interacted with MR and formed a protein complex with nucleosome remodeling deacetylase (Mi-2/NuRD), a corepressor complex with chromatin remodeling and histone deacetylation activity, which suppressed ENaCα and SGK1. These findings reveal a critical role of CASZ1b in regulating MR-mediated transcriptional activity and provide new insights into the pathophysiology of hypertension.

Association of childhood anthropometric measurements and laboratory parameters with high blood pressure in young adults.

Early intervention to manage high blood pressure (BP) in young adulthood is a promising approach for the prevention of future cardiovascular diseases. We aimed to examine the ability of childhood health information to predict the incidence of young adults with high BP. This cohort study included baseline clinical data of Japanese individuals aged 12-13 years. A total of 1129 participants were followed up for an average of 8.6 years. We examined the association of childhood variables consisting of body weight, body mass index, systolic BP, white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet count, uric acid, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol with the development of high BP defined as ≥120/80 mmHg at 18-22 years old. At follow-up, the prevalence of high BP was 42.2% in men and 7.7% in women. Young men with high BP had childhood baseline characteristics that included higher body weight, body mass index, systolic BP, red blood cell count, hemoglobin, hematocrit, and uric acid than normotensive men. Young women with high BP had higher body weight, systolic BP, and uric acid at baseline. Multivariable logistic regression analysis revealed that a model including body weight, systolic BP, hematocrit, and uric acid had the highest predictive power (AUC 0.65 [95% CI, 0.62-0.69]) for men, and a model including body weight, systolic BP, and uric acid had the highest predictive power (AUC 0.70 [95% CI, 0.58-0.81]) for women. Comprehensive childhood health information contributes to the prediction of high BP in young adults.

Mediastinal Cystic Parathyroid Adenoma Diagnosed by Somatostatin Receptor Scintigraphy.

A 71-year-old man complained of nausea and loss of appetite for eight months prior to admission. He was transported to a hospital with disorientation and diagnosed with primary hyperparathyroidism by laboratory examinations. However, ultrasonography, computed tomography, and technetium-99m labeled methoxyisobutyl isonitrile (99mTc-MIBI) with single-photon emission computed tomography did not yield definite results. In contrast, somatostatin receptor scintigraphy successfully identified the lesion responsible for the over-secretion of parathyroid hormone within the middle mediastinum. The tumor was successfully resected by surgery, and a histopathological analysis confirmed the parathyroid adenoma nature of the tumor.

SARS-CoV-2 Infection among Medical Institution Faculty and Healthcare Workers in Tokyo, Japan.

Objective To consider effective measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in medical institutions, this study estimated the SARS-CoV-2 infection rate among healthcare workers (HCWs) in Tokyo, Japan, and determined the specific findings for mild coronavirus disease 2019 (COVID-19) cases. Methods This study analyzed the results of serologic tests to detect immunoglobulin G antibodies against SARS-CoV-2 and evaluated the demographic and clinical characteristics of the faculty and HCWs at a Tokyo medical institution in August 2020. The demographic and clinical characteristics of participants with antibody-positive results were compared to those of participants with antibody-negative results. Materials This study recruited 2,341 faculty and HCWs at a Tokyo medical institution, 21 of whom had a COVID-19 history. Results Of the 2,320 participants without a COVID-19 history, 20 (0.862%) had positive serologic test results. A fever and dysgeusia or dysosmia occurred with greater frequency among the participants with positive test results than in those with negative results [odds ratio (OR), 5.475; 95% confidence interval (CI), 1.960-15.293 and OR, 24.158; 95% CI, 2.693-216.720, respectively]. No significant difference was observed in the positivity rate between HCWs providing medical care for COVID-19 patients using adequate protection and other HCWs (OR, 2.514; 95% CI, 0.959-6.588). Conclusion To reduce the risk of COVID-19 spread in medical institutions, faculty and HCWs should follow standard and necessary transmission-based precautions, and those with a fever and dysgeusia or dysosmia should excuse themselves from work as soon as possible.

Initial experience of transumbilical laparoendoscopic single-site surgery of partial adrenalectomy in patient with aldosterone-producing adenoma.

BACKGROUND: Laparoscopic single-site surgery has recently emerged in the field of urology and this minimally-invasive surgery has resulted in a further reduction in morbidity compared with traditional laparoscopy. We present our initial experience with laparoendoscopic single-site surgery of partial adrenalectomy (LESS-PA) to treat aldosterone-producing adenomas. CASE PRESENTATION: A 60-year-old woman was diagnosed with aldosterone-producing macroadenomas in the left adrenal and aldosterone-producing microadenomas in the right adrenal. A two-step operation was planned. The first step involved transumbilical LESS-PA for the left adrenal tumors. A multichannel port was inserted through the center of the umbilicus and the left adrenal gland was approached using bent instruments according to standard traditional laparoscopic procedures. The tumors were resected using an ultrasonic scalpel, and the resected site was coagulated using a vessel sealing instrument and then sealed with fibrin glue. Operative time was 123 minutes and blood loss was minimal. The patient was discharged from hospital within 72 hours. Her right adrenal microadenomas will be treated in the next several months. CONCLUSIONS: Although our experience is limited, LESS-PA appears to be safe and feasible for treating aldosterone-producing adenomas. More cases and comparisons with the multiport technique are needed before drawing any definite conclusions concerning the technique.

Low birth weight trends: possible impacts on the prevalences of hypertension and chronic kidney disease.

Worldwide, hypertension and chronic kidney disease (CKD) are highly prevalent disorders and are strong risk factors for cardiovascular disease and end-stage renal disease (ESRD). The developmental origins of health and disease (DOHAD) concept suggests that undesirable perinatal environmental conditions, such as malnutrition, contribute to disease development in adults. Among the known hypertension and CKD risk factors, DOHAD plays a potential role in determining susceptibility to the onset of these diseases in later adulthood. Since low birth weight (LBW) is a surrogate marker for adverse fetal environmental conditions, the high incidence of LBW in developing countries and its increasing incidence in most developed countries (attributed to multiple pregnancies and prepregnancy maternal factors, such as undernutrition, advanced maternal age, and smoking) is concerning. Thus, LBW is an important public health problem not only because of the associated infant mortality and morbidity but also because it is a risk factor for adult-onset hypertension/CKD. During their reproductive years, pregnant women who were born with LBWs have an increased risk of hypertensive disorders of pregnancy, which contribute to the risk of developing cardiovascular disease and ESRD. The offspring of LBW females are also likely to be LBW, which suggests that susceptibility to hypertension/CKD may reflect transgenerational inheritance. Therefore, there is global concern about the increasing prevalence of LBW-related diseases. This review summarizes the relevance of hypertension and CKD in conjunction with DOHAD and discusses recent studies that have examined the impact of the upward LBW trend on renal function and blood pressure.

The distributions of hematologic and biochemical values in healthy high-school adolescents in Japan.

Laboratory tests of adolescents are often interpreted by using reference intervals derived from adults, even though these populations differ in their physical and physiologic characteristics and disease susceptibility. Therefore, to examine the distribution of laboratory values specific for adolescents, we analyzed hematologic and biochemical measurements obtained from 12,023 healthy Japanese adolescents (ages 15 through 18 years; male, 9165; female, 2858) during 2009 through 2018. Distributions were shown as medians with 95% (2.5th and 97.5th percentiles) of values and were compared with those from previous studies that examined similar Asian populations. There were some differences between hematologic parameters, serum creatinine and uric acid concentration, and lipid levels of Japanese adults and adolescents. In comparison with other Asian populations, the distributions of serum uric acid and high-density-lipoprotein cholesterol in the present study were slightly higher than those in the other studies. Although further research is need, the distributions of hematologic and biochemical tests in adolescents may have the potential to facilitate the early identification and management of disease in this population.

Control of a Nosocomial Outbreak of COVID-19 in a University Hospital.

BACKGROUND: Nosocomial spread of coronavirus disease 2019 (COVID-19) causes clusters of infection among high-risk individuals. Controlling this spread is critical to reducing COVID-19 morbidity and mortality. We describe an outbreak of COVID-19 in Keio University Hospital, Japan, and its control and propose effective control measures. METHODS: When an outbreak was suspected, immediate isolation and thorough polymerase chain reaction (PCR) testing of patients and health care workers (HCWs) using an in-house system, together with extensive contact tracing and social distancing measures, were conducted. Nosocomial infections (NIs) were defined as having an onset or positive test after the fifth day of admission for patients and having high-risk contacts in our hospital for HCWs. We performed descriptive analyses for this outbreak. RESULTS: Between March 24 and April 24, 2020, 27 of 562 tested patients were confirmed positive, of whom 5 (18.5%) were suspected as NIs. For HCWs, 52 of 697 tested positive, and 40 (76.9%) were considered NIs. Among transmissions, 95.5% were suspected of having occurred during the asymptomatic period. Large-scale isolation and testing at the first sign of outbreak terminated NIs. The number of secondary cases directly generated by a single primary case found before March 31 was 1.74, compared with 0 after April 1. Only 4 of 28 primary cases generated definite secondary infection; these were all asymptomatic. CONCLUSIONS: Viral shedding from asymptomatic cases played a major role in NIs. PCR screening of asymptomatic individuals helped clarify the pattern of spread. Immediate large-scale isolation, contact tracing, and social distancing measures were essential to containing outbreaks.

Features of and preventive measures against hypertension in the young.

The Japanese hypertension guidelines report that essential hypertension is detected in 1-3% of upper elementary and high school students during blood pressure (BP) screenings. Hypertension in these age groups is an emerging public health concern mainly attributed to the rising rate of pediatric obesity. Considering the existence of BP tracking phenomenon, early preventive education and instruction are necessary, especially for male students with moderately elevated BP showing a tendency toward obesity, despite the low prevalence of hypertension in high school students. Students with a positive family history of hypertension and those born with low birth weight need the same measures. Lifestyle habits, such as increased alcohol intake, dramatically change once students begin university; thus, early education and instruction regarding the factors influencing BP are necessary. In particular, for male students with higher BP during high school, caution regarding increased body weight is required irrespective of their level of obesity. Young adults aged <40 years should be educated about the association between body weight and hypertension. Particular caution surrounding lifestyle habits, including drinking and smoking, is warranted in male hypertensive subjects because hypertension at a young age is strongly associated with obesity. BP monitoring and the management of obesity should be considered efficient approaches to the detection and treatment of hypertension. For the lifetime prevention of hypertension, it is essential to be aware of one's health status and learn about healthy lifestyles beginning in childhood. BP measurement may be an appropriate means to achieve this goal.