Iodine deficiency in Spain is a persisting public health problem and the prescription of potassium iodide is recommended during pregnancy. The purpose of this study was to develop an Artificial Neural Network (ANN) to predict the risk factors of iodine deficiency during pregnancy, and compare the results obtained with a logistic regression model. Two hundred forty-four healthy pregnant women were included in a descriptive and prospective study in their first trimester of pregnancy. The women enrolled were asked specifically about their use of supplements containing potassium iodide, iron, folic acid and/or multivitamins during pregnancy. The consumption of iodine-rich foods was assessed through a food frequency questionnaire. A median UIC of 57.4 μg/L (IQR 32.8-99.3) was obtained, with 89.3% < 150 μg/L, the minimum recommended ioduria level by the WHO. There was no correlation between urinary iodine concentrations and maternal age, BMI or gestation week at recruitment. The urinary iodine concentrations were significantly higher in women who reported taking iodized supplements and/or iodized salt than those who did not. Number of gestations, age, body mass index, and intake of iodized supplements and iodized salt were the most important predictors of iodine deficiency. Based on Receiver Operating Characteristic analysis, the diagnostic performance of the ANN model was superior to the logistic regression model. The ANN model, with variables on pregnancy and the intake of iodine rich foods, iodized supplement and iodized salt may be useful for predicting iodine deficiency in the early pregnancy.

Puberty is the transitional period from childhood to adult that leads to growth spurt, sexual maturation and attainment of reproductive capacity. Precocious puberty is defined when secondary sexual characteristics develop before the age of eight for girls and nine for boys. Central precocious puberty (CPP) is diagnosed when the process is driven by premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Many factors promote CPP, and the thyroid function is thought to be one of them. In our previous study, thyroid stimulating hormone (TSH) was higher in the CPP group than that of the participants without CPP. This elevation of TSH in CPP is said to be associated with pubertal luteinizing hormone (LH) elevation. The aim of this study was to evaluate the causal relationship between TSH and LH in CPP patients. A total of 221 girls diagnosed with CPP and treated with GnRH agonists were included. All participants except one showed LH suppression (peak LH < 3 IU/L), and serum levels of follicle stimulating hormone (FSH) were also lower after the treatment. These results indicate that puberty has slowed down and that the patients were successfully treated for CPP. As for thyroid hormones, TSH was significantly lower and free thyroxine (fT4) levels were higher after 12 months of GnRH agonist treatment compared with baseline. With GnRH agonist treatment, the serum levels of LH and TSH were decreased, suggesting that the increase in serum TSH levels is associated with premature LH elevation in girls with CPP.

Ependymal cells have an essential role in regulating the dynamics of the cerebrospinal fluid flow by the movement of their multiple cilia. Impaired generation or function of cilia could cause hydrocephalus due to the disordered dynamics of the cerebrospinal fluid flow. However, molecular bases regulating differentiation of the ependymal cells and their ciliogenesis have not been fully elucidated. We report here that bone morphogenetic proteins (BMPs), growth factors orchestrating tissue architecture throughout the body, inhibit ciliogenesis during ependymal cell differentiation in primary cell culture. Previous in vitro study has reported that ectopic expression of Smad6 and Smad7 promotes differentiation of embryonic stem cells into multi-ciliated ependymal-like cells. Since Smad6 and Smad7 have been known as the intracellular inhibitory factors of the BMP signaling pathway, the activation of the pathway could cause a deficit in ciliogenesis of ependymal cells. To examine whether activation of the pathway affects ciliogenesis, we investigated the effects of two BMPs, BMP2 and BMP4, on the ependymal differentiation of the primary cultured cells prepared from the neonatal mouse brain. Supplementation of BMP2 or BMP4 in culture media significantly reduced the number of cells with multiple cilia among the total cells, while most of the cells expressed FoxJ1, a master regulator of ciliogenesis. Activation of the pathway was confirmed by the phosphorylation of intracellular Smad1/5/8, downstream factors of the BMP receptors. These in vitro results suggest that inhibition of the BMP signaling pathway might be essential for ciliogenesis during the ependymal cell differentiation in vivo.

In thyroid pathology, the great variety of types and the wide range of aggressiveness of thyroid cancers complicate both diagnosis and management. In 2016, a subset of noninvasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as noninvasive follicular thyroid tumor with papillary-like nuclear features (NIFTP) to reduce overtreatment of this low-risk tumor that follows a benign course after surgery. Starting from a paradigmatic clinical case, in this short review, we will summarize the ultrasonography, cytological, histological and molecular features of this new entity. In the preoperative settings, the recognition of some peculiar elements may only suggest the possibility of a NIFTP, thus favoring a less aggressive surgical approach. However, the diagnosis of NIFTP can only be made after complete resection of the lesion by detecting well-defined inclusion and exclusion histopathological criteria. Since NIFTP is not ‘malignant,’ surgery may be considered curative with no further treatment or surveillance needed. NIFTP-related issues, including nodule size, multifocality, oncocytic changes, heterogeneous incidence across different geographical areas and its occurrence in the pediatric age, will be discussed.

Testicular cancer occurs in the testes of the male reproductive system and is the most common cancer in adolescent and young adult (AYA) men. However, recently, there have been more cases of testicular cancer in men older than 40 years. Therefore, trends of testicular cancer during the past 40 years were retrospectively examined, focusing on age and histology. Patients who were diagnosed with testicular cancer at our institution between 1980 and 2019 were enrolled in this study. The patients were divided into groups by the year of diagnosis (1980s, 1990s, 2000s, and 2010s), age at diagnosis (14, 15 to 39, and older than 40 years), and histological type (seminoma and non-seminoma). A total of 563 patients were diagnosed with testicular cancer over the 40-year period. The median age at diagnosis increased continuously, from 28 years to 31 years, 34 years, and 38 years in each period, respectively (p < 0.001). Moreover, most testicular cancer patients were of the AYA generation, whereas the ratio of patients older than 40 years increased significantly since 2000 (p < 0.001). The relative proportion of seminoma also increased more than 50% since 2000. In the seminoma group, median age increased from 31 years to 41 years during the 40-year period (p < 0.001). In conclusion, the age at diagnosis is rising for testicular cancer patients. Clinicians should recognize that testicular cancer affects not only the AYA generation, but there has been a shift to older than 40 years, especially in seminoma.

Urothelial carcinoma of the bladder (UCB) is potentially life-threatening; therefore, we aimed to discover a novel urine biomarker for diagnosis and prognostication of UCB. This is a retrospective case-control study. Exploration of a new biomarker using urine from 20 UCB patients in the present study revealed that urinary level of lactoferrin (LF), a multifunctional glycoprotein released from neutrophils, was higher in 11 of 15 with invasive/high-grade UCB than 5 with non-invasive one, and 2 healthy adults. We therefore focused on LF and assessed the value of urine LF normalized by urine creatinine concentration (LF/Cr) using an enzyme-linked immunosorbent assay. Diagnostic performance of urine LF/Cr was examined using urine from 92 patients with primary (newly diagnosed) untreated UCB and 166 controls without UCB, including 62 patients with pyuria, and 104 subjects without pyuria consisting of 84 patients and 20 healthy adults. However, the diagnostic accuracies were accompanied by the risk of bias. In 92 primary UCB patients, both pyuria and tumor-infiltrating neutrophils (TINs) were independent predictors for urine LF/Cr. In contrast, TINs or urine LF/Cr were independent predictors for invasive histology, whereas pyuria was not. In terms of prognostication, urine LF/Cr and nodal metastasis were independent predictors of disease-specific survival in 22 patients with muscle-invasive bladder cancer, characterized by a high mortality rate, in the Cox proportional hazards model. In conclusion, urine LF/Cr linked to TINs was a predictor of both invasive histology and prognosis in UCB. Urine LF/Cr is a potential biomarker reflecting the degree of malignancy in UCB.

With population aging, an increasing attention has been paid to quality of life rather than mere longevity. Now, it is urgently needed to clarify predictors of well-being in later life, i.e., “successful aging (SA).” The aim of this study is to investigate whether the number of remaining teeth impacts on maintenance of SA among Japanese older people. The present study was conducted in Tsurugaya district, a suburban area of Sendai, in northern Japan, and included older people aged ≥ 70 years who had met the criteria for SA at a 2003 baseline survey. At the baseline survey, dentists obtained data for the number of remaining teeth. We obtained information about Long-term Care Insurance certification, including the dates of incident functional disability and death between 2003 and 2012. Data pertaining to health-related quality of life (HRQOL) were collected at the 2003 baseline survey and the 2012 follow-up survey. Maintenance of SA was defined in terms of survival, disability-free status and high HRQOL in both 2003 and 2012. Among 450 participants, 108 (24.0%) were considered to have maintained a state of SA. When participants were classified into three groups according to previous studies, in comparison with participants who retained 0-9 teeth, the multivariate prevalence ratios (95% confidence intervals) were 1.39 (0.81-2.36) for those who retained 10-19 teeth and 1.58 (1.002-2.50) for those who retained ≥ 20 teeth (p trend = 0.046). The present results suggest that retaining ≥ 20 teeth is associated with maintenance of SA among Japanese older people.

Exercise habits are known as a protective factor for a variety of diseases and thus recommended worldwide; however, few studies have examined long-term effects of exercise habits on mortality. We continuously monitored death status in a nationwide population sample of 7,709 eligible persons from the National Integrated Project for Prospective Observation of Noncommunicable Disease and its Trends in the Aged in 1990 (NIPPON DATA90), for which baseline data were obtained in 1990. To investigate the long-term impact of baseline exercise habits, we calculated the relative risk of non-exercisers (participants without regular voluntary exercise habits) in reference to exercisers (those with these habits) for all-cause or cause-specific mortality using a Cox proportional hazard model, in which the following confounding factors were appropriately adjusted: sex, age, body mass index, total energy intake, smoking, drinking, and history of cardiovascular disease. During a median 20 years of follow-up, 1,747 participants died, 99 of heart failure. The risk for all-cause mortality was 12% higher in non-exercisers than in exercisers (95% confidence interval, 1%-24%), which was also observed for mortality from heart failure, as 68% higher in non-exercisers than in exercises (95% confidence interval, 3%-173%). These associations were similarly observed when the participants were divided to subgroups by sex, age, and the light, moderate, or vigorous intensity of physical activity, without any significant heterogeneities (P > 0.1). The present study has revealed significant impact of exercise habits on long-term mortality risks, supporting worldwide recommendations for improvement of exercise habits.

Behavioral and psychological symptoms of dementia (BPSD) challenge caregivers, leading to caregiver burden and subsequent nursing home or inpatient placement in a psychiatric hospital for dementia. Favorable positive emotions should be an important goal for the treatment of negative emotions of BPSD. Arts are one of the most profound areas to stimulate favorable emotions. We have asked a professional actor, who was not involved in the daily care and regular rehabilitations, to give a dramatic performance by reading selected stories as if the patients with BPSD felt to be in the audiences of a theater. We wondered whether a dramatic performance by the actor might be a way to respond to the complex needs of inpatients with BPSD, especially focused on favorable emotions. New inpatients (Alzheimer’s disease, vascular dementia, or dementia with Lewy bodies) were randomly assigned to a control group (n = 20) and a dramatic performance group (n = 14) in Sendai Tomizawa Hospital, a psychiatric hospital for dementia, in Japan. Dramatic performances were performed for one and half hours once per week for 3 months. Neuropsychiatric Inventory for BPSD decreased in both groups and delightful emotional index (DEI) for favorable emotions increased in the intervention group but not in the control group after 3 months. At 3 months, there was an increase of DEI in intervention group compared with control group. We conclude that dramatic performance may be one of the appropriate interventions in patients with BPSD, as it appears to help in their favorable emotional state.

White coat hypertension is defined as elevated blood pressure in the office, but a normal blood pressure out-of-office, whereas masked hypertension is defined as elevated blood pressure in the office, but normal out-of-office blood pressure. The objective was to investigate the associations between these blood pressure phenotypes and carotid artery changes. Conventional blood pressure, ambulatory blood pressure, and carotid ultrasonography were evaluated in 851 Ohasama residents (31.8% men; mean age 66.3 years). The blood pressure phenotypes were defined by the ordinary thresholds (140/90 mmHg for conventional blood pressure, 135/85 mmHg for daytime blood pressure) and then by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) thresholds for hypertension (130/80 mmHg for both conventional and daytime blood pressure), irrespective of antihypertensive medication treatment status. Blood pressure phenotypes were linearly associated with the mean intima-media thickness of the carotid artery in ascending order for sustained normal blood pressure, white coat hypertension, masked hypertension, and sustained hypertension according to the ordinary thresholds and the 2017 ACC/AHA thresholds (both linear trends P < 0.0001) after adjustments for possible confounding factors. The odds ratios for the presence of carotid plaques showed similar linear trends with the blood pressure phenotypes according to the 2017 ACC/AHA thresholds (linear trend P < 0.0191). In conclusion, there was a close relationship between blood pressure phenotypes and carotid artery changes, suggesting that blood pressure phenotypes as defined by ambulatory blood pressure are potentially useful for risk stratification of carotid artery changes in the Japanese general population.