Publications by authors named "Hideaki Suzuki"

243 Publications

Salvage Re-irradiation with Intensity-modulated Radiotherapy, Chemotherapy Combined with Hyperthermia for Local Recurrence of Nasopharyngeal Carcinoma After Chemoradiotherapy.

J UOEH 2021 ;43(3):355-361

Department of Radiology, University of Occupational and Environmental Health, Japan.

A sufficient dose of radiation is difficult to administer in re-irradiation for local recurrence of cancer after radiotherapy because of the dose limitation to organs at risk. Re-irradiation cases also include radioresistant tumors that are difficult to control locally, and their prognosis is poor in general. The effect of re-irradiation using intensity-modulated radiotherapy (IMRT) has recently been reported to significantly reduce the dose to organs at risk, and the efficacy of hyperthermia has been reported for radioresistant tumors. We report a case of local recurrence after concurrent chemoradiotherapy treated with salvage re-irradiation using IMRT and chemotherapy combined with hyperthermia in a patient with nasopharyngeal carcinoma, and include a discussion of the literature.
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http://dx.doi.org/10.7888/juoeh.43.355DOI Listing
January 2021

Detection of intracellular histological abnormalities using cardiac magnetic resonance T1 mapping in patients with Danon disease: a case series.

Eur Heart J Case Rep 2021 May 4;5(5):ytab145. Epub 2021 May 4.

Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.

Background: Danon disease is an X-linked dominant disorder with defects in the lysosome-associated membrane protein 2 (LAMP2) gene and is characterized histologically by intracellular autophagic vacuoles in skeletal and cardiac muscles. Cardiac magnetic resonance (CMR) T1 mapping potentially allows to differentiate intracellular and extracellular cardiac abnormalities with a combination of native T1 value and extracellular volume (ECV) fraction.

Case Summary: We assessed CMR T1 mapping in two Danon disease patients (a 22-year-old man and his 48-year-old mother), who had a LAMP2 c.864G>A p. Val288Val mutation, and two blood relatives without Danon disease (his 47-year-old maternal aunt and 49-year-old father). The male patient underwent a left ventricular (LV) assist device implantation at 15 months after the image acquisition because he was inotrope dependent (INTERMACS profile 3) and had no noticeable psychological or musculoskeletal symptoms. His mother was in New York Heart Association Class II with mildly reduced LV ejection fraction (46%). The Danon group showed late gadolinium enhancement (LGE) in the anterior and posterolateral LV walls. In the interventricular wall, where evident LGE was not noted, the Danon group had high native T1 value, compared with the T1 value in the non-Danon group, and normal ECV fraction. Cardiac biopsy from the interventricular wall showed intracytoplasmic autophagic vacuoles, which are characteristics of Danon disease.

Discussion: This characteristic pattern of high native T1 and normal ECV fraction in the areas without LGE, which may reflect the existence of intracytoplasmic autophagic vacuoles, may support the differential diagnosis of Danon disease from other cardiomyopathies.
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http://dx.doi.org/10.1093/ehjcr/ytab145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276603PMC
May 2021

Alcohol consumption in the general population is associated with structural changes in multiple organ systems.

Elife 2021 06 1;10. Epub 2021 Jun 1.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.

Background: Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample.

Methods: We assessed global effect sizes of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta, and liver of UK Biobank participants who reported drinking alcohol.

Results: We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (-1.7 × 10 ± 0.76 × 10 per doubling of alcohol consumption, p=3.0 × 10). Alcohol consumption was also associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption.

Conclusions: Our results imply that there is not a 'safe threshold' below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited.

Funding: See acknowledgements.
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http://dx.doi.org/10.7554/eLife.65325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192119PMC
June 2021

Sinusitis of actinomycosis infection : a case report.

J Med Invest 2021 ;68(1.2):202-204

Department of Otorhinolaryngology-Head and Neck Surgery.

Actinomycosis is an infection caused by anaerobic bacteria, primarily from the genus Actinomyces, which normally colonize the several regions including the mouth. Disruption of mucosa may lead to infection of virtually any site, but reports of involvement of the sinuses are rare. We report a case of an actinomycosis infection in the unilateral maxillary sinus. A 47-year-old female visited our hospital with a complaint of mild pain of left buccal region. Computed tomography (CT) revealed that the left maxillary and anterior ethmoidal sinus cavities were opacified along with a calcified fragment located close to the natural ostium. Thus, we provisionally diagnosed as a fungal sinusitis. She underwent trans-nasal endoscopic sinus surgery. The sinuses were opened and the caseous material was removed. The histopathological examination suggested an actinomycosis, but not fungal, infection. The patient's postoperative course was uneventful. No evidence of recurrence has been seen over the 30 months of the postoperative follow-up period. In case of the aggressive actinomycotic sinusitis, extension into the adjacent organs could be occurred. We should be aware that sinusitis of actinomycosis infection could progress in patients with risk factors such as diabetes and immunodeficiency. J. Med. Invest. 68 : 202-204, February, 2021.
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http://dx.doi.org/10.2152/jmi.68.202DOI Listing
January 2021

A Novel Cognitive Function Scale Using Functional Near-Infrared Spectroscopy for Evaluating Cognitive Dysfunction.

J Alzheimers Dis 2021 ;81(4):1579-1588

Medical Corporation Association Sochikai, Memory Clinic Ochanomizu, Tokyo, Japan.

Background: Maintaining cognitive function is integral to a healthy social life in the aged. Although neuropsychological tests and brain imaging methods can assess cognitive dysfunction, these techniques are subjective, psychologically burdensome, and cannot be conducted easily.

Objective: We sought to develop an objective, low-burden novel cognitive function scale based on functional near-infrared spectroscopy (fNIRS) of hemodynamic changes in the cerebral cortex during daily task performance.

Methods: A total of 63 participants (aged 60-80 years) identified as non-dementia controls (NDC) or with mild cognitive impairment (MCI) were recruited and randomly assigned to training and test data sets. Explanatory variables were hemodynamic responses during low-burden sensory and simple tasks without higher-order brain functioning.

Results: A logistic regression analysis of the fNIRS index in NDCs and MCI patients revealed area under the curve, sensitivity, specificity, and holdout results of 0.98, 94%, 88%, and 62% respectively. Correlation between fNIRS index and MCI odds showed positive linearity (R2 = 0.96).

Conclusion: Positive correlation between the fNIRS index and MCI odds indicated effectiveness of this fNIRS measurement. Although additional experiments are necessary, the fNIRS index representing degree of cognitive decline can be an onsite monitoring tool to assess cognitive status.
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http://dx.doi.org/10.3233/JAD-210072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293658PMC
September 2021

Calmodulin Regulates Ciliary Beats in the Human Nasal Mucosa Through Adenylate/Guanylate Cyclases and Protein Kinases A/G.

Int Arch Allergy Immunol 2021 21;182(9):800-806. Epub 2021 Apr 21.

Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Background: The ciliary beat of the airway epithelium, including the sinonasal epithelium, has a significant role in frontline defense and is thought to be controlled by the level of intracellular Ca2+. Involvement of calmodulin and adenylate/guanylate cyclases in the regulation of ciliary beats has been reported, and here we investigated the interrelation between these components of the ciliary beat regulatory pathway.

Methods: The inferior turbinates were collected from 29 patients with chronic hypertrophic rhinitis/rhinosinusitis during endoscopic sinonasal surgery. The turbinate mucosa was cut into thin strips, and mucociliary movement was observed under a phase-contrast light microscope equipped with a high-speed digital video camera.

Results: The ciliary beat frequency (CBF) was significantly increased by stimulation with 100 μM CALP3 (calmodulin agonist), which was completely suppressed by adding 100 µM SQ22536 (adenylate cyclase inhibitor) and 10 µM ODQ (guanylate cyclase inhibitor) together and by adding 1 µM KT5720 (protein kinase A inhibitor) and 1 µM KT5823 (protein kinase G inhibitor) together. The CBF was significantly increased by stimulation with 10 µM forskolin (adenylate cyclase activator) and 10 µM BAY41-2272 (guanylate cyclase activator) and by stimulation with 100 µM 8-bromo-cAMP (cAMP analog) and 100 µM 8-bromo-cGMP (cGMP analog), which was not changed by adding 1 µM calmidazolium (calmodulin antagonist).

Conclusions: These results confirmed that the regulatory pathway of ciliary beats in the human nasal mucosa involves calmodulin, adenylate/guanylate cyclases, and protein kinases A/G and indicate that adenylate/guanylate cyclases and protein kinases A/G act downstream of calmodulin, but not vice versa, and that these cyclases relay calmodulin signaling.
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http://dx.doi.org/10.1159/000515225DOI Listing
September 2021

Brain-heart connection in Takotsubo syndrome before onset.

Eur Heart J 2021 05;42(19):1909-1911

Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

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http://dx.doi.org/10.1093/eurheartj/ehab026DOI Listing
May 2021

Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect.

Nat Genet 2021 02 25;53(2):128-134. Epub 2021 Jan 25.

Department of Epidemiology and Biostatistics, Imperial College London, London, UK.

The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased LV contractility with HCM risk. A polygenic risk score explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that polygenic risk score may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.
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http://dx.doi.org/10.1038/s41588-020-00762-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611259PMC
February 2021

Cerebral small vessel disease genomics and its implications across the lifespan.

Nat Commun 2020 12 8;11(1):6285. Epub 2020 Dec 8.

University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35233, USA.

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
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http://dx.doi.org/10.1038/s41467-020-19111-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722866PMC
December 2020

Weekend and off-hour effects on the incidence of cerebral palsy: contribution of consolidated perinatal care.

Environ Health Prev Med 2020 Sep 10;25(1):52. Epub 2020 Sep 10.

Department of the Japan Obstetric Compensation System for Cerebral Palsy, Japan Council for Quality Health Care, Tokyo, Japan.

Objective: This study estimated the effects of weekend and off-hour childbirth and the size of perinatal medical care center on the incidence of cerebral palsy.

Methods: The cases were all children with severe cerebral palsy born in Japan from 2009 to 2012 whose data were stored at the Japan Obstetric Compensation System for Cerebral Palsy database, a nationally representative database. The inclusion criteria were the following: neonates born between January 2009 and December 2012 who had a birth weight of at least 2000 g and gestational age of at least 33 weeks and who had severe disability resulting from cerebral palsy independent of congenital causes or factors during the neonatal period or thereafter. Study participants were restricted to singletons and controls without report of death, scheduled cesarean section, or ambulance transportation. The controls were newborns, randomly selected by year and type of delivery (normal spontaneous delivery without cesarean section and emergency cesarean section) using a 1:10 case to control ratio sampled from the nationwide Japan Society of Obstetrics and Gynecology database.

Results: A total of 90 cerebral palsy cases and 900 controls having normal spontaneous delivery without cesarean section were selected, as were 92 cerebral palsy cases and 920 controls with emergent cesarean section. A significantly higher risk for cerebral palsy was found among cases that underwent emergent cesarean section on weekends (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.06-2.81) and during the night shift (OR 2.29, 95% CI 1.30-4.02). No significant risk was found among normal spontaneous deliveries on weekends (OR 1.63, 95% CI 0.97-2.73) or during the quasi-night shift (OR 1.26, 95% CI 0.70-2.27). Regional perinatal care centers showed significantly higher risk for cerebral palsy in both emergent cesarean section (OR 2.35, 95% CI 1.47-3.77) and normal spontaneous delivery (OR 2.92, 95% CI 1.76-4.84).

Conclusion: Labor on weekends, during the night shift, and at regional perinatal medical care centers was associated with significantly elevated risk for cerebral palsy in emergency cesarean section.
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http://dx.doi.org/10.1186/s12199-020-00889-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488476PMC
September 2020

Risk factors for cerebral palsy in neonates due to placental abruption.

J Obstet Gynaecol Res 2021 Jan 3;47(1):159-166. Epub 2020 Sep 3.

Department of the Japan Obstetric Compensation System for Cerebral Palsy in Public Interest Incorporated Foundation, Japan Council for Quality Health Care, Tokyo, Japan.

Aim: This study aimed to identify risk factors for the onset of cerebral palsy (CP) in neonates due to placental abruption and investigate their characteristics.

Methods: A retrospective case-control study was conducted using a nationwide registry from Japan. The study population included pregnant women (n = 122) who delivered an infant with CP between 2009 and 2015, where placental abruption was identified as the single cause of CP. The control group consisted of pregnant women with placental abruption, who delivered an infant without CP and were managed from 2013 to 2014. They were randomly identified from the prenatal database of the Japan Society of Obstetrics and Gynecology (JSOG-DB; n = 1214). Risk factors were investigated using multivariate analysis.

Results: Alcohol consumption (3.38, 2.01-5.68) (odds ratio, 95% confidence interval), smoking during pregnancy (3.50, 1.32-9.25), number of deliveries (1.28, 1.05-1.56), polyhydramnios (5.60, 1.37-22.6), oral administration of ritodrine hydrochloride (2.09, 1.22-3.57) and hypertensive disorders in pregnancy (2.25, 1.27-4.07) were significant risk factors. In contrast, intravenous administration of oxytocin (odds ratio, 95% confidence interval: 0.22, 0.09-0.58) and magnesium sulfate (0.122, 0.02-0.89) attenuated risk.

Conclusion: Alcohol consumption, smoking during pregnancy, number of deliveries, polyhydramnios, oral administration of ritodrine hydrochloride and hypertensive disorders in pregnancy were identified as risk factors for CP following placental abruption. Regarding alcohol consumption and smoking during pregnancy, the results suggest the importance of educational activities targeting pregnant women to increase their awareness of placental abruption.
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http://dx.doi.org/10.1111/jog.14447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818445PMC
January 2021

Insomnia and obstructive sleep apnea as potential triggers of dementia: is personalized prediction and prevention of the pathological cascade applicable?

EPMA J 2020 Sep 30;11(3):355-365. Epub 2020 Jul 30.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555 Japan.

Introduction: Sleep disorders ultimately result in sleep deficiency and poor-quality adversely impacts the immune system, glucose metabolism, body weight control, cardiovascular and cerebrovascular function, cognitive function, psychological stability, work productivity, quality of life, and social safety. Sleep disorders are very common among the elderly and are often comorbid with other diseases such as dementia, and further accelerating the underlying neurodegenerative processes. Initial studies have not clearly revealed the relationship between sleep disorders and dementia. Nonetheless, recent findings have suggested that insomnia and obstructive sleep apnea (OSA) are closely associated with dementia and perhaps they could be good predictors of occurrence of dementia and optimal treatments for sleep deficiencies may prevent or delay the onset dementia.

Methods: Here, we conducted a systematic review based on the criteria of predictive, preventive, and personalized medicine on the association of dementia in elderlies with sleep disorder, namely insomnia and OSA. We included 7432 studies and analyzed a total of 14 publications after applying appropriate exclusion criteria.

Results: We found that OSA patients had a large tendency to develop and/or experience accelerations of both Alzheimer's disease (AD) and also vascular dementia, whereas insomnia patients only develop and/or experience accelerations of AD. This may be reflected in the fact that AD and vascular dementia have similar and at the same time also different mechanisms of action. Several studies have also revealed that treating sleep disorders in elderly patients prevented or delayed the onset of dementia, mitigating the progression of symptoms in patients who already manifested dementic symptoms and even reversing neurodegeneration in particular brain areas.

Discussion: Currently, the general medical consensus has poorly addressed the role of sleep disorders in exacerbating the risk of dementia. Critically, studies such as the present one emphasizes that the treatment of sleep disorders could be one the preventive measures to evade or to improve dementia symptoms. Additionally, elderly individuals often manifest different sleep deficiency symptoms than younger ones. Given this, an improved age-specific categorization and evaluation methods for sleep deficiency need to be implemented in diagnosing dementia in order to enable personalized assessments and treatments. Collectively, these findings may also assist to improve efforts in predictively detecting and eventually treating dementia.
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http://dx.doi.org/10.1007/s13167-020-00219-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429588PMC
September 2020

A population-based phenome-wide association study of cardiac and aortic structure and function.

Nat Med 2020 10 24;26(10):1654-1662. Epub 2020 Aug 24.

Biomedical Image Analysis Group, Department of Computing, Imperial College London, London, UK.

Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart-brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers.
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http://dx.doi.org/10.1038/s41591-020-1009-yDOI Listing
October 2020

Osmotic perception of GABAergic synaptic transmission in the supraoptic nucleus of rats.

IBRO Rep 2020 Dec 2;9:58-64. Epub 2020 Jul 2.

Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Extracellular osmolality plays a crucial role in controlling the activation of neurons. Hypertonic stimulation modulates glutamatergic inputs to the supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs) putative vasopressin (VP) neurons through capsaicin-insensitive transient receptor potential vanilloid (TRPV) 1 channels on the presynaptic terminals. However, it remains unclear whether osmotic stimulation modulates GABAergic inputs to VP-secreting neurons within punched-out slices containing only the SON and the perinuclear zone. To answer this question, we studied the effects of various osmotic conditions on the miniature GABAergic postsynaptic currents (mGPSCs) using the whole-cell patch-clamp technique on rat SON putative VP-secreting neurons in small slice preparations. We revealed that incubation in hypertonic solution for 2 h reduced both the frequency and amplitude of the mGPSCs to the SON putative VP neurons, whereas the mGPSCs were unaffected when the external osmolality was changed from isotonic to hypotonic. Of interest, we found that changing from a hypertonic to hypotonic environment increased the frequency of the mGPSCs. This effect was independent of TRPV4. We hypothesize that two coordinated mechanisms may play an important role in the regulation of a wide range of physiological functions of VP.: 1) the modulation of GABA receptor properties by brain-derived neurotrophic factor (BDNF)-induced tyrosine kinase B receptor-mediated signaling under hypertonic conditions, and 2) cell swelling-induced activation of whole-cell anion currents under hypotonic conditions.
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http://dx.doi.org/10.1016/j.ibror.2020.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355382PMC
December 2020

Beneficial effects of riociguat on hemodynamic responses to exercise in CTEPH patients after balloon pulmonary angioplasty - A randomized controlled study.

Int J Cardiol Heart Vasc 2020 Aug 10;29:100579. Epub 2020 Jul 10.

Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: Although balloon pulmonary angioplasty (BPA) improves symptoms and pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH), the effects of riociguat on hemodynamics and exercise capacity in patients after BPA remain to be elucidated.

Methods And Results: This study was a single-center, prospective, randomized, open-label trial. From November 2015 to November 2018, we prospectively examined 21 patients with CTEPH (65 ± 9 years old, M/F 2/19) who showed hemodynamic improvement with mean pulmonary arterial pressure (mPAP) < 30 mmHg after BPA without any vasodilators. We performed hemodynamic evaluation and expired gas analysis both at rest and during exercise in supine position using cycle ergometer. After right heart catheterization during exercise, they were randomly assigned to 2 groups with minimized method, using age, sex, and resting mPAP; riociguat (N = 10) and control (N = 11) groups. After 6 months, exercise capacity evaluated by 6-min walk distance and cardiopulmonary exercise testing, and resting hemodynamic parameters were comparable in both groups. However, cardiac output (CO) (6.0 ± 1.7-7.4 ± 1.6, P < 0.01) and pulmonary vascular resistance (4.8 ± 1.8-3.2 ± 0.7 Wood units, P = 0.02) at peak workload were significantly improved in the riociguat group as compared with the control group. The slope of linearized mPAP-CO relationship was significantly decreased in the riociguat group [14.5 (7.8, 14.7) to 6.41 (5.1, 11.4), P < 0.01] but not in the control group.

Conclusions: These results indicate that riociguat exerts beneficial effects on hemodynamic response to exercise in CTEPH patients even after hemodynamic improvement by BPA.
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http://dx.doi.org/10.1016/j.ijcha.2020.100579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356201PMC
August 2020

Fetal heart rate pattern in term or near-term cerebral palsy: a nationwide cohort study.

Am J Obstet Gynecol 2020 12 1;223(6):907.e1-907.e13. Epub 2020 Jun 1.

Recurrence Prevention Committee, the Japan Obstetric Compensation System for Cerebral Palsy, Public Interest Incorporated Foundation, Japan Council for Quality Health Care, Tokyo, Japan; Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Mie, Japan.

Background: It is crucial to interpret fetal heart rate patterns with a focus on the pattern evolution during labor to estimate the relationship between cerebral palsy and delivery. However, nationwide data are not available.

Objective: The aim of our study was to demonstrate the features of fetal heart rate pattern evolution and estimate the timing of fetal brain injury during labor in cerebral palsy cases.

Study Design: In this longitudinal study, 1069 consecutive intrapartum fetal heart rate strips from infants with severe cerebral palsy at or beyond 34 weeks of gestation, were analyzed. They were categorized as follows: (1) continuous bradycardia (Bradycardia), (2) persistently nonreassuring, (3) reassuring-prolonged deceleration, (4) Hon's pattern, and (5) persistently reassuring. The clinical factors underlying cerebral palsy in each group were assessed.

Results: Hypoxic brain injury during labor (those in the reassuring-prolonged deceleration and Hon's pattern groups) accounted for 31.5% of severe cerebral palsy cases and at least 30% of those developed during the antenatal period. Of the 1069 cases, 7.86% were classified as continuous bradycardia (n=84), 21.7% as persistently nonreassuring (n=232), 15.6% as reassuring-prolonged deceleration (n=167), 15.9% as Hon's pattern (n=170), 19.8% as persistently reassuring (n=212), and 19.1% were unclassified (n=204). The overall interobserver agreement was moderate (kappa 0.59). Placental abruption was the most common cause (31.9%) of cerebral palsy, accounting for almost 90% of cases in the continuous bradycardia group (64 of 73). Among the cases in the Hon's pattern group (n=67), umbilical cord abnormalities were the most common clinical factor for cerebral palsy development (29.9%), followed by placental abruption (20.9%), and inappropriate operative vaginal delivery (13.4%).

Conclusion: Intrapartum hypoxic brain injury accounted for approximately 30% of severe cerebral palsy cases, whereas a substantial proportion of the cases were suspected to have either a prenatal or postnatal onset. Up to 16% of cerebral palsy cases may be preventable by placing a greater focus on the earlier changes seen in the Hon's fetal heart rate progression.
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http://dx.doi.org/10.1016/j.ajog.2020.05.059DOI Listing
December 2020

Frequency-specific efficacy of intratympanic steroid on idiopathic sudden sensorineural hearing loss.

Acta Otolaryngol 2020 Sep 4;140(9):756-760. Epub 2020 Jun 4.

Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Hearing recovery would be different in each sound frequency in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). To analyze frequency-specific efficacy of intratympanic steroid on ISSNHL. Of a total of 381 patients with ISSNHL (hearing threshold ≥40 dB; ≤30 days until treatment), 174 patients (174 ears) received systemic steroid plus hyperbaric oxygen therapy (HBO group), and 207 patients (208 ears) received systemic plus intratympanic steroid (IT group). Hearing thresholds at 125-8000 Hz were measured at every octave before and after treatment. % of patients with hearing gains ≥10 dB in the IT group was significantly higher for 500 Hz and the average of 5 mid-frequencies, tended to be higher for 1000 Hz, but was significantly lower for 8000 Hz, compared to the HBO group. Multiple regression analysis showed that hearing recovery was negatively correlated with patients' age for 125/2000/4000/8000 Hz and with days from onset to treatment for all frequencies, and also revealed better hearing recovery at 500/1000 Hz in the IT group than in the HBO group. Intratympanic steroid is more effective than hyperbaric oxygen to yield better hearing outcomes at mid-frequencies and would be advantageous to restore sound/speech perception. Superiority of intratympanic steroid over hyperbaric oxygen for treating ISSNHL was verified.
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http://dx.doi.org/10.1080/00016489.2020.1770331DOI Listing
September 2020

A case of thoracic endometriosis-related pneumothorax in a menopausal woman.

Gen Thorac Cardiovasc Surg 2020 Dec 14;68(12):1584-1586. Epub 2020 May 14.

Center of Chest Medicine and Surgery, Ehime University, Toon, Ehime, Japan.

Thoracic endometriosis-related pneumothorax (TERP) or thoracic endometriosis syndrome (TES) usually occurs in women of childbearing age and affects the right thorax. Menopausal and left-sided cases are rare. A case of left-sided TERP in a postmenopausal woman after adjuvant endocrine therapy for breast cancer is reported. A 51-year-old woman underwent video-assisted thoracic surgery for recurrent left pneumothorax. Immunohistological examination of the resected specimen from the apical bleb and a diaphragmatic blueberry spot demonstrated thoracic endometriosis. Even in the case of a left-sided pneumothorax in a menopausal woman, clinicians should be aware of the possibility of TERP.
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http://dx.doi.org/10.1007/s11748-020-01381-8DOI Listing
December 2020

Expression of Cl channels/transporters in nasal polyps.

Eur Arch Otorhinolaryngol 2020 Aug 24;277(8):2263-2270. Epub 2020 Apr 24.

Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.

Purpose: Nasal polyp formation is a common sequela of prolonged chronic rhinosinusitis, but the mechanism underlying this disease state is still controversial. We compared the expressions of Cl channels/transporters in nasal polyps with those in inferior turbinates to explore whether a deficiency in Cl transport may participate in the pathophysiology of nasal polyp formation as in patients with cystic fibrosis.

Methods: Nasal polyps and inferior turbinates were collected from 12 chronic rhinosinusitis patients with hypertrophic rhinitis and/or nasal polyps. Expressions of cystic fibrosis transmembrane conductance regulator (CFTR), pendrin, Na-K-2Cl cotransporter 1 (NKCC1), SLC26A3, TMEM16A and anion exchanger 2 (AE2) were examined by fluorescence immunohistochemistry using Alexa Fluor 488.

Results: CFTR was weakly expressed on the epithelial surface of the turbinate mucosa whereas the nasal polyps showed almost no fluorescence. Pendrin was mainly expressed on the epithelial surface in both tissues. The fluorescence was moderate in the nasal polyps and strong in the turbinate mucosa. For NKCC1, moderate fluorescence was observed throughout the entire epithelial layer of the nasal polyps, but the turbinate mucosa exhibited almost no fluorescence. On the other hand, no fluorescence for SLC26A3, TMEM16A or AE2 was seen in either tissue.

Conclusion: These results suggest that CFTR, pendrin and NKCC1 may participate in the pathogenesis of nasal mucosal edema and play roles in the mechanism of nasal polyp formation.
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http://dx.doi.org/10.1007/s00405-020-05981-1DOI Listing
August 2020

Pediatric nasopharyngeal cancer with repeated oligometastases involving the bone, liver and distant lymph nodes who achieved cure after radiotherapy.

Nagoya J Med Sci 2020 Feb;82(1):135-141

Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, Japan.

Systemic chemotherapy is a standard treatment for Stage IVc nasopharyngeal carcinoma (NPC). Stage IVc NPC patients with oligometastases have a better prognosis, and local therapy has an important role in further development of the disease. However, the efficacy of local therapy to the metastases in patients with multiple-site and/or multiple-organ metastases is limited due to the aggressive behavior of the tumor. We report a NPC case in a pediatric patient with repeated oligometastases involving the bone, liver and distant lymph nodes who achieved 10-year disease free status after initial chemotherapy and radiotherapy to all the metastases. This very rare case demonstrated that radiotherapy to oligometastatic lesions have a potential to cure repeated oligometastases which involved multiple-organ metastases in a pediatric NPC with stage IVc.
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http://dx.doi.org/10.18999/nagjms.82.1.135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103869PMC
February 2020

Large-scale Quality Control of Cardiac Imaging in Population Studies: Application to UK Biobank.

Sci Rep 2020 02 12;10(1):2408. Epub 2020 Feb 12.

Imperial College London, Department of Computing, BioMedIA Group, London, SW7 2AZ, UK.

In large population studies such as the UK Biobank (UKBB), quality control of the acquired images by visual assessment is unfeasible. In this paper, we apply a recently developed fully-automated quality control pipeline for cardiac MR (CMR) images to the first 19,265 short-axis (SA) cine stacks from the UKBB. We present the results for the three estimated quality metrics (heart coverage, inter-slice motion and image contrast in the cardiac region) as well as their potential associations with factors including acquisition details and subject-related phenotypes. Up to 14.2% of the analysed SA stacks had sub-optimal coverage (i.e. missing basal and/or apical slices), however most of them were limited to the first year of acquisition. Up to 16% of the stacks were affected by noticeable inter-slice motion (i.e. average inter-slice misalignment greater than 3.4 mm). Inter-slice motion was positively correlated with weight and body surface area. Only 2.1% of the stacks had an average end-diastolic cardiac image contrast below 30% of the dynamic range. These findings will be highly valuable for both the scientists involved in UKBB CMR acquisition and for the ones who use the dataset for research purposes.
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http://dx.doi.org/10.1038/s41598-020-58212-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015892PMC
February 2020

Impacts of hippocampal blood flow on changes in left ventricular wall thickness in patients with chronic heart failure.

Int J Cardiol 2020 07 10;310:103-107. Epub 2020 Jan 10.

Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address:

Background: Although depressive symptoms increased mortality and hospitalization in chronic heart failure (CHF) patients, the underlying mechanism remains unclear. The aim of this study was to investigate whether an alteration in hippocampal perfusion, which is the neural substrate of depressive symptoms, is associated with changes in cardiac structures and/or functions in CHF patients.

Methods: We used baseline data of 70 CHF patients (66.8 ± 8.9 yrs, 32.5% women), including cerebral blood flow (CBF) in the hippocampus, geriatric depression scale (GDS) scores and echocardiographic parameters, in the Brain Assessment and Investigation in Heart Failure Trial (B-HeFT) (UMIN000008584). Echocardiography was repeated at 3.1 ± 0.5 years after the baseline evaluation. We first tested voxel-wise regression model with hippocampal CBF as dependent variable and each of echocardiographic parameter change as independent variable, adjusted for age and sex. Structural equation modeling was used to test a mediation effect of cognitive test scores on associations between hippocampal perfusion and changes in cardiac structures and/or functions.

Results: Baseline anterior hippocampal CBF was negatively correlated with changes in left ventricular posterior wall thickness (PWT) (P < 0.05 with family-wise error corrections). An existence of depressive symptoms was positively correlated with the baseline anterior CBF and negatively with the PWT changes (P < 0.05, both). There were both direct effects of the baseline anterior hippocampal CBF on PWT thinning and effects mediated through the depressive symptoms (P < 0.05, both).

Conclusions: This study provides the first evidence that the alteration in hippocampal perfusion may lead to changes in cardiac structures via increase in depressive symptoms in CHF patients.
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http://dx.doi.org/10.1016/j.ijcard.2020.01.019DOI Listing
July 2020

Transcatheter aortic valve implantation and cognitive function in elderly patients with severe aortic stenosis.

EuroIntervention 2020 Apr 3;15(18):e1580-e1587. Epub 2020 Apr 3.

Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Aims: The aim of this study was to examine the mechanisms of cognitive impairment and reversibility in elderly patients with severe aortic stenosis (AS) after transcatheter aortic valve implantation (TAVI) with special reference to cerebral blood flow (CBF).

Methods And Results: We examined 15 elderly patients with severe AS (mean age 83.2±4.5 years, 12 female) who underwent TAVI. Before and three months after TAVI, we evaluated cognitive function with the Logical Memory II test (LM II), cardiac output (CO) with echocardiography, and CBF with 99mTc single-photon emission computed tomography (SPECT). LM II score and CO were significantly increased after TAVI compared with baseline (p<0.01 for LM II, p<0.005 for CO). Notably, CBF in the local regions, including that in the right hippocampus, was significantly increased after TAVI (p<0.005 at each voxel). The patients with increased CO after TAVI also showed significantly increased CBF in the right hippocampus compared with those without it (p<0.01). Importantly, CBF in the right hippocampus was positively correlated with LM II scores (p<0.05).

Conclusions: These results provide the first evidence that TAVI may improve cognitive functions associated with increased cerebral perfusion especially in the hippocampus in elderly patients with severe AS.
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http://dx.doi.org/10.4244/EIJ-D-19-00489DOI Listing
April 2020

Associations of Regional Brain Structural Differences With Aging, Modifiable Risk Factors for Dementia, and Cognitive Performance.

JAMA Netw Open 2019 12 2;2(12):e1917257. Epub 2019 Dec 2.

Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom.

Importance: Identifying brain regions associated with risk factors for dementia could guide mechanistic understanding of risk factors associated with Alzheimer disease (AD).

Objectives: To characterize volume changes in brain regions associated with aging and modifiable risk factors for dementia (MRFD) and to test whether volume differences in these regions are associated with cognitive performance.

Design, Setting, And Participants: This cross-sectional study used data from UK Biobank participants who underwent T1-weighted structural brain imaging from August 5, 2014, to October 14, 2016. A voxelwise linear model was applied to test for regional gray matter volume differences associated with aging and MRFD (ie, hypertension, diabetes, obesity, and frequent alcohol use). The potential clinical relevance of these associations was explored by comparing their neuroanatomical distributions with the regional brain atrophy found with AD. Mediation models for risk factors, brain volume differences, and cognitive measures were tested. The primary hypothesis was that common, overlapping regions would be found. Primary analysis was conducted on April 1, 2018.

Main Outcomes And Measures: Gray matter regions that showed relative atrophy associated with AD, aging, and greater numbers of MRFD.

Results: Among 8312 participants (mean [SD] age, 62.4 [7.4] years; 3959 [47.1%] men), aging and 4 major MRFD (ie, hypertension, diabetes, obesity, and frequent alcohol use) had independent negative associations with specific gray matter volumes. These regions overlapped neuroanatomically with those showing lower volumes in participants with AD, including the posterior cingulate cortex, the thalamus, the hippocampus, and the orbitofrontal cortex. Associations between these MRFD and spatial memory were mediated by differences in posterior cingulate cortex volume (β = 0.0014; SE = 0.0006; P = .02).

Conclusions And Relevance: This cross-sectional study identified differences in localized brain gray matter volume associated with aging and MRFD, suggesting regional vulnerabilities. These differences appeared relevant to cognitive performance even among people considered cognitively healthy.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.17257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991214PMC
December 2019

Prognostic value of the model for end-stage liver disease excluding INR score (MELD-XI) in patients with adult congenital heart disease.

PLoS One 2019 19;14(11):e0225403. Epub 2019 Nov 19.

Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Patients with adult congenital heart disease (ACHD) are at increased risk of developing late cardiovascular complication. However, little is known about the predictive factors for long-term outcome. The Model for End-Stage Liver Disease eXcluding INR (MELD-XI) score was originally developed to assess cirrhotic patients and has the prognostic value for heart failure (HF) patients. In the present study, we examined whether the score also has the prognostic value in this population. We retrospectively examined 637 ACHD patients (mean age 31.0 years) who visited our Tohoku University hospital from 1995 to 2015. MELD-XI score was calculated as follows; 11.76 x ln(serum creatinine) + 5.11 x ln(serum total bilirubin) + 9.44. We compared the long-term outcomes between the high (≥10.4) and the low (<10.4) score groups. The cutoff value of MELD-XI score was determined based on the survival classification and regression tree (CART) analysis. The major adverse cardiac event (MACE) was defined as a composite of cardiac death, HF hospitalization, and lethal ventricular arrhythmias. During a mean follow-up period of 8.6 years (interquartile range 4.4-11.4 years), MACE was noted in 51 patients, including HF hospitalization in 37, cardiac death in 8, and lethal ventricular arrhythmias in 6. In Kaplan-Meier analysis, the high score group had significantly worse MACE-free survival compared with the low score group (log-rank, P<0.001). Multivariable Cox regression analysis showed that the MELD-XI score remained a significant predictor of MACE (hazard ratio 1.36, confidence interval 1.17-1.58, P<0.001) even after adjusting for patient characteristics, such as sex, functional status, estimated glomerular filtration rate, and cardiac function. Furthermore, CART analysis revealed that the MELD-XI score was the most important variable for predicting MACE. These results demonstrate that the MELD-XI score can effectively predict MACE in ACHD patients, indicating that ACHD patients with high MELD-XI score need to be closely followed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225403PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863541PMC
March 2020

Cyclophilin A as a biomarker for the therapeutic effect of balloon angioplasty in chronic thromboembolic pulmonary hypertension.

J Cardiol 2020 04 12;75(4):415-423. Epub 2019 Oct 12.

Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: Although cardiac troponin and natriuretic peptide have been shown to decrease after balloon pulmonary angioplasty (BPA) with improved right ventricular afterload in chronic thromboembolic pulmonary hypertension (CTEPH), biomarkers to evaluate the effects of BPA independently of heart failure status remain to be developed.

Methods: In 39 consecutive CTEPH patients including 31 who underwent BPA, we measured plasma levels of cyclophilin A (CyPA), which we demonstrated is secreted from pulmonary vascular smooth muscle cells in response to mechanical stretch and hypoxia.

Results: CyPA levels were elevated in CTEPH patients (12.7, IQR: 7.6-16.0) compared with 8 thromboembolic controls with a history of venous thromboembolism (4.9, IQR: 2.4-11.2) or 18 healthy controls (4.1, IQR: 2.4-6.8) (both p< 0.05) and were linearly correlated with mean pulmonary arterial pressure (r=0.50, p = 0.0003) and pulmonary vascular resistance (r=0.32, p= 0.026). BPA reduced CyPA levels and tended to lower brain-type natriuretic peptide (BNP) levels (p< 0.01 and p = 0.07). When comparing the changes in CyPA before and after BPA in the two subgroups with higher (≥35pg/mL) and normal (<35pg/mL) BNP at baseline, CyPA decreased both in patients with higher BNP and those with normal BNP (both p< 0.05). In contrast, BNP decreased only in patients with higher BNP (p< 0.05). Also, CyPA decreased both in patients with lower (<25 kg/m) and higher (≥25kg/m) body mass index (BMI) at baseline (both p<0.05), whereas BPA tended to reduce BNP in patients with lower BMI (p = 0.12) but not in those with higher BMI (p = 0.55).

Conclusions: CyPA could be a useful biomarker to evaluate the effects of BPA even in patients with normal BNP or high BMI.
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http://dx.doi.org/10.1016/j.jjcc.2019.09.010DOI Listing
April 2020

Calmodulin and protein kinases A/G mediate ciliary beat response in the human nasal epithelium.

Int Forum Allergy Rhinol 2019 11 1;9(11):1352-1359. Epub 2019 Oct 1.

Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Background: Mucociliary clearance of the airway epithelium is an essential function for mucosal defense. We recently proposed a hypothetical mechanism of ciliary beat regulation, in which the pannexin-1 (Panx1)-P2X7 unit serves as an oscillator generating a periodic increase in intracellular Ca ([Ca ] ). In the present study, we examined the localization of Panx1 and P2X7 at the ultrastructural level, and investigated the regulatory pathway subsequent to [Ca ] increase.

Methods: The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic sinonasal surgery. The mucosa was examined by transmission immunoelectron microscopy for Panx1 and P2X7. Alternatively, the mucosa was cut into thin strips, and ciliary beat frequency (CBF) was measured under a phase-contrast light microscope with a high-speed digital video camera.

Results: In immunoelectron microscopy, immunoreactivities for Panx1 and P2X7 were localized along the plasma membrane of the entire length of the cilia. CBF was significantly increased by stimulation with 100 µM acetylcholine (Ach). The Ach-induced CBF increase was significantly inhibited by calmidazolium (calmodulin antagonist), SQ22536 (adenylate cyclase inhibitor), ODQ (guanylate cyclase inhibitor), KT5720 (protein kinase A inhibitor), and KT5823 (protein kinase G inhibitor). Fluorodinitrobenzene (creatine kinase inhibitor) completely inhibited the ciliary beat in a time- and dose-dependent manner.

Conclusion: These results indicate that Panx1 and P2X7 coexist at the cilia of the human nasal epithelial cells and that the ciliary beat is regulated by calmodulin, adenylate/guanylate cyclases and protein kinases A/G, and crucially depends on creatine kinase.
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http://dx.doi.org/10.1002/alr.22442DOI Listing
November 2019

Unsupervised breastfeeding was related to sudden unexpected postnatal collapse during early skin-to-skin contact in cerebral palsy cases.

Acta Paediatr 2020 06 9;109(6):1154-1161. Epub 2019 Sep 9.

University of Miyazaki, Miyazaki, Japan.

Aim: This study aimed to identify the clinical features of infants who were healthy at birth, but developed sudden unexpected collapse and were then diagnosed with cerebral palsy before 5 years of age.

Methods: We retrospectively analysed 1182 records from the no-fault Japan Obstetric Compensation System for Cerebral Palsy database up to 2016. This identified 45 subjects (3.8%) who were subsequently diagnosed with severe cerebral palsy due to sudden unexpected postnatal collapse (SUPC). They were all healthy at birth, based on the criteria of five-minute Apgar scores of seven or more, with normal umbilical cord blood gases and no need for neonatal resuscitation within five minutes of birth.

Results: The median birth weight of the 45 subjects (26 males) was 2770 g (range 2006-3695 g). Of these, 10 developed SUPC during early skin-to-skin contact (SSC). Medical personnel were not present in all 10 cases: nine were being breastfed at the time and eight of the mothers did not notice their infant's abnormal condition until medical staff alerted them.

Conclusion: This national study of children with cerebral palsy who appeared healthy at birth found that unsupervised breastfeeding was a common factor in cases of SUPC during early SSC.
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http://dx.doi.org/10.1111/apa.14961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318205PMC
June 2020

New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.

Nat Hum Behav 2019 09 29;3(9):950-961. Epub 2019 Jul 29.

Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.
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http://dx.doi.org/10.1038/s41562-019-0653-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711277PMC
September 2019

Gcm1 is involved in cell proliferation and fibrosis during kidney regeneration after ischemia-reperfusion injury.

Sci Rep 2019 05 27;9(1):7883. Epub 2019 May 27.

Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan.

In acute kidney injury (AKI), the S3 segment of the proximal tubule is particularly damaged, as it is most vulnerable to ischemia. However, this region is also involved in renal tubular regeneration. To deeply understand the mechanism of the repair process after ischemic injury in AKI, we focused on glial cells missing 1 (Gcm1), which is one of the genes expressed in the S3 segment. Gcm1 is essential for the development of the placenta, and Gcm1 knockout (KO) is embryonically lethal. Thus, the function of Gcm1 in the kidney has not been analyzed yet. We analyzed the function of Gcm1 in the kidney by specifically knocking out Gcm1 in the kidney. We created an ischemia-reperfusion injury (IRI) model to observe the repair process after AKI. We found that Gcm1 expression was transiently increased during the recovery phase of IRI. In Gcm1 conditional KO mice, during the recovery phase of IRI, tubular cell proliferation reduced and transforming growth factor-β1 expression was downregulated resulting in a reduction in fibrosis. In vitro, Gcm1 overexpression promoted cell proliferation and upregulated TGF-β1 expression. These findings indicate that Gcm1 is involved in the mechanisms of fibrosis and cell proliferation after ischemic injury of the kidney.
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http://dx.doi.org/10.1038/s41598-019-44161-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536531PMC
May 2019
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