Layer-specific dilation of penetrating arteries induced by stimulation of the nucleus basalis of Meynert in the mouse frontal cortex

To clarify mechanisms through which activation of the nucleus basalis of Meynert (NBM) increases cerebral cortical blood flow, we examined whether cortical parenchymal arteries dilate during NBM stimulation in anesthetized mice. We used two-photon microscopy to measure the diameter of single penetrating arteries at different depths (∼800 μm, layers I to V) of the frontal cortex, and examined changes in the diameter during focal electrical stimulation of the NBM (0.5 ms at 30 to 50 μA and 50 Hz) and hypercapnia (3% CO₂ inhalation). Stimulation of the NBM caused diameter of penetrating arteries to increase by 9% to 13% of the prestimulus diameter throughout the different layers of the cortex, except at the cortical surface and upper part of layer V, where the diameter of penetrating arteries increased only slightly during NBM stimulation. Hypercapnia caused obvious dilation of the penetrating arteries in all cortical layers, including the surface arteries. The diameters began to increase within 1 second after the onset of NBM stimulation in the upper cortical layers, and later in lower layers. Our results indicate that activation of the NBM dilates cortical penetrating arteries in a layer-specific manner in magnitude and latency, presumably related to the density of cholinergic nerve terminals from the NBM.     

Living and working environments are important determinants of glycemic control in patients with diabetes during the COVID‐19 pandemic: A retrospective observational study

AimTo investigate (1) the association of lifestyle changes and living and working conditions with glycemic control and (2) whether treatment was intensified appropriately in patients with diabetes under the first COVID‐19 state of emergency in Japan.Materials and MethodsA total of 321 participants were included. Participants completed a questionnaire regarding lifestyle changes, including diet, physical activity, and living and working conditions during the COVID‐19 pandemic. The change in hemoglobin A1c (HbA1c) levels was estimated before (June 1, 2019 to August 31, 2019) and during (June 1, 2020 to August 31, 2020) the pandemic. Factors associated with changes in HbA1c levels were examined by multiple linear regression analysis. The proportion of patients who received treatment intensification for diabetes was compared between before and during the pandemic.ResultsThere was no significant change in HbA1c levels before the pandemic and during the pandemic (7.13 ± 0.98% vs 7.18 ± 1.01%, P = 0.186). Teleworking (estimate 0.206, P = 0.004) and living with a dog (estimate −0.149, P = 0.038) were significantly associated with changes in HbA1c levels after adjusting for covariates. There was no significant difference in the proportion of patients who received treatment intensification for diabetes during the pandemic and before the pandemic in either the elderly or non‐elderly patients.ConclusionsOverall glycemic control did not worsen during the pandemic. Nonetheless, environmental factors, including telework, were found to influence glycemic control in patients with diabetes. Further studies are needed to clarify whether the COVID‐19 pandemic could affect treatment intensification for diabetes.     

Combining the Tumor Contact Length and Apparent Diffusion Coefficient Better Predicts Extraprostatic Extension of Prostate Cancer with Capsular Abutment: A 3 Tesla MR Imaging Study

Purpose: To assess the diagnostic performance of the tumor contact length (TCL) and apparent diffusion coefficient (ADC) for predicting extraprostatic extension (EPE) of prostate cancer with capsular abutment (CA).Methods: Ninety-three patients with biopsy-proven prostate cancer underwent 3-Tesla MRI, including diffusion-weighted imaging (b value = 0, 2000 s/mm²) and radical prostatectomy. Two experienced radiologists, blinded to the clinicopathological data, retrospectively assessed the presence of CA on T2-weighted imaging (T2WI). TCL on T2WI and ADC values were measured on detecting CA in prostate cancer. We used the receiver operating characteristic curves to assess the diagnostic performance of TCL and ADC values for predicting EPE.Results: CA was present in 58 prostate cancers among 93 patients. The cut-off value for TCL was 6.9 mm, which yielded an area under the curve (AUC) of 0.75. This corresponded to a sensitivity, specificity, and accuracy of 84.2%, 61.5%, and 69.0%, respectively. The cut-off value for ADC was 0.63 × 10^–3 mm²/s, which yielded an AUC of 0.76. This, in turn, corresponded to a sensitivity, specificity, and accuracy of 84.2%, 59.0%, and 67.2%, respectively. The combined cut-off value of TCL and ADC yielded an AUC of 0.82. The specificity (84.6%) and accuracy (81.0%) of the combined value were superior to their individual values (P < 0.05).Conclusion: A combination of TCL and ADC values provided high specificity and accuracy for detecting EPE of prostatic cancer with CA.     

Dietary Patterns of 479 Indonesian Adults and Their Associations with Sodium and Potassium Intakes Estimated by Two 24-h Urine Collections

The excess sodium (Na) intake and insufficient potassium (K) intake are frequently observed all over the world, including Indonesia. This study explored the dietary patterns of Indonesian people and evaluated their associations with Na and K intakes. Na and K intakes were assessed by repeated 24-h urine collection. The dietary patterns of the previous month were extracted by factor analysis using the Indonesian Food Frequency Questionnaire. The participants were community-dwelling Indonesian men and women (n = 479) aged 20 years and over. We identified four dietary patterns in each sex. After controlling for confounding factors, the high quantile of ‘Noodle, oil, and salty sea products’ pattern was associated with the high Na intake in both men and women (p = 0.02 and <0.001, respectively). The ‘Meat, vegetable, oil, and fruit’ pattern statistically significantly contributed to the high K intake in men (p = 0.04), but not in women (p = 0.26). The ‘Vegetable, non-oil, and milk’ pattern in men and ‘Meat, vegetable, and fruit’ pattern in women were associated with low Na:K ratios (p = 0.03 and 0.01, respectively). Neither ‘bread’ nor ‘fish’ appeared as a major determinant of any dietary patterns in this population. The ‘Noodle, oil, and salty sea products’ pattern should be avoided to reduce sodium intake.     

Involvement of DNase II-like acid DNase in the cataract formation of the UPL rat and the Shumiya cataract rat

The loss of organelles and DNA is important to ensure transparency of the lenses, and DNase II-like acid DNase (also called DNase IIbeta, DLAD) is related to the loss of organelles and DNA in the lenses. We investigated the relation between the degradation of DNA and DLAD mRNA expression in the lenses of two hereditary cataract rats, the UPL rat (UPLR) and the Shumiya cataract rat (SCR), during cataract development. Undigested DNA was detected in the lens cortexes of normal UPLRs and SCRs, and undigested DNA was degraded in the lens nuclei of normal UPLRs and SCRs. DLAD does not affect common cataract formation, since DLAD mRNA expression levels in the lenses of cataractous SCRs were not changed with an increase in age, and undigested DNA was degraded in the lens nuclei of cataractous SCRs. On the other hand, an accumulation of undigested DNA was found in the lens nuclei of cataractous UPLRs at 46 and 53 d of age with opaque lenses, and the decrease in DLAD mRNA expression levels occurred prior to the accumulation of undigested DNA in the lens nuclei. It is possible that UPLRs are a good model for cataract caused by a decrease of DNA degradation in the lenses.     

Epilepsy in Wolf-Hirschhorn syndrome (4p-)

PURPOSE: We investigated the evolution of epilepsy, seizure types, and effective drugs in Wolf-Hirschhorn syndrome, which is a malformation syndrome often with refractory seizures and status epilepticus. METHODS: We reviewed 11 cases of Wolf-Hirschhorn syndrome (age range, 2-25 years; SD, 7.2 years) and who were treated in Osaka University or Osaka Medical Center of Research Institute for Maternal and Child Health. RESULTS: In all patients, febrile or afebrile convulsions had developed. Epileptic seizures included alternative hemiconvulsions, generalized tonic-clonic seizures, focal clonic seizures, tonic seizures, and epileptic spasms. Seizures were often induced by a high fever or a hot bath. Status epilepticus occurred in all patients, including one patient who died at the first status epilepticus. In some cases, intratracheal intubation was needed because of respiratory insufficiency. The effective antiepileptic drugs for long-term use were sodium bromide (four of four), followed by clorazepate (CLP; one of two), and nitrazepam (NZP; two of four). Sodium bromide was particularly effective for preventing status epilepticus. The mean age of last status epilepticus in patients receiving sodium bromide (1 year 8 months) was significantly younger than that in those not treated with sodium bromide (3 year 4 months). CONCLUSIONS: We identified that, in most patients of Wolf-Hirschhorn syndrome, the frequency of both seizures and status epilepticus decreased gradually after age 5 years. However, during infancy, status epilepticus sometimes resulted in permanent disability or even death. We propose that sodium bromide should be used as the initial treatment for the prevention of the development of status epilepticus associated with Wolf-Hirschhorn syndrome.     

Estrogen receptor alpha polymorphism as a genetic marker for bone loss, vertebral fractures and susceptibility to estrogen

OBJECTIVE: The purpose of the present study was to investigate the possible roles of PvuII and XbaI polymorphisms of the estrogen receptor alpha (ER(alpha)) in bone mineral density (BMD), vertebral fracture, bone loss rate after menopause and response to hormone replacement therapy (HRT). METHODS: All 286 women were grouped according to the genotypes of PvuII or XbaI polymorphisms of the ER(alpha) gene. We compared the BMD Z-score, incidence of vertebral fracture, changes in Z-score after menopause and response of BMD to HRT among the genotypes. RESULTS: Subjects with the PPxx genotype had significantly (P<0.05) lower Z-scores than did subjects with the other genotypes. A negative correlation was observed between the length of time after menopause and the decrease of the Z-score only in women with the pp genotype, suggesting faster bone loss in this group. In the analysis of the ER(alpha) polymorphism with regard to the effect of HRT on BMD, there appears to be a significantly greater increase of BMD (P<0.01 and 0.05) in women with the pp genotype than in those with the Pp or PP genotype. CONCLUSIONS: PvuII and XbaI polymorphisms of the ER(alpha) gene were associated with BMD in postmenopausal Japanese women. Also, the polymorphisms may be useful genetic markers for predicting vertebral fracture in relatively young postmenopausal women. The PvuII polymorphism may be associated with susceptibility to changes in estrogen level.     

Relationships between the serum levels of soluble leptin receptor and free and bound leptin in non-pregnant women of reproductive age and women undergoing controlled ovarian hyperstimulation

BACKGROUND: The aim of this study was to investigate the relationships between the serum levels of soluble leptin receptor (SLEPR), and total, free and bound leptin, and the change in the serum SLEPR level during an IVF cycle. METHODS: Serum concentrations of leptin and SLEPR were measured in 50 Japanese women of reproductive age, and 20 patients participating in an IVF programme. The total leptin was fractionated into free and bound portions by gel filtration chromatography. RESULTS: The SLEPR level was negatively correlated with the body mass index (BMI) (r = -0.548, P < 0.0001), total leptin (r = -0.433, P < 0.0001), the percentage of free leptin (r = -0.732, P < 0.0001) and the absolute free leptin concentration (r = -0.506, P < 0.0001). The SLEPR level was positively correlated with the percentage of bound leptin (r = 0.730, P < 0.0001), whereas there was little variation in the absolute bound leptin concentration, regardless of the BMI or SLEPR concentration. During the IVF cycle, total and free leptin elevated during maximal ovarian stimulation, whereas there was no significant difference in the SLEPR concentration. CONCLUSIONS: The results demonstrate a skillful mechanism where a change in the serum SLEPR level regulates, in part, the biological activity of leptin in the circulation.